Pediatric IgA Nephropathy Workup

  • Author: Mohammad Ilyas, MD, FAAP; Chief Editor: Craig B Langman, MD   more...
 
Updated: Aug 3, 2010
 

Laboratory Studies

Upon initial evaluation, the studies below are directed at identifying immunoglobulin A (IgA) nephropathy. Evaluation from a renal standpoint should include consideration of any condition causing hematuria, proteinuria, hypertension, and/or reduced renal function.

  • Urinalysis (UA): These results should reveal hematuria, proteinuria, and leukocytes. Microscopic examination reveals dysmorphic RBCs and RBC casts suggestive of glomerular origin of RBC but not specific for IgA nephropathy, whereas normal RBC morphology indicates lower urinary tract involvement.
  • CBC count with differential count
  • A 24-hour urine collection: This is used is to estimate creatinine clearance (CrCl) and protein excretion. Proteinuria is associated with histologic lesion and a risk for progression.
  • Urine calcium (Ca) to creatinine (Cr) ratio: This is performed to measure hypercalciuria (normal is < 0.2) and the protein (Pr) to Cr ratio to measure proteinuria (normal is < 0.2).
  • Serum electrolyte levels
  • BUN and Cr levels: These estimate renal function.
  • Serum C3 levels: These levels are usually normal. C3 is routinely measured to eliminate the diagnosis of postinfectious glomerulonephritis or membranoproliferative glomerulonephritis.
  • Antistreptolysin-O (ASO) titer or streptozyme test
  • Serum IgA level: These are elevated in approximately 30-50% in adults but in only 8-16% of children with IgA nephropathy.
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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

The diagnosis of IgA nephropathy is based on the presence of IgA immunoglobulin in the glomerular mesangium.

Percutaneous renal biopsy is essential for the confirmation of IgA nephropathy. The indications for biopsy include the following:

  • Macroscopic hematuria
  • Microscopic hematuria with significant proteinuria (>2 mg/kg/d)
  • Acute nephritic syndrome (hematuria with hypertension or renal insufficiency)
  • Nephrotic syndrome
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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 intGlomerulus 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). FluoMesangial 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 electroElectron 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 and 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 & Dental Society, 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, and Southwest Pediatric Nephrology Study Group

Disclosure: The Osler Institute Honoraria Speaking and teaching

Specialty Editor Board

Deogracias Pena, MD  Medical Director of Dialysis, Department of Pediatrics, Cook Children's Medical Center; Clinical Associate Professor, Texas Tech University School of Medicine

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

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Adrian Spitzer, MD  Professor, Department of Pediatrics, Albert Einstein College of Medicine; Director of NIH Training Program, Children's Hospital at Montefiore Medical Center

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, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Howard Trachtman, MD  Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine

Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

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

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

Disclosure: Merck Grant/research funds None; NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

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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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