Journal Mobile Options
Table of Contents
Vol. 35, No. 4, 2012
Issue release date: May 2012
Am J Nephrol 2012;35:312–320

Tacrolimus Improves the Proteinuria Remission in Patients with Refractory IgA Nephropathy

Zhang Q. · Shi S. · Zhu L. · Lv J. · Liu L. · Chen Y. · Zhang H. · Wang H.
Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, PR China

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated. Methods: 14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05–0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission. Results: Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered. Conclusions: Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Reich HN, Troyanov S, Scholey JW, et al: Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 2007;18:3177–3183.
  2. Li PK, Leung CB, Chow KM, et al: Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 2006;47:751–760.
  3. Barratt J, Feehally J: Treatment of IgA nephropathy. Kidney Int 2006;69:1934–1938.
  4. Lv J, Zhang H, Chen Y, et al: Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis 2009;53:26–32.
  5. 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 2009;24:3694–3701.
  6. Tang S, Leung JC, Chan LY, et al: Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy. Kidney Int 2005;68:802–812.
  7. Lai KN, Lai FM, Ho CP, et al: Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. Clin Nephrol 1986;26:174–180.
  8. Duncan N, Dhaygude A, Owen J, et al: Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol Dial Transplant 2004;19:3062–3067.
  9. Loeffler K, Gowrishankar M, Yiu V: Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome. Pediatr Nephrol 2004;19:281–287.
  10. Faul C, Donnelly M, Merscher-Gomez S, et al: The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008;14:931–938.
  11. Mathieson PW: Proteinuria and immunity – an overstated relationship? N Engl J Med 2008;359:2492–2494.
  12. Zheng CX, Chen ZH, Zeng CH, et al: Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro. Kidney Int 2008;74:596–612.
  13. Ma YC, Zuo L, Chen JH, et al: Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 2006;17:2937–2944.
  14. Naesens M, Kuypers DR, Sarwal M: Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4:481–508.
  15. Cattran DC, Coppo R, Cook HT, et al: The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 2009;76:534–545.
  16. Haas M: Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis 1997;29:829–842.
  17. Saleem MA, O’Hare MJ, Reiser J, et al: A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol 2002;13:630–638.
  18. Schweda F, Liebl R, Riegger GA, et al: Tacrolimus treatment for steroid- and cyclosporin-resistant minimal-change nephrotic syndrome. Nephrol Dial Transplant 1997;12:2433–2435.
  19. Li X, Li H, Ye H, et al: Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant nephrotic syndrome and normal or mildly reduced GFR. Am J Kidney Dis 2009;54:51–58.
  20. Roberti I, Vyas S: Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 2010;25:1117–1124.
  21. Shankland SJ: The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int 2006;69:2131–2147.
  22. Patrakka J, Tryggvason K: New insights into the role of podocytes in proteinuria. Nat Rev Nephrol 2009;5:463–468.
  23. Lemley KV, Lafayette RA, Safai M, et al: Podocytopenia and disease severity in IgA nephropathy. Kidney Int 2002;61:1475–1485.
  24. Hishiki T, Shirato I, Takahashi Y, et al: Podocyte injury predicts prognosis in patients with IgA nephropathy using a small amount of renal biopsy tissue. Kidney Blood Press Res 2001;24:99–104.
  25. Wang Y, Jarad G, Tripathi P, et al: Activation of NFAT signaling in podocytes causes glomerulosclerosis. J Am Soc Nephrol 2010;21:1657–1666.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50