A case of thrombotic microangiopathy associated with polymyositis.

A 60-year-old Japanese woman with polymyositis (PM) developed hemolytic anemia (hemoglobin of 7.3 g/dL), thrombocytopenia (platelet of 9.1×104/µL), and acute kidney injury (Cre of 4.7 mg/dL) at 14 days after starting steroid therapy. Renal biopsy revealed glomerular endothelial swelling with fibrin thrombi and fragmented erythrocytes in the capillary lumens. Hemolytic uremic syndrome (HUS) with thrombotic microangiopathy (TMA) was diagnosed. Hemodialysis and plasma exchange/plasma transfusion were initiated, but HUS did not subside. After 45 days, the patient died of hemorrhagic respiratory failure. Autopsy showed fibrin thrombi filling the glomerular vascular pole and the small arteries in most glomeruli, resulting in glomerular collapse and glomerular basement membrane (GBM) duplication. Although renal involvement by PM is rare, HUS/TMA should be remembered as one of the serious renal complications of PM.

Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Tolvaptan is the only therapeutic drug for autosomal dominant polycystic kidney disease (ADPKD). The influence of mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) on the treatment effects of tolvaptan is not well documented in the literature. METHODS: We retrospectively evaluated the relationship between genotype and the efficacy of tolvaptan in 18 patients with ADPKD who had been treated at Toranomon Hospital and undergone genetic testing between April 2016 and February 2020. RESULTS: The annual change in estimated glomerular filtration rate (ΔeGFR/y) from before to after tolvaptan was from a median of -5.5 to -2.5 mL/min/1.73 m2 in the PKD1 truncating group, -3.3 to -2.4 mL/min/1.73 m2 in the PKD1 non-truncating group, -3.1 to -1.6 mL/min/1.73 m2 in the PKD2 group, and -1.9 to -2.6 mL/min/1.73 m2 in the group with no PKD1/2 mutation. The median degrees of improvement of ΔeGFR/y were 2.5 (45%), 0.4 (10%), 0.6 (28%), and -0.7 (-37%) mL/min/1.73 m2, respectively. Compared with the group of patients with any PKD1/2 mutation, the group with no PKD1/2 mutation showed significantly less improvement in ΔeGFR/y with tolvaptan (0.6 vs. -0.7 mL/min/1.73 m2, respectively; p = 0.01) and significantly less improvement in the annual rate of increase in total kidney volume (TKV) with tolvaptan (-6.7 vs. -1.1%, respectively; p = 0.02). CONCLUSION: Patients with ADPKD and no PKD1/2 mutation showed less improvement in ΔeGFR/y and the annual rate of increase in TKV with tolvaptan. Detecting PKD1/2 mutations may be useful for predicting the effectiveness of tolvaptan.

Genotype-Clinical Correlations in Polycystic Kidney Disease with No Apparent Family History.

BACKGROUND: Genetic characteristics of polycystic kidney disease (PKD) patients without apparent family history were reported to be different from those with a positive family history. However, the clinical course of PKD patients with no apparent family history is not well documented in the literature. METHODS: We evaluated the relationship between genotype and the clinical course of 62 PKD patients with no apparent family history. RESULTS: The annual decline of renal function was faster in the patients with PKD1/PKD2 mutation (PKD1 truncating [-3.08; 95% CI -5.30 to -0.87, p = 0.007], PKD1 nontruncating [-2.10; -3.82 to -0.38, p = 0.02], and PKD2 [-2.31; -4.40 to -0.23, p = 0.03]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, estimated glomerular filtration rate (eGFR), height-adjusted total kidney volume (TKV), and mean arterial pressure (MAP). There was no significant difference in the annual decline of renal function among the different PKD1/PKD2 groups, but Kaplan-Meier analysis showed that progression to eGFR < 15 mL/min/1.73 m2 was significantly faster in PKD1 truncating group (p = 0.05). The annual rate of TKV increase was larger in the patients with PKD1/PKD2 mutation (PKD1 truncating [4.63; 95% CI 0.62-8.64, p = 0.03], PKD1 nontruncating [3.79; 0.55-7.03, p = 0.02], and PKD2 [2.11; -1.90 to 6.12, p = 0.29]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, eGFR, and MAP. CONCLUSION: Detection of PKD1/PKD2 mutation, especially PKD1 truncating, is useful for predicting the renal outcome and rate of TKV increase in PKD patients with no apparent family history.

