Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Immunoglobulin G (IgG) nephropathy refers to a rare group of diseases characterized by deposits of IgG in the mesangial region. However, IgG nephropathy is controversial as a single disease entity, and its pathogenesis remains to be elucidated. In the present report, we discuss a case of IgG nephropathy in which we observed activation of the classical complement pathway.A 47-year-old woman was admitted to our hospital with nephrotic syndrome. Light-microscopic examination revealed neither proliferative nor sclerotic lesions in the glomeruli. However, unusual and large deposits were observed in the paramesangial area. An immunofluorescence study revealed predominant IgG and C1q and slight C3 deposits in the paramesangial area, suggesting immune-complex-type glomerular disease. An electron microscopic study also revealed different sizes of non-organized electron-dense deposits with a similar pattern of distribution, which were accompanied by foot process effacement. Clinically, there was no evidence of systemic diseases, such as infectious or autoimmune diseases (including systemic lupus erythematosus). Based on these findings, she was diagnosed with IgG nephropathy and treated with prednisolone. Steroid therapy was effective, and complete remission was maintained.Additional immunological examination revealed that IgG deposits were polyclonal and consisted mainly of the IgG1 and IgG3 subclasses. Furthermore, staining was positive for C4d and C5b-9. The present findings indicate that the pathogenesis of IgG nephropathy in our patient may have involved activation of the classical complement pathway.

DOI： 10.1007/s13730-022-00710-5

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Ponatinib is a novel multi-tyrosine kinase inhibitor (TKI) with potent inhibitory activity against refractory chronic myeloid leukemia (CML). Despite its high clinical efficacy, ponatinib induces various adverse events due to its multi-target characteristic. However, renal complications associated with ponatinib are rare. A 76-year-old woman had a history of chronic myeloid leukemia (CML) resistant to imatinib and nilotinib. Our patient developed proteinuria and renal function deterioration during treatment with ponatinib but not with imatinib or nilotinib. We herein report the first case of a patient with secondary focal segmental glomerulosclerosis (FSGS) with partial glomerular collapse induced by ponatinib treatment.

DOI： 10.2169/internalmedicine.1283-22

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The intrauterine adverse environment during nephrogenesis reduces the nephron number, probably associates with impaired ureteric bud (UB) branching. METHODS: The kidneys in C57/BL6 mice were irradiated with a single dose of 10 gray (10 Gy) as adverse environment on postnatal day 3 (irradiated PND3 kidneys) after UB branching ceased. The renal functions and pathological findings of irradiated PND3 kidneys were compared with those of non-irradiated control and 10 Gy irradiation on PND14 (irradiated PND14 kidney) from 1 to 18 months. RESULTS: The number and density of glomeruli in irradiated PND3 kidneys were reduced by 1 month with renal dysfunction at 6 months. The morphologically incomplete glomeruli with insufficient capillaries were involuted by 1 month in the superficial cortex. Reduced tubular numbers and developmental disability with shortening renal tubules occurred in irradiated PND3 kidneys with impaired urine concentration at 6 months. Hypertrophy of glomeruli developed, and occasional sclerotic glomeruli appeared in the juxtamedullary cortex with hypertension and albuminuria at 12 to 18 months. CONCLUSIONS: The reduced number of nephrons with shortening renal tubules occurred with impaired renal functions in a postnatal adverse environment after cessation of UB branching, and glomerular hypertrophy with occasional glomerulosclerosis developed accompanied with hypertension and albuminuria in the adulthood. IMPACT: The reduced number of nephrons with shortening renal tubules occurred with impaired renal functions in a postnatal adverse environment after cessation of ureteric bud branching. The reduced number of glomeruli were associated with not only the impaired formation of glomeruli but also involution of morphologically small incomplete glomeruli after an adverse environment. The insufficiently developed nephrons were characterized by the shortening renal tubules with impaired urine concentration. In addition, glomerular hypertrophy and occasional glomerulosclerosis developed with hypertension and albuminuria in adulthood. The present study can help to understand the risk of alternations of premature nephrons in preterm neonates.

DOI： 10.1038/s41390-022-02332-0

PubMed

researchmap

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

A 44-year-old woman was admitted due to gross hematuria and progressive renal dysfunction. Poststreptococcal acute glomerulonephritis (PSAGN) was suspected due to her elevated anti-streptolysin O and anti-streptokinase titers and hypocomplementemia. A renal biopsy showed crescent formation and endocapillary hypercellularity with neutrophil infiltrate. An immunofluorescence analysis showed granular immunoglobulin G and C3 deposition, suggesting immune-complex-type glomerulonephritis. However, myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA) was positive, and peritubular capillaritis was observed. Furthermore, citrullinated histone H3-positive neutrophils were detected as markers for neutrophil extracellular trap formation. Therefore, she was diagnosed with ANCA-associated vasculitis superimposed on PSAGN that was the main contributor to her progressive renal injury.

DOI： 10.2169/internalmedicine.8690-21

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ekir.2022.08.020

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

We report the case of an 80 year-old woman who developed bilateral lower extremity purpura and renal impairment with proteinuria a few days after a transient fever (day 0). High levels of both anti-streptolysin-O antibody (ASO) and anti-streptokinase antibody (ASK), as well as low levels of coagulation factor XIII in serum were noted. Skin biopsy was performed and showed a leukocytoclastic vasculitis with deposition of IgA and C3 in the cutaneous small vessels, indicating IgA vasculitis in the skin. After initiation of oral prednisolone, the skin lesions showed significant improvement. However, renal function and proteinuria gradually worsened from day 12. Kidney biopsy was performed on day 29, which demonstrated a necrotizing and crescentic glomerulonephritis with mesangial deposition of IgA and C3. In addition, the deposition of galactose-deficient IgA1 (Gd-IgA1) was positive on glomeruli and cutaneous small vessels, indicating that the purpura and glomerulonephritis both shared the same Gd-IgA1-related pathogenesis. In addition, the association between the acute streptococcal infection and the IgA vasculitis was confirmed by the deposition of nephritis-associated plasmin receptor (NAPlr) in glomeruli. The patient was treated with steroid pulse and intravenous cyclophosphamide, in addition to the oral prednisolone treatment. Renal function and proteinuria gradually improved, but did not completely recover, as is typically seen with courses of IgA vasculitis in the elderly. In this case, the streptococcal infectionrelated IgA vasculitis was confirmed pathologically by the deposition of both NAPlr and Gd-IgA1 in glomeruli, as well as Gd-IgA1 in the cutaneous small vessels.

DOI： 10.1007/s13730-022-00684-4

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation is associated with glomerular capillary injuries with focal mesangiolysis. Here, we report a case of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) presenting with multiple glomerular capillary microaneurysms. A 53-year-old woman presented with persistent proteinuria and microhematuria. She had no underlying diseases, such as hematopoietic or lymphoproliferative disorders. A renal biopsy showed diffuse membranoproliferative lesions with foam cell infiltration and multiple microaneurysms of the glomerular capillary on light microscopy. Immunofluorescence analysis showed granular deposits of monoclonal immunoglobulin G3 kappa (IgG3κ), C1q, C3, and C4 in the glomeruli. Electron microscopy revealed different sizes of non-organized electron-dense deposits in the mesangial, subendothelial, and subepithelial areas. In addition, glomerular endothelial cells showed swelling and loss of fenestra or diffuse formation of fenestrated diaphragms, accompanied by irregular thinning of the glomerular basement membrane. Furthermore, immunostaining for CD31 (a marker for endothelial cell) and low-vacuum scanning electron microscopy study identified loss of endothelial cells in microaneurysm, suggesting severe glomerular endothelial cell injury. After a renal biopsy, only the medication for dyslipidemia was continued because there were no physical symptoms, such as edema, and urinary abnormalities continued with stable renal function. Further studies are needed to elucidate the pathogenesis of glomerular capillary injury in PGNMID and clarify the clinical and pathological characteristics of PGNMID with glomerular capillary microaneurysms.

DOI： 10.1007/s13730-021-00676-w

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

INTRODUCTION: Focal segmental glomerular sclerosis (FSGS) is caused by podocyte injury. It is characterized by obliteration of glomerular capillary tufts with increased extracellular matrix (ECM). Altered communication between podocytes and glomerular endothelial cells (ECs) contributes to sclerosis progression. We focused on EC injury in the FSGS. METHODS: A total of 29 FSGS and 18 control biopsy specimens were assessed for clinicopathologic characteristics. CD34 (a marker for EC)-positive capillaries and ECM accumulation were evaluated quantitatively for each variant using computer-assisted image analysis. RESULTS: The estimated glomerular filtration rate (eGFR) in the FSGS group was significantly lower than that in the control group. The frequency of FSGS variants was 51.7% for cellular; 13.8% for perihilar (PH), tip, and not otherwise specified (NOS); and 6.9% for collapsing. Regarding sclerotic lesions in all FSGS, narrowing or loss of CD34-positive capillaries was observed. Electron microscopy results showed loss of fenestrae, subendothelial space enlargement, and cytoplasmic swelling, indicating EC injury. Computer-assisted image analysis revealed significantly smaller areas of glomerular capillaries in FSGS with or without sclerotic lesions, with increased ECM. Moreover, in comparison with each variant, narrowed capillaries and ECM accumulation were most prominent in the collapsing variant, whereas the tip variant had the least change. CONCLUSION: EC injury was observed in all FSGS cases, not only in sclerotic lesions but also in nonsclerotic lesions. Severity of EC injury may vary in each variant due to diverse alterations of glomerular capillary networks.

