Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study

Abstract

Current guidelines suggest treatment with corticosteroids (CS) in IgA nephropathy (IgAN) when proteinuria is persistently ≥1 g/d despite 3-6 months of supportive care and when eGFR is >50 ml/min per 1.73 m(2). Whether the benefits of this treatment extend to patients with an eGFR≤50 ml/min per 1.73 m(2), other levels of proteinuria, or different renal pathologic lesions remains unknown. We retrospectively studied 1147 patients with IgAN from the European Validation Study of the Oxford Classification of IgAN (VALIGA) cohort classified according to the Oxford-MEST classification and medication used, with details of duration but not dosing. Overall, 46% of patients received immunosuppression, of which 98% received CS. Treated individuals presented with greater clinical and pathologic risk factors of progression. They also received more antihypertensive medication, and a greater proportion received renin angiotensin system blockade (RASB) compared with individuals without immunosuppressive therapy. Immunosuppression was associated with a significant reduction in proteinuria, a slower rate of renal function decline, and greater renal survival. Using a propensity score, we matched 184 subjects who received CS and RASB to 184 patients with a similar risk profile of progression who received only RASB. Within this group, CS reduced proteinuria and the rate of renal function decline and increased renal survival. These benefits extended to those with an eGFR≤50 ml/min per 1.73 m(2), and the benefits increased proportionally with the level of proteinuria. Thus, CS reduced the risk of progression regardless of initial eGFR and in direct proportion to the extent of proteinuria in this cohort.

Keywords: IgA nephropathy; immunosuppression; pathology; progression of chronic renal failure; proteinuria; risk factors.

Figure 1.

Patient selection for the nested case control study on corticosteroids (CS). Individuals who did not receive renin-angiotensin system blockade (RASB) or received ITx without CS were excluded. Of the remaining 973 patients, 184 with CS+RASB could be matched to 184 with RASB only. ITx, any immunosuppressive therapy.

Figure 2.

Response to CS and RASB compared with RASB alone in propensity-matched individuals. (A) Entire propensity-matched cohort. (B) Stratified by initial eGFR. P values obtained using time-dependent Cox regression.

Figure 3.

Response to CS and RASB compared with RASB alone in propensity-matched individuals stratified by proteinuria during follow-up, prior to CS in the CS-RASB group. (A) Proteinuria <1 g/d. (B) Proteinuria 1 to <3 g/d. (C) proteinuria ≥3 g/d. Time-average proteinuria was prior to CS in the treated group. P values obtained using time-dependent Cox regression. There was no evident benefit of CS in those with a proteinuria <1 g/d.

Figure 4.

Response to CS and RASB compared with RASB alone in propensity-matched individuals having achieved a reduction in proteinuria to <1g/d (A) or not (B). P values obtained using time-dependent Cox regression. Of the propensity-matched patients, 140 did not have an initial proteinuria ≥1 g/d and were excluded from this analysis.