Treatments with glucocorticoids or immunosuppressants in IgA nephropathy remain controversial, especially in IgA nephropathy patients with renal insufficiency and small quantities of proteinuria. So far, no randomized controlled study has investigated whether cyclophosphamide has a protective effect on IgA nephropathy independent of glucocorticoids.
We conducted a single-center, randomized, controlled trial ((NCT01758120)). 135 IgA nephropathy patients with elevated plasma creatinine concentrations (1.3-3.0 mg/dl in males and 1.0-3.0 mg/dl in females), regardless of proteinuria level, were enrolled in and randomized 1:1 to the prednisone alone group or prednisone plus cyclophosphamide group. The daily dosage of oral prednisone was initiated at 0.5 mg/kg/d taken every morning for 2 months and then tapered by 20% each month for the next 4 months in prednisone alone group. In prednisone plus cyclophosphamide group cyclophosphamide was given in monthly pulses of 1.0 g for 6 months, while the prednisone dosage was the same as prednisone group. The two primary end points were a combination of reaching end-stage renal disease (ESRD) or doubling of serum creatinine or death and absolute changes in eGFR (estimated glomerular filtration rate) at 36 months.
Overall, 135 patients were enrolled in our study. There was no significant difference between the two groups at baseline. The two groups had similar primary composite renal outcomes, which occurred in 4 participants (5.97%) in the prednisone alone group and 5 (7.35%) in the prednisone plus cyclophosphamide group (hazard ratio, 1.13 [95% CI, 0.30 to 4.19]; P = 0.861). Additionally, no significant difference in eGFR absolute change in three years was found between the two groups (0.09 (-7.42, 12.00) ml/min/1.73 m2 in the prednisone alone group vs. 3.24 (5.025, 9.59) ml/min/1.73 m2 in the prednisone plus cyclophosphamide group; P = 0.578). Proteinuria was reduced similarly in both groups. Treatment with cyclophosphamide led to more adverse events.
Our study showed that corticosteroids plus cyclophosphamide did not increase the renal benefit of patients with advanced-stage IgA nephropathy but increased adverse effects compared with corticosteroids alone.
Trial registration: ClinicalTrials.gov, NCT01758120. Registered 1 July 2012, https://clinicaltrials.gov/ct2/show/NCT01758120