Is the Risk of Cardiovascular Disease Increased in Living Kidney Donors?

A Danish Population-Based Cohort Study

Philip Munch; Christian Fynbo Christiansen; Henrik Birn; Christian Erikstrup; Mette Nørgaard


American Journal of Transplantation. 2021;21(5):1857-1865. 

In This Article

Abstract and Introduction


Reduced renal function is associated with cardiovascular disease (CVD); however, how living donor nephrectomy affects the risk of CVD remains controversial. We conducted a nationwide cohort study including living kidney donors in Denmark from 1996 to 2018 to assess the risk of hypertension, atrial fibrillation/flutter (AF), major adverse cardiovascular events (MACE; composite of myocardial infarction, ischemic stroke, and death) and death after living kidney donation. As comparisons we identified: a cohort of healthy individuals from the general population and an external blood donor cohort. We followed kidney donors (1,103 when compared with the general population cohort; 1,007 when compared with blood donors) for a median of 8 years. Kidney donors had an increased risk of initiating treatment for hypertension when compared with blood donors (standardized incidence ratio [SIR], 1.40; 95% confidence interval [CI], 1.17–1.66) but they did not have increased risk of MACE neither when compared with the general population cohort (hazard ratio, 0.68; 95% CI, 0.52–0.89) nor with blood donors (SIR, 1.17; 95% CI, 0.88–1.55). Neither did they have increased risks of AF and death. Thus, living kidney donation may be associated with increased risk of hypertension; however, we did not identify increased risks of CVD or death.


Kidney transplantation is considered the best treatment for most patients with end-stage renal disease because it is associated with decreased mortality and morbidity compared with chronic dialysis.[1] Transplantation from a living donor is associated with shorter waiting time and longer graft survival compared with deceased donor transplantation;[2] however, it also involves potential increased risks for the otherwise healthy donor associated with the surgery and long-term consequences of removal of a kidney. Although the remaining kidney to some extent compensates for the loss of nephron mass by hyperfiltration, a nephrectomy in living kidney donors will lead to a reduction in glomerular filtration rate (GFR)[3] and possibly an elevated risk of increased urinary protein excretion.[3,4] In the general population, reduced GFR and proteinuria are associated with cardiovascular disease (CVD),[5,6] but it remains controversial if reduced renal function increases the risk of CVD in otherwise healthy kidney donors.[7–14] A majority of studies have not identified an increased risk of CVD among kidney donors,[8–13] however, a single study with a median follow-up of 15 years showed a 40% increased cardiovascular mortality in kidney donors when compared with a cohort of self-proclaimed healthy individuals.[14] Also, while chronic kidney disease and reduced GFR is associated with an increased risk of atrial fibrillation or flutter (AF)[15,16] the effect of kidney donation on this risk has not been assessed. Furthermore, how living kidney donation affects the risk of hypertension is equivocal;[3] however, two recently published studies identified increased risks of hypertension after living kidney donation.[17,18] Kidney donors are carefully selected, inherently healthy and often also biological and/or socially related to patients with kidney disease and thus, identifying a relevant comparison group remains a major challenge in observational studies. Consequently, the results of such studies might be confounded by a greater baseline risk of CVD in the comparison cohort leading to an underestimation of the relative risk in kidney donors.

The aim of this study was to examine the risk of hypertension, AF, ischemic stroke, ischemic heart disease, and death after living kidney donation in Denmark. To address the problem of a relevant comparison cohort, we included two different comparison cohorts: an age- and sex-matched cohort of individuals from the general population and an age- and sex-standardized cohort of blood donors. Because of the similarities in the requirements for living kidney and blood donation, we a priori expected blood donors to be more comparable to the living kidney donors than previously used comparison cohorts.