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.
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).
Also for normotensive patients for the treatment of proteinuria
Should be considered even if urinary protein excretion is < 1 g/24 h.
Raise the dose to the maximum tolerated level.
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.
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]