Transplant Library

Revisiting maintenance immunosuppression in patients with renal transplant failure: early weaning of immunosuppression versus prolonged maintenance-systematic review and meta-analysis

J Nephrol. 2023 Mar;36(2):537-550 doi: 10.1007/s40620-022-01458-y.

Springer

Abstract

INTRODUCTION:

Prolonged immunosuppression after dialysis start has been assumed to reduce sensitization, need for graft nephrectomy, and to favor re-transplantation. In contrast, immunosuppression is considered to increase the risk of mortality, infection, and malignancy. We aimed to assess the evidence regarding superiority of early or late withdrawal of maintenance immunosuppression post renal transplant failure.

METHODS:

A literature search of the PubMed, WOS, Ovid, and Scopus databases was conducted. Combined relative risks, (RRs), mean differences, and 95% confidence intervals (CIs) were calculated by using a random-effect model.

RESULTS:

Ten studies involving 1187 patients with kidney transplant failure were included. No difference could be detected between patients with early withdrawal of immunosuppressive drugs (≤ 3 months) or prolonged immunosuppressive treatment (> 3 months) regarding mortality (95% CI 0.91-2.28), panel reactive antibodies (PRAs) (95% CI - 0.75-30.10), re-transplantation rate (95% CI 0.55-1.35), infectious episodes (95% CI 0.67, 1.17), cancer (95% CI 0.26-1.54), and graft nephrectomy (95% CI 0.82-1.63). Similarly, no difference was found between immunosuppressive drug withdrawal over < 6 or ≥ 6 months regarding mortality (95% CI 0.16, 2.89), re-transplantation rate (95% CI 0.85-1.55), cancer (95% CI 0.37-1.63), and allograft nephrectomy (95% CI 0.87-4.33).

CONCLUSION:

Prolonged maintenance immunosuppression post kidney transplant failure is not associated with increased risk of mortality, infection, or malignancy, or reduced risk of sensitization or allograft nephrectomy compared with early withdrawal.

CET Conclusion

Reviewer:	Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:	This systematic review and meta-analysis investigated the role of continued immunosuppression in the patient with a failed kidney transplant. The authors identified 10 studies including 1,187 patients. There was no difference in overall survival, sensitisation, malignancy, infection or retransplant rates between patients who withdrew immunosuppression early or remained on maintenance immunosuppression. Review methodology appears good, with independent reference screening and searches across multiple databases. The majority of studies were retrospective cohorts with a risk of selection bias. Many meta-analyses included only 2 or 3 studies, with quite wide confidence intervals around estimated effect sizes and some degree of heterogeneity. It is possible, therefore, that a true effect could have been missed due to selection bias or lack of power.

Reviewer:

Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford

Conclusion:

This systematic review and meta-analysis investigated the role of continued immunosuppression in the patient with a failed kidney transplant. The authors identified 10 studies including 1,187 patients. There was no difference in overall survival, sensitisation, malignancy, infection or retransplant rates between patients who withdrew immunosuppression early or remained on maintenance immunosuppression. Review methodology appears good, with independent reference screening and searches across multiple databases. The majority of studies were retrospective cohorts with a risk of selection bias. Many meta-analyses included only 2 or 3 studies, with quite wide confidence intervals around estimated effect sizes and some degree of heterogeneity. It is possible, therefore, that a true effect could have been missed due to selection bias or lack of power.

Study Details

Aims:	This study aimed to evaluate whether early or late withdrawal of maintenance immunosuppression in patients with kidney transplant failure is linked with better outcomes.
Interventions:	Electronic databases including PubMed, WOS, Ovid, and Scopus databases were searched. Titles and abstracts were screened for eligiblity by four independent reviewers. Data extraction was conducted by two independent reviewers. The Newcastle–Ottawa Scale was used to assess the methodological quality of the included studies.
Participants:	10 studies were included in the review.
Outcomes:	The outcomes of interest were incidence of infection, cancer, mortality (infection-related, malignancy-related, cardiovascular-related), transplant nephrectomy, re-transplantation, panel reactive antibody (PRA) and admission to hospital.
Follow Up:	N/A

Metadata

Funding:	Funding not described
Publication type:	Meta-Analysis, Review, Systematic Review
Organ:	Kidney
Language:	English
Author email:	m_gaafar1984@hotmail.com
MeSH terms:	Humans; Kidney Transplantation; Weaning; Immunosuppression Therapy; Immunosuppressive Agents; Immune Tolerance; Renal Insufficiency; Graft Rejection; 0 (Immunosuppressive Agents)