Clinicopathological predictors for progression of chronic kidney disease in nephrosclerosis: a biopsy-based cohort study.

BACKGROUND: Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. METHODS: We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell's C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. RESULTS: During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35-0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54-0.94), eGFR (SHR 0.98; 95% CI 0.97-0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08-1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00-1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20-1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. CONCLUSIONS: The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.

Immunoglobulin G subclass 3 in ISN/RPL lupus nephritis classification
.

OBJECTIVES: In lupus nephritis, the immune complex plays a very important role in kidney disease progression, and immunoglobulin G subclass 3 (IgG3) may play an important role in endothelial damage as lupus nephropathy progresses. We evaluated the association between IgG3 positivity and lupus nephritis activity. MATERIALS AND METHODS: We identified 71 biopsies taken from 57 patients who had lupus nephritis with enough tissue to allow light and immunofluorescence microscopy. We compared the intensity of IgG subclass staining (on a scale of 0 - 3+) with IgG subclass dominance among lupus nephritis classes as defined by the ISN/RPS 2003 classification. RESULTS: The proportion of IgG3-positive patients with capillary loop lesion was significantly higher in the class IV group compared with other groups (p < 0.01). Interestingly, in most patients IgG1 was the strongest subclass; in class IV groups, IgG3 was the strongest in 21% of the biopsies. IgG3 deposition in capillary loops was significantly associated with C1q deposition in those loops. According to Kaplan-Meier analysis, renal survival rates in the patients with IgG3 deposition was lower (82.2%) than in patients without IgG3 deposition (93.3%), but the difference was not significant. CONCLUSION: Our results suggest that capillary loop deposition of IgG3 is associated with disease activity in lupus nephritis.
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Significance of urinary albumin excretion in patients with cast nephropathy
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BACKGROUND: This study was performed to determine whether the urinary albumin excretion rate (%UAE) could distinguish myeloma cast nephropathy (MCN) without glomerular amyloid deposition from MCN with glomerular amyloid deposition. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data on 16 patients with MCN diagnosed by renal biopsy at Toranomon Hospital from 2004 to 2014. RESULTS: A total of 10 patients had pure MCN without glomerular amyloid deposition (group 1), and 6 patients had MCN with glomerular amyloid deposition (group 2). In all 10 patients from group 1, the underlying disease was multiple myeloma (MM), while 4 patients had MM, and 2 patients had lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in group 2. Total protein did not show a significant difference between the two groups, but serum albumin was significantly higher in group 1 than group 2 (p = 0.0101). Serum-adjusted calcium did not show a significant difference between the groups, while serum creatinine (Cre) was significantly higher in group 1 than group 2 (p = 0.0343). Although urinary protein excretion did not differ significantly between the groups, the %UAE was significantly lower in group 1 than group 2 (p = 0.00198). In group 2, 3 of the 4 patients with MM died within 15 months of diagnosis, but the 2 patients with LPL/WM are alive after 32 months. In group 1, only 1 patient died (of unknown causes) within 15 months after diagnosis. CONCLUSION: In patients with MCN, %UAE may be a useful marker for the detection of coexistence of glomerular lesions, such as amyloidosis, which are associated with a poor outcome.

Association between renal outcome and the number of steroid pulse therapies after tonsillectomy in patients with IgA nephropathy.

