Pro: STOP immunosuppression in IgA nephropathy?

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a 6-month course of corticosteroids (CS) for IgA nephropathy (IgAN) patients with persistent proteinuria ≥1 g/day despite 3-6 months of renin-angiotensin system (RAS) blockers and glomerular filtration rate (GFR) >50 mL/min/1.73 m2 In December 2015, Rauen et al. (N Engl J Med 2015; 373: 2225-2236) published an article entitled 'Intensive supportive care plus immunosuppression in IgA nephropathy' (STOP-IgAN), which presented results from 379 IgAN patients from 32 nephrology centres in Germany. During a run-in phase of 6 months, patients received supportive care therapy including RAS blockers, dietary counselling, advice to stop smoking and avoid nephrotoxic drugs, and statins if required. After 6 months, 177 patients with proteinuria >0.75 g/day (non-responder patients) were randomized to either receive continued supportive care or supportive care plus immunosuppression (monotherapy with CS or combined therapy with three immunosuppressants). The authors reported that, after 36 months of observation, the addition of immunosuppressants to ongoing comprehensive supportive care was not beneficial in IgAN patients with moderate proteinuria and chronic kidney disease stages 1-3. These conclusions are questionable for several reasons: (i) studies on time-average proteinuria have shown that beneficial effects on renal survival, not evident after 36 months, emerge over the course of longer observation periods; (ii) supportive care in the STOP-IgAN study resulted in a small loss of renal function during the 36 months of observation (annual decrease in the estimated GFR of 1.6 mL/min/1.73 m2 ), but was unable to reduce proteinuria below 1 g/day; in contrast, 6 months of steroid therapy lowered proteinuria below 1 g/day; and (iii) the lack of any assessment of the histological data does not allow the importance of the morphological lesions on renal survival and therapy effects to be monitored. Further evaluation with a longer follow-up period is needed to obtain more reliable answers than the weak evidence of this study.