IgA nephropathy with severe chronic renal failure: a randomized controlled trial of corticosteroids and azathioprine.

BACKGROUND: Therapeutic nihilism is common in IgA nephropathy (IgAN) and renal insufficiency. METHODS: In a randomized controlled trial comparing steroids alone or combined with azathioprine in 253 IgAN patients, we used a separate randomization list for patients with creatinine >2.0 mg/dL. Twenty patients (group 1) were randomized to 3 intravenous pulses of methylprednisolone 1 g at months 1, 3 and 5, and oral prednisone 0.5 mg/kg every other day plus azathioprine 1.5 mg/kg/day for 6 months, followed by oral prednisone 0.2 mg/kg every other day plus azathioprine 50 mg/day for a further 6 months; 26 patients (group 2) received steroids alone. The primary outcome was renal survival (50% increase in plasma creatinine from baseline); secondary outcomes were proteinuria over time and adverse events. RESULTS: Six-year renal survival was not different between the 2 groups (50% vs. 57%; log-rank p=0.34). Median proteinuria decreased during follow-up in the whole population (from 2.45 g/day [interquartile range (IQR) 1.50-3.78] to 1.09 g/day [IQR 0.56- 2.46]; p<0.001), with no between-group difference. Multivariate predictors associated with renal survival were sex of patient, proteinuria during follow-up, number of antihypertensive drugs, angiotensin-converting enzyme inhibitors and treatment including azathioprine. Six patients in group 1 (30%) and 4 in group 2 (15%) did not complete the therapy, because of side effects (p=0.406). CONCLUSIONS: Six-year renal survival was similar in the 2 groups. At Cox analysis the addition of azathioprine may be slightly more effective than corticosteroids alone in patients with chronic renal insufficiency, although with an increase of side effects.

[Kidney damage caused by treatment for hematological malignancies: from tumor lysis syndrome to post-transplant kidney failure]. / Terapie onco-ematologiche e danno renale: dalla sindrome da lisi tumorale alla nefropatia post-trapianto di midollo.

In the wide spectrum of therapies for hematological malignancies, hematopoietic stem cell transplantation, whether autologous or allogeneic, is a common procedure. In addition to other transplant-related organ toxicities, renal failure is a common complication following transplantation. This paper discusses the incidence, timing, etiologies, risk factors and prognosis of renal failure associated with three commonly used transplantation procedures: myeloablative autologous, myeloablative allogeneic, and non-myeloablative allogeneic transplantation. The epidemiology and prognosis of renal failure are different after these three procedures. Severe renal failure occurs with all three varieties, but the frequency increases from myeloablative autologous to non-myeloablative allogeneic to myeloablative allogeneic. In all three types of transplantation, the mortality is clearly associated with the severity of renal injury, and it is greater than 80% when dialysis is required. Strategies to improve renal failure following transplantation may have a beneficial impact on these patients. Reduction of acute renal failure will likely reduce the severity of non-renal organ dysfunction, the incidence and severity of chronic kidney disease, and the mortality.

Multicenter study on hepatitis C virus-related cryoglobulinemic glomerulonephritis.

BACKGROUND: Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key factor affecting prognosis. METHODS: Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. RESULTS: Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mkappa [IgMkappa]/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 mumol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. CONCLUSION: Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past.

Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation.

The most efficient therapeutic approach for immunoglobulin light chain amyloidosis (AL) is autologous stem cell transplantation (ASCT); however, the toxicity of ASCT limits its feasibility to a minority of patients. Patients ineligible for ASCT are usually treated with standard oral melphalan and prednisone, but the response rate to this regimen is unsatisfactory, and time to response is long. High-dose dexamethasone provides a rapid response time in patients with AL. We evaluated the combination of oral melphalan and high-dose dexamethasone (M-Dex) in 46 patients with AL ineligible for ASCT. Thirty-one (67%) achieved a hematologic response and 15 (33%) a complete remission. In 22 (48%) of the responsive patients functional improvement of the organs involved was observed. Five patients (11%) experienced severe adverse events, 3 required hospitalization, and no treatment-related deaths were observed. M-Dex represents a feasible and effective therapeutic option for patients with advanced AL who are ineligible for ASCT.