Approach

IgA nephropathy (IgAN) can only be diagnosed with a kidney biopsy.[40] No combination of clinical, serologic, and immunologic parameters can be used to replace the kidney biopsy.

Clinical evaluation

Visible hematuria is reported by about half of patients and is usually preceded by an upper respiratory tract infection (synpharyngitic nephritis) or gastroenteritis. Visible hematuria is usually painless but may occasionally be accompanied by loin pain and dysuria. Rarely, patients develop acute kidney injury, resulting from heavy glomerular hematuria leading to tubular occlusion and damage by red blood cells. This phenomenon is usually reversible, although incomplete recovery of kidney function may occur.

Approximately one third of patients have invisible hematuria and mild proteinuria. Less than 10% present with the nephrotic syndrome or a rapidly progressive glomerulonephritis (RPGN).[8][41][42]

Patients aged between 20 and 30 years are more commonly diagnosed than other age groups.[13][14] IgAN affects males more than females with a ratio of at least 2:1 in North America and western Europe, but the sexes are equally affected in Asia.[37] Although IgAN is commonly sporadic, familial cases have been reported.[16][17][18][19]  

IgAN may also be identified during investigation of patients with established chronic kidney disease and hypertension (approximately 20% of cases). Less common presentations include nephrotic syndrome (<5% cases); RPGN characterized by edema, hypertension, hematuria, and kidney failure (<5% cases); and malignant hypertension (<1% cases).[8][9] Malignant hypertension commonly presents with chest pain (angina or myocardial infarction), shortness of breath (pulmonary edema), or neurologic symptoms (headaches, visual disturbances, altered mental state, seizures).[8][9]

All patients with IgAN should be assessed for secondary causes (e.g., underlying HIV or viral hepatitis infection, inflammatory bowel disease, autoimmune disease, liver cirrhosis, or features suggesting IgA-dominant infection-related glomerulonephritis or IgA vasculitis).[40]

Laboratory evaluation

There are no specific laboratory or serologic diagnostic tests for IgAN.

Urine microscopy is likely to show erythrocyturia with dysmorphic erythrocytes consistent with glomerular bleeding. Rarely red cell casts may also be seen.

Proteinuria is commonly present, with approximately 60% of patients having <1 g/day and up to 10% of patients presenting with nephrotic-range proteinuria.[8][37]

Kidney function (serum creatinine and estimated glomerular filtration rate) is routinely checked at diagnosis and regularly during follow-up to monitor the course of the disease.

Complement levels (C3 and C4) are usually within normal limits and should only be ordered to exclude other causes of kidney disease where appropriate.[9][43][44]

Kidney and skin biopsy

A diagnosis of IgAN can only be made by kidney biopsy, which will confirm mesangial IgA deposition either by immunofluorescence or immunoperoxidase studies. [Figure caption and citation for the preceding image starts]: Immunofluorescence staining for IgA showing strong granular staining in the mesangium globally (anti-IgA immunofluorescence, x200)Courtesy of Drs Hwei Yee Lee, Cristine Ding, and Yong Howe Ho (Tan Tock Seng Hospital, Singapore) [Citation ends].com.bmj.content.model.Caption@5e6fa934[Figure caption and citation for the preceding image starts]: Electron dense deposits in mesangial and paramesangial regions (electron micrograph, x1000)Courtesy of Drs Hwei Yee Lee, Cristine Ding, and Yong Howe Ho (Tan Tock Seng Hospital, Singapore) [Citation ends].com.bmj.content.model.Caption@59c01346

Indications for kidney biopsy vary from center to center. In general, it is indicated in any patient with consistently impaired kidney function and/or persistent protein excretion of >1 g/day, but not for isolated invisible hematuria.

Skin biopsy is only performed when IgA vasculitis is suspected and has no role in diagnosing IgAN. In IgA vasculitis, there may be evidence of dermal capillary deposits of IgA, C3, properdin, and fibrin.[45][46][47][48]

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