Growth differentiation factor 15 is decreased by kidney transplantation

Background: Growth differentiation factor 15 (GDF15) is markedly increased in end-stage kidney disease and has been related to increased mortality in patients on dialysis. We hypothesized that kidney transplantation would decrease both GDF15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and that GDF-15 decrease relates to post-kidney transplantation allograft function. Methods: End-stage kidney disease patients on dialysis awaiting a living donor kidney transplantation (n = 39), and those expected to be on the deceased donor waitlist for at least 12 months (n = 43) were enrolled at three transplant centers. Serum GDF15 and NT-proBNP were measured at 0, 3, and 12 months post-kidney transplantation or post-enrollment. Change in serum GDF15 and NT-proBNP concentrations, and their relation to estimated glomerular filtration rate (eGFR) were assessed by non-parametric tests and regression analyses. Results: Median baseline GDF15 was 4744 pg/ml and 5451 pg/ml for the kidney transplantation and dialysis groups, respectively (p = 0.09). Kidney transplantation resulted in a significant decrease in GDF15 (month 12 median 1631 pg/ml, p < 0.0001 vs. baseline), whereas there was no change for the dialysis group (month 12 median 5658 pg/ml, p = 0.31). Post-kidney transplantation NT-proBNP highly correlated with GDF15 (rho = 0.64, p < 0.0001). GDF15 inversely correlated with post-transplant eGFR for the kidney transplantation group (rho = -0.42, p = 0.0081). Month 12 NT-proBNP explained 15.8% and 40.1% of the variance in month 12 GDF15 in the dialysis and kidney transplantation groups, respectively. The relationship of GDF15 with eGFR was no longer significant when NT-proBNP was included in the models. Conclusions: Kidney transplantation significantly decreases serum GDF15 concentrations. The post-kidney transplantation association of GDF15 with NT-proBNP is consistent with a gradient of post-kidney transplantation cardiovascular risk.