Nephropathy, Immunoglobulin A

Key Features

• Primary renal disease with IgA deposition in the glomerular mesangium

• Inciting cause unknown but is likely deficient O-linked glycosylation of IgA subclass 1 molecules

• Can be a primary (renal-limited) disease

• Can be secondary to

  • Hepatic cirrhosis

  • Celiac disease

  • HIV infection

  • Cytomegalovirus infection

• Most common primary glomerular disease worldwide, particularly in Asia

• Usually occurs in children and young adults

• Males affected 2–3 times more often than females

Clinical Findings

• Gross hematuria, frequently associated with a mucosal viral infection, often an upper respiratory tract infection (URI)

• Urine becomes red or smoky-colored 1–2 days after onset of URI

• Can present anywhere along the nephritic spectrum from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis

• Rarely, a nephrotic syndrome can be present as well

Diagnosis

• Proteinuria: minimal to nephrotic range

• Glomerular hematuria: microscopic is common; macroscopic (gross) can occur after mucosal infection

• Positive IgA staining on kidney biopsy

• Serum complement levels usually normal

• No serologic tests aid in diagnosis; serum IgA subclass 1 testing may be possible in future

• Renal biopsy

  • Light microscopy shows focal glomerulonephritis with proliferation of mesangial cells

  • Immunofluorescence shows diffuse mesangial IgA and C3 deposits

Treatment

• Patients with low risk for progression (no hypertension, normal glomerular filtration rate [GFR], minimal proteinuria) can be monitored annually

• Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)

  • Recommended for patients at higher risk for progression (proteinuria > 1.0 g/day, decreased GFR, and/or hypertension)

  • Therapy should be titrated to reduce proteinuria to < 1 g/day and to reduce blood pressure to between 125/75 mm Hg and 130/80 mm Hg

• Prior trials suggested that corticosteroids reduced proteinuria when administered to patients with GFR > 50 mL/min/1.73 m² and persistent proteinuria > 1 g/day

• However, more recent trials failed to demonstrate slowing of GFR loss with corticosteroid therapy compared with use of ACE inhibitors or ARB alone; therefore, enthusiasm for glucocorticoid therapy has waned

• Azathioprine and mycophenolate mofetil

  • Have also been used in patients at high-risk for progression

  • However, studies with these agents are small

  • Therefore, routine use is not recommended

• Cyclophosphamide and corticosteroid therapy should be considered for the rare patient with a rapidly progressive clinical course with crescent formation on biopsy

• ~33% of patients experience spontaneous remission

• Chronic microscopic hematuria but stable serum creatinine occurs in 50–60%; progression to end-stage kidney disease occurs in 20–40%

• Proteinuria > 1 g/day is most unfavorable prognostic indicator; others include

  • Hypertension

  • Tubulointerstitial fibrosis

  • Glomerulosclerosis or glomerular crescents on biopsy

  • Abnormal GFR on presentation

• Kidney transplantation

  • An excellent option for patients with end-stage kidney disease

  • However, recurrent disease has been documented in 30% of patients by 5–10 years posttransplant