Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide.

Abstract

The use of immunosuppressive therapy for IgA nephropathy patients with renal insufficiency and severe proteinuria is controversial. This was a monocentric retrospective study. We reviewed 132 consecutive IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease and proteinuria ≥ 1.0g/d who received uncontrolled supportive care (n = 41), corticosteroids (CS) (n = 22) or low-dose CS combined with oral cyclophosphamide (CTX) (n = 69) between January 2008 and December 2016. The combined endpoint was defined as either a ≥ 50% reduction in eGFR or ESRD. All patients were followed for a medial of 33.2months, and 67 (50.8%) patients experienced the combined endpoint. The rate of renal function decline was - 4.5 (- 12.6, - 0.1) ml/min/1.73m2peryear. In multivariate Cox regression analyses, immunosuppressive therapy (HR = 0.349, 95% CI 0.194-0.629, P < 0.001) was associated with reduced risk of combined events after adjusting for age, sex, MAP, proteinuria, eGFR, mesangial hypercellularity score > 0.5 (M1), endocapillary hypercellularity present (E1), segmental glomerulosclerosis present (S1), tubular atrophy/interstitial fibrosis > 25% (T1-2), crescents present (C1-2), and RAAS blockers. Immunosuppressive therapy was also analyzed as a categorical variable, and multivariate Cox analyses showed that CS did not reduce the risk of combined events, whereas CS + CTX significantly reduced the risk of combined events. In the matched cohort, the CS + CTX group had a significantly lower reduction in TP-A [1.2 (0.6, 2.3) g/d verse 1.8 (1.2, 2.5), P = 0.023] and a better renal survival rate (39.4% verse 66.7%, P = 0.026) than the uncontrolled supportive care group. The number of hospitalizations required for infection was similar in the three study groups. Other adverse events did not differ significantly among the three groups. Low-dose CS combined with oral CTX treatment is possibly more effective than uncontrolled supportive care for IgAN patients with reduced renal function. The results need to be further confirmed by randomized controlled studies.