DOI： 10.1016/j.ekir.2022.03.007

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Low-vacuum scanning electron microscopy (LV-SEM) is applied to diagnostic renal pathology. METHODS: To demonstrate the usefulness of LV-SEM and to clarify the optimal conditions of pathology samples, we investigated the alterations of glomerular basement membrane (GBM) and podocytes in control and experimental active Heymann nephritis (AHN) rats by LV-SEM. RESULTS: On week 15 following induction of AHN, spike formation on GBM with diffuse deposition of IgG and C3 developed. Using LV-SEM, diffuse crater-like protrusions were clearly noted three-dimensionally (3D) on surface of GBM in the same specimens of light microscopy (LM) and immunofluorescence (IF) studies only after removal coverslips or further adding periodic acid-silver methenamine (PAM) staining. These 3D ultrastructural findings of GBM surface could be detected in PAM-stained specimens by LV-SEM, although true GBM surface findings could not be obtained in acellular glomeruli, because some subepithelial deposits remained on surface of GBM. Adequate thickness was 1.5-5 μm for 10% formalin-fixed paraffin-embedded (FFPE) and 5-10 μm for the unfixed frozen sections. The foot processes and their effacement of podocytes could be observed by LV-SEM using 10%FFPE specimens with platinum blue (Pt-blue) staining or double staining of PAM and Pt-blue. These findings were obtained more large areas in 2.5% glutaraldehyde-fixed paraffin-embedded (2.5%GFPE) specimens. CONCLUSION: Our findings suggest that LV-SEM is a useful assessment tool for evaluating the alterations of GBM and podocytes in renal pathology using routine LM and IF specimens, as well as 2.5%GFPE specimens.

DOI： 10.1007/s10157-021-02147-z

PubMed

researchmap

Authorship：Lead author   Language：English  

DOI： 10.1007/s10157-021-02076-x

PubMed

researchmap

Language：English  

DOI： 10.1093/omcr/omab103

PubMed

researchmap

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch-Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.

DOI： 10.1038/s41598-021-92655-5

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

DOI： 10.1007/s10157-021-02077-w

researchmap

Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/his.14247

researchmap

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/his.14247

Language：English   Publishing type：Research paper (scientific journal)  

Leriche syndrome is an aortoiliac occlusive disease with three chief symptoms: claudication, impotence, and weak femoral pulse. It can also cause occlusion of the aorta up to the level of the renal arteries. We report a case in which aortoiliac bypass and renal artery thrombectomy were effective in ameliorating acute kidney injury caused by bilateral renal artery thrombosis.

DOI： 10.1272/jnms.JNMS.2021_88-610

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Depletion of ATP in renal tubular cells plays the central role in the pathogenesis of kidney diseases. Nevertheless, inability to visualize spatiotemporal in vivo ATP distribution and dynamics has hindered further analysis. METHODS: A novel mouse line systemically expressing an ATP biosensor (an ATP synthase subunit and two fluorophores) revealed spatiotemporal ATP dynamics at single-cell resolution during warm and cold ischemic reperfusion (IR) with two-photon microscopy. This experimental system enabled quantification of fibrosis 2 weeks after IR and assessment of the relationship between the ATP recovery in acute phase and fibrosis in chronic phase. RESULTS: Upon ischemia induction, the ATP levels of proximal tubule (PT) cells decreased to the nadir within a few minutes, whereas those of distal tubule (DT) cells decreased gradually up to 1 hour. Upon reperfusion, the recovery rate of ATP in PTs was slower with longer ischemia. In stark contrast, ATP in DTs was quickly rebounded irrespective of ischemia duration. Morphologic changes of mitochondria in the acute phase support the observation of different ATP dynamics in the two segments. Furthermore, slow and incomplete ATP recovery of PTs in the acute phase inversely correlated with fibrosis in the chronic phase. Ischemia under conditions of hypothermia resulted in more rapid and complete ATP recovery with less fibrosis, providing a proof of concept for use of hypothermia to protect kidney tissues. CONCLUSIONS: Visualizing spatiotemporal ATP dynamics during IR injury revealed higher sensitivity of PT cells to ischemia compared with DT cells in terms of energy metabolism. The ATP dynamics of PTs in AKI might provide prognostic information.

DOI： 10.1681/ASN.2020050580

PubMed

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a clinicopathological syndrome characterized by nephrotic-range proteinuria with high incidence of progression to end-stage renal disease (ESRD). In primary FSGS, 40-60% of patients develop ESRD within 10-20 years. SUMMARY: Recurrence of FSGS after kidney transplantation is frequent and is associated with poor allograft survival. The risk factors for recurrent FSGS include onset of FSGS during childhood, rapid progression of primary FSGS to ESRD, history of recurrent FSGS in previous allograft, and diffuse mesangial hypercellularity or collapsing variant of FSGS in the native kidney. The early histological findings of recurrent FSGS consist of unremarkable glomerular changes on light microscopy but significant podocyte effacement on electron microscopy; the loss of foot processes with eventual dropout of podocytes leads to the development of segmental lesions in the glomerulus. Experimental and clinical data suggest the existence of circulating permeability factors, such as soluble urokinase-type plasminogen activator receptor (suPAR), cardiotrophin-like cytokine factor-1 (CLCF-1), CD40 axis, and apolipoprotein A-Ib (ApoA-Ib), in the pathogenesis of recurrent FSGS. These biomarkers including circulating permeability factors may facilitate earlier diagnosis of FSGS posttransplant and may guide in the development of novel therapies that may be more effective and improve long-term outcomes in kidney transplantation. Key Messages: Several studies have suggested the possible circulating permeability factors, such as suPAR, CLCF-1, CD40 axis, and ApoA-Ib, in the pathogenesis and disease progression of FSGS and recurrent FSGS. Further studies should be performed to elucidate the true essential biomarker(s) associated with the onset and progression of FSGS as well as recurrent FSGS.

DOI： 10.1159/000510748

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Acute kidney injury (AKI) and chronic kidney disease (CKD) are considered common complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES AND METHOD: In this study, 114 patients who had undergone allo-HSCT were retrospectively analyzed to investigate the risk factors for onset of posttransplant AKI and CKD as defined by the new Kidney Disease Improving Global Outcomes criteria. RESULTS: Seventy-four patients (64.9%) developed AKI and 25 (21.9%) developed CKD. The multivariate analysis showed that the risk factors for developing stage 1 or higher AKI were age ≥46 years at the time of transplant (p = 0.001) and use of ≥3 nephrotoxic drugs (p = 0.036). For CKD, the associated risk factors were disease status other than complete remission at the time of transplantation (p = 0.018) and onset of AKI after transplant (p = 0.035). The 5-year overall survival (OS) was significantly reduced by development of AKI (p < 0.001), but not CKD. Posttransplant AKI significantly increased the 5-year nonrelapse mortality (p < 0.001), whereas posttransplant CKD showed an increasing tendency, but the difference was not significant. CONCLUSIONS: Posttransplant AKI impacts OS, significantly increases the risk of CKD, and is significantly associated with disseminated intravascular coagulation and use of ˃3 nephrotoxic drugs.

DOI： 10.1159/000504354

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

The neutrophil gelatinase-associated lipocalin (NGAL) receptor (24p3R) is expressed in distal nephron and contributes to the endocytosis of NGAL in urine. This study was undertaken to evaluate an influence of renal ischaemia-reperfusion injury on 24p3R. Unilateral renal pedicle was clamped for 0, 10, 20, 30, or 45 minutes in male Wistar rats. Urine was collected for 24 hours after reperfusion, and ischaemic kidney and blood sample were obtained. Apparent histological injury in the ischaemic kidney was detected in the 30 and 45 minutes-treated groups. Urinary NGAL excretion elevated in rats with renal ischaemia for more than 20 minutes, while serum creatinine increased in rats for more than 30 minutes of ischaemia. Renal protein expression of NGAL did not significantly change. Renal mRNA expressions of megalin and cubilin, which are expressed at renal proximal tubules and uptake NGAL, decreased in animals with renal ischaemia for more than 20 minutes. Renal protein expression of 24p3R, which is expressed at renal distal tubules and uptake NGAL, decreased in rats with renal ischaemia for 45 min. This study showed for the first time that renal 24p3R decreased in response to renal ischaemia. As relatively longer renal ischaemia (45 minutes) decreased renal 24p3R protein and increased urinary NGAL excretion, the down-regulation of 24p3R protein might contribute to the elevated urinary excretion of NGAL in rats with unilateral ischaemia-reperfusion injury.

DOI： 10.1111/1440-1681.13129

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.1272/jnms.jnms.2020_87-102

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Thin basement membrane nephropathy (TBMN) is diagnosed by diffuse thinning of the glomerular basement membrane (GBM) without any clinical and pathologic findings of Alport syndrome and the other renal diseases. TBMN is characterized clinically by benign familial hematuria but rarely develops into end-stage renal disease. METHODS: In 27 cases of biopsy-proven TBMN, we evaluated the pathologic characteristics of TBMN, and examined the correlation between these pathologic characterizations and renal dysfunction. RESULTS: All patients had hematuria, and 21 patients (77.8%) had proteinuria. In six patients (28.6%) who were more than 50 years of age, the estimated glomerular filtration rate (eGFR) decreased from G3a to G4 in the chronic kidney disease stage. Pathologically, an irregular decrease in intensity of type IV collagen α5(IV) chain was seen in GBM, and irregular thinning with diffuse rough etched images was observed on the GBM surface with several sizes of holes by low-vacuum scanning electron microscopy. The glomerular morphology of TBMN was characterized by an increased number of small glomerular capillaries with an increased extracellular matrix (ECM). These characteristic morphologic alterations were evident from a young age in patients with TBMN, but were not correlated directly with the decrease of eGFR, the degree of hematuria, and proteinuria. The decrease of eGFR in patients with TBMN who were more than 50 years of age might be primarily mediated by arteriolosclerosis-associated glomerulosclerosis and interstitial fibrosis. CONCLUSION: Characteristic pathological glomerular findings and GBM alterations occurred from a young age but were not associated directly with renal impairment in biopsy-proven TBMN.

