Three-year randomized controlled trial of dipyridamole and low-dose warfarin in patients with IgA nephropathy and renal impairment

Activation of platelets and the coagulation pathway are factors which may contribute to the progression of renal disease in IgA nephropathy (IgAN). Of 21 patients with IgAN and serum creatinines between 1.6 and 3.0 mg/dL, 10 were assigned to treatment with dipyridamole and low-dose warfarin (keeping the thrombotest between 30 and 50%) and 11 to no treatment in a prospective randomized 3-year study. At entry into the trial, patients in the treatment group were younger (35+/-6 years us 42+/-9 years) and had worse histological scores for tubular atrophy (1.7+/-0.7 vs 1.1+/-0.5) and arteriolar hyperplasia (1.4+/-0.7 vs 0.7+/-0.8) than those in the non-treatment group. There were no differences in serum creatinine values, creatinine clearances, urinary protein excretions, serum albumins or urinary erythrocyte counts. At the end of the trial, patients on treatment did not experience a significant increase in serum creatinine values (1.9+/-0.3 mg/dL to 2.5+/-1.2) or reduction in creatinine clearances (52+/-20 mL/min to 52+/-27). Untreated patients, however, experienced a significant rise in serum creatinine values (2.1+/-0.5 mg/dL to 3.3+/-1.1, P<0.01) and a fall in creatinine clearances (51+/-26 mL/min to 31+/-22, P=0.06). There was no significant change in the proteinuria in either group (treatment group: 1.2+/-1.2 g/day to 1.3+/-1.1, non-treatment group: 1.9+/-1.4 to 1.5+/-1.1) and there was also no change in serum albumins and urinary erythrocyte counts. Four untreated and one treated patient developed end-stage renal failure during the course of the trial. This study suggests that treatment of patients with IgAN and renal impairment with dipyridamole and low-dose warfarin retards the deterioration of renal function, as measured by the serum creatinine and creatinine clearance.