Systematic review and meta-analysis of the effect of calcineurin inhibitors on long-term prognosis in kidney transplant recipients

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Objective. Comparison of the long-term results of the use of cyclosporine (CsA) and tacrolimus (TL) in kidney transplant recipients (KTR), obtained in City Clinical Hospital № 52 of the Moscow Healthcare Department, with a systematic analysis of published studies on this topic.

Material and methods. In a 30-year (1989–2018) retrospective study conducted from 2007 to 2012, there were statistically significant differences in estimated glomerular filtration rate (eGFR, ml/min/1.73 m2) between the two KTR groups receiving CsA or TL respectively. Patients receiving TL were younger, more male, and had better survival (p<0.05). We performed a meta-analysis to compare the effects of CsA and TL on GFR and survival. The electronic PubMed, MEDLINE, Scopus and the Cochrane Library databases were searched for studies comparing maintenance immunosuppression options based on TL and CsA in the experimental and control groups, respectively, for at least a year after kidney allotransplantation. The primary outcome of the study was patient survival, the secondary outcome was renal graft function, determined by creatinine clearance (GFR, ml/min) according to the Rehberg test or the Cockcroft-Gault formula, or by eGFR in the CKD-EPI, MDRD, Nankivell equation. Meta-analysis of proportions was performed using the Freeman–Tukey transformation to calculate weighted summary proportions from a fixed and random effects model. Odds ratios (ORs) were used to assess dichotomous variables, and mean differences (MDs) and 95% confidence intervals (CIs) for both variables were used for continuous variables. Of the total 678 studies found, 16, including our own, were included in the systematic review and meta-analysis, with a total of 12,181 patients (treatment n=6504 and control n=5677 groups).

Results. The meta-analysis included 12 randomized and 4 non-randomized controlled trials. There were no differences between the two groups in age, sex, creatinine level, or patient survival. GFR was significantly higher for TL-based immunosuppressive regimens than for CsA in the fixed model (HR=0.451, 95% CI 0.39 to 0.5; p<0.001) and in the random model (HR=0.641, 95% CI from 0.286 to 0.996; p<0.001). Meta-analysis data on GFR were significantly heterogeneous: I2=96.96%, 95% CI 95.8 to 97.79, Q test; p < 0.0001, however, Begg's test (p=0.815) and Egger's test (p = 0.456) do not suggest the presence of publication bias in this case.

Conclusion. A meta-analysis showed that, compared with CsA, TL has an advantage only in its effect on GFR. Differences in baseline GFR determination and creatinine calibration may likely explain the heterogeneity of findings in this meta-analysis. These factors should be considered by researchers and clinicians when interpreting GFR estimates. In this regard, the use of a single eGFR for KTR is relevant.

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作者简介

Maria Novikova

Central State Medical Academy of the Administrative Department of the President of the Russian Federation, Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology; Endocrinological Dispensary of the Moscow Healthcare Department

编辑信件的主要联系方式.
Email: citrus7474@mail.ru

Cand.Sci. (Med.), Nephrologist, Associate Professor at the Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology, Central State Medical Academy of the Administrative Department of the President of the Russian Federation, Endocrinological Dispensary of the Moscow Healthcare Department

俄罗斯联邦, Moscow; Moscow

Larisa Minushkina

Central State Medical Academy of the Administrative Department of the President of the Russian Federation, Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology

Email: minushkina@mail.ru

Dr.Sci. (Med.), Professor at the Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology, Central State Medical Academy of the Administrative Department of the President of the Russian Federation

俄罗斯联邦, Moscow

Oleg Kotenko

City Clinical Hospital № 52 of the Moscow Healthcare Department; Pirogov Russian National Research Medical University

Email: olkotenko@yandex.ru

Cand.Sci. (Med.), Chief External Expert in Nephrology of the Moscow Healthcare Department, Head of the Scientific and Practical Center for Nephrology and Transplanted Kidney Pathology, City Clinical Hospital № 52 of the Moscow Healthcare Department, Associate Professor of the Department of General Therapy of the Pirogov Russian National Research Medical University, Moscow, Russia

俄罗斯联邦, Moscow; Moscow

Dmitry Zateyshchikov

Central State Medical Academy of the Administrative Department of the President of the Russian Federation, Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology; N.E. Bauman City Clinical Hospital №. 29 of the Moscow Healthcare Department

Email: dz@bk.ru

Dr.Sci. (Med.), Professor, Head of the Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology, Central State Medical Academy of the Administrative Department of the President of the Russian Federation, Head of the Primary Vascular Department of the N.E. Bauman City Clinical Hospital No. 29 of the Moscow Healthcare Department

俄罗斯联邦, Moscow; Moscow

Olga Boeva

Central State Medical Academy of the Administrative Department of the President of the Russian Federation, Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology

Email: citrus7474@mail.ru

Dr.Sci. (Med.), Professor at the Department of Therapy, Cardiology and Functional Diagnostics with a Course of Nephrology, entral State Medical Academy of the UDP of the Russian Federation

俄罗斯联邦, Moscow

Sona Allazova

Sechenov Uivercity, Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine named after. N.V. Sklifosovsky

Email: tallisasoto@rambler.ru

Postgraduate Student at the Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine named after. N.V. Sklifosovsky, Sechenov University

俄罗斯联邦, Moscow

Evgeniy Shilov

Sechenov Uivercity, Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine named after. N.V. Sklifosovsky

Email: emshilov@mma.ru

Dr.Sci. (Med.), Professor at the Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine named after. N.V. Sklifosovsky, Sechenov University

俄罗斯联邦, Moscow

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2. Fig. 1. Study selection flowchart

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3. Fig. 2. Comparison of the age of recipients in the TL and CsA groups

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4. Fig. 3. The funnel plot for age did not show a publication error

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5. Fig. 4. Comparison of the gender of recipients in the TL and CsA groups

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6. Fig. 5. The floor funnel plot did not show a publishing error.

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7. Fig. 6. Comparison of creatinine in the TL and CsA groups

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8. Fig. 7. Funnel plot for creatinine did not show publication bias

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9. Fig. 8. Comparison of GFR of recipients in the TL and CsA groups

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10. Fig. 9. The funnel plot for GFR did not show a publication error

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11. Fig. 10. Comparison of recipient survival in the TL and CsA groups

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12. Fig. 11. Survival funnel plot did not show publication bias

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