IgA Nephropathy

Berger first described the glomerulonephritis termed IgA nephropathy. It is classically characterized by episodic hematuria associated with the deposition of IgA in the mesangium.

IgA nephropathy is one of the most common forms of glomerulonephritis worldwide.

 There is a male preponderance, a peak incidence in the second and third decades of life, and rare familial clustering.

 Clinical and laboratory evidence suggests close similarities between Henoch-Schönlein purpura and IgA nephropathy. Henoch-Schönlein purpura is distinguished clinically from IgA nephropathy by prominent systemic symptoms, a younger age (<20 years old), preceding infection, and abdominal complaints.

 Deposits of IgA are also found in the glomerular mesangium in a variety of systemic diseases, including chronic liver disease, Crohn's disease, gastrointestinal adenocarcinoma, chronic obstructive bronchiectasis, idiopathic interstitial pneumonia, dermatitis herpetiformis, mycosis fungoides, leprosy, ankylosing spondylitis, relapsing polychondritis, and Sjögren's syndrome. IgA deposition in these entities is not usually associated with clinically significant glomerular inflammation or renal dysfunction and thus is not called IgA nephropathy.

IgA nephropathy is an immune complex-mediated glomerulonephritis defined by the presence of diffuse mesangial IgA deposits often associated with mesangial hypercellularity. IgM, IgG, C3, or immunoglobulin light chains may be codistributed with IgA. IgA deposited in the mesangium is typically polymeric and of the IgA1 subclass, the pathogenic significance of which is not clear.

The two most common presentations of IgA nephropathy are recurrent episodes of macroscopic hematuria during or immediately following an upper respiratory infection in children (Henoch-Schönlein purpura) or asymptomatic microscopic hematuria most often seen in adults. Between episodes, the urinalysis is normal.

When the hematuria persists, one finds increasing amounts of proteinuria; nephrotic syndrome, however, is uncommon. The presence or absence of proteinuria at the time of diagnosis often determines whether patients with asymptomatic hematuria are biopsied, which reflects the bias in habits of clinical practice. Proteinuria can occur late in the course of the disease. Rarely, patients can present with acute renal failure and a rapidly progressive clinical picture.

IgA nephropathy is a benign disease for the majority of patients, with progression to renal failure seen in only 25–30% over 20–25 years; in fact, 5–30% of patients go into complete remission. Risk factors for the loss of renal function include the presence of hypertension or proteinuria, the absence of episodes of macroscopic hematuria, male age, older age of onset, and more severe changes on renal biopsy.
There is no agreement on optimal treatment. Both large studies that include patients with multiple glomerular diseases or small studies of patients with IgA nephropathy support the use of angiotensin-converting enzyme (ACE) inhibitors in patients with proteinuria or declining renal function. Tonsillectomy, steroid therapy, and fish oil have all been suggested in small studies to benefit select patients with IgA nephropathy. When presenting as RPGN, patients typically receive steroids, cytotoxic agents, and plasmapheresis.