IgA nephropathy is a common glomerular disease that is an important cause of kidney failure. The latest review in our Medical Progress series discusses advances in the therapy and understanding of the molecular basis of IgA nephropathy, a common glomerulopathy that not infrequently leads to kidney failure.
IgA nephropathy is the most prevalent primary chronic glomerular disease worldwide. However, requirement of a kidney biopsy for diagnosis hinders delineation of the full impact of this disease.
• What is the typical clinical presentation of IgA nephropathy?
In North America about 75% of affected children and young adults with IgA nephropathy are diagnosed after macroscopic hematuria is discovered during an upper respiratory or gastrointestinal illness. Evidence of acute kidney injury may be present. Older adults usually present with proteinuria, microscopic hematuria or hypertension, alone or in combination. In the United States, over 50% of adults over age 30 at diagnosis have chronic kidney disease stage 3 to 5. North American cohorts show a male predominance of about 2:1 for children and adults, while the gender ratio approximates 1:1 in Asia. Nephrotic syndrome at presentation is uncommon, except in patients with minimal-change-disease pathology on kidney biopsy.
• What is the prevalence of IgA nephropathy in the United States?
In the United States, IgA nephropathy was the most frequently diagnosed primary glomerular disease in adults from biopsy series, and the leading primary glomerular disease causing end-stage renal disease (ESRD) in young Caucasian adults. Limited data from population-based studies from the United States indicate that the annual incidence of biopsy-documented IgA nephropathy is about 1 case per 100,000 persons, representing a lifetime risk for biopsy-proven IgA nephropathy of about 1 in 1400. In New Mexico, from 2000 to 2005 the incidence was highest for Native Americans, intermediate for Hispanics, and lowest for non-Hispanic whites. The annual incidence for children in the United States is about 0.5 cases per 100,000.
Morning Report Questions
Q: What are the clinical prognostic features for IgA nephropathy?
A: Impaired glomerular filtration rate, sustained hypertension, and significant proteinuria independently predict a poor clinical course. While proteinuria at diagnosis has been the focus in many studies, proteinuria calculated as the average of several measurements during serial 6-month intervals after biopsy has better prognostic power. Notably, patients with time-averaged proteinuria >1.0 g/day have a 46-fold higher risk for ESRD than those with rates <0.5 g/day. Furthermore, renal outcome is better when time-averaged proteinuria is <0.5 g/day versus 0.5 to 1.0 g/day. For reasons not yet clear, the prognosis for patients with IgA nephropathy is worse than that for patients with other glomerular diseases with similar magnitudes of proteinuria.
Q: What are current recommendations for treatment of IgA nephropathy?
A: The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and the National Kidney Foundation Kidney Disease Outcomes Quality Initiatives both emphasize control of proteinuria and blood pressure by suppression of angiotensin II with an ACE inhibitor or angiotensin II type 1 receptor blocker (ARB). The target systolic blood pressure is <130 mm Hg with proteinuria <1g/day but <125 mm Hg if proteinuria is >1g/day. For proteinuria persistently >1 g/day despite 3 to 6 months of optimal supportive care (ACE inhibitor, ARB, or both, and blood pressure control) and eGFR >50 ml/min/1.73 m2, KDIGO guidelines suggest adding fish oil, a 6-month course of corticosteroids, or both. Intensive immunosuppression (glucocorticoids with cyclophosphamide or azathioprine) is reserved for patients with crescents in more than half of the glomeruli with rapid decline in renal function. Patients presenting with mild disease (normal blood pressure, normal eGFR, and a urinary protein-to-creatinine ratio consistently <0.20) do not require treatment. Extended serial assessments of renal clearance function, proteinuria and hematuria, perhaps annually, should continue because some patients eventually develop progressive disease and need therapy.