IgA Nephropathy Clinical Presentation

  • Author: Mona Brake, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Jan 5, 2012
 

History

Two common presentations of patients with IgA nephropathy are episodic gross hematuria and persistent microscopic hematuria. Recurrent macroscopic hematuria, usually associated with an upper respiratory tract infection, or, less often, gastroenteritis is the most frequent clinical presentation and is observed in 40-50% of presenting patients. In 30-40% of patients, the disease is asymptomatic, with erythrocytes (RBCs), RBC casts, and proteinuria discovered on urinalysis. Patients with IgA nephropathy can also present with acute or chronic renal failure.

  • Hematuria: Many patients present with episodes of recurrent macroscopic hematuria.
    • Eighty percent of these episodes are associated with upper respiratory tract infections, mainly acute pharyngotonsillitis. This synchronous association of pharyngitis and macroscopic hematuria has been dubbed synpharyngitic nephritis.
    • Gross hematuria usually appears simultaneously or within the first 48-72 hours after the infection begins; persists less than 3 days; and, in about a third of patients, is accompanied by loin pain, presumably due to renal capsular swelling.
    • Urine is usually brown rather than red, and clots are unusual.
    • The presenting illness of episodic, grossly visible hematuria is more common in younger people, whereas that of abnormal urine sediment is more frequent in older individuals.
    • Episodes of gross hematuria in IgA nephropathy have been associated with a variety of other infections.
      • Urinary tract infections
      • Pneumonia
      • Staphylococcal sepsis
      • Staphylococcal osteomyelitis
      • Acute gastroenteritis
      • Influenza
      • Infectious mononucleosis
    • Gross hematuria has also followed tonsillectomy, vaccinations, strenuous physical exercise, and trauma.
    • Between episodes of gross hematuria, many patients have persistent microhematuria, proteinuria, or both.
  • It is rare for proteinuria to occur without microscopic hematuria in IgA nephropathy.
    • Mild proteinuria is common.
    • Nephrotic-range proteinuria is uncommon, occurring in only 5% of patients with IgA nephropathy, and is more commonly seen in children and adolescents. Nephrotic-range proteinuria can be seen at different stages of the disease, both in patients early in the disease course and in patients with advanced disease.
    • Patients with heavy proteinuria and nephrotic syndrome are likely to have IgA deposition with diffuse proliferative glomerular lesions or minimal-change light microscopic findings.
  • Acute renal failure: Acute renal failure, with edema, hypertension, and oliguria, occurs in fewer than 5% of patients. It can develop from either of 2 distinct mechanisms.
    • Acute severe immune injury can manifest as necrotizing glomerulonephritis and crescent formation.
    • Alternatively, only mild glomerular injury is observed with gross hematuria, and renal failure is presumably due to tubular occlusion by RBCs. This is reversible, and renal function recovers with supportive measures.
  • Hypertension: Hypertension seldom occurs at the time of initial presentation but more commonly manifests as the course of the disease lengthens or when patients develop chronic kidney disease and ESRD.
  • Chronic renal failure: Chronic kidney disease (stage II and higher) seldom develops but is usually slowly progressive. Approximately 1-2% of all patients with IgA nephropathy develop ESRD each year.
Next

Physical

A minority of patients have hypertension; otherwise, physical examination findings in patients with IgA nephropathy are usually unremarkable.

Previous
Next

Causes

Most cases of IgA nephropathy are idiopathic, but the onset or exacerbation of the disease is often preceded by a respiratory tract infection. Association with some bacteria, such as Haemophilus parainfluenzae, has been reported. A variety of other disorders have also been linked with IgA nephropathy, as discussed below.

