Nephropathy, Immunoglobulin A

Primary renal disease with IgA deposition in the glomerular mesangium

Inciting cause unknown but is likely due to 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

Gross hematuria, frequently associated with a mucosal viral infection often of the upper respiratory tract infection

Urine becomes red or smoky-colored 1–2 days after illness onset

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

Rarely, a nephrotic syndrome can be present as well

Can present anywhere along the nephritic spectrum from asymptomatic microscopic hematuria with minimal proteinuria and preserved eGFR to RPGN

Rarely, nephrotic syndrome can occur, as well

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

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

Addition of corticosteroids (eg, methylprednisolone, 1 g/day intravenously for 3 days during months 1, 3, and 5, plus prednisone 0.5 mg/kg orally every other day for 6 months) in those with GFR > 50 mL/min/1.73 m² and persistent proteinuria > 1 g/day

• Has been shown to reduce proteinuria

• However, there seems to be little durable effect

• Risks of infection and dysglycemia are significant

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

Kidney transplantation

~33% of patients experience spontaneous remission

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

Most unfavorable prognostic indicator: proteinuria > 1 g/day

Other unfavorable prognostic indicators

• Hypertension

• Tubulointerstitial fibrosis

• Glomerulosclerosis or glomerular crescents on biopsy

• Abnormal GFR on presentation