Key messages
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Steroids are commonly used after a kidney transplant to help prevent the body from rejecting the new kidney. However, they can cause side effects, such as weight gain, high blood sugar, and weaker bones. There are different options to reduce steroid use, but they need to be carefully weighed against the possible risk of kidney rejection (where the body's immune system attacks the transplanted kidney).
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We found that avoiding or withdrawing steroids in adult kidney transplant recipients may have little or no effect on death or how long the transplanted kidney continues to work. Avoiding steroids may increase the risk of kidney rejection, but withdrawing steroids later may have little or no effect on the risk of rejection.
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Avoiding steroids may reduce the risk of developing diabetes after transplantation. Avoiding or withdrawing steroids may have little or no effect on infection or heart-related complications.
What is the issue?
Kidney transplantation is usually the preferred treatment for people with kidney failure (when the kidneys stop working properly). Most people with a kidney transplant receive steroids as part of their treatment. Steroids help prevent rejection of the new kidney (where the body's immune system attacks the transplanted kidney) but can also cause side effects such as weight gain, high blood sugar, and weaker bones.
What did we want to find out?
We wanted to know the benefits and risks of reducing steroid use after kidney transplantation. In particular, we looked at two main strategies.
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Steroid avoidance, where steroids are used for less than 14 days after the transplant.
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Steroid withdrawal, where steroids are used for longer than 14 days but then stopped at some point afterwards.
What did we do?
We searched for studies that looked at the benefits and risks of avoiding or withdrawing steroids after kidney transplantation.
We compared and summarised the studies’ results and rated our confidence in the information based on factors such as study methods and sizes.
What did we find?
We reviewed 53 studies that involved 8317 kidney transplant recipients; three of these studies enrolled children. The number of participants randomised in these studies ranged from 21 to 560, and most studies were undertaken in Europe and the USA. These studies compared different ways to reduce steroid use.
In adult kidney transplant recipients, we found that avoiding or withdrawing steroids may have little or no effect on death or how long the transplanted kidney continues to work. Avoiding steroids may increase the risk of kidney rejection, but withdrawing steroids later may have little or no effect on the risk of rejection.
Avoiding steroids may reduce the risk of developing diabetes after transplantation.
Avoiding or withdrawing steroids may have little or no effect on infection or heart-related complications.
What are the limitations of the evidence?
We have very little to moderate confidence in the evidence because studies used different types of additional treatments, and most studies were published more than 10 years ago. Moreover, these strategies might only be appropriate for some kidney transplant recipients, particularly those at low risk of kidney rejection. Also, most studies included adults with a kidney transplant. We have very little confidence in the results found for children. Decisions regarding steroid use should be made in discussions between the patient and their transplant doctor, taking into account the risk of rejection and other health conditions.
How up to date is this review?
The review is current to April 2025.
Read the full abstract
Steroid-sparing strategies have been attempted in recent decades to avoid morbidity from long-term steroid intake among kidney transplant recipients. Previous systematic reviews of steroid withdrawal after kidney transplantation have shown a significant increase in acute rejection. There are various protocols to withdraw steroids after kidney transplantation and their possible benefits or harms are subject to systematic review. This is an update of a review first published in 2009.
Objectives
To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients.
Search strategy
We searched the Cochrane Kidney and Transplant Specialised Register, CENTRAL, MEDLINE, Embase and two trials registers up to 29 April 2025.
Selection criteria
All randomised and quasi-randomised controlled trials (RCTs) in which steroids were avoided or withdrawn at any time point after kidney transplantation were included.
Data collection and analysis
Assessment of risk of bias and data extraction was performed by two authors independently and disagreement resolved by discussion. Statistical analyses were performed using the random-effects model and dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals.
Main results
We included 48 studies (224 reports) that involved 7803 randomised participants. Of these, three studies were conducted in children (346 participants). The 2009 review included 30 studies (94 reports, 5949 participants). Risk of bias was assessed as low for sequence generation in 19 studies and allocation concealment in 14 studies. Incomplete outcome data were adequately addressed in 22 studies and 37 were free of selective reporting.
The 48 included studies evaluated three different comparisons: steroid avoidance or withdrawal compared with steroid maintenance, and steroid avoidance compared with steroid withdrawal. For the adult studies there was no significant difference in patient mortality either in studies comparing steroid withdrawal versus steroid maintenance (10 studies, 1913 participants, death at one year post transplantation: RR 0.68, 95% CI 0.36 to 1.30) or in studies comparing steroid avoidance versus steroid maintenance (10 studies, 1462 participants, death at one year after transplantation: RR 0.96, 95% CI 0.52 to 1.80). Similarly no significant difference in graft loss was found comparing steroid withdrawal versus steroid maintenance (8 studies, 1817 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.17, 95% CI 0.72 to 1.92) and comparing steroid avoidance versus steroid maintenance (7 studies, 1211 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.09, 95% CI 0.64 to 1.86). The risk of acute rejection significantly increased in patients treated with steroids for less than 14 days after transplantation (7 studies, 835 participants: RR 1.58, 95% CI 1.08 to 2.30) and in patients who were withdrawn from steroids at a later time point after transplantation (10 studies, 1913 participants, RR 1.77, 95% CI 1.20 to 2.61). There was no evidence to suggest a difference in harmful events, such as infection and malignancy, in adult kidney transplant recipients. The effect of steroid withdrawal in children is unclear.
Authors' conclusions
There was no evidence to suggest a difference in patient death or graft loss up to one year after transplantation with steroid avoidance or withdrawal compared to maintenance, but steroid avoidance may reduce patient death at five years in adult kidney transplant recipients. Steroid avoidance may increase the risk of biopsy-proven acute rejection, but the risk may be similar when steroid avoidance is paired with tacrolimus, antimetabolite and induction therapy. The risk of biopsy-proven acute rejection in steroid withdrawal regimens may be similar to steroid maintenance regimens. We found no evidence to suggest differences in cardiovascular events or infection, but steroid avoidance compared to steroid maintenance may reduce the risk of post-transplant diabetes mellitus.
Funding
LO is supported by a Río Hortega predoctoral fellowship from the Instituto de Salud Carlos III.
Registration
Protocol and previous versions available via https://doi.org/10.1002/14651858.CD005632, https://doi.org/10.1002/14651858.CD005632.pub2, and https://doi.org/10.1002/14651858.CD005632.pub3.