  • Cirrhosis and other liver diseases
    • Glomerular IgA deposition is a common finding in cirrhosis, occurring in up to a third of patients. Liver disease is accompanied by impaired removal of IgA-containing complexes by the Kupffer cells, predisposing patients to IgA deposition in the kidney.
    • Glomerular IgA deposits are common in advanced liver disease, but most adults have no clinical signs of glomerular disease, whereas up to 30% of children may have asymptomatic hematuria or proteinuria. Those abnormalities usually resolve after successful liver transplantation.
  • Gluten enteropathy (celiac disease)
    • Glomerular IgA deposition occurs in up to a third of patients with gluten enteropathy.
    • Most of these patients have no clinical manifestations of the disease. However, IgA nephropathy and gluten hypersensitivity are associated, and withdrawal of gluten from the diet of these patients has resulted in clinical and immunological improvement of the renal disease.
  • HIV disease
    • IgA nephropathy has been reported in patients with HIV infection, both whites and blacks, despite the rarity of typical IgA nephropathy in the black population.
    • Clinically, patients have hematuria, proteinuria, and, possibly, renal insufficiency.
    • Histologically, findings range from mesangial proliferative glomerulonephritis to collapsing glomerulosclerosis with mesangial IgA deposits.
    • Several patients have circulating immune complexes containing IgA antibodies against viral proteins.
  • Familial IgA nephropathy
    • While IgA nephropathy is usually a sporadic disease, data suggest that genetic factors are important in susceptibility to development of mesangial glomerulonephritis. Several cases of familial disease have been reported in Italy and the United States, and an autosomal dominant form has been linked to band 6q22-23.
    • Additionally, increased frequency of specific HLA groups has been reported in some patients.
Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Mona Brake, MD  Assistant Professor, Department of Internal Medicine, Kansas University School of Medicine

Mona Brake, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Douglas Somers, MD  Assistant Professor, Department of Internal Medicine, Division of Nephrology, University of Iowa Medical Center

Douglas Somers, MD is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

Specialty Editor Board

James H Sondheimer, MD, FACP  Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director of Hemodialysis, Harper University Hospital at Detroit Medical Center; Medical Director, DaVita Greenview Dialysis (Southfield)

James H Sondheimer, MD, FACP is a member of the following medical societies: American College of Physicians and American Society of Nephrology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Christie P Thomas, MBBS, FRCP, FASN, FAHA  Professor, Department of Internal Medicine, Division of Nephrology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

The authors thank Dr. Tim Timmerman, pathologist, for his invaluable help with the pathology slides.

References

  1. Glassock RJ. IgA nephropathy: challenges and opportunities. Cleve Clin J Med. Aug 2008;75(8):569-76. [Medline]. [Full Text].

  2. Cattran DC, Coppo R, Cook HT, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. Jul 1 2009;[Medline].

  3. Coppo R, Troyanov S, Camilla R, et al. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int. Mar 3 2010;[Medline].

  4. Walsh M, Sar A, Lee D, et al. Histopathologic features aid in predicting risk for progression of IgA nephropathy. Clin J Am Soc Nephrol. Mar 2010;5(3):425-30. [Medline].

  5. Hahn WH, Suh JS, Cho BS, et al. The enabled homolog gene polymorphisms as a novel susceptibility gene for childhood IgA nephropathy. Exp Mol Med. Jul 30 2009;[Medline]. [Full Text].

  6. Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int. Jun 2006;69(11):1939-44. [Medline].

  7. Gharavi AG, Yan Y, Scolari F, et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet. 26(3):354-7. [Medline].

  8. Manno C, Torres DD, Rossini M, et al. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant. Jul 23 2009;[Medline].

  9. Tang SC, Tang AW, Wong SS, et al. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. Mar 2010;77(6):543-9. [Medline].

  10. Liu LJ, Lv JC, Shi SF, et al. Oral calcitriol for reduction of proteinuria in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis. Jan 2012;59(1):67-74. [Medline].

  11. Yu L, Jiang L, Zhou XJ, et al. Common genetic variants in the chromogranin a promoter are associated with renal injury in IgA nephropathy patients with malignant hypertension. Ren Fail. Jan 2010;32(1):41-6. [Medline].

  12. Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. Mar 31 1994;330(13):877-84. [Medline].

  13. Levey AS, Adler S, Caggiula AW, et al. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. May 1996;27(5):652-63. [Medline].

  14. Shen PC, He LQ, Tang Y, et al. Clinicopathological characteristics and prognostic factors of asymptomatic IgA nephropathy. J Investig Med. Mar 2010;58(3):560-5. [Medline].

  15. Pozzi C, Bolasco PG, Fogazzi GB, et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet. 353(9156):883-7. [Medline].