DOI： 10.1007/s10157-018-01687-1

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10157-018-1648-1

Scopus

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13730-018-0351-0

PubMed

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41379-018-0036-4

PubMed

researchmap

Other Link： http://www.nature.com/articles/s41379-018-0036-4.pdf

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Inc  

DOI： 10.1016/j.ekir.2017.12.013

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：W.B. Saunders  

The Renal Pathology Society proposed a pathological classification for diabetic nephropathy (DN) (RPS 2010). We retrospectively examined the renal structural-functional relationships using the RPS 2010 classification in 49 DN cases. We also evaluated the importance of the percentage of glomeruli with nodular diabetic glomerulosclerosis and their morphological characteristics (cellular, cellular and extracellular matrix [ECM] or ECM types) in the pathology of DN. The classes of DN (RPS 2010) were significantly correlated with the duration of diabetes mellitus (DM), degree of proteinuria, a decreased estimated glomerular filtration rate (eGFR), and the stages of Japanese clinical DM and chronic kidney disease (CKD). When the percentage of glomeruli with nodular glomerulosclerosis (IIIA &lt
25%, IIIB 25–50%, IIIC 50–75%, and IIID &gt
75%) was added to class III in this classification, the classes of DN had a greater correlation with the levels of proteinuria. The morphological characteristics of nodular glomerulosclerosis such as cellular, cellular and ECM, or ECM type were associated with several clinical parameters including the duration of DM, degree of proteinuria, a decreased eGFR, and/or the stages of clinical DM and CKD. Mesangial red blood cell fragments that is indicative of microvascular injury was found in cellular or cellular and ECM types of nodular glomerulosclerosis. The RPS 2010 classification is useful as a DN pathological classification that indicates a good correlation with the clinical characteristics of DN. In addition, the frequency and morphological characteristics of nodular diabetic glomerulosclerosis is important for the evaluation of the pathology in DN.

DOI： 10.1016/j.humpath.2018.01.019

Scopus

PubMed

researchmap

Authorship：Corresponding author   Language：English   Publisher：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.2018_85-11

Scopus

PubMed

researchmap

Language：English   Publisher：WILEY  

DOI： 10.1111/nep.12944

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Aim: Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction.
Methods: The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (&lt; 60mL/min per 1.73m(2)), high albuminuria (30mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis.
Results: Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR &gt; 31.2mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P=0.0005) was independently associated with a poor outcome, while a low eGFR was not associated.
Conclusions: A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke.

DOI： 10.1111/nep.12745

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Atrial fibrillation (AF) is one of the major risk factor for ischemic stroke, and oral anticoagulation is generally indicated for prevention of stroke. However, the utility of oral anticoagulation for AF in dialysis patients remains controversial. In this single-center, retrospective, observational study, data from 1120 patients on maintenance hemodialysis were analyzed. Baseline medical data were collected from dialysis records including age, gender, the cause of end-stage renal disease, dialysis vintage, and comorbidities. We evaluated outcomes including stroke, major hemorrhage, and death. A total of 106 (11.4 %) patients had AF. After exclusion criteria were applied, 84 patients had analyzable data. Warfarin was prescribed in 30 (35.7 %) of these patients. The remaining 54 patients were classified as the non-warfarin group. CHADS2 score was not significantly different between the warfarin and non-warfarin group. During the mean 47 months of follow up, 7 strokes occurred. However, warfarin use was not associated with the risk for stroke [hazard ratio (HR) 1.07; 95 % confidence interval (CI) 0.20-5.74]. Kaplan-Meier analysis showed no statistically significant difference in the overall survival, stroke-free survival or bleeding-free survival between the warfarin and non-warfarin group. AF is common in Japanese dialysis patients. Despite a certain prevalence of oral anticoagulation, the present study demonstrated neither beneficial nor detrimental effects. A large randomized controlled trial should be considered.

DOI： 10.1007/s00380-015-0777-7

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor+ (p75NTR+) fibroblasts and homeostatic chemokine-producing fibroblasts inside TLTs, and retinoic acid-producing fibroblasts around TLTs. Deletion of CD4+ cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly.

DOI： 10.1172/jci.insight.87680

PubMed

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background
Focal segmental glomerulosclerosis (FSGS) lesions have often been discussed as a negative predictor in idopathic membranous nephropathy (MN). The mechanism of the development of FSGS lesion in MN is still uncertain.
Methods
From 250 cases of MN, 26 cases contained FSGS lesion. We compared the clinicopathological characteristics between MN cases with FSGS lesion [MN-FSGS(+)] and MN without FSGS lesion [MN-FSGS(-)], matched for gender, age, stage of MN.
Results
The glomerular filtration rate (eGFR) was significantly lower in MN-FSGS(+) cases compared to MN-FSGS(-), although nephrotic syndrome, hematuria, and systolic blood pressure levels were not significantly different between the two groups. Pathologically, glomeruli in MN-FSGS(+) cases showed narrowing and loss of glomerular capillaries with separating from GBM or disappearance of CD34+ endothelial cells, and accumulation of extracellular matrix (ECM) in capillary walls, indicating the development of glomerular capillary injury. These findings of endothelial injury were seen even in MN-FSGS(-) cases, but they were more prominent in MN-FSGS(+) than MN-FSGS(-) by computer assessed morphometric analysis. In MN-FSGS(+) cases, 44 out of 534 glomeruli (8.2%) contained FSGS lesions (n = 31, NOS lesion; n = 13, perihilar lesion). Significant thickness of GBM with ECM accumulation was evident in MN-FSGS(+) cases. Podocyte injury with effacement of foot processes was also noted, but the expression of VEGF on podocytes was not different between the two groups, which suggests that the significant thickness of capillary walls may influence the function of VEGF from podocyte resulting in the glomerular capillary injury that contribute to the development of FSGS lesion in MN.
Conclusion
Glomerular capillary injury was seen in all MN cases. Furthermore, the prominent injuries of glomerular capillaries may be associated with the deterioration of eGFR and the formation of FSGS lesions in MN.

DOI： 10.1371/journal.pone.0116700

Web of Science

PubMed

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background: The associations of glomerular capillary and endothelial injury with the formation of necrotizing and crescentic lesions in cases of crescentic glomerulonephritis (GN) have not been evaluated in detail.
Methods: Glomerular capillary and endothelial cell injury were assessed in renal biopsy specimens of crescentic GN, including those from patients with anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated GN (n=45), anti-glomerular basement membrane (GBM) GN (n=7), lupus GN (n=21), and purpura GN (n=45) with light and electron microscopy and immunostaining for CD34.
Results: In ANCA-associated GN, anti-GBM GN, lupus GN, and purpura GN, almost all active necrotizing glomerular lesions began as a loss of individual CD34-positive endothelial cells in glomerular capillaries, with or without leukocyte infiltration. Subsequently, necrotizing lesions developed and were characterized by an expansive loss of CD34-positive cells with fibrin exudation, GBM rupture, and cellular crescent formation. With electron microscopy, capillary destruction with fibrin exudation were evident in necrotizing and cellular crescentic lesions. During the progression to the chronic stage of crescentic GN, glomerular sclerosis developed with the disappearance of both CD34-positive glomerular capillaries and fibrocellular-to-fibrous crescents. In addition, the remaining glomerular lobes without crescents had marked collapsing tufts, a loss of endothelial cells, and the development of glomerular sclerosis.
Conclusions: The loss of glomerular capillaries with endothelial cell injury is commonly associated with the formation of necrotizing and cellular crescentic lesions, regardless of the pathogeneses associated with different types of crescentic GN, such as pauci-immune type ANCA-associated GN, anti-GBM GN, and immune-complex type GN. In addition, impaired capillary regeneration and a loss of endothelial cells contribute to the development of glomerular sclerosis with fibrous crescents and glomerular collapse.

DOI： 10.1272/jnms.82.27

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 65-year-old man was admitted to our hospital with edema and renal dysfunction. He had received a diagnosis of psoriatic arthritis at 50 years of age. As a renal biopsy showed IgA nephropathy (IgAN), bilateral tonsillectomy was performed, and one course of steroid pulse therapy with an oral steroid and mizoribine were subsequently administered. The patient's proteinuria gradually reduced in association with an improvement in the renal function. In addition, the rash and arthralgia were ameliorated. In this case, adding treatment for chronic epipharyngitis accelerated the curative effects, and focal infection therapy consisting of immunosuppressive drugs was effective for both IgAN and psoriatic arthritis.

DOI： 10.2169/internalmedicine.54.3510

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Allogeneic hematopoietic cell or bone marrow transplantation (BMT) causes graft-versus- host-disease (GVHD). However, the involvement of the kidney in acute GVHD is not well-understood. Acute GVHD was induced in Lewis rats (RT1(l)) by transplantation of Dark Agouti (DA) rat (RT1(a)) bone marrow cells (6.0x10(7) cells) without immunosuppression after lethal irradiation (10 Gy). We examined the impact of acute GVHD on the kidney in allogeneic BMT rats and compared them with those in Lewis-to-Lewis syngeneic BMT control and non-BMT control rats. In syngeneic BMT and non-BMT control rats, acute GVHD did not develop by day 28. In allogeneic BMT rats, severe acute GVHD developed at 21-28 days after BMT in the skin, intestine, and liver with decreased body weight (&gt; 20%), skin rush, diarrhea, and liver dysfunction. In the kidney, infiltration of donor-type leukocytes was by day 28. Mild inflammation characterized by infiltration of CD3+ T-cells, including CD8+ T-cells and CD4+ T-cells, and CD68+ macrophages to the interstitium around the small arteries was noted. During moderate to severe inflammation, these infiltrating cells expanded into the peritubular interstitium with peritubular capillaritis, tubulitis, acute glomerulitis, and endarteritis. Renal dysfunction also developed, and the serum blood urea nitrogen (33.9 +/- 4.7 mg/dL) and urinary N-acetyl-beta-D-glucosaminidase (NAG: 31.5 +/- 15.5 U/L) levels increased. No immunoglobulin and complement deposition was detected in the kidney. In conclusion, the kidney was a primary target organ of acute GVHD after BMT. Acute GVHD of the kidney was characterized by increased levels of urinary NAG and cell-mediated injury to the renal microvasculature and renal tubules.

