Written by Milica Maksimovic
Reviewed by Charles Ferro
The first successful human organ transplant took place in 1954, when 23-year-old Ronald Herrick donated a kidney to his identical twin brother. Ronald eventually developed end-stage renal disease (ESRD) requiring haemodialysis and died at age 79 of cardiovascular disease . The critical questions whether donating a kidney causes or contributes to ESRD, cardiovascular disease or other complications known to be associated with chronic kidney disease (CKD) remain unanswered still today. A study of 430 Swedish donors followed up from 15 to 31 years reported no evidence of increased mortality due to renal diseases or of a decreased overall survival as compared to mortality data for Swedish general population . Similarly and even more reassuring, survival and the risk of ESRD in carefully screened 3698 kidney donors matched with NHANES controls on the basis of age, sex, race or ethnic group, and body-mass index, appeared to be comparable to those in the general population . Relying on these data Mark Paulson donated a kidney to a non-related member at the age of 18 . He went on to become a doctor and did a research project into the effects of kidney donation on mortality and renal survival. He was a bit horrified when he found a 2014 study showing a greater long-term risk of developing ESRD in kidney donors . Whereas in the previous studies the risk of ESRD in kidney donors has been compared with the risk faced by the general population, this study included a comparison to similarly screened healthy non-donors which presumably would be a better control group for comparison. Another study that same year raised the possibility that kidney donors may face a heightened risk of dying of cardiovascular disease and all-cause mortality as well, compared with a control group of non-donors who would have been eligible for donation .
Informed consent policy has changed since then, and it is nowadays a legal requirement in the US, at least, to inform potential donors that although the risk to develop ESRD does not exceed that of the general population with the same demographic profile, it can, however, exceed that of healthy non-donors with medical characteristics similar to living kidney donors. KDIGO Guidelines for the evaluation of living kidney donors include similar recommendations. Despite that the estimated absolute risk of developing ESRD is only 0.3% at 15 years, the relative risk to develop ESRD of living donors is 3.5 to 5.3 fold higher than of healthy persons in the absence of donation.
Association of living kidney donation with increased cardiovascular mortality
The mechanisms by which CKD exerts adverse effects on cardiovascular structure and function are diverse. Potential mediators include increased arterial stiffness, hypertension, increased left ventricular (LV) mass and abnormal bone mineral metabolism, which may increase vascular calcification.
The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR without the multiple confounding factors associated with renal disease. The ALTOLD , the CRIB-Donor  and the EARNEST  studies are prospective, longitudinal studies comparing living kidney donors with similarly healthy control on structural and functional cardiovascular effects.
The CRIB-Donor study showed that in donors as compared to controls, there were significant increases in LV mass, which had a graded independent association with the reduction in GFR after adjustment for demographic and hemodynamic factors . The data suggest that reduced GFR is an independent risk factor for adverse LV remodelling, independent of blood pressure. All the studies unequivocally show that kidney donation causes increases in weight, PTH, FGF23, uric acid, and tubular excretion of phosphate. With respect to the effects of kidney donation on peripheral blood pressure, the data are inconclusive. Uninephrectomy may be regarded as an “acute kidney injury,” with an immediate 50% reduction in GFR followed by a compensatory hypertrophy in the remaining kidney, possibly increasing the albuminuria.