INTRODUCTION — The number of patients awaiting kidney transplantation has increased over time.
The increased use of organs from living donors is one strategy that addresses the need for transplants. However, despite the urgent need for living donors, 2018 marked the first substantial increase in living kidney donation in the United States after more than a decade of declining or stagnant living donor transplant rates [1], and growth was hampered during the COVID-19 pandemic. Uncertain risks or inadequate risk mitigation can pose one barrier to increasing opportunities for living donation [2,3].
Sex imbalances in rates of living donation are well described. In the United States, more than half of living donors are females, and disparities are higher when considered in terms of base population rate: 30 per million population (pmp) in females versus 19 pmp in males [4]. In one study, although donation declined in both males and females in lower income levels over the study period, the decline was larger among males and spanned all but the highest income levels [4], suggesting that concern for financial impact may affect donation rates.
Recipients of allografts from living donors receive a significant graft survival advantage over those who receive deceased-donor grafts. In addition, living-donor transplants may be performed with minimal delay and controlled scheduling, providing opportunity for pre-emptive transplantation (transplantation prior to dialysis) or transplantation early in a recipient's course of kidney failure. (See "Kidney transplantation in adults: Risk factors for graft failure" and "Kidney transplantation in adults: Dialysis issues prior to and after kidney transplantation".)
However, donor nephrectomy exposes the donor to risks associated with surgery. In addition, some studies have suggested that living kidney donation may confer small but measurable increases in the risks of hypertension, preeclampsia, gout, and end-stage kidney disease (ESKD).
In February 2013, the Organ Procurement and Transplantation Network (OPTN) implemented policy requirements for all living kidney donor recovery hospitals in the United States in order to promote consistency in the informed consent, medical and psychosocial evaluation, and follow-up of living donors [5]. In 2014, these requirements were incorporated within global policies for living donors. These policies define the minimum general and kidney-specific requirements for the evaluation and acceptance of living kidney donor candidates. These requirements are generally expanded upon at individual transplant programs, based on local experience or clinical practice guidelines [6], and may be tailored for individual donor characteristics.
The risks associated with living kidney donation are discussed in this topic review. The evaluation of a living kidney donor candidate, including the OPTN requirements, is discussed elsewhere (see "Kidney transplantation in adults: Evaluation of the living kidney donor candidate"). The evaluation of the kidney transplant recipient is discussed separately. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)
OVERVIEW — The complications from kidney donation can be divided into those arising immediately from the nephrectomy surgery and those that may emerge many years after the kidney was donated. There are also risks associated with the evaluation itself, chiefly including the risks of discovery (such as misattributed paternity, health conditions that could have implications for insurance, and reportable infections).
The Organ Procurement and Transplant Network (OPTN) policy defines minimum requirements for elements that must be discussed and documented in the informed consent of living donors [7].
Perioperative risks — The most important perioperative risks due to donor nephrectomy include the following:
●Hemorrhage
●Ileus
●Pneumothorax
●Pneumonia
●Urinary tract infection
●Wound complications including hernia
●Deep vein thrombosis with or without pulmonary embolism
●Death
Based on integration of national United States donor registry data from 2008 to 2012 with administrative records from a consortium of 98 academic hospitals, one study found that 16.8 percent of donors experienced a diagnosis or procedure for a perioperative complication, most commonly gastrointestinal (4.4 percent), bleeding (3 percent), respiratory (2.5 percent), and surgical/anesthesia-related injuries (2.4 percent) [8]. However, major complications affected only 2.5 percent of donors. After adjustment for demographic, clinical (including comorbidities), procedure, and center factors, compared with White donors, Black donors had a 26 percent increased risk of experiencing any complication and a 56 percent increased risk of experiencing major complications. Other significant correlates of major complications included obesity, predonation blood disorders, psychiatric conditions, and robotic nephrectomy, while greater annual hospital volume predicted lower risk.
Surgical mortality with living kidney donation is very low. In one study of over 80,000 living kidney donors, 90-day mortality was 3.1 per 10,000 donors, a rate that was unchanged over 15 years (1994 to 2009) [9].
To reduce the risk for perioperative thromboembolism, some centers require females to discontinue hormonal contraception or hormone replacement therapy four to six weeks prior to donor nephrectomy. Estrogen-containing intrauterine devices and vaginal rings should be removed six weeks prior to surgery since they also carry a risk of thromboembolism. Low-dose progesterone-only (<30 mcg of levonorgestrel) medications or intrauterine devices may be continued since available data do not support an increased risk for thrombosis with use of these agents.
Most living-donor nephrectomies are performed laparoscopically versus an open approach. Surgical approaches to living-donor nephrectomy are discussed in detail separately. (See "Kidney transplantation in adults: Benefits and complications of minimally invasive live-donor nephrectomy".)
Long-term risks
Mortality and cardiovascular disease — Studies suggest that, beyond the perioperative period, survival after living kidney donation is the same as for similar matched individuals who did not donate, at least over approximately 10 to 18 years [9-12], including one study of donors older than 55 years [13]. However, long-term follow-up data are limited [14]. As an example, in one long-term study of more than 80,000 living kidney donors, the risk of death over a median 6.3 years of follow-up (maximum 12 years) was the same for kidney donors and demographically matched, healthy National Health and Nutrition Examination Survey (NHANES) III participants screened for baseline good health, including among subgroups stratified by race [9].
