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The Evolving Role of Calcineurin Inhibitors in Treating Lupus Nephritis

Yonatan Peleg, Andrew S. Bomback and Jai Radhakrishnan
CJASN July 2020, 15 (7) 1066-1072; DOI: https://doi.org/10.2215/CJN.13761119
Yonatan Peleg
Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
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Andrew S. Bomback
Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
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Jai Radhakrishnan
Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
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Abstract

The overall kidney survival among lupus nephritis patients has improved with currently used induction immunosuppression regimens of corticosteroids and either cyclophosphamide or mycophenolate mofetil; however, there still remains a significant number of lupus nephritis patients who do not achieve remission with these regimens. Investigators have looked at other immunosuppressive regimens for lupus nephritis, and there has been interest in the use of calcineurin inhibitors in this regard. Calcineurin inhibitors are potentially an attractive option because of their established ability to inhibit T cell function, attenuate proteinuria through non-immunologic means, and their safety in pregnancy and lactation. In this review, we discuss the findings and limitations of selected trials that evaluated the use of calcineurin inhibitors in the treatment of lupus nephritis, either with corticosteroids alone or as a component of multitarget therapy when combined with mycophenolate mofetil. There may be a role for calcineurin inhibitors among patients with heavy proteinuria, as well as younger patients with refractory lupus nephritis. The multitarget therapy trials reveal higher rates of remission compared with mycophenolate mofetil alone and cyclophosphamide; however, some trials highlight the possibility of more infectious adverse events. We discuss the need for further study of calcineurin inhibitors in more diverse patient populations and the need for trials with longer follow-up with “hard” endpoints beyond proteinuria reduction, such as worsening CKD or repeat protocol biopsies, given the calcineurin inhibitors ability to reduce proteinuria non-immunologically and thus increased rate of relapse when the drug is tapered. While there may indeed be a space for calcineurin inhibitors to help increase remission rates in lupus nephritis patients, more work is needed to help address the questions the studies available to date have yet to answer.

  • Pregnancy
  • lupus nephritis
  • Calcineurin Inhibitors
  • Mycophenolic Acid
  • Follow-Up Studies
  • T-Lymphocytes
  • Cyclophosphamide
  • Immunosuppressive Agents
  • immunosuppression
  • proteinuria
  • Lactation
  • Adrenal Cortex Hormones
  • Recurrence
  • Biopsy
  • Infections
  • Renal Insufficiency
  • Chronic
  • Copyright © 2020 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 15 (7)
Clinical Journal of the American Society of Nephrology
Vol. 15, Issue 7
July 01, 2020
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The Evolving Role of Calcineurin Inhibitors in Treating Lupus Nephritis
Yonatan Peleg, Andrew S. Bomback, Jai Radhakrishnan
CJASN Jul 2020, 15 (7) 1066-1072; DOI: 10.2215/CJN.13761119

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The Evolving Role of Calcineurin Inhibitors in Treating Lupus Nephritis
Yonatan Peleg, Andrew S. Bomback, Jai Radhakrishnan
CJASN Jul 2020, 15 (7) 1066-1072; DOI: 10.2215/CJN.13761119
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  • Article
    • Abstract
    • Introduction
    • Rationale for Calcineurin Inhibition in Lupus Nephritis
    • Experience Using Calcineurin Inhibitor Therapy in Lupus Nephritis
    • The Future Landscape of Calcineurin Inhibitors in Lupus Nephritis
    • Safety Profile of Calcineurin Inhibitor Therapy in Lupus Nephritis
    • Limitations of Published Data on Calcineurin Inhibitors in Lupus Nephritis
    • Disclosures
    • Footnotes
    • References
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More in this TOC Section

  • Klotho in Clinical Nephrology
  • Decision Algorithm for Prescribing SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease
  • Cuffless Blood Pressure Monitoring
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Keywords

  • pregnancy
  • lupus nephritis
  • Calcineurin Inhibitors
  • Mycophenolic Acid
  • Follow-Up Studies
  • T-Lymphocytes
  • Cyclophosphamide
  • Immunosuppressive Agents
  • immunosuppression
  • proteinuria
  • Lactation
  • Adrenal Cortex Hormones
  • Recurrence
  • Biopsy
  • Infections
  • renal insufficiency
  • chronic

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