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Background. Renalinvolvementremainsamajordeter-minant in antineutrophil cytoplasmic autoantibody-associated small vessel vasculitis (AASV). While somepatients may develop persistent renal damage, othershave a favourable outcome.Methods. To identify patients at risk for poor renaloutcome, we evaluated 95 renal biopsies (67 initialbiopsies and 28 repeat biopsies) of 67 patients withAASV for the presence and extent of active (AI)and chronic (CI) lesions, retrospectively. AI, CI, levelsof proteinuria and dose of cyclophosphamide (CYC)were related to renal outcome.Results. Recovery of renal function in patients ini-tially dialysis dependent was associated with a lowerCI compared with patients who remained on dialysis(P

Mycophenolate mofetil (MMF), being effectively used as immunosuppressant in transplant medicine, has recently attracted interest as therapeutic agent for autoimmune diseases (AID). For these patients, no pharmacokinetic (PK) data are available. This study is an investigation of single-dose concentration-time profiles of 1 g off MMF in 16 patients with AID, including 10 patients with ANCA-associated vasculitis and 6 patients with systemic lupus erythematosus, and compares them with profiles of 16 renal transplant recipients (RTX). Mycophenolic acid (MPA) blood levels were measured by both HPLC and EMIT, and MPA-glucuronide was determined by HPLC. In AID, mean MPA concentrations at 12 h were significantly higher compared with RTX (4.1 +/- 3.27 versus 1.8 +/- 1.15 mg/L; P = 0.018), whereas peak concentrations were lower (P = 0.017). However, mean MPA-AUC at 12 h as well as at 24 h were comparable between both groups. In contrast to RTX, there was an association in AID between MPA trough levels at 12 h and at 24 h with AUC(0-12) (P < 0.05 and P < 0.01). MPA trough concentrations at 24 h provided an estimation of AUC(0-24 h) in both patient groups (P < 0.001 and P < 0.01; AID and RTX, respectively). Compared with RTX, MPA-PK seems to be less affected in AID by renal function. Inter-individual variability of PK parameters was high in both groups. These data indicate that there are differences of MPA-PK between RTX and AID. The use of therapeutic drug monitoring in patients with AID appears to be clinically practicable and may be valuable to optimize individual immunosuppressive therapy.

Nephrogenic adenomas are benign, tumor-like lesions within the urothelial mucosa of the urinary tract that are not uncommon in renal-transplant recipients. We investigated the origin of nephrogenic adenomas in renal-transplant recipients.Tissue sections were analyzed by fluorescence in situ hybridization with the use of probes for the X and Y chromosomes, by immunohistochemical methods with the use of antibodies to renal tubular antigens, and by lectin histochemical methods. Forty-six nephrogenic adenomas from 29 patients were analyzed.All nephrogenic adenomas in 14 female recipients of transplants from male donors and 10 male recipients of transplants from female donors showed the same sex-chromosome status as the donor kidney, but not the same sex-chromosome status as the recipient's surrounding bladder tissue. The nephrogenic adenomas from all 6 female recipients of transplants from female donors showed female chromosomes, and those from the 16 male recipients of transplants from male donors showed male chromosomes. The presence of aquaporin 1, PAX2, and lectin-binding capacity for peanut agglutinin, Lotus tetragonolobus agglutinin, and Sophora japonica agglutinin in nephrogenic adenomas indicated an origin from renal tubular cells.Nephrogenic adenomas in renal-transplant recipients are derived from tubular cells of the renal transplants and are not metaplastic proliferations of the recipient's bladder urothelium.

Objective To analyze the effect of individual adaptation of the dialysis prescription in continuous ambulatory peritoneal dialysis (CAPD), as compensation for the decline of residual renal function (RRF), on peritoneal (Kpt/V) and total (Kprt/V) urea clearance as well as on peritoneal (Kpcr) and total weekly creatinine clearances (CCr). Design Retrospective analysis of a 2-year period. Patients We analyzed 18 patients [15 male, 3 female; mean age 58.2 (24 – 80) years]. Main Outcome Measures Correlations between increased dialysis prescription and Kpt/V, Kprt/V, and Kpcr. Kprt/V and CCr measurements were based on a 24-hour dialysate and urine collection. Measurements were performed over a time period of 3 to 6 months. Results The results show a linear correlation between Kpt/V and Kpcr and the prescribed volume by kilogram body weight. Kprt/V was increased slightly by increasing the dialysis prescription. Dialysate-to-plasma (D/P) ratios of urea and creatinine remained unchanged. The mean prescribed dialysate volume increased from 7.4 ± 1.1 L to 10.6 ± 2.5 L. Mean Kprt/V could be maintained on a stable level for a 36-month period. Conclusion By adapting the dialysis prescription on an individual basis to the continuous decline of RRF, and taking the patient's body weight into account in the prescription decision, the increases in Kpt/V offset the decline in RRF. We recommend early individualization of prescription for patients on CAPD.

Background. In small vessel vasculitis and its renallimited form, idiopathic crescentic glomerulonephritis, renal damage is characterized by pauci-immune necrotizing crescentic glomerulonephritis (CGN) without histological evidence of immunoglobulin (Ig) deposition. In some patients, however, significant amounts of immune deposits may be detected. Therefore, we evaluated the clinical significance of these immune deposits in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune CGN. Methods. Renal biopsies of 45 consecutive patients with new onset of Wegener’s granulomatosis, microscopic polyangiitis and idiopathic CGN were retrospectively evaluated by light microscopy, immunohistochemistry and electron microscopy and the findings compared with renal function and outcome. Results. Typical pauci-immune CGN was found in 37 patients (group I). In eight patients (18%; group II), however, histopathological examination revealed substantial deposition of Ig in the mesangium anduor along the glomerular basement membrane. Five of these eight patients were cANCA positive; two initially had pANCA and developed a cANCA pattern and one was pANCA positive. There were no differences between groups in age, gender, renal function or extrarenal organ involvement at the time of biopsy. However, patients in group II had significantly more proteinuria (5.4"3.1 vs 1.3"1.0 gu24 h; Ps0.016). We also observed a trend for a worse outcome with respect to renal function and mortality in group II patients; however, the differences did not reach significance. Conclusions. Our results confirm that in ANCAassociated CGN a substantial percentage of patients have evidence of Ig deposition in renal biopsies. In this subgroup, Ig deposition was associated with a significantly greater degree of proteinuria. Further investigations are necessary to define the full clinical impact of immune-complex deposition on the clinical course of renal disease in pauci-immune CGN.