  16. Schena FP, Cerullo G, Rossini M, et al. Increased risk of end-stage renal disease in familial IgA nephropathy. J Am Soc Nephrol. Feb 2002;13(2):453-60. [Medline]. [Full Text].

  17. Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol. Jul 2005;16(7):2088-97. [Medline].

  18. Bazzi C, Rizza V, Paparella M, et al. Fractional urinary excretion of IgG is the most powerful predictor of renoprotection by ACE inhibitors in IgA nephropathy. J Nephrol. May-June 2009;22(3):387-396. [Medline].

  19. Berger J, Hinglais N. [Intercapillary deposits of IgA-IgG]Les Depots Intercapillaires d'IgA-IgG. J Urol Nephrol (Paris). Sep 1968;74(9):694-5. [Medline].

  20. D'Agati V, Appel GB. HIV infection and the kidney. J Am Soc Nephrol. Jan 1997;8(1):138-52. [Medline].

  21. Dillon JJ. Fish oil therapy for IgA nephropathy: efficacy and interstudy variability. J Am Soc Nephrol. Nov 1997;8(11):1739-44. [Medline].

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

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

  24. Donadio JV Jr, Larson TS, Bergstralh EJ, Grande JP. A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. J Am Soc Nephrol. 12(4):791-9. [Medline].

  25. Falk RJ, Jennette JC, Nachman PH. IgA nephropathy. In: Brenner & Rector's The Kidney. 6th ed. WB Saunders; 2000:1302-1310.

  26. Galla JH. IgA nephropathy. Kidney Int. Feb 1995;47(2):377-87. [Medline].

  27. Ibels LS, Gyory AZ, Caterson RJ, et al. Primary IgA nephropathy: natural history and factors of importance in the progression of renal impairment. Kidney Int Suppl. 61:S67-70. [Medline].

  28. Kloke HJ, Branten AJ, Huysmans FT, et al. Antihypertensive treatment of patients with proteinuric renal diseases: risks or benefits of calcium channel blockers?. Kidney Int. Jun 1998;53(6):1559-73. [Medline].

  29. Nolin L, Courteau M. Management of IgA nephropathy: evidence-based recommendations. Kidney Int Suppl. Jun 1999;70:S56-62. [Medline].

  30. Pozzi C, Andrulli S, Del Vecchio L, et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol. Jan 2004;15(1):157-63. [Medline].

  31. Radford MG Jr, Donadio JV Jr, Bergstralh EJ, Grande JP. Predicting renal outcome in IgA nephropathy. J Am Soc Nephrol. 8(2):199-207. [Medline].

  32. Reich HN, Troyanov S, Scholey JW, et al. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. Dec 2007;18(12):3177-83. [Medline].

  33. Rodicio JL. Idiopathic IgA nephropathy. Kidney Int. Apr 1984;25(4):717-29. [Medline].

  34. Russo D, Minutolo R, Pisani A, et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis. Jul 2001;38(1):18-25. [Medline].

  35. Russo D, Pisani A, Balletta MM, et al. Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis. May 1999;33(5):851-6. [Medline].

  36. Sayegh MH. IgA nephropathy: recurrence after transplantation. Up-to-Date. 2000;8.

  37. Scolari F, Amoroso A, Savoldi S, et al. Familial clustering of IgA nephropathy: further evidence in an Italian population. Am J Kidney Dis. May 1999;33(5):857-65. [Medline].

  38. Shoji T, Nakanishi I, Suzuki A, et al. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis. 35(2):194-201. [Medline].

  39. van Es LA. IgA nephropathy. In: Massry and Glassock's Textbook of Nephrology. Lippincott Williams & Wilkins; 2001:733-741.

  40. van Es LA. Pathogenesis of IgA nephropathy. Kidney Int. Jun 1992;41(6):1720-9. [Medline].

  41. Wyatt RJ, Julian BA, Baehler RW, et al. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project. J Am Soc Nephrol. May 1998;9(5):853-8. [Medline].

 
Previous
Next
 
Light microscopy of a glomerulus from a patient with immunoglobulin A nephropathy showing increased mesangial matrix and cellularity.
Electron microscopy showing large dark mesangial deposits.
Immunofluorescence microscopy demonstrating large mesangial immunoglobulin A (IgA) deposits diagnostic of IgA nephropathy.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.