DOI： 10.1371/journal.pone.0115399

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Publishing type：Research paper (scientific journal)  

PubMed

researchmap

Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

DOI： 10.1016/j.humpath.2013.02.012

Web of Science

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10157-012-0746-8

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Background: The mechanisms and morphological characteristics of lymphatic vascular development in embryonic kidneys remain uncertain. Methods: We examined the distribution and characteristics of lymphatic vessels in developing rat kidneys using immunostaining for podoplanin, prox-1, Ki-67, type IV collagen (basement membrane: BM), and α-smooth muscle actin (αSMA: pericytes or mural cells). We also examined the expression of VEGF-C. Results: At embryonic day 17 (E17), podoplanin-positive lymphatic vessels were observed mainly in the kidney hilus. At E20, lymphatic vessels extended further into the developing kidneys along the interlobar vasculature. In 1-day-old pups (P1) to P20, lymphatic vessels appeared around the arcuate arteries and veins of the kidneys, with some reaching the developing cortex via interlobular vessels. In 8-week-old adult rats, lymphatic vessels were extensively distributed around the blood vasculature from the renal hilus to cortex. Only lymphatic capillaries lacking continuous BM and αSMA-positive cells were present within adult kidneys, with none observed in renal medulla. VEGF-C was upregulated in the developing kidneys and expressed mainly in tubules. Importantly, the developing lymphatic vessels were characterized by endothelial cells immunopositive for podoplanin, prox-1, and Ki-67, with no surrounding BM or αSMA-positive cells. Conclusion: During nephrogenesis, lymphatic vessels extend from the renal hilus into the renal cortex along the renal blood vasculature. Podoplanin, prox-1, Ki-67, type IV collagen, and αSMA immunostaining can detect lymphatic vessels during lymphangiogenesis. © 2012 Japanese Society of Nephrology.

DOI： 10.1007/s10157-012-0637-z

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

The mechanisms and morphological characteristics of lymphatic vascular development in embryonic kidneys remain uncertain.
We examined the distribution and characteristics of lymphatic vessels in developing rat kidneys using immunostaining for podoplanin, prox-1, Ki-67, type IV collagen (basement membrane: BM), and alpha-smooth muscle actin (alpha SMA: pericytes or mural cells). We also examined the expression of VEGF-C.
At embryonic day 17 (E17), podoplanin-positive lymphatic vessels were observed mainly in the kidney hilus. At E20, lymphatic vessels extended further into the developing kidneys along the interlobar vasculature. In 1-day-old pups (P1) to P20, lymphatic vessels appeared around the arcuate arteries and veins of the kidneys, with some reaching the developing cortex via interlobular vessels. In 8-week-old adult rats, lymphatic vessels were extensively distributed around the blood vasculature from the renal hilus to cortex. Only lymphatic capillaries lacking continuous BM and alpha SMA-positive cells were present within adult kidneys, with none observed in renal medulla. VEGF-C was upregulated in the developing kidneys and expressed mainly in tubules. Importantly, the developing lymphatic vessels were characterized by endothelial cells immunopositive for podoplanin, prox-1, and Ki-67, with no surrounding BM or alpha SMA-positive cells.
During nephrogenesis, lymphatic vessels extend from the renal hilus into the renal cortex along the renal blood vasculature. Podoplanin, prox-1, Ki-67, type IV collagen, and alpha SMA immunostaining can detect lymphatic vessels during lymphangiogenesis.

DOI： 10.1007/s10157-012-0637-z

Web of Science

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13730-012-0041-2

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is a recently described disease entity, characterized by nonorganized electron-dense deposits in glomeruli and immunofluorescence findings indicating monoclonal immunoglobulin G deposits. The pathogenesis of many cases of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits remains unknown. We herein report 2 patients with parvovirus B19 infection who developed acute nephritic syndrome with hypocomplementemia (patient 1) or persistent proteinuria and congestive heart failure (patient 2); however, neither patient had detectable levels of scrum monoclonal immunoglobulin G. Renal biopsy in both patients showed diffuse endocapillary proliferative glomerulonephritis with monoclonal immunoglobulin G3 kappa deposits, and electron microscopy showed nonorganized electron-dense deposits mainly in the subendothelial and mesangial areas. Clinical symptoms, abnormal laboratory findings, and urinary abnormalities recovered spontaneously in both cases within 4 weeks. Our 2 cases may be the first reported patients with proliferative glomerulonephritis with monoclonal immunoglobulin G deposits possibly associated with parvovirus B19 infection. Virus infection associated immune disorders could be implicated in the pathogenesis of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits. (C) 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.humpath.2012.04.004

Web of Science

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10157-012-0673-8

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13730-012-0023-4

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

A 63-year-old man with hepatitis C virus infection was admitted to our hospital for nephrotic syndrome. Light microscopic analysis of a percutaneous renal biopsy showed thickening of the glomerular capillary walls and spike formation. Immunofluorescence revealed granular deposition of monoclonal immunoglobulin G1-lambda and C3 complement along the glomerular basement membrane. Urinary protein excretion decreased slightly after combined treatment with steroid and an immunosuppressive agent. Monoclonal immunoglobulin deposition disease with membranous feature is rare. Additional reports of such cases are needed to elucidate the mechanisms and optimal therapy for this rare entity.

DOI： 10.1007/s10157-011-0579-x

Web of Science

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13730-012-0006-5

PubMed

researchmap

Language：English   Publisher：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.cca.2011.09.024

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background/Aims: Renal tubular cell death in ischemia-reperfusion does not follow the classical apoptosis or necrosis phenotype. We characterized the morphological and biochemical features of injured tubular epithelial cells in ischemic acute kidney injury (AKI). Methods: Ischemic AKI was induced in rats by 60 min of ischemia followed by 24 h of reperfusion. Light and electron microscopic TUNEL (LM-TUNEL and EM-TUNEL), gel electrophoresis of extracted DNA, and caspase-3 involvement were examined during the development of death. Results: Damaged tubular epithelial cells with condensed and LM-TUNEL-positive (+) nuclei were prominent at 12 and 18 h after reperfusion with DNA 'ladder' pattern on gel electrophoresis. EM-TUNEL+ cells were characterized by nuclei with condensed and clumping chromatin, whereas the cytoplasm showed irreversible necrosis. The protein levels and activity of caspase-3 did not increase in kidneys after reperfusion. In addition, caspase inhibitor (ZVAD-fmk) failed to inhibit DNA fragmentation and prevent tubular epithelial cell death in ischemic AKI. Conclusion: Caspase-3-independent internucleosomal DNA fragmentation occurs in injured tubular epithelial cells undergoing irreversible necrosis in ischemic AKI. The manner of this cell death may be identical to the cell death termed apoptotic necrosis, aponecrosis, or necrapoptosis. Ischemia-reperfusion injury activates caspase-3-independent endonuclease, which in turn induces irreversible damage of tubular epithelial cells, and may contribute to the initiation and development of AKI. Copyright (c) 2012 S. Karger AG, Basel

DOI： 10.1159/000337358

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIMS: Renal tubular cell death in ischemia-reperfusion does not follow the classical apoptosis or necrosis phenotype. We characterized the morphological and biochemical features of injured tubular epithelial cells in ischemic acute kidney injury (AKI). METHODS: Ischemic AKI was induced in rats by 60 min of ischemia followed by 24 h of reperfusion. Light and electron microscopic TUNEL (LM-TUNEL and EM-TUNEL), gel electrophoresis of extracted DNA, and caspase-3 involvement were examined during the development of death. RESULTS: Damaged tubular epithelial cells with condensed and LM-TUNEL-positive (+) nuclei were prominent at 12 and 18 h after reperfusion with DNA 'ladder' pattern on gel electrophoresis. EM-TUNEL+ cells were characterized by nuclei with condensed and clumping chromatin, whereas the cytoplasm showed irreversible necrosis. The protein levels and activity of caspase-3 did not increase in kidneys after reperfusion. In addition, caspase inhibitor (ZVAD-fmk) failed to inhibit DNA fragmentation and prevent tubular epithelial cell death in ischemic AKI. CONCLUSION: Caspase-3-independent internucleosomal DNA fragmentation occurs in injured tubular epithelial cells undergoing irreversible necrosis in ischemic AKI. The manner of this cell death may be identical to the cell death termed apoptotic necrosis, aponecrosis, or necrapoptosis. Ischemia-reperfusion injury activates caspase-3-independent endonuclease, which in turn induces irreversible damage of tubular epithelial cells, and may contribute to the initiation and development of AKI.

