Rituximab in relapsing and de novo MPO ANCA-associated vasculitis with severe renal involvement: a case series.

BACKGROUND: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of diseases associated in most cases with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs). Rituximab- based remission induction has been proven effective in ANCA associated vasculitis but scarce data exist in forms with severe renal involvement. In this case series, we report the outcomes in patients with de novo or recurrent MPO-AAV and severe renal involvement treated with rituximab without cyclophosphamide (CYC). METHODS: In this single centre retrospective study, we analysed patients with a clinical diagnosis of de novo or recurrent AAV who met the following criteria: detection of P-ANCA, creatinine clearance lower than 30 ml/min, induction of remission therapy with rituximab without concomitant CYC and a follow up period of at least 6 months. The primary outcomes were complete remission after induction therapy, renal function recovery and mortality after the induction treatment. RESULTS: Eight patients met the inclusion criteria. The M:F ratio was 1:7, the average age was 54 years old and the median follow up was 10 months (7-72); in 2 patients there was a MPA renal limited vasculitis. A renal biopsy was performed in 7 patients. The median BVAS score at rituximab induction was 14(range 6-21). Two patients required haemodialysis before the induction treatment. Four patients developed end stage renal disease (ESRD) that required haemodialysis. These data show a remission of the disease, associated with a stabilization of the kidney function in 50% of patients. In 3 patients who did not show a response, there was also no response to CYC. CONCLUSIONS: This study shows a partial efficacy of rituximab in renal function recovery and a low risk of infectious complications in patients with MPO vasculitis with severe renal involvement, in particular in the short term. The optimal treatment in this subgroup of patients still has to be established because data are lacking.

Anemia and Immunosuppressive Regimen in Renal Transplanted Patients: Single-Center Retrospective Study.

We compared retrospectively the level of hemoglobin and the percentage of patients with anemia among 59 kidney transplant recipients receiving everolimus, cyclosporine, and corticosteroids and 128 treated with cyclosporine, mycophenolic acid, and corticosteroids. We also compared age at the time of transplantation, sex and ferritine, serum creatinine, creatinine clearance, folic acid, cyanocobalamine levels, use od recombinant erythropoietin, mean corpuscolar volume at the last ambulatory control. Statistical analysis included Student t test, χ(2) test, and logistic regression. The analysis was performed using SPSS software. We observed no difference in terms of hemoglobin levels in patients treated with everolimus (12.9 ± 1.6 vs 12.7 ± 1.5 g/dL). Anemia (defined as hemoglobin <13 g/dL in men and <12 g/dL in women, or need to use erythropoietin) was found in 49% and 45% of patients in the 2 groups respectively (P = .6). The other parameters evaluated were similar except for the mean corpuscular volume, which was significantly lower in the everolimus group. In the multivariate analysis only serum creatinine and estimated glomerular filtration rate influenced the level of hemoglobin. We observed no differences in terms of development of anemia in renal transplanted patients treated with everolimus-based regimen.

5 year comparison of very low-dose cyclosporine and high-dose everolimus vs standard cyclosporine and enteric-coated mycophenolate in renal transplantation patients.

In this retrospective study, we compared the outcome of renal transplanted patients who received everolimus (EVR) (C0: 8-12 ng/mL)+cyclosporine (CsA) (C2: 150-300 ng/mL)+steroids, vs those who received enteric-coated mycophenolate sodium (EC-MPS) (1,440 mg/d)+CsA (C2: 500-700 ng/mL)+steroids. Efficacy was evaluated at 5 years. We found a nonsignificant trend toward a better 5-year graft survival (81.2% vs 68.6%) and better graft function (estimated glomerular filtration rate 71.8±35.7 vs 60.0±26.2 mL/min, P=.114) in favor of the EVR group. In our experience, EVR with a very low dose of CsA was associated with a nonstatistical trend toward better renal function and graft survival compared to a standard regimen of CsA and EC-MPS.

Effect of familial hypertension on glomerular hemodynamics and tubulo-glomerular feedback after uninephrectomy.

