Warfarin-related nephropathy with acute kidney injury in a patient with immunoglobulin A nephropathy.

A 55-year-old man with Marfan syndrome taking warfarin for anticoagulant therapy after aortic valve replacement developed acute kidney injury (serum creatinine level of 9.01 mg/dL) and gross macrohematuria. Renal biopsy showed red cell casts in the renal tubules, glomerular crescent formation in the glomeruli with immunoglobulin A deposition, and global sclerosis. Based on these findings, the patient was diagnosed with warfarin-related nephropathy with acute kidney injury characterized by immunoglobulin A nephropathy with crescents. The warfarin was withdrawn, and his hematuria and renal function improved without immunosuppressive agents.

[A case of rapidly progressive glomerulonephritis exhibiting granulomatosis with polyangiitis (GPA) and extremely high level of PR3-ANCA with improvement of renal dysfunction after plasma exchange therapy].

A 68-year-old Japanese man was diagnosed with left otitis media with effusion and left uveitis more than 5 months before admission. He was urgently admitted to our hospital for progressive deterioration of his renal function [serum creatinine(Cr) 7.59 mg/dL] with proteinuria and urinary red blood cell casts, inflammation, and anemia. Additionally, his serum proteinase 3 antinuclear antibody (PR3-ANCA) level, determined by using the chemiluminescence enzyme immunoassay method, had increased to more than 3,500 U/mL. Hemodialysis (HD) was initiated on the third day after admission and renal biopsy was performed on the eighth day. The histological findings showed necrotic cellar crescents, hence, he was diagnosed as granulomatosis with polyangiitis on the basis of the clinical criteria. Methylprednisolone pulse therapy was administered from the 11th day. Thereafter, the administration of oral prednisolone (PSL) was started, and plasma exchange was initiated for the purpose of RP3-ANCA removal. In his clinical course, PSL was tapered as soon as possible because of the development of steroid psychosis, and we started intravenous cyclophosphamide on the 25th day instead of tapering the PSL. Subsequently, his renal function improved even without HD, and he was discharged on the 49th day. Although his PR3-ANCA level was still high after discharge, the administration of azathioprine led to a decrease in the PR-3 ANCA levels. About 2 years after discharge, the PR3-ANCA level decreased to 10.0 U/mL, and there has been no sign of GPA recurrence.

Effects of a new bicarbonate/lactate-buffered neutral peritoneal dialysis fluid for peritoneal failure in patients undergoing peritoneal dialysis.

BACKGROUND: The highly concentrated lactate in peritoneal dialysis fluid (PDF) has been considered to contribute to peritoneal failure in patients undergoing PD. A new PDF containing a lower lactate concentration, physiological bicarbonate concentration, and neutral pH (bicarbonate/lactate-buffered neutral PDF) was recently developed. We compared the clinical effects of this bicarbonate/lactate-buffered neutral PDF and a lactate-buffered neutral PDF. METHODS AND DESIGN: Patients undergoing PD were changed from a lactate-buffered neutral PDF to a bicarbonate/lactate-buffered neutral PDF. We then investigated the changes in peritoneal functions as estimated by a peritoneal equilibration test (PET) and the following surrogate markers of peritoneal membrane failure in the drained dialysate: fibrin degradation products (FDP), vascular endothelial growth factor (VEGF), cancer antigen 125 (CA125), interleukin-6 (IL-6), and transforming growth factor beta 1 (TGF-ß1). RESULTS: Fourteen patients undergoing PD were enrolled. The PET results were not different before and after use of the bicarbonate/lactate-buffered neutral PDF. The FDP concentration significantly decreased from 15.60 ± 13.90 to 6.04 ± 3.49 µg/mL (p = 0.02) and the VEGF concentration significantly decreased from 37.83 ± 15.82 to 27.70 ± 3.80 pg/mL (p = 0.02), while the CA125 and IL-6 concentrations remained unchanged before and after use of the bicarbonate/lactate-buffered neutral PDF. TGF-ß1 was not detected in most patients. CONCLUSION: The bicarbonate/lactate-buffered neutral PDF decreased the FDP and VEGF concentrations in the drained dialysate. These results suggest that the decreased lactate level achieved by administration of bicarbonate with a neutral pH in PDF may contribute to decreased peritoneal membrane failure in patients undergoing PD.

An adult case of fulminant Epstein-Barr virus infection with acute tubulointerstitial nephritis.

