More than 85,000 individuals are on the kidney transplant waiting list, according to the United Network for Organ Sharing (UNOS). Living kidney transplantation confers a survival benefit as well as a cost savings to the Medicare system.1
Although strategies for increasing the deceased donor pool—such as the use of kidneys donated after cardiac death and kidneys from expanded criteria donors (ECDs)—have been modestly successful, they have still been unable to keep pace with the annual growth of eligible kidney transplant recipients. Therefore, the impetus for increasing sources of potential kidney donors has never been greater.
The first successful living kidney transplantation was performed between identical twins in Boston in 1954 by Joseph Murray. At that time, it was considered experimental and highly controversial to be doing a kidney transplant for end-stage renal disease (ESRD), let alone putting the life of another individual at risk by removing a kidney with no medical benefit to the donor. Fifty-six years later, living kidney donation happens at transplant centers across the nation on a daily basis for those at ESRD who are lucky enough to have a living donor willing to share the gift of life with them.
But what do we really know about the safety of living kidney donation? The short term risks of surgical complications, including mortality and morbidity, are well defined and so informing the potential donor about his risk of dying, developing a wound infection, bleeding, chronic pain, and so forth are fairly well established. However, when it comes to providing information about long-term risks to the living donor, this information is more nebulous. The dearth of safety data two, three, and four decades after kidney donation creates some uncertainty when obtaining informed consent from a young potential donor.
Perioperative Risk of Death
Perioperative risk is characterized as any death within a defined period of time after surgical donation of a kidney. Studies have defined this period anywhere from 30 days up to 90 days after donation. The risk of death due to donation has been reported from 0 per 1,000 2-3 donations up to 3.1 per 100,000 donations4. The study by Segev et al. was the largest study of donors to date and was therefore best powered to detect a difference in mortality as compared to most of the previous single-center studies.
The study also noted an increased risk in males, blacks, and those with hypertension. It is interesting to note that the mortality rate did not increase despite the increasing age of the donors over the study period. In general, this is considered an acceptable rate of surgical death. This mortality rate is similar to that seen with laparoscopic cholecystectomy but with one tremendous difference: the living kidney donor receives no medical benefit.
Long Term Risk of Death
Many single-center studies have found no increased risk of death in long-term living kidney donors, and some researchers have even suggested improved overall survival of kidney donors 3,5,6. But these studies have been hampered by small size, frequent patient loss to follow up, and lack of an adequate control group to adequately study this question. Standard mortality rates for the general population are often used as a control but these rates can potentially fail to adequately control for co-morbid diseases found in the general population. In one of the largest single-center studies of living donors, there did not appear to be an increased risk of death compared with the general population even up to 40 years after donation7. However, the number of donors studied beyond 20 years after donation is limited, so it is difficult to draw long-term conclusions. This lack of long-term data has further bolstered the call for a unified national donor registry in the United States.
The Risk of Hypertension
The risk of developing hypertension (HTN) after living kidney donation is a complex issue. First, there are often subtle differences in what each center defines as HTN. Some centers have defined HTN as a systolic BP greater than 130 mm Hg 6,8, whereas others have used a systolic BP greater than 140 mm Hg as their cut off.
Also, there is a high rate of donors who display white coat HTN at evaluation. Not surprisingly, the risk of developing HTN after living kidney donation has been evaluated in multiple studies with conflicting results. Saran and colleagues noted that up to 75% of their donors had developed HTN, which was significantly above the rate predicted by data from the National Health and Nutritional Examination Survey. However, the number of donors—47—was small 9.
It is well known that as a person ages the elasticity of the arteries decreases. This, combined with cardiovascular calcification, is felt to be at the root of age-related HTN. Whether there is an increased risk of HTN due to the decrease in renal mass following living kidney donation as suggested by Kasiske and colleagues remains unclear.10
This makes interpreting the normal age-related risk of HTN difficult to assess versus an increased risk due to living kidney donation. Gossmann et al. found an increase in systolic pressures 11 years after living kidney donation. It is interesting to note that none of the donors were hypertensive prior to donation, but 30% were taking antihypertensive medications 11 years after donation11. However, when comparing age-matched controls they noted that there was no significant difference in BP after living kidney donation. And when Williams, et al. compared BP in living donors versus non-donor siblings—thus controlling for genetic susceptibility, they found no increased risk of hypertension after kidney donation.12
However, in a meta-analysis of 5,145 living donors, Boudville et al., found a 5 mm Hg increase in BP five to 10 years after living kidney donation.13 The researchers noted that a higher risk for developing hypertension occurred in donors older than 60 years, donors with higher pre-donation BP, African-American donors, and those with low pre-donation glomerular filtration rate (GFR). This seems like a relatively small increase in BP but it should be kept in mind that a 10 mm Hg increase in systolic pressure and a 5 mm Hg increase in diastolic pressure translate into a 1.5 fold increase risk of death from myocardial infarction and ischemic stroke.14.
With the continued shortage of living donors, some centers have begun the practice of accepting certain donors who are hypertensive prior to kidney donation.15 Although short-term results demonstrate no adverse outcomes, it remains a group where long-term data are sorely needed.
Proteinuria, specifically albuminuria, is generally considered a marker of early renal disease. It often signals endothelial dysfunction within the glomerulus and is correlated with increased cardiovascular mortality risk.16 Whether this holds true for living kidney donors after donation is unclear. There is a suggestion that the proteinuria following living kidney donation may occur through a different mechanism than normally occurs in renal disease, suggesting the risk of developing progressive CKD is reduced.17
In either case, proteinuria has been noted as a long-term consequence of living kidney donation in 5%-56% of donors.3,6,9,11,12,18 In the study by Gossmann et al., there was a particularly high rate of proteinuria after living kidney donation (56%) but the number of patients with albuminuria was much lower. This suggests that their method for detecting proteinuria was extremely sensitive, leading to an unusually high rate of proteinuria after kidney donation.
Similar to studies assessing the risk of hypertension, most studies looking the proteinuria following living kidney donation were small single-center studies with many donors lost to follow up and relatively homogenous donor ethnicity, which limited the applicability of the findings to all populations. In a recent large study, Ibrahim et al. found that the risk of developing proteinuria increased with time after donation and in male donors.7
Their results demonstrated microalbuminuria in 11.5% of living donors; 1.2% had macroalbuminuria. A recent meta-analysis designed to assess the risk of proteinuria after living kidney donation determined the rate of proteinuria to be 12% at an average of seven years post donation.17 Therefore, it appears the true incidence is close to the findings of the two aforementioned studies.