DOI： 10.1159/000337358

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.79.496

Scopus

researchmap

Other Link： http://orcid.org/0000-0003-4495-7982

Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background/Aims: Matrix metalloproteinases (MMPs) are zinc endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of ischemic damage in acute kidney injury (AKI). In the present study, we analyzed the role of MMP-2 in the repair process in ischemic AKI. Methods: AKI was induced in MMP-2 wild-type (MMP-2(+/+)) and MMP-2-deficient (MMP-2(-/-)) mice by 90-min renal artery clamping followed by reperfusion. Renal histology and the activity and distribution of MMP-2 were examined from day 1 to day 14. During the recovery from AKI, MMP-2(+/+) mice were also treated with MMP-2/MMP-9 inhibitor. Results: In both MMP-2(+/+) and MMP-2(-/-) mice, AKI developed on day 1 after ischemia/reperfusion with widespread acute tubular injury, but subsequent epithelial cell proliferation was evident on days 3-7. During the repair process, active MMP-2 and MMP-9 increased in regenerating tubular epithelial cells in MMP-2(+/+) mice on days 7-14, and the tubular repair process was almost complete by day 14. On the other hand, in MMP-2(-/-) mice, less prominent proliferation of tubular epithelial cells was evident on days 3 and 7, and damaged tubules that were covered with elongated and immature regenerated epithelial cells were identified on days 7 and 14. Incomplete recovery of injured microvasculature was also noted with persistent macrophage infiltration. Similarly, treatment with MMP-2/MMP-9 inhibitor resulted in impaired recovery in MMP-2(+/+) mice. Conclusion: MMP-2 is involved in tubular repair after AKI. The use of the MMP-2/MMP-9 inhibitor was a disadvantage when it was administered during the repair stage of ischemic AKI. Treatment with MMP inhibitor for AKI needs to be modified to enhance recovery from AKI. Copyright (C) 2013 S. Karger AG, Basel

DOI： 10.1159/000346569

Web of Science

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Thrombotic microangiopathy (TMA) is a major complication after hematopoietic stem cell transplantation (HSCT). In this study, we examined the clinical and pathologic features of 2 patients and 5 autopsy cases with HSCT-associated renal TMA to clarify the association between graft-versus-host disease (GVHD) and renal TMA. The median interval between HSCT and renal biopsy or autopsy was 7 months (range 3-42 months). Clinically, acute and chronic GVHD occurred in 7 and 4 patients, respectively. Clinical evidence for TMA was detected in 2 patients, while chronic kidney disease developed in all patients. The main histopathological findings were diffuse endothelial injury in glomeruli, peritubular capillaries (PTCs), and small arteries. In addition, all cases showed glomerulitis, renal tubulitis, and peritubular capillaritis with infiltration of CD3+ T cells and TIA-1+ cytotoxic cells, suggesting that GVHD occurred during the development of TMA. Diffuse and patchy C4d deposition was noted in glomerular capillaries and PTCs, respectively, in 2 biopsy and 2 autopsy cases, suggesting the involvement of antibody-mediated renal endothelial injury in more than 50% of renal TMA cases. In conclusion, the kidney is a potential target of chronic GVHD that may induce the development of HSCT-associated TMA. Importantly, some cases are associated with chronic humoral GVHD.

DOI： 10.1111/j.1440-1827.2011.02704.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

A 72-year-old man was admitted to our hospital because of progressive renal dysfunction persisting for 1.5 months. Physical examination showed livedo reticularis of the toes of both feet, peripheral edema, and gait disturbance due to the toe pain. The levels of blood urea nitrogen (50.0 mg/dL) and creatinine (2.81 mg/dL) were elevated, and eosinophilia (10%, 870/mu L) was noted. A biopsy of the area of livedo reticularis revealed cholesterin crystals. The patient had not undergone angiography, anticoagulation therapy, or antithrombotic treatment. Idiopathic cholesterol crystal embolization was diagnosed. Transesophageal echocardiography revealed intimal thickening of the aorta and plaque. Oral steroid therapy was started because of the progressive renal dysfunction. After steroid therapy, the symptoms improved. Early diagnosis and treatment are important. Renal dysfunction is a common symptom in elderly patients. Cholesterol crystal embolization should also be considered as a cause of unexplained renal dysfunction, especially in such patients. (J Nippon Med Sch 2011; 78: 252-256)

DOI： 10.1272/jnms.78.252

Web of Science

PubMed

researchmap

Language：English   Publisher：WILEY-BLACKWELL  

Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic syndrome of proteinuria, usually of nephrotic range, associated with focal and segmental sclerotic glomerular lesions. Therefore, FSGS is diagnosed by clinical features and histopathological examination of renal biopsy. The natural history of the condition varies, and although it may respond to treatment, FSGS is an important disease in the etiology of end-stage renal disease (ESRD). Furthermore, after kidney transplantation, approximately 30% of patients with FSGS develop recurrent FSGS. The risk factors for recurrence of FSGS include childhood onset and age &lt; 15 yr, rapid progression of the primary FSGS to ESRD, recurrence of FSGS in a previous allograft, diffuse mesangial hypercellularity in the native kidney, collapsing FSGS, and podocin gene mutation. In addition, after kidney transplantation, de novo FSGS also develops in approximately 10-20% of allografts, associated with a complication of hyperfiltration injury, chronic transplant glomerulopathy, and calcineurin inhibitor toxicity. FSGS is considered a podocyte disease, and the pathology is characterized by segmental FSGS lesion with glomerular epithelial hypercellularity. The pathological diagnosis of FSGS is based on the 2004 Columbia classification system. In the present minireview, we discuss the pathology of recurrence and de novo FSGS after kidney transplantation.

DOI： 10.1111/j.1399-0012.2011.01452.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix and involved in ischemic organ injuries. The present study was designed to determine the role of MMP-2 in the development of ischemic acute kidney injury (AKI). AKI was induced in MMP-2 wild-type (MMP-2(+/+)) mice by 30, 60, 90, and 120min renal ischemia and reperfusion. Renal histology, expression and activity of MMP-2 and MMP-9, and renal function were examined during the development of AKI. AKI was also induced in MMP-2-deficient (MMP-2(-/-))mice and MMP-2(+/+) mice treated with inhibitor of MMPs (minocycline and synthetic peptide MMP inhibitor). In MMP-2(+/+) mice, MMP-2 and MMP-9 activities increased significantly at 2 to 24 h, peaked at 6 h, after reperfusion. Immunohistochemical analysis identified MMP-2 in the interstitium around tubules and peritubular capillaries in the outer medulla. Acute tubular injury (ATI), including apoptosis and necrosis, was evident in the outer medulla at 24 h, along with renal dysfunction. As ischemia period increases, MMP-2 and MMP-9 activities at 6 h and severity of AKI at 24 h increased depending on the duration of ischemia between 30 and 120min. However, the kidneys of MMP-2(-/-) mice showed minimal ATI; serum creatinine 24 h after reperfusion was significantly low in these mice. Inhibitors of MMPs reduced ATI and improved renal dysfunction at 24 h. We conclude that MMPs, especially MMP-2 have a pathogenic role in ischemia-reperfusion AKI, and that inhibitors of MMPs can protect against ischemic AKI. Laboratory Investigation (2011) 91, 170-180; doi:10.1038/labinvest.2010.174; published online 18 October 2010

DOI： 10.1038/labinvest.2010.174

Web of Science

PubMed

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

Thrombotic microangiopathy (TMA) is a known complication of hematopoietic stem cell transplantation (HSCT). The pathogenesis of TMA is controversial but considered to involve various factors such as total body irradiation, use of calcineurin inhibitors for prophylaxis against graft versus host disease (GVHD), viral infection, and GVHD. Herein we describe a case with renal TMA after HSCT, which was probably associated with antibody-mediated endothelial cell injury from chronic GVHD (termed here &apos;chronic humoral GVHD&apos;). A 49-year-old man presented two years after HSCT with renal dysfunction and proteinuria but without the clinical features of TMA. Histopathological examination of renal biopsy showed chronic glomerular endothelial cell injury with double contour of the glomerular basement membrane, microthrombi and the deposition of complement split product C4d along the glomerular capillaries. Renal tubulitis and peritubular capillaritis were also noted with a multilayered basement membrane and patchy C4d deposition on peritubular capillaries. These findings resemble those of chronic antibody-mediated rejection after kidney transplantation. Furthermore, C4d deposition suggests complement activation. Although circulating anti-blood type and anti-human leukocyte antigen antibodies were not detected, the renal TMA in this case was probably associated with chronic humoral GVHD.

DOI： 10.1111/j.1440-1827.2010.02608.x

Web of Science

PubMed

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through the use of steroids and immune system suppressors. Case 1 was a 55-year-old male. He was being treated for alcoholic liver cirrhosis, but as bloody urine was noticed macroscopically, his renal function rapidly decreased. Specimens from a renal biopsy showed endocapillary proliferative lesions accompanying necrotic lesions. Granular deposition of IgA(IgA1) and C3 was seen along the capillary walls and in the mesangial areas. After the combined treatments of bilateral palatotonsillectomy, three courses of steroid semi-pulse therapy and post-therapy with steroids and mizoribin (MZR) were started, his hematuria and proteinuria disappeared and renal function improved markedly. Case 2 was a 37-year-old male with alcoholic liver cirrhosis complicated with hepatic encephalopathy. Although he was being treated at another hospital, nephritic syndrome occurred with rapidly worsening renal function and massive ascites. After continuous drainage of the ascites, we performed a renal biopsy. Mild proliferative lesions and notable wrinkling, thickening and doubling of the basal membrane were seen. Crescent formations were found in about half of the glomeruli. The fluorescent antibody technique showed positive pictures of IgA (IgA1) and C3. When three courses of steroid semi-pulse therapy and post therapy with steroids and MZR were combined, his proteinuria and serum Cre level decreased and stagnated ascites markedly decreased. The two cases were diagnosed as having secondary IgA nephropathy induced by the deposition of the IgA1 derived mainly from the intestinal tract, which had increased in the blood due to alcoholic liver cirrhosis. Active use of immune system suppressor therapy was effective.