Epstein-Barr virus (EBV) infection is common in adolescence, but fulminant infection is very rare. A 40-year-old man presented with high fever and sore throat. Symptoms, including cervical lymphadenopathy, jaundice, atypical lymphocytosis, respiratory distress and oliguria, suggested infectious mononucleosis with multiple organ failure that required mechanical ventilation and renal replacement therapy. Virus markers were consistent with primary EBV infection. Renal function was gradually improved by corticosteroid therapy. Renal biopsy revealed acute tubulointerstitial nephritis. In situ hybridizaion EBV-encoded RNA 1 did not show the presence of virus in the kidney, but acute kidney injury may be explained by cytotoxic/suppressor T lymphocyte infiltration.

Para-capillary electron-dense deposits reduce glomerular filtration in patients with primary glomerular diseases.

BACKGROUND: Electron-dense deposits are often found around glomerular capillary lumens in patients with glomerulonephritis, forming a portion of the blood-urine barrier (BUB). METHODS: Four hundred and four patients with primary glomerular diseases or donors for living-related kidney transplantation who underwent both percutaneous renal biopsy and renal clearance tests were included in the study. Sodium thiosulfate and paraamino hippurate double-clearance studies were performed with catheterized urinary collection. The filtration fraction (FF) was determined as follows: FF = sodium thiosulfate clearance/paraamino hippurate clearance (CPAH: ). Histomorphometric analyses were performed in 53 patients with overt para-capillary electron-dense deposits (PCEDD) by electron microscopic observations. RESULTS: Patients with membranous nephropathy and membranoproliferative glomerulonephritis showed significantly lower levels of FF than the donors for living-rebated kidney transplantation (normal controls). FF levels were significantly lower in patients with PCEDD than in those without (P < 0.001), while the levels of mean blood pressure and CPAH: were comparable in the two groups. The PCEDD/BUB ratio demonstrated a significant negative correlation with FF (P < 0.0001; r(2) = 0.331). Patients with a ratio of 0.5 or more showed significantly lower FF levels than those with a ratio of 0.25 or less. CONCLUSIONS: PCEDD significantly affected FF levels in patients with primary glomerular diseases. FF may not be an accurate indicator of intraglomerular blood pressure in patients with overt PCEDD.

Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy.

BACKGROUND: Monocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet. METHODS: We investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene. RESULTS: The incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype. CONCLUSIONS: The AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.

The morphological compensatory change of peritubular capillary network in chronic allograft rejection.

To clarify the compensatory hemodynamic alterations in the interstitium of renal allograft biopsies with chronic rejection, we evaluated the morphological changes in the peritubular capillary (PTC) network. Seven renal biopsy specimens from recipients with chronic rejection presenting with elevation of serum creatinine of 1.9 +/- 0.5 mg/dL were examined. Renal biopsy specimens from their counterpart donors were used as normal controls. In each specimen, non-pathological interstitial areas without fibrosis, tubular atrophy or cell infiltration were compared with pathological areas (PA) showing fibrosis and/or tubular atrophy using a computer image analysis. Morphological measurements revealed that the mean cut surface area of the PTC in the non-pathological and pathological interstitial areas in the recipient biopsies were significantly larger than that of the normal controls (p < 0.001 and 0.001, respectively). In the recipient biopsies, both of the mean cut surface areas of the tubules and PTC in the non-pathological areas were significantly higher than those in the PA (p < 0.001). The mean glomerular diameter in the recipient biopsies was also significantly higher than that of the donors (p < 0.01). In this study, we provided pathological evidence for the compensatory interstitial and glomerular hemodynamic alterations in kidney graft with chronic rejection and the condition as single kidney.

A clinicopathological study on the long-term efficacy of tonsillectomy in patients with IgA nephropathy.

Our study evaluated the clinical efficacy of tonsillectomy on the long-term renal survival in patients with primary IgA nephropathy (IgAN). Forty-six patients underwent tonsillectomy, and 74 patients did not. The mean of follow-up duration of all patients was 197.0+/-29.3 months (61-339 months). The baseline clinical and histological data at renal biopsy were not statistically different between the two groups with and without tonsillectomy. Five (10.9%) of the tonsillectomy group reached end stage renal failure (ESRF), whereas 19 (25.8%) of the non-tonsillectomy group did. The chi-square test between the two groups showed a significant difference (p <0.05). The renal survival of the tonsillectomy group was significantly higher than that of the non-tonsillectomy group by the Kaplan-Meier method with log-rank test (p <0.05). The Cox regression model also revealed that tonsillectomy had a significant favorable impact on the renal survival in long-term follow-up duration (p <0.05). Although our study was done by retrospective analyses, all the results proved that tonsillectomy had significant favorable effects on the long-term renal survival in patients with IgAN.