BACKGROUND: Tonsillectomy performed on patients with Immunoglobulin A glomerulonephritis (IgAN) improved the clinical remission rate as defined by urinary protein. But the number of times steroid pulse therapies (SP) should be administered remained poorly understood. METHOD: Multicenter, observational, retrospective cohort study at four hospitals in the Tokyo metropolitan area between March 1981 and December 2013. We divided patients into two groups: those treated with SP three times and those treated without SP or with SP only once or twice, and we analyzed standard Cox proportional hazard model unadjusted and adjusted the confounding covariates to estimate the hazard ratio for the primary outcome, the 30% estimated decline in glomerular filtration rate, in four models: model 1, unadjusted; model 2, adjusted for age, sex, body mass index, estimated glomerular filtration rate, biopsy year, proteinuria, hematuria, Japanese historical grade, systolic blood pressure, smoking history, and diabetes as a comorbidity; model 3, adjusted for propensity score, which was estimated by multiple logistic regressions; model 4, multilevel mixed-effects parametric survival models, whose facilities comprise the second level. RESULTS: Patients that received three times SP therapy were significantly associated with better renal outcome compared with patients with less number of SP therapy (HR 0.66; 95% CI 0.37-1.17 in model 1, 0.40 (0.20-0.78) in model 2, 0.46 (0.25-0.88) in model 3, 0.36 (0.18-0.71) in model 4). CONCLUSIONS: For treatment of IgAN, SP administered three times after tonsillectomy was associated with better renal prognosis compared with SP administered only once or twice.

Increase of 1,25 dihydroxyvitamin D in sarcoidosis patients with renal dysfunction.

INTRODUCTION: In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction. MATERIALS AND METHODS: We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90). RESULTS: Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients. CONCLUSION: While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.

Long-term outcome of biopsy-proven cholesterol crystal embolism.

BACKGROUND: Cholesterol crystal embolism (CCE) causes renal damage, and there is an extremely high risk of end-stage renal disease. However, the time course of CCE-related renal deterioration varies and little is known about the subsequent risk of dialysis among patients with biopsy-proven CCE. METHODS: We performed a retrospective cohort study of 38 Japanese patients in whom a histological diagnosis of CCE was made from September 1992 to July 2005. Competing risk regression analysis was used to investigate the association between declining renal function ( ≥ 1.5 elevation of serum creatinine within 26 weeks after CCE) or its subtypes (acute [ < 1 week after CCE], subacute [1 to < 6 weeks], and chronic [6 to < 26 weeks]) and the risk of dialysis, with adjustment for age, baseline serum creatinine, and the precipitating event (iatrogenic or spontaneous). RESULTS: During a median follow-up period of 25.9 weeks, 14 patients (35.9%) started dialysis. Multivariable analysis showed that patients with declining renal function had a higher risk of commencing dialysis than those without declining function (subdistribution hazard ratio [SHR] 9.47; 95% confidence interval [CI] 1.34-66.8). Patients with different renal presentations had a similarly increased risk of commencing dialysis, with the risk being significantly higher for the subacute and chronic patterns of declining renal function (adjusted SHR [95% CI] for acute, subacute, and chronic declining renal function[vs. no decline]: 7.36 [0.85-63.6], 11.9 [1.36-101], and 10.7 [1.49-77.0], respectively). CONCLUSION: Declining renal function after CCE, even later than 6 weeks, was significantly associated with the subsequent risk of dialysis.

PKD1-associated autosomal dominant polycystic kidney disease with glomerular cysts presenting with nephrotic syndrome caused by focal segmental glomerulosclerosis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) may manifest non-nephrotic range proteinuria, but is rarely complicated with nephrotic syndrome. Limited number of reports describe the histology of ADPKD with nephrotic syndrome in detail. CASE PRESENTATION: We encountered a 23-year-old man with polycystic kidney disease (PKD) with small kidney volume and nephrotic syndrome, which eventually progressed to end-stage renal disease. Renal histology showed typical focal segmental glomerulosclerosis and remarkable glomerular cyst formation, but did not reveal tubular cysts. PKD1 mutation was detected in him and his father, who also had PKD with small kidney volume. CONCLUSIONS: In contrast to tubular cysts which develop along ADPKD progression, glomerular cysts may likely be associated with ADPKD with slower volume progression manifesting small kidney volume. Although previous investigations report that ADPKD with smaller kidney volume is attributed to slower decline in renal function, coexistence of nephrotic-range proteinuria implies complication of other glomerular diseases and needs histological evaluation since it may lead to poor renal outcome.

