IgA Nephropathy

Detailed Overview

IgAN typically presents in young adults with episodic macroscopic hematuria concurrent with mucosal (e.g., upper respiratory) infections (synpharyngitic hematuria), or as microscopic hematuria found incidentally. The pathogenesis involves a multi-hit process starting with galactose-deficient IgA1. While many have a benign course, roughly 30-40% progress to End-Stage Renal Disease (ESRD) over 20 years. Treatment focuses on blood pressure control and reducing proteinuria with RAAS blockade.

Epidemiology & Demographics

Most common glomerulonephritis globally. Peak incidence in the 20s and 30s. More common in males (2:1) and populations of East Asian and Caucasian descent.

Etiological Mechanism

Autoimmune condition triggered by abnormal IgA1 glycosylation.

Primary Causes

Galactose-deficient IgA1 immune complex deposition

• Genetics: Familial clustering suggests a genetic component linked to the HLA locus.

The '4-hit hypothesis': 1) Production of galactose-deficient IgA1 (Gd-IgA1). 2) Synthesis of autoantibodies against Gd-IgA1. 3) Formation of pathogenic immune complexes in the circulation. 4) Deposition of these complexes in the glomerular mesangium, triggering complement activation, mesangial cell proliferation, and release of profibrotic cytokines leading to glomerulosclerosis.

Characteristic Clinical Presentation

• Macroscopic Hematuria: Cola or tea-colored urine occurring simultaneously with a URI or GI infection.
• Flank Pain: Dull ache due to stretching of the renal capsule during acute hematuric episodes.

Physical Examination Signs

• Hypertension.
• Edema (if nephrotic-range proteinuria is present, though uncommon).

• End-Stage Renal Disease: Requires dialysis or transplant.
• Acute Kidney Injury: Due to crescentic glomerulonephritis or massive gross hematuria causing tubular occlusion.

Diagnostic Criteria & Guidelines

Renal biopsy showing prominent, global IgA deposits in the mesangium on immunofluorescence.

Differential Diagnosis

• Post-streptococcal Glomerulonephritis (occurs weeks AFTER infection, not during)
• Alport Syndrome
• IgA Vasculitis (Henoch-Schönlein Purpura)

Laboratory Tests & Biomarkers

• Urinalysis: Dysmorphic RBCs and RBC casts, variable proteinuria.
• Serum IgA: Elevated in 50% of patients (not diagnostic).
• Serum Complement (C3/C4): Normal (unlike post-infectious GN or lupus).

Imaging Modalities & Findings

• Renal Ultrasound:

• Benign Hematuria
  Microscopic hematuria, normal GFR, <0.5 g/day proteinuria.
• Progressive IgAN
  Proteinuria > 1 g/day, hypertension, slowly declining GFR.
• End-Stage Renal Disease
  GFR < 15 mL/min/1.73m2 requiring dialysis.

Second-Line & Adjunctive Therapy

For persistent proteinuria > 1 g/day despite 3-6 months of optimized supportive care: Systemic corticosteroids (Prednisone 1 mg/kg/day for 2 months, then taper) OR Targeted release Budesonide (Tarpeyo) 16 mg PO daily for 9 months.

Surgical & Procedural Management

Kidney transplantation for ESRD. (Note: IgAN can recur in the allograft in ~30% of cases).

Recommended Lifestyle Changes

• Low sodium diet (<2g/day) to assist blood pressure control.
• Fish oil (omega-3 fatty acids) supplementation may be considered, though evidence is weak.

Patient Counseling & Advice

Reassure that gross hematuria during colds is typical and usually resolves. Emphasize strict adherence to BP medications, as hypertension heavily drives disease progression.

Follow-Up & Monitoring Schedule

Check BP, eGFR, and Urine Protein-to-Creatinine Ratio (UPCR) every 3-6 months.

Preventive Strategies

None.

Highly variable. 30-40% progress to ESRD over 20-25 years. Proteinuria > 1 g/day and hypertension are the strongest predictors of poor outcome.