Familial hypertension, glomerular hemodynamic alterations, and dysregulation of tubulo-glomerular feedback (TGFB) have all been associated with the development of chronic renal failure. In the present study we evaluated renal and glomerular hemodynamics and TGFB responses in healthy kidney donors either with or without familial hypertension, before and after nephrectomy. Para-amino-hippurate plasma clearance (CPAH) and inulin plasma clearance (CInu) were measured in 15 kidney donors before and 1 year after nephrectomy. All subjects were normotensive and were kept in a sodium-replete state. Both clearances were measured after 40 min of constant infusion of PAH and Inu, as well as 20, 30, 50, and 60 min after the intravenous administration of acetazolamide (5 mg/kg). Glomerular hemodynamics were calculated by means of the Gomez formulae. Nephrectomy caused the expected decreases in CPAH and CInu and increase in the filtration fraction (all P < .0001). The decrease in renal resistances of the remaining kidney was greater at the afferent (-24%, P = .0075) than at the efferent arteriolar level (-17%, P < .0001). The TGFB activation was not altered by nephrectomy or by familial hypertension. Effective renal plasma flow (ERPF) decrease after TGFB activation appeared earlier than glomerular filtration rate (GFR) decrease before (P = .01), but not after, nephrectomy (P = .48). The presence of familial hypertension was associated with increased glomerular pressure (P = .0004). This study suggests that uninephrectomy in healthy human subjects causes a greater decrease in afferent arteriolar resistances, but that TGFB responses are not quantitatively altered. Familial hypertension is associated with a tendency toward higher glomerular pressures.

Which urinary proteins are decreased after angiotensin converting--enzyme inhibition?

It is believed that angiotensin converting-enzyme (ACE) inhibitors lower proteinuria by acting on glomerular hemodynamics. This hypothesis predicts that the urinary excretion of a tubular protein should be unaffected by ACE inhibition. In the present study we have compared the excretion of albumin and Tamm-Horsfall Glycoprotein (THGP), a protein secreted only by renal tubules, before and after ACE inhibition. Urinary protein excretion was measured with the Phast System, a method based on SDS polyacrylamide gel electrophoresis followed by silver staining, in 15 essential hypertensives, after at least 4 weeks of wash-out from any drug and after 2 months of ACE inhibition with oral Quinapril. After 2 months of ACE inhibition, blood pressure (BP), body weight, urinary output, heart rate, plasma glucose, plasma and urinary creatinine, urate and electrolytes, and creatinine clearance, were not different from baseline values. Plasma ACE activity decreased from 76 +/- 7 to 10 +/- 4 U/mL (mean +/- SEM, 2 tails paired t test, p = 0.0001). Both albumin and THP urinary excretions decreased from 51 +/- 6 to 43 +/- 4 mg/ 24 h (p = 0.05) and from 19 +/- 3 to 12 +/- 1 mg/24 h (p = 0.02), respectively. This unexpected result suggests that ACE inhibitors may act also at the level of renal tubular cells.

Accuracy of the urinary albumin titrator stick 'Micral-Test' in kidney-disease patients.

BACKGROUND: A quick, accurate, and easy measurement of microalbuminuria can be useful for the management of many patients. The Micral-Test stick (Boehringer Mannheim, Germany) gives a semiquantitative estimation of urinary albumin concentration at discrete readings of 0, 10, 20, 50 or 100 mg/l. The purpose of this study was to test its accuracy. METHODS: From 46 non-diabetic patients, 491 urinary samples were analysed both with Micral-Test and with immunochemical nephelometry. RESULTS: Of 491 samples, 308 were from non-proteinuric patients (urinary albumin < 300 mg/day). In these patients the correlation coefficient of nephelometric values versus the stick readings was 0.79: 120/123 samples from non-microalbuminuric (< or = 30 mg/24 h) and 164/185 from microalbuminuric patients were correctly identified by the stick, giving an 89% sensitivity and a 98% specificity. The readings around the threshold for microalbuminuria (20 and 50 mg/l patches) were the most reliable ones. Analysis of the correct/uncorrect readings' ratio for every patch in the 245 samples in the 0-150 mg/l range shows a relative uniformity (chi2 = 8.5, P = 0.07), while analysis of the over/correct/underreadings for the 10, 20 and 50 patches, shows that incorrect responses tend to be underestimations for the 10 patch and overestimations for the 20 and 50 mg/l patches (chi2 = 10.5, P = 0.03). CONCLUSIONS: The Micral-Test stick is useful for screening, but less reliable for follow-up, unless considerable changes in albumin excretion are expected.

Urinary salt titrator stick: a useful and quick estimate of dietary sodium intake?

Repeated measures of urinary salt excretion are the best compromise between reliability and convenience for estimating dietary salt intake. In order to assess the accuracy of the Uropaper urinary salt titrator stick (giving discrete readings of 4, 6, 8, 10, 12 or 14 g/l of NaCl), 312 urine samples were analysed both with the stick and with an ion-selective electrode. There was a good stick-electrode correlation in all the 312 samples (r = 0.84). With a tolerance of +/- 1 g/l, the percentages of correct estimations dropped from 82% to 33% with increasing concentrations of NaCl in the urinary sample. For NaCl concentrations greater than 8 g/l (137 mmol/l) the error in the stick measurement consisted almost exclusively of overestimation of the electrode readings. These results were unaffected by the concentration of urinary potassium. No discrepancies were found among three different readers. This stick is easy to use and measures, with reasonable accuracy, low urinary NaCl concentrations. It could be useful for self-monitoring during low NaCl diets.