renal survival rate is about 90% among adults15,61,65 and children13,66 with normal renal function at diagnosis. Some patients have a prolonged clinical remission (normal serum creatinine concentration, normal findings on urinalysis, normal quantitative urinary protein excretion, and normal blood pressure), but repeat biopsy usually shows glomerular IgA.67 Most patients with acute kidney injury associated with macroscopic hematuria have spontaneous recovery of renal function within several weeks. In the small subgroup of patients with histologic features of minimalchange disease, proteinuria resolves after glucocorticoid therapy. Clinical Prognostic Features An impaired GFR, sustained hypertension, and substantial proteinuria independently predict a poor clinical course.15,68 Although proteinuria at diagnosis has been the focus in many studies, urinary protein excretion calculated as the average of several measurements during serial 6-month intervals after biopsy has better prognostic power.69,70 Notably, patients with time-averaged urinary protein excretion of more than 1.0 g per day have a risk of ESRD that is 46 times the risk among patients with values of less than 0.5 g per day.71 Furthermore, the renal outcome is better with a value for time-averaged urinary protein excretion that is less than 0.5 g per day than with a value of 0.5 to 1.0 g per day. For reasons that are not yet clear, the prognosis for patients with IgA nephropathy is worse than that for patients with other glomerular diseases with a similar magnitude of proteinuria.72 Pathological Prognostic Markers The Oxford classification renewed interest in the prognostic value of the histologic features of the diagnostic biopsy and the use of renal histologic analysis for risk stratification in treatment trials.11 Entry criteria for the Oxford study excluded patients with an estimated GFR of less than 30 ml per minute per 1.73 m2 of body-surface area (thereby excluding patients with stage 4 or 5 chronic kidney disease), and the outcome measure was progression to ESRD or a decrease in the estimated GFR of more than 50% from the rate at study entry.11 Three histologic features showed an independent value for predicting the outcome of renal function, even after clinical indicators at the time of biopsy and during follow-up observation were taken into account: mesangial hypercellularity, segmental glomerulosclerosis or adhesion, and tubular atrophy and interstitial fibrosis (Fig. 1).11 A fourth histologic feature, endocapillary proliferation, showed an interaction with glucocorticoid or immunosuppressive therapy that suggested benefit from treatment. Subgroup analysis of the Oxford cohort validated the classification in children.73 A recent review of 13 Oxford replication studies confirmed the independent prognostic value of tubular atrophy and interstitial fibrosis in 10 studies, mesangial hypercellularity in 4 studies, and segmental sclerosis in 4 studies.74 Other histologic features that may be associated with a poor clinical outcome include glomerular deposits of mannose-binding lectin,6 C4d,5 and IgG75,76; thrombotic microangiopathy77; and an increased glomerular diameter.78 Tr e atmen t Despite a better understanding of pathogenic mechanisms, there is no disease-targeted treatment for IgA nephropathy. Furthermore, relatively few randomized, controlled clinical trials have been conducted. Two expert panels have published approaches to the treatment of glomerular diseases. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines focus on specific diseases,33 whereas recommendations in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative address broader categories of kidney disease (www.kidney.org/ professionals/kdoqi/guidelines). Both panels emphasized control of proteinuria and blood pressure by suppression of angiotensin II with an ACE inhibitor or angiotensin II–receptor blocker (ARB) (Table 2, and Table S1 in the Supplementary Appendix). The target systolic blood pressure is less than 130 mm Hg with urinary protein excretion of less than 1 g per day but less than 125 mm Hg when the initial urinary protein excretion is more than 1 g per day. For urinary protein excretion that is persistently more than 1 g per day despite 3 to 6 months of proper supportive care (ACE inhibitor, ARB, or both and blood-pressure control) and an estimated GFR of more than 50 ml per minute per 1.73 m2, the KDIGO guidelines suggest adding fish oil, a 6-month course of glucocorticoids, or both. In- medical progress n engl j med 368;25 nejm.org june 20, 2013 2411 tensive immunosuppression (glucocorticoids with cyclophosphamide or azathioprine) is reserved for patients with crescents in more than half the glomeruli and a rapid decline in renal function. Patients with fewer crescents and stable renal function should be treated with an ACE inhibitor or ARB. The KDIGO guidelines do not support the use of mycophenolate mofetil or antiplatelet drugs. Tonsillectomy has been recommended by some centers, particularly in Japan, but this approach was not included in the KDIGO guidelines because of the lack of data from randomized, controlled trials. Patients presenting with mild disease (normal blood pressure, normal estimated GFR, and a urinary protein-to-creatinine ratio consistently 1 g/day; increase dose depending