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Pediatric IgA Nephropathy Workup

  • Author: Mohammad Ilyas, MD, FAAP; Chief Editor: Craig B Langman, MD  more...
 
Updated: Feb 27, 2014
 

Laboratory Studies

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 [11]
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Imaging Studies

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.

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Procedures

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)
  • Nephrotic syndrome

A skin biopsy, looking for IgA deposition in the dermal capillaries, has not proven to be sufficiently predictive in IgA nephropathy.[12]

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Histologic Findings

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.

Glomerulus with mesangial hypercellularity and int Glomerulus with mesangial hypercellularity and intact capillary loops. Trichrome Stain, original magnification 400x. Image courtesy of Patrick D Walker, MD.
Mesangial deposits of immunoglobulin A (IgA). Fluo Mesangial deposits of immunoglobulin A (IgA). Fluoresceinated Anti-IgA Antibody, Immunofluorescence microscopy, original magnification 400x. Image courtesy of Patrick D Walker, MD.
Electron photomicrograph showing mesangial electro Electron photomicrograph showing mesangial electron dense deposits (arrow). Uranyl acetate and lead citrate stain, original magnification 12,000x. Image courtesy of Patrick D Walker, MD.

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.

Minimal lesion

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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Contributor Information and Disclosures
Author

Mohammad Ilyas, MD, FAAP Assistant Professor of Pediatrics, University of Florida College of Medicine; Consulting Staff, Department of Pediatrics, Section of Nephrology, Wolfson Children Hospital and Shands Hospital Jacksonville

Mohammad Ilyas, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Richard Neiberger, MD, PhD Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical and Dental Associations, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, Southwest Pediatric Nephrology Study Group

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Adrian Spitzer, MD Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine

Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, International Society of Nephrology

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Raptor Pharmaceuticals; Eli Lilly and Company; Dicerna<br/>Received grant/research funds from NIH for none; Received grant/research funds from Raptor Pharmaceuticals, Inc for none; Received grant/research funds from Alexion Pharmaceuticals, Inc. for none; Received consulting fee from DiCerna Pharmaceutical Inc. for none.

Additional Contributors

Deogracias Pena, MD Medical Director of Dialysis, Medical Director of Pediatric Nephrology and Transplantation, Cook Children's Medical Center; Clinical Associate Professor, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Medical Director of Pediatric Nephrology, Florida Hospital for Children

Deogracias Pena, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

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Glomerulus with mesangial hypercellularity and intact capillary loops. Trichrome Stain, original magnification 400x. Image courtesy of Patrick D Walker, MD.
Mesangial deposits of immunoglobulin A (IgA). Fluoresceinated Anti-IgA Antibody, Immunofluorescence microscopy, original magnification 400x. Image courtesy of Patrick D Walker, MD.
Electron photomicrograph showing mesangial electron dense deposits (arrow). Uranyl acetate and lead citrate stain, original magnification 12,000x. Image courtesy of Patrick D Walker, MD.
 
 
 
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