Combination therapy of low-dose cyclosporine and steroid in adults with IgA nephropathy

Background: A few clinical trials in IgA nephropathy (IgAN) have shown that cyclosporine A (CyA) had therapeutic efficacy in reducing proteinuria. Materials and methods: This is a retrospective study, and all cases were selected based on kidney biopsy-proven IgAN. We reviewed the data of IgAN patients in the glomerulonephritis registry at Kyung Hee University Medical center and collected data on 86 patients with urinary protein/Cr ratio (PCR; g/g) > 0.5 and estimated GFR (eGFR) of > 50 mL/min/1.73m(2) who were treated with combination therapy of low-dose CyA plus low-dose steroid (C+P: n = 37) and high-dose steroid single therapy (P; n = 49). Results: In the C+P group, the mean duration of therapy was 14.5 +/- 13.1 months, and the mean duration of follow-up 66.2 +/- 36.3 months. In the C+P group, the urine PCR levels significantly declined after treatment (p < 0.05). After 6 months of treatment, 12 (32%) patients were in complete remission and 7 (19%) in partial remission in the C+P group, compared with 21 (42%) and 11 (22%) in the P group, respectively. Urine PCR levels were also significantly reduced in 12 patients in the C+P group who had initial urine PCR between 0.5 and 1.0. The degree of hematuria was significantly reduced after treatment in the C+P group. These effects of C+P therapy on proteinuria and hematuria were very comparable to high-dose P therapy. After 2 years, a decline in renal function, > 25% decrease in eGFR from baseline levels, developed in 3 (8.1%) in the C+P group, compared with 4 (8.2%) in the P group. The rate of decline in renal function during follow-up was -0.14 +/- 0.40 mL/ min/1.73m(2)/month in the C+P group compared with -0.12 +/- 0.22 mL/min/1.73m(2)/ month in the P group. There were no changes of mean eGFR during the first 24 months, but the eGFR significantly decreased at last follow-up in both groups. When patients in the C+P group were divided into progressive (n = 9) and nonprogressive (n = 28) groups, a significant reduction in the amount of proteinuria after treatment was observed in the nonprogressive group, in contrast to the progressive group. In the C+P group, there were no severe adverse effects, especially no acute renal impairment, requiring discontinuation of CyA in this study. The incidence of infection was much lower in the C+P group than that in the P group. The limitation is that Cy A acts to nonspecifically reduce proteinuria, so it requires long-tenn follow-up off CyA therapy for more than 2 years to determine. Conclusion: Our retrospective uncontrolled study provides only weak evidence that combination therapy of low-dose C+P could be an alternative to high-dose P therapy and be safe in adult IgAN patients with relatively normal renal function and proteinuria of > 0.5 g/g. Development of safe and effective therapy is still a major challenge requiring well-controlled prospective studies with this or other combination therapies.