Glycated albumin versus hemoglobin A1c and mortality in diabetic hemodialysis patients: a cohort study.

Background: For glycemic control in diabetic patients on dialysis it was unclear what level of glycated albumin (GA) was associated with the lowest mortality and GA's utility. Accordingly, we examined the difference in association between GA and hemoglobin A1c (HbA1c) with 1-year mortality in a cohort of the Japanese Society for Dialysis Therapy. Methods: We examined 84 282 patients with prevalent diabetes who were on maintenance hemodialysis (HD) (female 30.3%; mean age 67.3 ± 11.2 years; mean dialysis vintage 6.4 ± 4.5 years). Of them, 22 441 had both GA and HbA1c. We followed these for a year, 2013-14, using Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence limits for 1-year mortality after adjusting for potential confounders such as baseline age, sex, smoking and diabetes type. Results: One-year mortality was lowest in diabetic HD patients who had GA levels of 15.6-18.2% and HbA1c levels of 5.8-6.3%. The associations were linear or J-shaped for GA and U-shaped for HbA1c. Adjusted HRs were significantly higher in patients with GA <12.5% and GA ≥22.9%. This trend flattened in elderly patients, those with higher hemoglobin or those with prior cardiovascular disease. In addition, the C-statistics, Harrell's C and category-free net reclassification improvement to predict 1-year mortality were better when GA was added to the model than when HbA1c was added. Conclusions: There was a linear or J-shaped association between GA and 1-year mortality, with the lowest mortality at GA 15.6-18.2%. Furthermore, our analyses suggest the potential superiority of GA over HbA1c in predicting mortality.

Renal histology and MRI in a 25-year-old Japanese man with nephronophthisis 4
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We investigated a 25-year-old Japanese man who had polycystic kidneys and end-stage renal failure without a positive family history. Ultrasonography revealed enlarged kidneys with increased echogenicity and multiple cystic lesions. MRI showed replacement of both kidneys by cystic lesions without definite walls. Renal biopsy demonstrated interstitial fibrosis, especially at the corticomedullary junction. The residual tubular system showed starfish-like disruption. Tubules with cystic dilation were mainly the distal loop of Henle and the distal tubules since immunohistochemical staining was positive for cytokeratin 7 (the distal loop of Henle and the distal tubule) and Tamm-Horsfall protein (the distal loop of Henle), while being negative for aquaporin 3 (the collecting duct) and CD10 (proximal tubule). Comprehensive genetic analysis identified compound heterozygous missense mutations of NPHP4 with autosomal recessive inheritance since his asymptomatic parents each had a single heterozygous missense mutation of NPHP4. In conclusion, MRI and immunohistochemical analysis of renal biopsy specimens may be useful for evaluation of this disease.
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Clinical and histological features of antineutrophil cytoplasmic antibody-associated vasculitis related to antithyroid drugs
.

