Cyclosporine-associated thrombotic microangiopathy (CsA-TMA) is characterized by anemia, acute renal failure, and renal TMA. We report a case-control study of 13 patients (seven kidney-alone transplant recipients and six kidney-pancreas transplant recipients) who developed TMA (12 CsA, 1 FK506). Once CsA-TMA was identified, CsA or FK506 was discontinued and isradipine, aspirin, and pentoxifylline were started. Cyclosporine was reinstituted in all patients once serum creatinine reached the previous baseline value. Patients developing further decreases in renal function on rechallenge with CsA were converted to FK506 (n = 3). Rechallenge with CsA was successful in nine of the 13 patients (69%), with three (23%) converted to FK506 for a total salvage rate of 92%. The creatinine clearance at 6 months, 1 year, and 2 years following transplantation was 73.2 +/- 25.7 mL/min, 54.7 +/- 18.8 mL/min, and 57.0 +/- 32.0 mL/min, respectively, for patients successfully rechallenged with CsA compared with 67 +/- 17 mg/min, 71.8 +/- 21.2 mL/min, and 69 +/- 19 mg/min, respectively, for controls (P = NS). The average creatine clearance for patients converted to FK506 was 44.7 +/- 31.2 mL/min at 6 months following transplantation (n = 3) and 27.0 +/- 11.3 mL/min at 1 year. In this case-controlled retrospective series of renal transplant patients with documented CsA-TMA, the triple-drug combination of isradipine, aspirin, and pentoxifylline allowed for the successful reinstitution of CsA or conversion to FK506 in the setting of TMA, and resulted in increased transplant survival compared with previous reports.