Corticosteroid reduction with tacrolimus (CORRETA) TRIAL: a prospective Brazilian multicenter, randomized trial of early corticosteroid reduction versus regular corticosteroid dosage maintenance on a tacrolimus (Prograf) and mycophenolate mofetil (Cellcept) immunosuppression regimen in kidney transplant recipients: interim analysis.

Corticosteroids are a cornerstone of immunosuppressive therapy in renal transplantation despite their side effects and morbidity. Newer immunosuppressive agents may be more effective to allow corticosteroid sparing. An interim analysis of 60 completed out of 100 planned primary kidney transplant recipients is presented. All patients on tacrolimus (Prograf) and MMF (Cellcept) were randomized into two groups following a 1:1 distribution for early steroid reduction at posttransplant day 7 (G1; n = 31) versus to long-term maintenance steroids (G2; n = 29). Primary efficacy endpoints were composite endpoint of death, graft loss, or severe acute rejection at 6 and 12 months follow-up. Safety evaluation included severity and frequency of diabetes mellitus, hypertension, hyperlipidemia, leukopenia, infection, malignancy, and severe adverse events. Mean age was 39.1 years, with 45.0% males and 66.7% Caucasians. African-Americans were 25.8% in G1 and 27.6% in G2. One death occurred in each group, as well as one case of severe (Banff III) rejection in G1 (P = 1.00). The incidence of rejection episodes between groups was not significant, namely, 41.9% in G1 and 20.7% in G2 (P = .077). There were no differences between groups concerning mean, systolic and diastolic blood pressure, HbA1c, or creatinine at 12 months. This interim analysis showed no evidence of an increased risk of poorer performance among the early steroid reduction or safety differences in kidney transplant recipients versus a regular dosage steroid group of patients. Further analysis of the complete study data is underway.

Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil.

BACKGROUND: After a drought in February, 1996, all 126 patients in a haemodialysis unit in Caruaru, north-east Brazil, developed signs and symptoms of acute neurotoxicity and subacute hepatotoxicity following the use of water from a lake with massive growth of cyanobacteria (blue-green algae). 60 patients died. METHODS: Besides recording clinical details and outcome at follow-up, we arranged laboratory, radiological, and histological investigations on the patients and toxicological studies of serum and haemodialysis water filters. FINDINGS: The acute presentation was with malaise, myalgia and weakness, nausea and vomiting, and tender hepatomegaly, with a range of neurological symptoms from tinnitus, vertigo, headaches, and deafness to blindness and convulsions. Liver injury ranged from abnormal liver-function test results to rapidly progressive and fatal hepatic failure. Biochemical investigations revealed gross hyperbilirubinaemia, abnormal liver enzyme activities, and hypertriglyceridaemia, but there was no evidence of haemolysis or microangiopathy. Histology revealed a novel acute toxic hepatitis with diffuse panlobular hepatocyte necrosis, neutrophil infiltration, canalicular cholestasis, and regenerative multinucleate hepatocytes. Samples of serum, dialysis filters, and water-treatment columns contained microcystins, the highly toxic low-molecular-weight hepatotoxins produced by cyanobacteria. INTERPRETATION: Cyanobacteria present water-borne hazards to health via drinking water and recreational water. Haemodialysis presents an additional high-risk exposure route: when they enter directly into the circulation, microcystins can lead to fatal clinical syndromes ranging from acute neurotoxic illness to subacute liver failure.