eMedicine Specialties > Pediatrics: General Medicine > Nephrology

IgA Nephropathy: Differential Diagnoses & Workup

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
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
Contributor Information and Disclosures

Updated: Dec 15, 2008

Differential Diagnoses

Acute Poststreptococcal Glomerulonephritis
Medullary Sponge Kidney
Alport Syndrome
Minimal-Change Disease
Anti-GBM Antibody Disease
Nephritis
Antiphospholipid Antibody Syndrome
Nephritis, Interstitial
Diabetic Nephropathy
Nephrotic Syndrome
Glomerulonephritis, Acute
Polyarteritis Nodosa
Glomerulonephritis, Chronic
Polycystic Kidney Disease
Glomerulonephritis, Crescentic
Pyelonephritis
Glomerulonephritis, Diffuse Proliferative
Sickle Cell Anemia
Glomerulonephritis, Nonstreptococcal Associated With Infection
Systemic Lupus Erythematosus
Glomerulonephritis, Poststreptococcal
Uric Acid Stones
Glomerulonephritis, Rapidly Progressive
Urinary Tract Infection
Goodpasture Syndrome
Urolithiasis
Hematuria
Wegener Granulomatosis
Henoch-Schoenlein Purpura
Hypercalciuria
Medullary Cystic Disease

Workup

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.

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.

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

Histologic Findings

The diagnostic histopathologic hallmark of IgA nephropathy by light, immunofluorescence, and electron microscopy is the presence of IgA in the glomerular mesangium. 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.

  • 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.
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.

More on IgA Nephropathy

Overview: IgA Nephropathy
Differential Diagnoses & Workup: IgA Nephropathy
Treatment & Medication: IgA Nephropathy
Follow-up: IgA Nephropathy
Multimedia: IgA Nephropathy
References
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References

  1. Lai FM, Szeto CC, Choi PC, et al. Characterization of early IgA nephropathy. Am J Kidney Dis. Oct 2000;36(4):703-8. [Medline].

  2. Dillon JJ. Treating IgA nephropathy. J Am Soc Nephrol. Apr 2001;12(4):846-7. [Medline].

  3. Donadio JV Jr, Grande JP. Immunoglobulin A nephropathy: a clinical perspective. J Am Soc Nephrol. Aug 1997;8(8):1324-32. [Medline].

  4. Yoshikawa N, Ito H, Sakai T, et al. A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy. The Japanese Pediatric IgA Nephropathy Treatment Study Group. J Am Soc Nephrol. Jan 1999;10(1):101-9. [Medline].

  5. Yoshikawa N, Tanaka R, Iijima K. Pathophysiology and treatment of IgA nephropathy in children. Pediatr Nephrol. May 2001;16(5):446-57. [Medline].

  6. Hotta O, Furuta T, Chiba S, et al. Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis. Mar 2002;39(3):493-502. [Medline].

  7. Odum J, Peh CA, Clarkson AR, et al. Recurrent mesangial IgA nephritis following renal transplantation. Nephrol Dial Transplant. 1994;9(3):309-12. [Medline].

  8. Park SB, Joo I, Suk J, et al. IgA nephropathy in renal transplant recipients: is it a significant cause of allograft failure?. Transplant Proc. Jun 1996;28(3):1540-2. [Medline].

  9. Wang AY, Lai FM, Yu AW, et al. Recurrent IgA nephropathy in renal transplant allografts. Am J Kidney Dis. Sep 2001;38(3):588-96. [Medline].

  10. D'Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol. May 2004;24(3):179-96. [Medline].

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  15. Kobayashi Y, Sano T, Nakamura I, et al. Long-term effect of 2-year steroid therapy in progressive IgA nephropathy: A 30-year follow-up study compared with a non-steroid group. Nephrology (Carlton). Jan 2003;8 Suppl 4:A113-4. [Medline].

  16. Oortwijn BD, Rastaldi MP, Roos A, Mattinzoli D, Daha MR, van Kooten C. Demonstration of secretory IgA in kidneys of patients with IgA nephropathy. Nephrol Dial Transplant. Jun 2007;22(11):3191-5. [Medline]. [Full Text].

  17. IgA nephropathy. In: van Es LA, Massery SG, Glassock RJ, eds. Textbook of Nephrology. Vol 1. 2001:733-41.

  18. Wardle EN. Is IgA nephropathy induced by hyperproduction of interferon-alpha?. Med Hypotheses. 2004;62(4):625-8. [Medline].

  19. White RHR, Yoshikawa N, Freehally J. IgA nephropathy and Henoch-Schonlein nephritis. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology. 4th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 1999:691-706.

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Further Reading

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Keywords

IgA nephropathy, IgAN, immunoglobulin A nephropathy, glomerulonephritis, focal glomerulonephritis, Berger focal glomerulonephritis, Berger's focal glomerulonephritis, Berger nephropathy, Berger's nephropathy, hypertension, proteinuria, Henoch-Schönlein purpura, HSP, Henoch-Schönlein nephropathy, HSN, end-stage renal disease, renal insufficiency, pharyngitis, poststreptococcal glomerulonephritis, PSGN, nephrotic syndrome, systemic lupus erythematosus, SLE, celiac disease, chronic ulcerative colitis, Crohn disease, dermatitis herpetiformis, psoriasis, cystic fibrosis, sarcoidosis, lung cancer, colon cancer, monoclonal IgA gammopathy, non-Hodgkin lymphoma, pancreatic cancer, human immunodeficiency virus, HIV, mycoplasma infection, toxoplasmosis, cirrhosis, pulmonary hemosiderosis, cryoglobulinemia, polycythemia, hepatitis B, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis

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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

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

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: Amgen Grant/research funds None; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

 
 
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