*Purpose: Recently, proton pump inhibitor (PPI) intake has been linked to acute kidney injury and chronic kidney disease. In the setting of renal transplantation, it was hypothesized that PPI have a clinically relevant drug interaction with mycophenolate mofetil, potentially leading to rejection. However, current data is inconsistent and the causal pathways are still unknown. Objective of this study was to assess the effect of PPIs on renal function and rejection rate in kidney transplant patients.

*Methods: We performed a single center, explorative, retrospective analysis of 474 patients who received a kidney transplant between May 2010 and July 2015. Mean follow-up time was 3.4 years. PPI prescription was assessed in half-year intervals. Primary outcome parameters were eGFR, change in eGFR (ΔeGFR), 30% and 50% eGFR decrease for different time periods (two to five years). Secondary outcome parameters were: delayed graft function (DGF), first and second year biopsy proven acute rejections (BPAR), patient and graft survival. Where statistically feasible, tests were repeated on a subgroup of patients (N=228) with stable mycophenolate mofetil intake (MMF-subgroup).

*Results: ΔeGFR, 30% and 50% eGFR-decrease showed no association with PPI mean daily intake in our patient cohort (multivariable analysis). Noticeable, a negative correlation of 2- and 3-year eGFR-values (not ΔeGFR) with mean daily PPI intake was found. Further analysis, however, indicated that this was not an effect of PPI therapy but likely attributed to a worse transplant function since the time of transplantation in patients with longer, higher dose PPI therapy. In the entire cohort DGF was recorded in 86 (18.7%) patients and correlated with baseline PPI-dose (p=0.041). BPAR occurred in 122 patients in the first year and in 39 in the second year after transplantation but did not relate to mean PPI daily intake. This result remained consistent for the MMF-subgroup and further analysis of the different BPAR types. Lastly, neither patient nor graft survival showed any relevant association with our measures of PPI intake in multivariable Cox-regressions.

*Conclusions: Our findings indicate that prolonged PPI-intake has no relevant adverse effect on transplant function or outcome. They also highlight the need to examine changes in eGFR (ΔeGFR) rather than single eGFR measurements in similar studies, to avoid confounding. Polypharmacotherapy however, remains a problem in renal transplant recipients, and it is thus advisable to question necessity of PPI-prescriptions when clear indications are missing.

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