Steroid avoidance or withdrawal for kidney transplant recipients
Abstract
Background
Steroid‐sparing strategies have been attempted during the last two decades in order to avoid morbidity in kidney transplant recipients. Previous systematic reviews of steroid withdrawal after kidney transplantation have shown significant increases in acute rejection and an increase in graft failure rates. Steroid avoidance in kidney transplantation is increasingly attempted and the possible benefits or harms have never been a subject of a systematic review.
Objectives
To assess the safety and efficacy of steroid withdrawal or avoidance in patients receiving a kidney transplant.
Search methods
We searched CENTRAL, MEDLINE and EMBASE, references lists and abstracts from international transplantation society scientific meetings.
Selection criteria
Randomised controlled studies (RCTs) of steroid avoidance or withdrawal were included providing that one treatment arm consisted in steroid avoidance or withdrawal and intention‐to‐treat rates of acute rejection and graft failure were clearly established after steroid avoidance or use or withdrawal or continuation. Observational studies were tabulated.
Data collection and analysis
Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).
Main results
We included 30 RCTs (5949 participants). Steroid‐sparing strategies showed no effect on mortality or graft loss including death. Patients on any steroid‐sparing strategy showed a higher risk of graft loss excluding death than those with conventional steroid use (RR 1.23, 95% CI 1.00 to 1.52), especially in those not receiving MMF/Myf or everolimus (RR 1.70, 95% CI 1.00 to 2.90). Acute rejection was more frequent with a steroid‐sparing strategy (RR 1.27, 95% CI 1.14 to 1.40) and more frequent after steroid withdrawal or avoidance when compared with standard steroid treatment when cyclosporin (CsA) was used. Steroid‐sparing and withdrawal strategies showed benefits in reducing antihypertensive drug need, serum cholesterol, antihyperlipidaemic drug need, new‐onset diabetes after transplantation (NODAT) requiring any treatment and cataracts. Steroid avoidance did not alter serum cholesterol, but was associated with less frequent NODAT requiring any treatment. Cardiovascular events were reduced with steroid avoidance. Reduced antihypertensive drug need and serum cholesterol were similar with CsA or tacrolimus (TAC). Reduced antihyperlipidaemic drug need was only evident with TAC, whereas the reduction in NODAT requiring any treatment was only evident with CsA. Infection was lower in steroid‐sparing patients using CsA (RR 0.88, 95% CI 0.78 to 1.00). NODAT requiring any treatment was less frequent with steroid avoidance than with steroid withdrawal.
Authors' conclusions
This review confirms that steroid avoidance and steroid withdrawal strategies in kidney transplantation are not associated with increased mortality or graft loss despite an increase in acute rejection. These immunosuppression strategies may allow safe steroid avoidance or elimination a few days after kidney transplantation if antibody induction treatment is prescribed or after three to six months if such induction is not used.
PICOs
Plain language summary
Steroid avoidance or withdrawal for kidney transplant recipients
More than 20,000 kidney transplant procedures are performed world‐wide each year and transplantation is the treatment of choice for people with end‐stage kidney disease. However, despite short‐term results continuing to improve, long term results have only shown marginal improvement and death with a functioning graft and chronic kidney disease are the most common causes of graft loss. More than 95% of transplant recipients are treated with corticosteroids as a usual component of clinical immunosuppressive regimens. They are effective in reducing the incidence of acute rejection but are an important cause of morbidity and probably mortality. This review looked at two strategies ‐ steroid avoidance and steroid withdrawal ‐ to investigate their impact on short‐ and long‐term outcomes. Thirty studies were identified and evaluated in this review. Only one randomised study was identified in children. Steroid avoidance and steroid withdrawal strategies in kidney transplantation were not associated with increased mortality or graft loss despite an increase in acute rejection. These strategies could be used in adults in the first few days after transplantation when used in combination with antibody induction treatment or at a later time (three to six months post‐transplant) without antibody treatment. Studies in children need to be undertaken to determine if these results are applicable.