BACKGROUND: Antithyroid drugs such as propylthiouracil and methimazole have been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but little is known about long-term outcomes. MATERIALS AND METHODS: We identified AAV patients who underwent renal biopsy and retrospectively assessed their clinical and histological findings. Patients with AAV who had received propylthiouracil or methimazole were defined as having antithyroid drug-associated AAV (ATD-AAV), and the other patients were defined as having primary AAV. RESULTS: Seven patients with ATD-AAV and 83 patients with primary AAV were identified. Compared with the primary AAV group, the patients with ATD-AAV were significantly younger (mean ± standard deviation; 45.4 ± 21.4 years vs. 65.9 ± 13.8 years, p < 0.01), and had lower serum creatinine (median [interquartile range]; 0.7 mg/dL [0.6 - 1.5] vs. 2.3 mg/dL [1.0 - 4.0], p = 0.02), as well as a higher frequency of positivity for MPO--ANCA/PR3-ANCA (42.9 vs. 4.8%, p < 0.01). While glomerular crescents varied, interstitial fibrosis and tubular atrophy were milder in ATD-AAV patients. Kaplan-Meier analysis showed a significantly higher kidney survival rate in patients with ATD-AAV than in those with primary AAV (p = 0.05). CONCLUSION: Patients with ATD-AAV were younger and had milder kidney involvement, resulting in a better long-term outcome compared with primary AAV.
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Risk factors of ceftriaxone-associated biliary pseudolithiasis in adults: influence of renal dysfunction.

BACKGROUND: Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL) mainly in children. Biliary elimination of CTRX increases in patients with renal dysfunction. However, the influence of renal dysfunction on the incidence of CTRX-associated BPL has not been well investigated. The aim of this study was to investigate the cumulative incidence of CTRX-associated BPL in adults and to assess if renal dysfunction is a risk factor. METHODS: We retrospectively analyzed the medical records of 478 patients treated with CTRX to assess the incidence and risk factors of CTRX-associated BPL. We examined age, sex, body weight, dosage, and duration of CTRX therapy, and the concentrations of serum creatinine, estimated glomerular filtration rate (eGFR), albumin, and serum calcium in all the patients. The cumulative incidence of BPL was calculated using a competing risk model. The multivariate analysis of each variable for the development of BPL was assessed by a Cox proportional hazards model. RESULTS: A total of 362 patients (75.7%) had renal dysfunction (eGFR: < 60 mL/min). The cumulative incidence of BPL in patients with renal dysfunction was significantly higher than that in patients with normal kidney function (4.1 vs. 0.6%, p = 0.017). Renal dysfunction (Hazard ratio (HR) 8.14, 95% CI 1.05-63.0, p = 0.045) and female sex (HR 5.35, 95% CI 1.17-24.5, p = 0.031) were independent risk factors of CTRX-associated BPL, which was confirmed using multivariate analysis (renal dysfunction: HR 7.93, 95% CI 1.04-60.5, p = 0.046) (female sex HR 4.65, 95% CI 1.03-21.1, p = 0.046). CONCLUSIONS: Renal dysfunction is an independent risk factor of CTRX-associated BPL in adults.

Autosomal dominant form of type IV collagen nephropathy exists among patients with hereditary nephritis difficult to diagnose clinicopathologically.

AIM: Type IV collagen nephropathies include Alport Syndrome and thin basement membrane nephropathy (TBMN), which are caused by mutations in COL4A3/A4/A5 genes. Recently, reports of patients with heterozygous mutations in COL4A3/A4 have been increasing. The clinical course of these patients has a wide variety, and they are diagnosed as TBMN, autosomal dominant Alport syndrome (ADAS), or familial focal segmental glomerular sclerosis. However, diagnosis, frequency and clinicopathological manifestation of them remains unclear. We tested COL4A3/A4/A5 genes in patients with hereditary nephritis that was difficult to diagnose clinicopathologically, and investigated who should undergo such testing. METHODS: We performed immunostaining for α5 chain of type IV collagen [α5 (IV)] in 27 patients from 21 families who fitted the following criteria: (i) haematuria and proteinuria (± renal dysfunction); (ii) family history of haematuria, proteinuria, and/or renal dysfunction (autosomal dominant inheritance); (iii) no specific glomerulonephritis; and (iv) thinning, splitting, or lamellation of the glomerular basement membrane (GBM) on electron microscopy. Then we performed genetic testing in 19 patients from 16 families who showed normal α5 (IV) patterns. We conducted a retrospective analysis of their clinicopathological findings. RESULTS: Among 16 families, 69% were detected heterozygous mutations in COL4A3/A4, suggesting the diagnosis of TBMN/ADAS. Twenty-one percent of patients developed end stage renal disease. All patients showed thinning of GBM, which was accompanied by splitting or lamellation in seven patients. CONCLUSION: A considerable fraction of patients with hereditary nephritis that is difficult to diagnose clinicopathologically have TBMN/ADAS. It is important to recognize TBMN/ADAS and perform genetic testing in appropriate patients.