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The pathological process of glomerulonephritis (GN) includes glomerular capillary damage, and vascular endothelial growth factor (VEGF) has an important role in glomerular capillary repair in GN. We examined the effect of inhibition of glomerular capillary repair after capillary injury in GN. Experimental Thy-1 GN was induced in rats that were divided into two groups: rats that received anti-VEGF neutralizing antibody (50 mg per 100 g body weight per day) and those treated with the vehicle from day 2 to day 9. We assessed the renal function and histopathology serially until week 6. Rats of the Thy-1 GN group showed diffuse glomerular mesangiolysis with ballooning destruction of the capillary network by day 3. VEGF164 protein levels increased in the damaged glomeruli during days 5 to 10, and endothelial-cell proliferation increased with capillary repair in the vehicle-injected group. Proliferative GN resolved subsequently with decreased mesangial hypercellularity, and recovery of most of the glomeruli to the normal structure was evident by week 6. In contrast, administration of anti-VEGF antibody significantly decreased endothelial-cell proliferation and capillary repair in glomeruli by week 2. Thereafter, glomerular mesangial-cell proliferation and activation continued with persistent infiltration of macrophages. At week 6, segmental glomerular sclerosis developed with mesangial matrix accumulation and proteinuria. Deposition of type I collagen was also noted in sclerotic lesions. We conclude that impaired capillary repair was the underlying mechanism in the prolongation of glomerular inflammation in proliferative GN and in the development of glomerular sclerosis. Capillary repair has an important role in the recovery of glomerular damage and in the resolution of proliferative GN. Laboratory Investigation (2010) 90, 1468-1481; doi: 10.1038/labinvest.2010.130; published online 19 July 2010

DOI： 10.1038/labinvest.2010.130

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC INVESTIGATIVE PATHOLOGY, INC  

Macrophages are heterogeneous and include classically activated M1 and alternatively activated M2 macrophages, characterized by pro- and anti-inflammatory functions, respectively. Macrophages that express heme oxygenase-1. also exhibit anti-inflammatory effects. We assessed the anti-inflammatory effects of statin in experimental anti-glomerular basement membrane glomerulonephritis and in vitro, focusing on the macrophage heterogeneity. Rats were induced anti-glomerular basement membrane glomerulonephritis and treated with atorvastatin (20 mg/kg/day) or vehicle (control). Control rats showed infiltration of macrophages in the glomeruli at day 3 and developed crescentic glomerulonephritis by day 7, together with increased mRNA levels of the M1 macrophage-associated cytokines, interferon-gamma, tumor necrosis factor-a, and interleukin-12. In contrast, stain reduced the level of proteinuria, reduced infiltration of macrophages in glomeruli with suppression of monocyte chemotactic protein-1 expression, and inhibited the formation of necrotizing and crescentic lesions. The number of glomerular ED3-positive macrophages decreased with down-regulation of M1 macrophage-associated cytokines. Furthermore, statin augmented ED2-positive M2 macrophages with up-regulation of the M2 macrophage-associated chemokines and cytokines, chemokine (C-C motif) ligand-17 and interleukin-10. Statin also increased the glomerular interleukin-10-expressing heme oxygenase-1-positive macrophages. Statin inhibited macrophage development, and suppressed ED3-positive macrophages, but augmented ED2-positive macrophages in M2-associated cytokine environment in vitro. We conclude that the anti-inflammatory effects of statin in glomerulonephritis are mediated through inhibition of macrophage infiltration as well as augmentation of anti-inflammatory macrophages. (Am J Pathol 2010, 177:1143-1154; DOI: 10.2353/ajpath.2010.090608)

DOI： 10.2353/ajpath.2010.090608

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

Aki K, Shimizu A, Masuda Y, Kuwahara N, Arai T, Ishikawa A, Fujita E, Mii A, Natori Y, Fukunaga Y, Fukuda Y. ANG II receptor blockade enhances anti-inflammatory macrophages in antiglomerular basement membrane glomerulonephritis. Am J Physiol Renal Physiol 298: F870-F882, 2010. First published January 13, 2010; doi:10.1152/ajprenal.00374.2009.-Macrophages are heterogeneous immune cell populations that include classically activated and alternatively activated (M2) macrophages. We examined the anti-inflammatory effect of ANG II type 1 receptor (AT(1)R) blocker (ARB) on glomerular inflammation in a rat model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). The study focused on infiltrating CD8(+) and CD4(+) cells and macrophages, as well as the heterogeneity of intraglomerular macrophages. Wistar-Kyoto rats were treated with high-dose olmesartan (3 mg.kg(-1).day(-1)), low-dose olmesartan (0.3 mg.kg(-1).day(-1)), or vehicle (control) 7 days before induction of anti-GBM GN. Control rats showed mainly CD8(+) cells and ED1(+) macrophages, with a few CD4(+) cells infiltrating the glomeruli. Necrotizing and crescentic glomerular lesions developed by day 7 with the increase of proteinuria. AT1R was expressed on CD8(+) and CD4(+) cells and on ED1(+) macrophages. Low-dose ARB had no anti-inflammatory effects in anti-GBM GN. However, high-dose ARB reduced glomerular infiltration of CD8(+) cells and ED1(+) macrophages and suppressed necrotizing and crescentic lesions by days 5 to 7 (P &lt; 0.05). In addition, high-dose ARB reduced the numbers of ED3(+) -activated macrophages, suppressed glomerular TNF-alpha and IFN-gamma production, and downregulated M1-related chemokine and cytokines (monocyte chemoattractant protein type 1, IL-6, and IL-12). High-dose ARB also enhanced ED2(+) M2 macrophages by day 7 with upregulation of glomerular IL-4 and IL-13 and augmented CCL17, IL-1 receptor antagonist, and IL-10. We concluded that high-dose ARB inhibits glomerular inflammation by increasing the numbers of M2 macrophages and upregulation of anti-inflammatory cytokines and by suppressing M1 macrophage development with downregulation of M1-related proinflammatory cytokines.

DOI： 10.1152/ajprenal.00374.2009

Web of Science

PubMed

researchmap

Authorship：Lead author   Language：English   Publisher：SPRINGER  

C1q nephropathy, first proposed by Jennette and Hipp [Am J Clin Pathol 83:415-420, 1985; Am J Kidney Dis 6:103-110, 1985], was described as a distinct glomerular disease entity characterized by extensive mesangial deposition of C1q, with associated mesangial immune complexes, and the absence of any clinical and laboratory evidence of systemic lupus erythematosus. Now, 20 years since the first report, the disease entity is gradually attaining recognition, particularly in the field of pediatrics. C1q is the subcomponent of C1 in the classical pathway of complement activation. Generally, C1q deposition is caused by the activation of C1 by immunoglobulin G (IgG) and IgM; therefore, C1q nephropathy is considered as an immune complex glomerulonephritis. However, in C1q nephropathy, it remains unclear whether the deposition of C1q in the glomeruli is in response to the deposition of immunoglobulin or immune complex, or whether deposition is non-specific trapping that accompanies increased glomerular protein trafficking associated with proteinuria. Since not only the pathogenesis of C1q deposition in glomeruli but also its significance are still uncertain, it has not yet been established as an independent disease. From recent publications of the clinical and pathological characterizations, C1q nephropathy has been thought to be a subgroup of primary focal segmental glomerular sclerosis. However, many reports describe different symptoms, histopathologies, therapeutic responses and prognoses, suggesting that C1q nephropathy is not a single disease entity, but that it may be a combination of several disease groups. There are many uncertain areas requiring further investigation, though it is hoped that a detailed examination of future cases will clarify the subgroups making up C1q nephropathy and their clinicopathological characteristics, and will lead to the establishment of C1q nephropathy as an independent disease entity.

DOI： 10.1007/s10157-009-0159-5

Web of Science

PubMed

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Angiotensin II receptor blockade (ARB) suppresses the progression of chronic kidney disease. However, the renoprotective effect of ARB in the active phase of glomerulonephritis (GN) has not been evaluated in detail. We examined the alteration of angiotensin II receptors' expression and the action of ARB on acute glomerular injuries in GN. Thy-1 GN was induced in rats that were divided into three groups (n=7, in each group)
high dose (3 mg/kg/day) or low dose (0.3 mg/kg/day) olmesartan (Thy-1 GN+HD- or LD-ARB group), and vehicle (Thy-1 GN group). Renal function and histopathology were assessed by week 2. In the Thy-1 GN group, diffuse mesangiolysis and focal aneurysmal ballooning developed by day 3. Marked mesangial proliferation and activation progressed with glomerular epithelial injury. We confirmed that both angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) were expressed on glomerular endothelial, mesangial, epithelial cells, and macrophages, and increased 7 days after disease induction. However, ARB treatment caused a decrease in AT1R and a further increase in AT2R expression in glomeruli. ARB prevented capillary destruction and preserved eNOS expression after diffuse mesangiolysis. Mesangial proliferation and activation was suppressed markedly with low levels of PDGF-B expression. Glomerular desmin expression, which is a marker for injured glomerular epithelial cells, was diminished significantly with retained expression of nephrin and podoplanin. Glomerular macrophage infiltration was also inhibited. Proteinuria was suppressed significantly. Furthermore, these effects of ARB showed dose dependency. These results provide insights that ARB affects individual glomerular cells and macrophages through angiotensin II receptors, with the alteration of both AT1R and AT2R expressions, and leads to inhibition of the acute destructive and proliferative glomerular lesions in GN. © 2009 USCAP, Inc All rights reserved.

DOI： 10.1038/labinvest.2008.128

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Background The ultrastructural findings of membranous nephropathy (MN) are well described. Recently, podocyte infolding in the glomerular basement membrane (GBM) has been observed to be a unique ultrastructural finding formed from diffuse spherical microparticles and microtubules in the GBM. However, these alterations of glomerular epithelial cells have not been well characterized in MN.
Methods We selected 126 renal biopsies of primary MN that were diagnosed by light microscopy and immunofluorescence. In these biopsies, we investigated the ultrastructural alterations of GBM and podocytes, especially the presence of podocyte invagination, podocyte infolding, and spherical microparticles in the GBM. Results In 98 cases (77.8%) we ultrastructurally detected occasional invagination of podocytes in the GBM within or around electron-dense or lucent deposits in mainly stage II-III of MN. In 40 cases (31.7%), we found spherical microparticles in addition to the podocyte invaginations in the GBM. In our cases, spherical microparticles were divided into three types; podocyte infolding, cell debris and virus-like particle types. Only one case displayed numerous spherical microparticles (microspheres) that were probably caused by infolding of podocytes. These microspheres, about 80 nm in diameter, were covered by unit membrane, and were accompanied by similar-sized microtubules and protrusions of podocytes. The spherical microparticles in the other cases were associated with cell debris (n = 23) or virus-like particles (n = 16) and were not connected with podocytes.
Conclusion Podocyte invagination associated with subepithelial deposits was a common pathological finding of primary MN, especially stage II-III of MN. The spherical microparticles in GBM in the case of MN may be associated with not only podocyte infolding but also cell debris and virus-like particles. The spherical microparticles in GBM due to diffuse podocyte infolding was considered as a new pathology finding of the GBM and may appear to be a new glomerular disease entity termed podocytic infolding glomerulopathy.

