PREDICTORS OF CLINICAL AND HISTOPATHOLOGICAL OUTCOMES FOR IGA NEPHROPATHY AND EFFECT OF TREATMENT IN AN INDIAN COHORT

INTRODUCTION AND AIMS: Although IgA nephropathy (IgAN) is the most common primary glomerular disease world-wide, there is paucity of data on predictors of outcome and especially effect of treatment among Indian patients.

METHODS: We analysed a retrospective cohort of IgAN patients from 2006 to 2011. We evaluated clinical and pathological predictors of renal survival (time to reach end-stage renal disease requiring dialysis) by cox proportional hazards model and effect of treatment such as renin-angiotensin system (RAS) blockade and immunosuppression.

RESULTS: Of 436 patients with biopsy proven IgAN, 315 patients had follow up data. Median follow-up was 30 months (range 16 - 82 months). Mean age was 38.7±11.0 years, predominantly males (M:F - 1.9:1) with baseline serum creatinine of 2.06 ± 1.33 mg/dL (eGFR = 51.02 ± 30.69 ml/min/1.73sq.m), proteinuria of 2.7 ± 2.3g/day, and 34% hypertension. At baseline Oxford classification MEST score were: M0=90.2%, M1=9.8%, E0=66.3%, E1=33.7%, S0=37.8%, S1=62.2%, T0=15.9%, T1=42.9%, T2=41.3% and others were Crescents =10.5%, capillary wall IgA deposits =11.4%. Over 74% of subjects were treated with RAS blockers and over 71% received immunosuppression. Among immunosuppression, the agents used were steroid alone in 37%, steroid along with MMF in 40% of the patients, and steroid with other agents in the rest. In clinical parameters, the independent predictors of poor renal survival were young age (HR 0.941, 95%CI 0.903-0.980, p = 0.004), hypertension (HR 1.049, 95%CI 1.003-1.097, p = 0.003), baseline renal dysfunction (HR 0.925, 95%CI 0.892-0.959, p < 0.001), where macroscopic hematuria was found to have good prognosis (HR 0.154, 95%CI 0.034-0.692, p = 0.015). Among MEST score, independent histological predictors of poor renal survival were endocapillary proliferation (E1) (HR 4.534, 95%CI 2.006-10.246, p < 0.001), segmental sclerosis (S1) (HR 2.651, 95%CI 0.968-7.258, p = 0.048) and tubular atrophy/interstitial fibrosis (T2) (HR 2.891, 95%CI 0.927-13.578, p = 0.041). Especially T2 had accelerated rate of decline in renal function (HR 2.166, 95%CI 0.019-0.386, p = 0.031) where as E1 and S1 did not independently predict rate of decline of GFR. Interestingly mesangial co-deposition of C3 along with IgA was an independent predictor of slow progression of renal disease (HR 1.641, 95%CI 1.014-2.656, p = 0.044). Proliferative lesions in biopsy (both endo and extra-capillary) were associated with the use of immunosuppression. Treatment with immunosuppression (HR 0.163, 95%CI 0.065-0.405, p < 0.001) and renin-angiotensin blockade (HR 0.353, 95%CI 0.141- 0.883, p = 0.026) had better renal survival. Combined steroid and MMF therapy did not have any improvement in outcome over steroid monotherapy

CONCLUSIONS: In the Indian cohort, clinical parameters such as young age, baseline hypertension and renal dysfunction, and Oxford histological score E1, S1, T2 had poor renal survival and aid in predicting prognosis. Treatment with immunosuppression had better renal survival in Indian patients in contradictory with other studies.