section name header

Information

Editors

KatiKaartinen

Iga Nephropathy

Essentials

  • An incidental finding of asymptomatic microscopic haematuria and proteinuria should arouse the suspicion of IgA nephropathy, or IgA glomerulonephritis.
  • Blood pressure may be elevated.
  • ACE inhibitors and ARBs are the first-line drugs for treating also normotensive patients with proteinuria.
  • There is no curative treatment available.

Epidemiology, aetiology and pathogenesis

  • This is the most common type of primary glomerulonephritis worldwide (see also Glomerulonephrites). It was previously also called Berger's disease.
  • Annual incidence in Finland 5/100 000
  • Encountered in all age groups, but the diagnosis is most commonly established at the age of 20 to 30 years.
  • More common in men than in women
  • Fundamental underlying mechanism unknown
    • In addition to structurally abnormal IgA immunoglobulin, an external factor (such as a microbe or dietary antigen) is needed to trigger autoantibody production finally leading to the accumulation of immune complexes in renal corpuscles.
  • Mainly immunoglobulin IgA1 deposits occur in the renal tissue.
  • Most cases are sporadic. Less than 10% of patients have the familial type of the disease.

Symptoms and findings

  • Microscopic haematuria and various degrees of proteinuria are the usual incidental findings.
    • About 10% of patients have microscopic haematuria and about 5% nephrotic syndrome as the sole finding Nephrotic Syndrome.
  • About half of the patients have macroscopic haematuria in association with febrile diseases.
  • Hypertension is a common finding.
  • Renal failure may be present at diagnosis, already.
  • Rapidly progressive glomerulonephritis or nephrotic syndrome with sudden onset (minimal change type glomerulonephritis) Glomerulonephrites are clinically rare but possible.
  • May present as isolated glomerulonephritis Glomerulonephrites or as part of the Henoch-Schönlein syndrome Henoch-Schönlein Purpura.
  • Secondary disease may be seen in association with diseases such as chronic liver diseases, HIV infection or coeliac disease.

Diagnosis

  • Microscopic haematuria (urinalysis, urine basic particle count) and/or proteinuria (urinalysis, urine albumin/creatinine ratio or 24-hour urinary protein excretion), often associated with high blood pressure lead to suspecting the disease.
  • The diagnosis is always based on renal biopsy.
    • Biopsy if proteinuria at least 1 g/24 h or eGFR is decreased
    • If the patient has just microscopic or macroscopic haematuria, biopsy should be considered only if it is especially important to confirm the diagnosis.
    • In immunofluorescence testing, IgA deposits in glomeruli
    • Light microscopic findings may be varied.
  • Even mild IgA nephropathy or suspicion of the disease requires follow-up, since an indication for biopsy or a need for intensification of treatment develops in some patients.
  • The disease cannot be distinguished with certainty from other glomerulonephritides on clinical grounds or by laboratory tests but the occurrence of macroscopic haematuria soon (within less than 2 days) after the onset of a febrile disease is indicative of IgA nephropathy.
  • Serum IgA is elevated in half of the patients.

Prognosis

  • In 20- to 25-year follow-up, end-stage renal failure develops in about 25 to 30% of patients.
  • The clinically most significant factors suggesting a poor prognosis are, at the time of diagnosis or during follow-up:
    • already existing renal failure
    • proteinuria exceeding 1 g/24 h
    • hypertension.
  • Haematuria is insignificant for the prognosis.
  • All urinary findings may be spontaneously reversible in a small proportion (< 10%) of the patients. Histological regression and disappearance of IgA deposits is rare but possible.
  • In histological classification (MEST classification) certain findings in renal biopsy independently affect the prognosis (mesangial or endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy / interstitial fibrosis).
  • The disease may also recur in a renal transplant.
  • In adults, a risk score calculator may be used when assessing prognosis (http://qxmd.com/calculate/calculator_499/international-igan-prediction-tool).

Treatment and follow-up

  • There is no curative treatment available.
  • An ACE inhibitor or ARB for all patients with urinary protein excretion > 1 g/24 h
  • Blood pressure targets:
    • below 125/75 mmHg, if urinary protein excretion > 1 g/24 h
    • below 130/80 mmHg, if urinary protein excretion < 1 g/24 h.
  • A combination of ACE inhibitor and ARB should only be considered in selected patients. It involves a risk of hyperkalaemia and aggravation of significant renal failure.
  • The rapidly progressive form of disease should be treated like vasculitis.
  • Minimal change glomerulonephritis-type nephrotic disease of sudden onset should be treated like minimal change glomerulonephritis.
  • Glucocorticoid therapy for 6 months Corticosteroids in Iga Nephropathy should be considered in specialized care:
    • if the level of proteinuria remains at > 1 g/24 h despite 3-6 months of optimal treatment (with ACE inhibitor or ARB and blood pressure on target) and GFR ≥ 50 ml/min; may be considered even at a lower level of renal filtrate but no benefit is likely at GFR levels of < 30 ml/min.
    • if the only problem is GFR decreased to below the optimal level despite the treatment of high blood pressure and proteinuria, and there is no other evident cause for this.
  • There is no evidence to support repeated glucocorticoid treatment in the slowly progressive form of disease.
  • Chronic renal failure should be treated as in patients with other types of renal disease.
  • Mild forms of the disease and patients with a good prognosis can be followed up in primary health care every 6 to 12 months.
    • Optimal control of blood pressure
    • Creatinine, potassium, sodium, chemical urinalysis and urinary albumin/creatinine ratio or 24-hour urinary protein excretion
    • If creatinine levels rise progressively or proteinuria increases despite optimal treatment or blood pressure control becomes essentially more difficult, consult specialized care.

References

  • Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med 2013;368(25):2402-14. [PubMed]
  • Rodrigues JC, Haas M, Reich HN. IgA Nephropathy. Clin J Am Soc Nephrol 2017;12(4):677-686.[PubMed]
  • Barbour SJ, Coppo R, Zhang H ym. Evaluating a New International Risk-Prediction Tool in IgA Nephropathy. JAMA Intern Med 2019;179(7):942-952. [PubMed]