Long-term health consequences of living kidney donation: From the perspective of donors

To the Editors, Kidney transplantation is the gold standard therapeutic modality for patients enduring end-stage renal disease (ESRD), especially from living kidney donors.[1] Living kidney donors establish the substantial part of available kidneys and drive kidney transplantation forward in this progressive economy.[2] However, the field of kidney transplantation confers enormous challenge to the transplantation team as it involves the interaction with the third-party, the deceased, or living organ donors. Regardless of the better substitute of dialysis for diseased population, the kidney transplantation is restrained by the paucity of available organs. Ironically, there is a huge mismatch between the number of renal failure cases and the number of kidneys available.[3] The role of living kidney donation in sustaining and improving lives of ESRD patients is indispensable. However, in the not-too-distant past, attention has been diverted toward the long-term safety of living kidney donation for donors. Unfortunately, the posttransplantation pathophysiologic sequelae of living kidney donation for donors are still under scrutiny. Lately, three published reports, which unearthed adverse consequences of living kidney donation among donors in contrast to non-donor population, have provoked a healthy discussion.[456] A research study by Muzaale et al followed 96,217 living kidney donors and 20,024 nondonors for ESRD outcome in US. The prognosticated likelihood of ESRD was calculated to be 30.8/10,000 patients postdonation and 3.9/10,000 patients in the nondonor population (P <0.001). Black donors were more vulnerable to develop ESRD. The estimated lifetime risk was significantly higher among living kidney donors than in general and nondonor healthy population.[4] Similarly, a longitudinal study in Norway by Mjøen et al compared the risk of developing kidney, cardiovascular diseases, and all-cause mortality in 1901 live kidney donors and 32,621 nondonors. The crude incidence of ESRD was 302 per million individual in live kidney donors, while 100 per million individual in population in general. The hazard ratios in this study were all-cause mortality (1.3), cardiovascular mortality (1.4), and ESRD (11.38) for living kidney donors. Interestingly, 80% of the living kidney donors were the first-degree relatives of the kidney transplant candidates. It was also reported that immunological causes (seven out of nine) account for most of the ESRD cases later in life among live kidney donors.[5] The findings presented in above two studies regarding risk of ESRD postkidney removal were quite similar, but the questions have been raised on the methodological design of the studies. Strikingly, the study estimates reflect relative risk instead of absolute risk which is of more clinical significance. Indeed, the absolute risk of ESRD was identified as fairly small in both the research studies (0.04% and 0.06%, respectively). A cohort study conducted by Garg et al in Canada retrospectively included 131 living kidney donor women and 788 healthy non-donor women. Frequency of gestational hypertension or preeclampsia was high among live donors compared to nondonors (11% vs. 5%, P = 0.01). No adverse consequences were reported among live donors with respect to maternal and neonatal outcomes.[6] O'Keeffe et al, likewise, recently published a meta-analysis, which reviewed 52 observational studies conducted over a period of last 50 years concluded that there is no relation between living kidney donation and elevated risk of all-cause mortality and chronic diseases such as cardiovascular diseases, diabetes, and psychosocial issues in living kidney donors compared with nondonor population.[7] On the contrary, a longitudinal follow-up study conducted in Pakistan by Rizvi et al demonstrated new-onset ESRD in 0.6% of living kidney donors.[2] The statement that living kidney donation harbors a very small risk for adverse health consequences was also confirmed by Hamid et al; however, they also suggested that the risk can be substantially reduced by meticulously selecting the donor and by providing good surgical management.[8] The primary worrying aspect in living kidney donation is that kidney removal results in extra overload being shifted toward the remaining kidney. A study done on rat model to elaborate the significance of phenomenon revealed that kidney removal (5/6) resulted in glomerular hypertension and a series of events including albuminuria and focal segmental glomerulo-sclerosis, culminating in kidney failure.[9] A prospective research study argued that the disease progression model of rat does not fit to donor kidney removal and that the remaining kidney encounters the physiological hyper-filtration, i.e., an increase in glomerular filtration rate (GFR). Hyperfiltration ensues as a result of hypertrophy and hyperperfusion without glomerular hypertension.[10] These findings have also been attested by two prospective follow-up studies. GFR improved in donors, expectedly, and controls were found to have an age-driven downturn in kidney function.[1112] With literature regarding the adverse outcomes among living kidney donors and explanation of physiological adaptation in glome-rular dynamics after kidney removal, it is still not suffice to comprehend the scenario of long-term risk of ESRD. It can be presumed that in the presence of “de novo” kidney disease, reduced renal reserve after kidney removal will lead to ESRD.[13] It is, therefore, mandatory to recognize prospective donor candidates at high risk of developing kidney diseases postliving kidney donation to ascertain long-term ESRD risk. At the time of donation, such donor candidates may present with characteristics such as young age, old age, genetically related, near-normal GFR, obesity, and hypertension. Interestingly, increased risk is more prevalent among young age group donors in spite of normal workup. They are perhaps the most difficult age group to identify later life risks of kidney diseases.[14] It is also imperative to understand that some risk factors are modifiable with healthy lifestyle behaviors, regular medical screening for kidney function, and by prompt treatment for new-onset risk factors such as albuminuria or hypertension. Importantly, patients need to be educated to the fullest so that risk associated with post-donation could be neutralized. Taken together, it can be concluded that living kidney donation is a safe practice. However, there is an inevitable risk associated with living kidney donation, 1 in 200 (0.5%), which is far more less than the general population.[15] Potential living donors must be well-informed of such risks before proceeding to transplantation. Living kidney donors have similar or even better overall survival, good quality of life, and no increase in risk of ESRD in comparison with general population. Vigilant donor evaluation, selection, and rigorous follow-up should be the plan of action while embarking on living kidney donation to ensure appropriate health status and avoid future disease events for prospective donors post-transplantation. Conflict of interest None declared.

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