81. IgA nephropathy

Page created on May 24, 2021. Last updated on December 18, 2024 at 16:58

Definition and epidemiology

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. In Europe, it accounts for 1/3 of primary GN patients. It almost always causes chronic glomerulonephritis, rarely acute.

The age of onset is usually 15 – 30 years, and the male-to-female ratio is 2:1. In Northern Europe, it’s even higher, up to 6:1.

Etiology

The etiology of IgA nephropathy is unknown. However, there are many conditions which can cause secondary IgA deposition in the kidney, which may have similar presentation and histology:

  • Infections (HBV, CMV, etc.)
  • Systemic diseases (SLE, HSP)
  • Rheumatic diseases
  • Liver cirrhosis
  • GI diseases (Coeliac, Crohn’s)
  • Dermatological diseases

Pathomechanism

The key feature of IgA nephropathy is the formation of IgA1 antibodies which are deficient of galactose, usually in response to a mucosal infection.

For the disease to develop, antibodies against these galactose deficient IgA1 antibodies must be formed. The anti-Gd-IgA1 antibodies form immune complexes with the Gd-IgA1 antibodies, which deposit in the mesangium of the glomeruli, triggering a hypersensitivity type III reaction.

Clinical features

IgA nephropathy usually presents with macroscopic haematuria a few (0 – 3) days after an upper respiratory tract infection. Alternatively, it be discovered as proteinuria or microscopic haematuria during screening. Rarely, it can present as AKI, RPGN, CKD, or nephrotic syndrome.

Patients with IgA nephropathy may sometimes only temporarily experience symptoms for a while after mucosal infections like URTIs.

Diagnosis and evaluation

As this is a glomerulonephritis, the haematuria is of glomerular type. Elevated serum IgA is found in 50% of patients.

In the case of macroscopic haematuria 0 – 3 days after an URTI, the diagnosis is strongly suspected. PSGN, in contrast, occurs 10 – 14 days after the URTI.

Definite diagnosis can only be made with renal biopsy, and so renal biopsy is required in all suspected cases. Immunofluorescence shows IgA deposits in the mesangium.

Treatment

IgA nephropathy is a chronic disease, and the treatment involves reducing the complications related to it, most importantly the kidney function decline. For patients with good prognostic factors, we use supportive therapy only, including:

  • Low protein diet
  • Low sodium diet
  • Correction of dyslipidaemia
  • Smoking cessation
  • Avoid nephrotoxins
  • Antibiotic treatment in case of infections causing macrohaematuria

For patients with poor prognostic factors (heavy proteinuria, hypertension, decreased GFR), we use RAAS inhibitors in addition to supportive therapy.

Prognosis

20 years after the diagnosis:

  • 30% have normal kidney function
  • 40% have decreased kidney function
  • 30% have end-stage renal disease

Patients may have macro-or-microscopic haematuria and/or proteinuria for life.