Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
EDITORIAL
You have accessRestricted Access

Treating IgA Nephropathy

JOHN J. DILLON
JASN April 2001, 12 (4) 846-847; DOI: https://doi.org/10.1681/ASN.V124846
JOHN J. DILLON
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • View PDF
Loading

IgA nephropathy may be the most common type of glomerulonephritis, worldwide. Once thought benign, it causes end-stage renal disease in 15 to 20% of individuals within 10 yr of onset (1) and in 30 to 35% of individuals within 20 yr of onset. Proteinuria, an elevated serum creatinine concentration, and hypertension predict progression (1) as does a renal biopsy demonstrating focal proliferative glomerulonephritis with crescents, diffuse proliferative glomerulonephritis, or advanced, chronic disease (2). Despite having knowledge of these markers, predicting the course of the disease in individuals is difficult.

The chronic nature of IgA nephropathy and the possibility of a good outcome without therapy suggest that treatments should be relatively nontoxic. One nontoxic treatment is fish oil (omega-3 fatty acids), which may have an anti-inflammatory effect. Donadio et al. (3) have championed fish oil since publishing a 2-yr, 106-patient, randomized, placebo-controlled trial in 1994. The results were striking. Fish oil reduced the risk of the primary outcome—a 50% increase in serum creatinine concentrations—by 82%. It reduced the risk of death or end-stage renal disease by 67%. Creatinine clearances fell only 0.3 ml/min per 1.73 m2/yr among fish oil-treated patients versus 7.1 ml/min per 1.73 m2/yr among placebo-treated patients. No patient discontinued fish oil because of side effects. These benefits persisted after 6.4 yr of follow-up (4).

In this issue, Donadio, et al. report the results of a trial in which they randomized patients with severe IgA nephropathy to two doses of omega-3 fatty acids, one approximately equal to and one approximately double the dose used in the 1994 study. The outcomes were similar in both groups, and the authors recommend treating high-risk patients with the lower dose.

Questions remain about fish oil. Two smaller, randomized trials of fish oil for IgA nephropathy failed to demonstrated a benefit (5,6). The duration of one (5) was only 6 mo, perhaps too short. The duration of the other (6) was, like the 1994 Donadio trial, 2 yr. Using meta-analysis, I calculated that there was only a 75% probability that fish oil was beneficial (7). A dose-response effect, in the trial by Donadio et al. in this issue, would have provided strong evidence favoring fish oil; the lack of one, at least over the range studied, is weak evidence against it. Finally, neither the 1994 Donadio trial nor the trial in this issue demonstrated a significant reduction in proteinuria. Proteinuria is a key therapeutic target because it may, itself, cause renal injury (8) and because its reduction correlates with preservation of renal function (9).

What of other therapies? Proteinuria fell 21 to 61% in three short-term trials of angiotensin-converting enzyme (ACE) inhibitors in IgA nephropathy (10,11,12). Cattran et al. (13), studying IgA nephropathy patients with at least 1 g/d urinary protein retrospectively, found that creatinine clearances fell 4.8 ml/min per yr among ACE inhibitor—treated patients versus 12 ml/min per yr among similar patients who were treated with other antihypertensive medications. We do not have prospective, randomized, controlled data demonstrating that the ACE inhibitors preserve GFR in this disease. However, the REIN trial, in which the GFR fell 4.4 ml/min per 1.73 m2/yr among ramipril-treated patients versus 6.1 ml/min per 1.73 m2/yr among patients who were treated with other antihypertensive medications, provided such evidence for chronic, proteinuric nephropathies, in general (14). The benefit increased with increasing pretreatment proteinuria; patients who excreted less than 2 g/d urinary protein did not benefit. Greater reductions in proteinuria after 3 mo of therapy led to greater long-term preservation of GFR.

The ACE inhibitors, although effective, may not accomplish enough among high-risk patients. The proteinuria reduction is modest, and patients who lose GFR at 4.4 or 4.8 ml/min eventually will develop end-stage renal disease. Adding an angiotensin receptor antagonist is one possibly effective strategy. The angiotensin receptor antagonists and ACE inhibitors have reduced proteinuria equally (11,12), but the combination has been additive, reducing proteinuria 73% (11). We do not know whether this combination preserves GFR more effectively than ACE inhibitors alone. Adding a hepatic 3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor is another possibly effective strategy. In a small, randomized trial, 6 mo of fluvastatin decreased proteinuria 41% among patients with IgA nephropathy (15). There was no effect on GFR, and the long-term effects on GFR are not known.

