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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 HASH(0x2f82cc8) 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]