Multicentre cross-sectional study for bone-articular lesions associated with dialysis related amyloidosis in Japan.

AIM: Dialysis-related amyloidosis (DRA) exhibits multiple bone-articular lesions, such as carpal tunnel syndrome (CTS), trigger finger (TF), spinal canal stenosis (SCS), destructive spondyloarthropathy (DSA), bone cysts, and joint pains. DRA leads to a decrease in activities of daily living (ADL). We investigated the initiation of CTS and TF, and evaluated the relationship between walking disturbances and bone-articular lesions or joint pains. METHODS: A multicentre cross-sectional study was performed. Eighty-two patients with clinical DRA from 20 hospitals in Japan were evaluated. RESULTS: Of the 82 patients, the first symptom of DRA was CTS in 39 patients (47.6%) and TF in 21 (25.6%). The mean new-onset vintages of 21 earlier cases in the CTS and TF groups were 86.1 ± 36.3 and 133.2 ± 56.4 (mean ± SD) months, respectively (P = 0.0091). The development of SCS and DSA appeared to be later than CTS and TF. Multiple regression analysis revealed that knee joint pain was a significant contributor to walking disturbances. CONCLUSION: Carpal tunnel syndrome appeared significantly earlier than TF since the initiation of dialysis. In the advanced phase, knee joint pain was a major cause of decreased ADL in patients with clinical DRA.

Clinical and pathological features of anti-neutrophil cytoplasmic antibody-associated vasculitis in patients with minor urinary abnormalities.

AIM: Kidney biopsy is the gold standard for diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but it is unknown whether vasculitis can be detected from AAV patients with minor urinary abnormalities. METHODS: Ninety ANCA-positive patients undergoing kidney biopsy were evaluated retrospectively after being divided into two groups, which were group A (minor urinary abnormalities with both proteinuria <0.5 g/day and red blood cells ≤5/high power field) and group B (major urinary abnormalities except group A). RESULTS: Thirteen patients were included in group A and 77 patients were in group B. Crescentic glomeruli were detected less frequently in group A than in group B (61.5% vs. 92.2%, P < 0.01). The percentage of crescentic glomeruli relative to total glomeruli was significantly lower in group A than in group B (median [interquartile range]; 2.7% [0-5.2%] vs. 27.3% [8.1-56.1%], P < 0.01). Vasculitis of the small renal arteries was detected more frequently in group A than in group B without significant difference (30.8% vs. 19.5%, P = 0.46). Overall renal vasculitis (crescentic glomeruli and/or small renal artery vasculitis) was detected less frequently in group A than in group B (69.2% vs. 92.2%, P = 0.03). CONCLUSIONS: These findings indicate that renal biopsy can be a useful tool for histological diagnosis of ANCA-associated vasculitis in ANCA-positive patients with minor urinary abnormalities, even though the rate of renal vasculitis to the total number of glomeruli sampled is lower in patients with minor urinary abnormalities than patients with major abnormalities.

Cyst infection in autosomal dominant polycystic kidney disease: penetration of meropenem into infected cysts.