DOI： 10.1007/s10157-008-0100-3

Web of Science

PubMed

researchmap

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

In this manuscript, we describe a case of lupus nephritis with diffuse podocytic infolding in the glomerular basement membrane (GBM). A 23-year-old woman presenting with proteinuria, leukopenia, a high value of antinuclear antibody, and positive for anti-dsDNA and anti-Sm antibodies was diagnosed with systemic lupus erythematosus. A renal biopsy was performed which showed diffuse change in the GBM and focal segmental mesangial hypercellularity under light microscopy. The GBM showed diffuse mild thickening and diffuse irregular stippling (bubble-like appearance) on staining with periodic acid-silver methenamine. However, spike formation was only occasionally seen. An immunofluorescence study was conducted which revealed fine granular deposition of IgG (2+) along the glomerular capillary walls; however, granular deposits of C1q (1+) and C3 (1+) were primarily detected in the mesangial areas. Diffuse irregular GBM thickening with dispersed distribution of microspheres and microtubules was observed using electron microscopy. In addition, these structures were chiefly detected on the epithelial side of the GBM. Since these structures seemed to connect to podocytes, we believed that the formation of these microspheres and microtubules is caused by the infolding of podocytes. This case shows a unique pathological finding, and may belong to a new glomerular disease entity characterized by podocytic infolding. After a renal biopsy, the patient received oral prednisolone 0.8 mg/kg day initially, and her complete remission status continued for 5 years.

DOI： 10.1007/s10157-008-0097-7

Web of Science

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: Not all genetic factors predisposing phenotypic features of dyslipidemia have been identified. We studied the association between the low density lipoprotein-related protein 2 gene (LRP2) and levels of plasma total cholesterol (T-Cho) and LDL-cholesterol (LDL-C) among 352 adults in Japan.
Methods: Subjects were obtained from among participants in a cohort study that was carried out with health-check screening in an area of east-central Japan. We selected 352 individuals whose LDL-C levels were higher than 140 mg/dL from the initially screened 22,228 people. We assessed the relation between plasma cholesterol levels and single-nucleotide polymorphisms (SNPs) in the LRP2 gene.
Results: We identified significant correlations between plasma cholesterol levels and two of 19 examined SNPs in LAP2, c. + 193826T/C and IVS55 -147A/G. In particular, the association of c. + 193826T/C with the T-Cho level was prominent (p = 0.003), showing a co-dominant effect of the minor C-allele on lowering T-Cho and LDL-C levels: for 24 homozygous C-allele carriers, T-Cho=240.7 +/- 24.2 mg/dL and LDL-C=166.1 +/- 21.0 mg/dL); for 130 heterozygous carriers, 248.5 +/- 23.5 mg/dL and 166.6 +/- 19.3 mg/dL; and for 196 homozygous T-allele carriers, 253.9 +/- 23.5 mg/dL and 172.0 +/- 21.0 mg/dL. Linkage disequilibrium (LD) analyses based on 19 selected SNPs showed that c. + 193826T/C and IVS55 -147A/G were in tight LD and that both were located in an LD block covering the genomic sequence from exon 55 to exon 61.
Conclusion: We confirm the association between LRP2 and levels of T-Cho and LDL-C in human plasma. The results suggest that genetic variations in LRP2 are important factors affecting lipoprotein phenotypes of patients with hypercholesterolemia.

DOI： 10.5551/jat.E494

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

A 64-year-old male patient with diabetic nephropathy had been treated with maintenance hemodialysis therapy for 4 years, and had developed disturbed consciousness. The disturbance was firstly noticed by a primary care doctor who recognized slow responses in conversation. Prior to developing this symptom, the patient had noticed a loss of appetite for about 2 weeks. During a period of observation at an outpatient clinic, the symptoms became worse. He was admitted to a primary care hospital for 10 days, but his consciousness level deteriorated and he became unconscious (JCS 200). About 1 month after the onset of symptoms, the patient was transferred to our hospital. A brain computed tomography (CT) scan and magnetic resonance imaging (MRI) showed typical abnormal lesions in the aquaduct of the midbrain and thalamus, and a diagnosis of Wernicke's encephalopathy was made. In addition, the patient's serum thiamine level was extremely low (7 ng/ml). He received immediate treatment with intravenous thiamine administration (150 mg/day), and this significantly improved his symptoms (JCS 2). Dialysis patients may develop water-soluble vitamin deficiency as a result of the combination of reduced oral intake and increased loss of vitamins into the dialysate. Wernicke's encephalopathy should be considered as one of many causes of disturbed consciousness in hemodialysis patients. A rapid diagnosis and adequate treatment are essential in order to minimize long-term neurological sequelae. © 2006 Japanese Society of Nephrology.

DOI： 10.1007/s10157-006-0440-9

Scopus

PubMed

researchmap

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00714&link_issn=&doc_id=20210601070007&doc_link_id=%2Faq9jintd%2F2021%2F009005%2F008%2F0676-0683%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9jintd%2F2021%2F009005%2F008%2F0676-0683%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J00714&link_issn=&doc_id=20200930150006&doc_link_id=10.24479%2FJ00714.2020401508&url=https%3A%2F%2Fdoi.org%2F10.24479%2FJ00714.2020401508&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese  

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J00714&link_issn=&doc_id=20200318090013&doc_link_id=%2Faq9jintd%2F2020%2F008803%2F014%2F0383-0389%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9jintd%2F2020%2F008803%2F014%2F0383-0389%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese  

researchmap

researchmap

Language：Japanese  

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01159&link_issn=&doc_id=20180119160014&doc_link_id=10.2169%2Fnaika.107.103&url=https%3A%2F%2Fdoi.org%2F10.2169%2Fnaika.107.103&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

ネフローゼ症候群の診断には腎生検が必須であり,その病理診断に基づいて治療方針が決定される.ネフローゼ症候群を呈する疾患は多岐にわたるが,高度蛋白尿の発症に関わる尿蛋白制御機構の破綻という共通した病理所見が存在する.尿蛋白制御機構の破綻は,病理組織学的には足細胞と糸球体係蹄基底膜の障害として観察される.(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00974&link_issn=&doc_id=20130926230007&doc_link_id=issn%3D0022-1961%26volume%3D112%26issue%3D4%26spage%3D677&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D112%26issue%3D4%26spage%3D677&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese  

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00974&link_issn=&doc_id=20130603200163&doc_link_id=issn%3D0022-1961%26volume%3D111%26issue%3D6%26spage%3D1256&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D111%26issue%3D6%26spage%3D1256&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese  

researchmap

researchmap

Language：Japanese  

●急性尿細管傷害(ATI)とは異なる積極的な治療が可能な疾患を確実に診断する。●臨床所見から、糸球体腎炎や間質性腎炎、血管炎などが疑われる場合は積極的に腎生検を行い、治療方針を決定する。●ATIが考えられる場合でも、経過中に腎機能の回復が遷延する場合や、他の病態の存在が疑われる場合は腎生検が考慮される。●ATIの組織像の基本は尿細管上皮の変性・細胞死・その後の増生・再生像である。微小血管傷害や間質の傷害が病理像を修飾する。●腎生検の得られた組織から可能な限り病理所見を拾い出し、各症例の背景となる病態、詳細な臨床経過・臨床所見を統合して的確な診断を行う。(著者抄録)

researchmap

researchmap

Total pages：356p   Language：Japanese  

CiNii Books

researchmap

Language：Japanese  

急性腎傷害(AKI)の原因となる疾患・病態は単一ではなく、さまざまな因子が複雑に絡みあって発症・進展する。AKIの原因を鑑別することは治療の選択および予後の推定には必須であり、腎生検は、その原因や腎機能低下にかかわる病態の把握、腎傷害の病期や重症度、予後の推定に有用な検査法となる。とくに血管性や糸球体性のAKIや間質性腎炎によるAKIでは治療に著効する症例も多く、積極的な腎生検による診断を行う。AKIの主要な成因である急性尿細管傷害(ATI)の場合は全身状態が悪く腎生検を行えないことも多いが、原因が不明確で、予想される臨床経過と異なる場合や予後の推定のために腎生検を行う場合もある。腎生検の所見と、各症例の背景となる病態、詳細な臨床経過・臨床所見を統合して迅速に的確な診断を行い、治療に反映させる必要がある。(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2009&ichushi_jid=J00060&link_issn=&doc_id=20091009120004&doc_link_id=%2Faa7ayuma%2F2009%2F023102%2F005%2F0142-0149%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2009%2F023102%2F005%2F0142-0149%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese  

急性腎傷害(AKI)の原因となる疾患・病態は単一ではなく、さまざまな因子が複雑に絡み合って発症・進展する。AKIの原因を鑑別することは、治療の選択および予後の推定には必須であり、腎生検は、その原因や腎機能低下に関わる病態の把握、腎傷害の病期や重症度、予後の推定に有用な検査法となる。AKIの主要な成因である急性尿細管傷害(ATI)の尿細管間質病変は、特異的な変化が少ないため、組織像のみからの診断や、病変の解釈は困難な場合が多い。腎生検の所見と、各症例の背景となる病態、詳細な臨床経過・臨床所見を統合して、迅速に的確な診断を行い、治療に反映する必要がある。(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2008&ichushi_jid=J00974&link_issn=&doc_id=20080627070015&doc_link_id=issn%3D0022-1961%26volume%3D102%26issue%3D1%26spage%3D69&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D102%26issue%3D1%26spage%3D69&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese  