The ACE inhibitors do not attack the inflammatory component of this disease. Potent anti-inflammatory and immunosuppressive therapy with corticosteroids is effective for IgA nephropathy. Pozzi et al. (16) conducted the largest trial, randomizing 86 IgA nephropathy patients to corticosteroids (intravenous methylprednisolone 1 g/d for 3 d at the beginning of months 1, 3, and 5, plus oral prednisone 0.5 mg/kg on alternate days for 6 mo) or supportive therapy. Proteinuria fell 50% at 6 mo and 65% at 1 yr among treated patients. With 5 yr of follow-up, corticosteroid therapy reduced the risk of a 50% increase in the serum creatinine concentration by 36%. GFR data were not provided. The authors observed no major side effects. Two smaller, randomized trials demonstrated similar reductions in proteinuria from corticosteroids (17,18). Neither demonstrated an effect on GFR, but Shoji et al. (18) observed significant improvements in renal histology after 1 yr of corticosteroid therapy. Relapses after steroid therapy and steroid dependence have been described (17). Whether the benefits outweigh the toxicities over the entire course of the disease is not known.

How should we treat our patients? Compelling evidence favors the ACE inhibitors. Patients with hypertension or with more than 1 to 2 g/d urinary protein, with or without hypertension, should receive them. Individuals who are intolerant of the ACE inhibitors probably should be treated with an angiotensin receptor antagonist. High-risk patients or those in whom ACE inhibitor therapy fails to reduce proteinuria to less than 1 to 2 g/d may require additional therapy. Individuals with inflammatory biopsy findings (especially crescentic or diffuse proliferative glomerulonephritis) may benefit from anti-inflammatory therapy with corticosteroids or, possibly, fish oil. Individuals with heavy proteinuria may benefit from corticosteroids, an angiotensin receptor antagonist, or an HMG-CoA reductase inhibitor. We do not know which of these approaches is most effective.

A placebo-controlled, randomized trial with fish oil and corticosteroid arms is under way and has completed enrollment (19). Other immunosuppressive strategies could be more effective or less toxic than corticosteroids. A trial comparing corticosteroids plus azathioprine with corticosteroids alone is in progress (20). Combining antiproteinuric and anti-inflammatory therapies is attractive theoretically and worthy of additional study. Likewise, the HMG-CoA reductase inhibitors are worthy of additional study in this and other glomerular diseases.

