IgA Nephropathy 

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

Background

Immunoglobulin A (IgA) nephropathy (also known as Berger disease) was first described by Berger and Hinglais in 1968. IgA nephropathy is characterized by predominant IgA deposition in the glomerular mesangium. Long-term follow-up data illustrated that some patients with IgA nephropathy progress to end-stage renal disease (ESRD).[1] IgA nephropathy is the most common cause of glomerulonephritis in the world.[2, 3]

IgA nephropathy is highly variable, both clinically and pathologically. Clinical features range from asymptomatic hematuria to rapidly progressive glomerulonephritis (RPGN). IgA nephropathy is most often associated with microscopic hematuria or recurrent macroscopic hematuria, and spontaneously resolving acute renal failure can occur. The condition can sometimes lead to chronic kidney disease as well. Pathologically, a spectrum of glomerular lesions can be seen, but mesangial proliferation with prominent IgA deposition is observed in almost all biopsies.

Light microscopy of a glomerulus from a patient wiLight microscopy of a glomerulus from a patient with immunoglobulin A nephropathy showing increased mesangial matrix and cellularity. Immunofluorescence microscopy demonstrating large Immunofluorescence microscopy demonstrating large mesangial immunoglobulin A (IgA) deposits diagnostic of IgA nephropathy.

Although IgA nephropathy is a limited nonsystemic renal disease, many systemic diseases are sporadically associated with mesangial IgA deposition. Henoch-Schönlein purpura (HSP), a systemic illness, has been closely linked to IgA nephropathy. Other systemic diseases in which mesangial deposits of IgA are regularly observed include systemic lupus erythematosus, hepatitis, dermatitis herpetiformis, and ankylosing spondylitis.

Recent studies

In a retrospective study of 146 patients with IgA nephropathy, Walsh et al investigated the efficacy of using the histopathologic features of this condition as prognostic indicators for primary outcome (defined in the study as a composite of doubling of serum creatinine levels, end-stage renal disease, or death). Employing a median follow-up period of 5.8 years and using multivariable models adjusted for clinical characteristics, the authors determined that interstitial fibrosis, glomerular sclerosis, and crescent formation independently predicted adverse outcomes in the study's patients. They also noted that an increased risk for progressive IgA nephropathy arose from even a relatively small amount of interstitial fibrosis.[4]

Next

Pathophysiology

The pathogenesis of IgA nephropathy remains incompletely understood.[5] The characteristic pathologic findings by immunofluorescence microscopy of granular deposits of IgA and complement 3 (C3) in the glomerular mesangium suggest that this disease is the result of the deposition of circulating immune complexes leading to the activation of the complement cascade.

Deposited IgA is predominantly polymeric IgA1, which is mainly derived from the mucosal immune system. The association of some cases of IgA nephropathy with syndromes that affect the respiratory tract or gastrointestinal tract, such as celiac disease, led to the suggestion that IgA nephropathy is a disease of the mucosal immune system. This concept is also supported by the clinical observation that hematuria worsens during or after upper respiratory tract or gastrointestinal tract infections.

The role of the complement system in the pathogenesis of IgA nephropathy is controversial. While IgA antibodies cannot activate complement through the classic pathway, studies have shown that complement can be activated by the alternate pathway.

IgA in the mesangium is likely to be deposited from the circulation as IgA-containing immune complexes. This hypothesis is supported by the high recurrence rate of IgA nephropathy in renal transplant recipients who have IgA nephropathy and, conversely, by the disappearance of the deposits from donor kidneys with IgA nephropathy when transplanted into donors without the disease. Furthermore, the mesangial pattern of IgA deposits suggests that circulating IgA complexes are responsible for the disease.

Serum IgA levels are elevated in approximately half of patients with IgA nephropathy, but that increase is unlikely to play a role in the pathogenesis of the disease, as markedly elevated IgA levels are observed in patients with AIDS who do not have IgA nephropathy. However, IgA is probably accumulated and deposited because of a systemic abnormality rather than a defect intrinsic to the kidney.

Previous
Next

Epidemiology

Frequency

United States

Distribution of IgA nephropathy varies in different geographic regions throughout the world. The condition accounts for about 10% of biopsies performed for glomerular disease in the United States. Prevalence rates are lower in the United States compared to Asian countries. These lower rates may be influenced by a conservative approach by nephrologists in the United States who are reluctant to perform renal biopsies in asymptomatic patients with only mild abnormalities on urinalyses.

International

IgA nephropathy is observed in up to 40% of all biopsies performed for glomerular disease in Asia, compared to 20% in Europe and 10% in North America. High prevalence rates are observed in Singapore, Japan, Australia, Hong Kong, Finland, and southern Europe, whereas low prevalence rates are the rule in the United Kingdom, Canada, and the United States.

In Asia, routine urinalyses are performed for schoolchildren, and renal biopsies are performed for patients with asymptomatic hematuria, thus raising the reported prevalence of the disease.

Mortality/Morbidity

This disorder is thought to follow a benign course in most cases. However, many patients are at risk for slow progression to ESRD, which develops in approximately 15% of patients by 10 years and 20% by 20 years, though these percentages depend on how the disease is defined.

Race

IgA nephropathy is more common in whites and Asians and is rare in blacks, both in the United States and in Africa. The condition is frequently observed in American Indians of the Zuni and Navajo tribes.

Sex

IgA nephropathy is more common in males than in females. Virtually all studies show a male predominance of at least 2:1, with reported ratios of up to 6:1. The higher male predilection is observed in white patients in northern Europe and the United States.

Age

IgA nephropathy can affect all ages but is most common in the second and third decades of life. Eighty percent of patients are aged 16-35 years at the time of diagnosis. The condition is uncommon in children younger than 10 years.

Previous
Proceed to Clinical Presentation
 
 
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.