近年の血管生物学の進歩は著しく、血管壁を構築する細胞の発生と分化にかかわる分子が次々と解明され、高次血管構造の形成機構が明らかにされている。腎臓においても、今までは形態の上で理解されていた血管形成過程が、それを誘導する分子を含めて明らかにされてきている。腎臓は、血液中の不要物や有害な老廃物を選択的に排泄し、体液の浸透圧を調節し、体内の恒常性を維持する臓器であり、非常に分化した血管系を構築している。腎発生を理解するために、また血管再生による腎疾患の進展・制御を目指す腎再生療法や腎臓そのものをin vitroで形成するためには、腎血管系の発生機構の詳細な解明が必要である。本稿では、まだ不明な点も数多く残されているが、腎臓の血管系の形成機構について、解析が進められている糸球体毛細血管網の形成機構を中心に概説する。(著者抄録)

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：日本内科学会-関東地方会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：English   Publisher：(一社)日本骨髄腫学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00714&link_issn=&doc_id=20210924140017&doc_link_id=%2Faq9jintd%2F2021%2F009103%2F018%2F0429-0434%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9jintd%2F2021%2F009103%2F018%2F0429-0434%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：日本内科学会-関東地方会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本臨床薬理学会  

researchmap

Language：Japanese   Publisher：(NPO)日本高血圧学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：日本内科学会-関東地方会  

researchmap

Language：Japanese   Publisher：日本内科学会-関東地方会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：日本臨床分子医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(有)科学評論社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

卵管采巻絡再発に対し、腹腔鏡下に卵管采巻絡解除および前腹壁へのカテーテル固定術(PWAT)を施行し、注排液良好となった65歳女性の症例について報告した。慢性糸球体腎炎に対し、65歳時に腹膜透析(PD)カテーテル挿入術施行し、SPIED法でPD導入となった。導入約1ヵ月後に排液不良、退院後数日で再度排液不良を認め、精査加療目的で再入院となった。腹部CT所見で子宮・卵巣付近でのPDカテーテル走行異常がみられ、卵管采巻絡によるPDカテーテル閉塞が疑われた。腹腔鏡を施行したところ、卵管采巻絡によるカテーテル閉塞を認め、巻絡を解除した。一時的に排液良好となったが、退院後に再度排液不良を認め、再入院となった。卵管采巻絡の再発が疑われたため、卵管采巻絡再発の加療目的に転院、腹腔鏡で精査加療を行う方針となった。再発防止のため前腹壁のPWATを行った。術後2日目よりPDを再開し、注排液良好で術後13日目に自宅退院となった。

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本臨床リウマチ学会  

22歳女性。発熱・多関節痛を主訴に来院、SLEと診断した。SLEDAI高値・ループス腎炎IIIA/Cより疾患活動性が高くステロイドハーフパルス療法を施行した。一時症状改善したがプレドニン40mg後療法中に再燃したためタクロリムス・ミゾリビン併用を開始した。タクロリムスの血中濃度が上昇せず、薬物代謝酵素の遺伝子多型による影響を疑いシクロスポリンに変更すると有効血中濃度に達し著効した。後の測定で血中濃度の上昇しにくいCYP3A5*1/*1であることが判明した。(著者抄録)

DOI： 10.14961/cra.27.219

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

アルコール性肝硬変にIgA沈着を伴う糸球体硬化症を合併しやすいことは以前から報告されているが、ネフローゼ症候群や急速進行性腎炎症候群をきたすことは比較的稀といわれている。急速進行性腎炎症候群を合併したアルコール性肝硬変患者に対し、副腎皮質ステロイド薬(以下、ステロイド)、免疫抑制薬を使用し良好な経過を得た2例を経験した。症例1は55歳、男性。アルコール性肝硬変にて消化器内科通院中であったが、肉眼的血尿を認めた後、急速に腎機能が低下した。腎生検像は壊死性病変を伴う管内増殖性病変を呈し、蛍光抗体法ではIgAとC3のparamesangiumから係蹄壁への沈着を認めた。沈着しているIgAのサブタイプはIgA1であった。両側口蓋扁桃摘出術および、3クールのステロイドセミパルス療法、後療法としてステロイドにミゾリビン(MZR)を併用した。血尿および蛋白尿は陰性化し、腎機能も著明な改善を示した。症例2は37歳、男性。アルコール性肝硬変から肝性脳症をきたし、他院で加療中であったが、ネフローゼ症候群に加え腎機能も急速に悪化、大量の腹水を認めたため当科に転院となった。腹水持続ドレナージ後に腎生検を施行、糸球体は全体的にやや虚脱傾向を伴い、分節性から全節性の軽度の増殖性病変を認め、係蹄基底膜のwrinkling、肥厚や二重化が目立った。また、約半分の糸球体に半月体の形成を認めた。蛍光抗体法ではIgAとC3を主体とした陽性像が見られ、IgAのサブタイプはIgA1であった。3クールのステロイドセミパルス療法、後療法としてステロイドにMZRを併用したところ、蛋白尿の減少とともに血清Cre値の低下を認め、腹水の貯留も劇的に減少した。2症例ともアルコール性肝硬変により血中に上昇した、主に腸管由来IgA1の糸球体への沈着が引き金となった二次性IgA腎症と診断した。積極的な免疫抑制療法が有効であった。(著者抄録)

researchmap

Language：Japanese   Publisher：(株)新興医学出版社  

●急性尿細管傷害(ATI)とは異なる積極的な治療が可能な疾患を確実に診断する。●臨床所見から、糸球体腎炎や間質性腎炎、血管炎などが疑われる場合は積極的に腎生検を行い、治療方針を決定する。●ATIが考えられる場合でも、経過中に腎機能の回復が遷延する場合や、他の病態の存在が疑われる場合は腎生検が考慮される。●ATIの組織像の基本は尿細管上皮の変性・細胞死・その後の増生・再生像である。微小血管傷害や間質の傷害が病理像を修飾する。●腎生検の得られた組織から可能な限り病理所見を拾い出し、各症例の背景となる病態、詳細な臨床経過・臨床所見を統合して的確な診断を行う。(著者抄録)

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

51歳男。高血圧、糖尿病、慢性腎不全にて通院中であり、膜透析導入されていた。今回、腹痛が出現し、血性の排液を認め入院となった。腹部CTで上腸間膜動脈走行部位に造影効果のない腫瘤を認め、MRIのT1強調画像でhigh、T2でlowを呈したため血腫が疑われ、同部位からの漏出が血性排液の原因と判断した。腹部透析は一時中止し、腹腔内洗浄のみとして血液透析を実施したところ、腹痛は入院後2日で消失し、血性排液は数日後に自然消失した。

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：日本内科学会-関東地方会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

Chronic kidney disease (CKD) is defined by two criteria. One criterion is abnormal renal function or morphology, especially proteinuria. A second criterion is an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m² calculated with the serum creatinine concentration. CKD is classified on the basis of eGFR from stage 1 to stage 5. CKD is a common cause of cardiovascular disease (CVD). CVD is a major cause of morbidity and mortality in patients with CKD. Management of hypertension in patients with CKD aims to prevent CVD and provide renoprotection. First-line agents for controlling blood pressure are inhibitors of the renin-angiotensin system: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. These agents are superior to other classes of antihypertensive agents in reducing the amount of urinary protein and in preserving renal function. In CKD, the target blood pressure is less than 130/80mmHg, and 125/75mmHg, if the amount of urinary protein is more than 1g/day. To achieve the target blood pressure, other classes of antihypertensive agents, such as diuretics and calcium channel blockers, should also be administered.<br>

DOI： 10.1272/manms.6.17

researchmap

Language：Japanese   Publisher：(一社)日本内科学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：医歯薬出版(株)  

急性腎傷害(AKI)の原因となる疾患・病態は単一ではなく、さまざまな因子が複雑に絡みあって発症・進展する。AKIの原因を鑑別することは治療の選択および予後の推定には必須であり、腎生検は、その原因や腎機能低下にかかわる病態の把握、腎傷害の病期や重症度、予後の推定に有用な検査法となる。とくに血管性や糸球体性のAKIや間質性腎炎によるAKIでは治療に著効する症例も多く、積極的な腎生検による診断を行う。AKIの主要な成因である急性尿細管傷害(ATI)の場合は全身状態が悪く腎生検を行えないことも多いが、原因が不明確で、予想される臨床経過と異なる場合や予後の推定のために腎生検を行う場合もある。腎生検の所見と、各症例の背景となる病態、詳細な臨床経過・臨床所見を統合して迅速に的確な診断を行い、治療に反映させる必要がある。(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2009&ichushi_jid=J00060&link_issn=&doc_id=20091009120004&doc_link_id=%2Faa7ayuma%2F2009%2F023102%2F005%2F0142-0149%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2009%2F023102%2F005%2F0142-0149%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：日本内科学会-関東地方会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

近年の血管生物学の進歩は著しく、血管壁を構築する細胞の発生と分化にかかわる分子が次々と解明され、高次血管構造の形成機構が明らかにされている。腎臓においても、今までは形態の上で理解されていた血管形成過程が、それを誘導する分子を含めて明らかにされてきている。腎臓は、血液中の不要物や有害な老廃物を選択的に排泄し、体液の浸透圧を調節し、体内の恒常性を維持する臓器であり、非常に分化した血管系を構築している。腎発生を理解するために、また血管再生による腎疾患の進展・制御を目指す腎再生療法や腎臓そのものをin vitroで形成するためには、腎血管系の発生機構の詳細な解明が必要である。本稿では、まだ不明な点も数多く残されているが、腎臓の血管系の形成機構について、解析が進められている糸球体毛細血管網の形成機構を中心に概説する。(著者抄録)

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本病理学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(株)東京医学社  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(一社)日本腎臓学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：(一社)日本透析医学会  

researchmap

Language：Japanese   Publisher：日本内科学会-関東地方会  

researchmap

Language：Japanese   Publisher：(一社)日本脳卒中学会  

researchmap

Event date： 2014.5

Language：Japanese  

researchmap

Event date： 2013.4

Language：Japanese  

researchmap

Event date： 2013.4

Language：Japanese  

researchmap

Event date： 2010.5

Language：Japanese  

researchmap

Event date： 2009.4

Language：Japanese  

researchmap