  • © 2001 American Society of Nephrology

References

  1. ↵
    D'Amico G: Natural history of idiopathic IgA nephropathy: Role of clinical and histological prognostic factors. Am J Kidney Dis 36: 227-237,2000
    OpenUrlCrossRefPubMed
  2. ↵
    Haas M: Histologic subclassification of IgA nephropathy: A clinicopathologic study of 244 cases. Am J Kidney Dis29 : 829-842,1997
    OpenUrlCrossRefPubMed
  3. ↵
    Donadio JV Jr, Bergstralh EJ, Offord KP, Spencer DC, Holley KE: A controlled trial of fish oil in IgA nephropathy. N Engl J Med 331:1194 -1199, 1994
    OpenUrlCrossRefPubMed
  4. ↵
    Donadio JV Jr, Grande JP, Bergstralh EJ, Dart RA, Larson TS, Spencer DC: The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. J Am Soc Nephrol 10:1772 -1777, 1999
    OpenUrlAbstract/FREE Full Text
  5. ↵
    Pettersson EE, Rekola S, Berglund L, Sundqvist KG, Angelin B, Diczfalusy U, Bjorkhem I, Bergstrom J: Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: A prospective, double-blind, randomized study. Clin Nephrol 41:183 -190, 1994
    OpenUrlPubMed
  6. ↵
    Bennett WM, Walker RG, Kincaid-Smith P: Treatment of IgA nephropathy with eicosapentanoic acid (EPA): A two-year prospective trial. Clin Nephrol 31:128 -131, 1989
    OpenUrlPubMed
  7. ↵
    Dillon JJ: Fish oil therapy for IgA nephropathy: Efficacy and interstudy variability. J Am Soc Nephrol8 : 1739-1744,1997
    OpenUrlAbstract/FREE Full Text
  8. ↵
    Perna A, Remuzzi G: Abnormal permeability to proteins and glomerular lesion: A meta-analysis of experimental and human studies. Am J Kidney Dis 27:34 -41, 1996
    OpenUrlCrossRefPubMed
  9. ↵
    The GISEN Group: Randomized placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 349:1857 -1863, 1997
    OpenUrlCrossRefPubMed
  10. ↵
    Maschio G, Cagnoli L, Claroni F, Fusaroli M, Rugiu C, Sanna G, Sasdelli M, Zuccala A, Zucchelli P: ACE inhibition reduce proteinuria in normotensive patients with IgA nephropathy: A multicentre, randomized, placebo-controlled study. Nephrol Dial Transplant9 : 265-269,1994
    OpenUrlPubMed
  11. ↵
    Russo D, Pisani A, Balletta MM, De Nicola L, Savino FA, Andreucci M, Minutolo R: Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis 33:851 -856, 1999
    OpenUrlPubMed
  12. ↵
    Perico N, Remuzzi A, Sangalli F, Azzollini N, Mister M, Ruggenenti P, Remuzzi G: The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indomethacin. J Am Soc Nephrol 9:2308 -2317, 1998
    OpenUrlAbstract/FREE Full Text
  13. ↵
    Cattran DC, Greenwood C, Ritchie S: Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin a nephropathy: A comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy. Am J Kidney Dis 23:247 -254, 1994
    OpenUrlPubMed
  14. ↵
    Ruggenenti P, Perna A, Gherardi G, Benini R, Remuzzi G: Chronic proteinuric nephropathies: Outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury. Am J Kidney Dis 35:1155 -1165, 2000
    OpenUrlCrossRefPubMed
  15. ↵
    Buemi M, Allegra A, Corica F, Aloisi C, Giacobbe M, Pettinato G, Corsonello A, Senatore M, Frisina N: Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy. Clin Pharmacol Ther 67: 427-431,2000
    OpenUrlCrossRefPubMed
  16. ↵
    Pozzi C, Bolasco PG, Fogazzi GB, Andrulli S, Altieri P, Ponticelli C, Locatelli F: Corticosteroids in IgA nephropathy: A randomized controlled trial. Lancet 353:883 -887, 1999
    OpenUrlCrossRefPubMed
  17. ↵
    Lai KN, Lai FM, Ho CP, Chan Kw: Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: A long-term controlled trial. Clin Nephrol 26:174 -180, 1986
    OpenUrlPubMed
  18. ↵
    Shoji T, Nakanishi I, Suzuki A, Hayashi T, Togawa M, Okada N, Imai E, Hori M, Tsubakihara Y: Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis 35: 194-201,2000
    OpenUrlCrossRefPubMed
  19. ↵
    Hogg RJ: A randomized, placebo-controlled, multicenter trial evaluating alternate-day prednisone and fish oil supplements in young patients with immunoglobulin A nephropathy. Scientific Planning Committee of the IgA Nephropathy Study. Am J Kidney Dis26 : 792-796,1995
    OpenUrlPubMed
  20. ↵
    Locatelli F, Pozzi C, Del Vecchio L, Andrulli S, Pani A, Fogazzi G, Altieri P, Ponticelli C: Combined treatment with steroids and azathioprine in IgA nephropathy: Design of a prospective randomised multicentre trial. J Nephrol 12:308 -311, 1999
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 12 (4)
Journal of the American Society of Nephrology
Vol. 12, Issue 4
1 Apr 2001
  • Table of Contents
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Treating IgA Nephropathy
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Treating IgA Nephropathy
JOHN J. DILLON
JASN Apr 2001, 12 (4) 846-847; DOI: 10.1681/ASN.V124846

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Treating IgA Nephropathy
JOHN J. DILLON
JASN Apr 2001, 12 (4) 846-847; DOI: 10.1681/ASN.V124846
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • References
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Molecular Characterization of Membranous Nephropathy: Quo Vadis?
  • More than a Marker: Arginase-1 in Kidney Repair
  • Further Evidence for the Mucosal Origin of Pathogenic IgA in IgA Nephropathy
Show more Editorial

Cited By...

  • Single Application of Low-Dose Mycophenolate Mofetil-OX7-Immunoliposomes Ameliorates Experimental Mesangial Proliferative Glomerulonephritis
  • IgACE: A Placebo-Controlled, Randomized Trial of Angiotensin-Converting Enzyme Inhibitors in Children and Young People with IgA Nephropathy and Moderate Proteinuria
  • Immunoliposome Targeting to Mesangial Cells: A Promising Strategy for Specific Drug Delivery to the Kidney
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe to ASN Journals

© 2022 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire