Pediatric IgA Nephropathy Workup
- Author: Mohammad Ilyas, MD, FAAP; Chief Editor: Craig B Langman, MD more...
The diagnosis of IgA nephropathy is based on clinical history and laboratory data, but it can only be confirmed by kidney biopsy. The IgA deposits within mesangium visualized by immunofluorescence or immunoperoxidase studies confirm the IgA nephropathy.
Although circulating autoantibodies, including antiendothelin antibodies, have been reported in IgA nephropathy, none appears to be disease specific.
The following studies are used to identify immunoglobulin A (IgA) nephropathy and to rule out other causes of nephropathy:
Urinalysis (UA) usually reveals hematuria, proteinuria, and leukocytes. Microscopic examination shows dysmorphic RBCs and RBC casts suggestive of glomerular origin of RBC but not specific for IgA nephropathy
CBC count with differential to identify anemia, leukocytosis, and thrombocytopenia help exclude other underlying causes for nephritis
A 24-hour urine collection estimates creatinine clearance (CrCl) and protein excretion; proteinuria is associated with histologic lesions and a risk for progression; proteinuria also helps determine therapeutic course as discussed in the treatment section
The ratio of urine calcium (Ca) to creatinine (Cr) measures hypercalciuria (normal is < 0.2), a common cause for microhematuria
Serum electrolyte levels; Na, K +, Cl, and HCO 3 could help detect early abnormalities
BUN and Cr levels estimate renal function and help in further management decisions
Serum C3 and C4 levels are usually normal; C3 is routinely measured to eliminate the diagnosis of postinfectious glomerulonephritis (PSAGN) or membranoproliferative glomerulonephritis (MPGN); low C3 and C4 suggest lupus nephritis
Antistreptolysin-O (ASO) titer or streptozyme tests help exclude PSAGN
Plasma polymeric IgA1 levels are elevated in 30-50% of cases, but this suggestive finding is not sufficiently specific to establish the diagnosis; measurement of the proportion of poorly galactosylated IgA1 O-glycoforms in the serum with or without measurement of poorly galactosylated IgA1-specific IgG has been proposed as a clinically useful diagnostic test 
Renal ultrasonography is an excellent diagnostic tool to detect structural abnormalities leading to hematuria, such as renal stone, neoplasm, cystic lesion, hydronephrosis, dilated urinary tract, and bladder abnormalities. However, it cannot be used to confirm, support, or reject the diagnosis of IgA nephropathy.
Percutaneous renal biopsy is essential for the confirmation of IgA nephropathy. The diagnosis of IgA nephropathy is based on the presence of IgA in the glomerular mesangium. The indications for biopsy include the following:
Macroscopic (gross) hematuria
Microscopic hematuria with significant proteinuria (>2 mg/kg/d)
Acute nephritic syndrome (hematuria with hypertension or renal insufficiency)
A skin biopsy, looking for IgA deposition in the dermal capillaries, has not proven to be sufficiently predictive in IgA nephropathy.
The diagnostic histopathologic hallmark of IgA nephropathy by light, immunofluorescence, and electron microscopy is the presence of IgA in the glomerular mesangium. See the images below.
With light microscopy, the most characteristic abnormality is mesangial enlargement produced by hypercellularity and mesangial matrix increase. The severity of renal involvement can be graded based on mesangial cell proliferation.
Immunofluorescence microscopy demonstration of predominately mesangial deposition of IgA is pathognomonic of IgA nephropathy. Mesangial immunoglobulin G (IgG), immunoglobulin M (IgM), C3, and properdin may also be observed. Electron microscopy reveals mesangial or perimesangial deposits occurring in the same distribution as observed with immunofluorescence microscopy.
The glomeruli appear normal. The number of mesangial cells per peripheral mesangial area does not exceed 3. Small foci of tubular atrophy and interstitial lymphocyte infiltration may be present.
Focal mesangial proliferation
The glomeruli show moderate to severe mesangial cell proliferation (ie, >3 mesangial cells per peripheral mesangial area). The proliferation may be associated with increased matrix, small crescent, capsular adhesions and prolapsed.
Diffuse mesangial proliferative and crescentic glomerulonephritis can occur. A small number of patients may have global sclerosis, tubular atrophy, interstitial fibrosis, and interstitial lymphocyte infiltrate.
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