BACKGROUND: Cyst infection is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often refractory. Carbapenems are frequently needed to treat to patients with refractory cyst infection, but little is known about the penetration of newer water-soluble carbapenems into cysts. This study investigated the penetration of meropenem (MEPM) into infected cysts in patients with ADPKD. METHODS: Between August 2013 and January 2014, 10 ADPKD patients (14 infected cysts) receiving MEPM at Toranomon Hospital underwent drainage of infected cysts and definite cyst infection was confirmed through detection of neutrophils by cyst fluid analysis. The serum concentration of MEPM was measured just after intravenous administration and was compared with that in fluid aspirated from infected cysts. RESULTS: In the patients undergoing cyst drainage, the mean serum MEPM concentration was 35.2 ± 12.2 µg/mL (range: 19.7 to 59.2 µg/mL, while the mean cyst fluid concentration of MEPM in the drained liver cysts (n = 12) or kidney cysts (n = 2) was 3.03 ± 2.6 µg/mL (range: 0 to 7.3 µg/mL). In addition, the mean cyst fluid/serum MEPM concentration ratio was 9.46 ± 7.19% (range: 0 to 18.8%). There was no relationship between the cyst fluid concentration of MEPM and the time until drainage after MEPM administration or between the cyst fluid/serum MEPM concentration ratio and the time until drainage. CONCLUSION: These findings suggest that MEPM shows poor penetration into infected cysts in ADPKD patients. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN) as "Penetration of meropenem into cysts in patients with autosomal dominant polycystic kidney disease (ADPKD)", UMIN ID 000011292 on July 26th, 2013.

Corticosteroids pulse therapy and oral corticosteroids therapy for IgA nephropathy patients with advanced chronic kidney disease: results of a multicenter, large-scale, long-term observational cohort study.

BACKGROUND: Corticosteroids are widely used to reduce the urine protein levels of patients with immunoglobulin A nephropathy (IgAN). However, their potential preventive effects on end-stage kidney disease (ESKD) are unclear. METHODS: We previously performed a large-scale, long-term multicenter cohort study of patients with biopsy-proven IgAN treated between 1981 and 2013 (n = 1923). Based on the results, we reported that corticosteroids pulse therapy was potentially effective for the treatment of patients with an eGFR ≥30 ml/min/1.73m2 and a urine protein amount of ≥1 g/gCr. In the present study, we extracted 766 patients with chronic kidney disease (CKD), stage G3-G4 (15 ≤ estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) from the same cohort. We divided these patients into a steroid pulse (SP) group, oral steroid (OS) group, and no steroid (NS) group, and analyzed the risk of end-stage kidney disease (ESKD) stratified by eGFR and urine protein (UP) amounts. RESULTS: Over the median long-term follow-up of 70 ± 115 months, 37.1% of the patients with UP ≥1.0 g/day and 11.2% of the patients with UP < 1.0 g/day reached ESKD. Among the patients with UP ≥1 g/gCr, the SP group showed significantly better renal outcome (p < 0.001) than the OS and NS groups. In patients with UP < 1 g/gCr, there were no differences in renal survival among the treatment groups. These trends appeared even in the CKD stage G4 patients, and were also apparent in patients taking renin-angiotensin system inhibitors. The unprecedented long-term observation period in this study may have been necessary to reveal the favorable effect of corticosteroids on ESKD progression. CONCLUSIONS: In our long-term multicenter study, Corticosteroids pulse therapy was associated with better renal outcomes in IgAN patients with higher UP values, even if their eGFR values were low.

Cryoglobulinemic vasculitis with primary Sjögren's syndrome: A case report.

A 63-year-old Japanese woman with Sjögren's syndrome and peripheral neuropathy was admitted for evaluation of purpura on her lower extremities. Skin biopsy revealed leukocytoclastic vasculitis with the deposition of IgM, and serum cryoglobulin was positive. Accordingly, cryoglobulinemic vasculitis was diagnosed. There was no response to high-dose steroid therapy and plasmapheresis, but intravenous cyclophosphamide pulse therapy was effective for 4 years. Thereafter, proteinuria and hematuria developed, with cryoglobulinemic glomerulopathy being diagnosed by renal biopsy. Because the total dose of cyclophosphamide had reached 8000 mg, treatment with rituximab was selected. While rituximab was initially effective for her skin lesions and nephropathy, relapse occurred within 2 years and additional administration of this agent was required. The long-term efficacy of treatment for cryoglobulinemic vasculitis remains uncertain in patients with Sjögren's syndrome.