In a study comparing 2028 living kidney donors in Ontario, Canada (1992 to 2009) with 20,280 healthy, demographically matched nondonors, the risk of death or major cardiovascular events over a median seven years follow-up (maximum 18 years) was lower in donors than in healthy nondonors (2.8 versus 4.1 events per 1000 person-years; hazard ratio [HR] 0.66, 95% CI 0.48-0.90) [15]. The risk of death-censored major cardiovascular events was similar among donors and nondonors (1.7 versus 2.0 events per 1000 person-years; HR 0.85, 95% CI 0.57-1.27).
One study with longer follow-up (a median follow-up of 15 years, maximum 25 years) compared cardiovascular and all-cause mortality in 1901 kidney donors with a control group of 32,621 healthy, matched controls selected from a population-based survey carried out in Norway between 1984 and 1987 (Nord-Trøndelag Health Study [HUNT] I) [16].
Mortality curves were similar for donors and nondonors over the first 15 years but subsequently diverged. At 25 years after donation, the cumulative all-cause mortality was approximately 18 percent among donors and 13 percent among healthy nondonors (adjusted HR [aHR] 1.3, 95% CI 1.1–1.5). However, the absolute mortality during the observation period was low in both groups: 224 deaths among 1901 donors and 2425 deaths among 32,621 controls (or 0.12 versus 0.074 percent, respectively).
Limited data are available on the effects of donation on cardiovascular pathophysiology. The Chronic Renal Impairment in Birmingham (CRIB)-Donor study prospectively examined changes in left ventricular (LV) mass and other cardiovascular disease surrogate markers among 124 donors at two United Kingdom centers (2011 to 2014) at 12 months postdonation [17].
Compared with healthy nondonors, donors had larger increases in LV mass (-3±8 versus +7±10 g, respectively) and LV mass/volume ratio (-0.01±0.09 versus +0.06±0.12 g/mL) but decreased aortic distensibility. Donors were also more likely than controls to develop detectable highly sensitive troponin T levels and microalbuminuria. The increase in LV mass among donors was independently associated with the magnitude of decrease in measured glomerular filtration rate (GFR). These observations warrant replication efforts in larger cohorts with longer follow-up to better define the impacts of donation on cardiovascular disease surrogates and clinical events.
End-stage kidney disease — When compared with well-matched, equally healthy controls, donor nephrectomy appears to increase the risk of end-stage kidney disease (ESKD), although the absolute risk is low [11,18,19]. Consistent with recommendations of a 2015 American Society of Transplantation (AST) consensus statement [20] and Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines [6], OPTN policy requires informing donor candidates that the risk of ESKD after donation may exceed that of healthy nondonors with medical characteristics similar to living kidney donors [6,20].
Although 50 percent of the functioning kidney mass is removed during donor nephrectomy, compensatory hypertrophy in the remaining normal kidney returns the GFR to approximately 70 percent of baseline at 10 to 14 days [21] and approximately 75 to 85 percent of baseline at long-term follow-up [22-25]. In the prospective Assessing Long-Term Outcomes in Living Kidney Donors (ALTOLD) study of 182 kidney donors (94.6 percent were White donors) and paired healthy nondonors, the GFR measured by iohexol clearance declined 0.36 mL/min per year in control individuals but increased 1.47 mL/min per year in donors between 6 and 36 months of follow-up [26,27]. The trajectory of change in GFR beyond 36 months postdonation requires characterization in larger, demographically diverse samples. In the general population, GFR declines with age, although the rate of decline appears widely variable across individuals [28].
Studies that have looked at this issue include the following:
●In one study, 1901 kidney donors were compared with 32,621 healthy, demographically matched controls from a population-based survey carried out in Norway between 1984 and 1987 (HUNT I) [16]. Compared with controls, the risk of ESKD was higher among donors (with HR adjusted for age, sex, systolic blood pressure, smoking, and body mass index [BMI] of 11.4, 95% CI 4.4-29.6). Among 1901 donors, 9 (0.47 percent) developed ESKD compared with 22 of 32,621 (0.07 percent) control individuals. The crude incidence of ESKD after donation was 302 per million person-years, whereas the estimated incidence of ESKD in the general population in Norway is 100 per million person-years. The median time to ESKD among donors was 18.7 years.
ESKD among the Norwegian donors was mostly due to immunologic diseases including glomerulonephritis (three), systemic lupus erythematosus (one), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (two), sarcoidosis (one), and diabetes/nephrosclerosis (two). Thus, it is possible that the increase in risk of ESKD was related to genetically determined immunologic factors rather than the nephrectomy itself [29]. As 84 percent of the study sample were biologically related and related donors contributed the longest observation time due to temporal patterns of donor acceptance, associations of family history with renal outcomes within the donor population remain uncertain and warrant continued study [30].
●A United States registry study compared 96,217 donors with healthy participants in NHANES III [19]. Among 20,024 NHANES participants, 9364 had no identified contraindications to kidney donation (based upon patient self-report, physical examination, and radiologic and laboratory evaluation at NHANES enrollment) and were demographically matched 1:1 to donors with replacement, such that individual NHANES participants served as controls for multiple kidney donors. Sixty-eight percent of donors were biologically related to recipients.
ESKD developed in 99 donors a mean of 8.6 years after donation. ESKD developed in 36 matched nondonors (drawn from 17 events among the unmatched nondonor cohort). Among donors who developed ESKD, 83 were biologically related to the recipient.
The estimated cumulative incidence of ESKD at 15 years was 30.8 per 10,000 in donors compared with 3.9 per 10,000 in matched donors (absolute risk increase 26.9 per 10,000). Estimated lifetime ESKD risk based on splicing observations for donors observed at different ages was 90 per 10,000 among donors compared with 14 per 10,000 among healthy nondonors. ESKD risk was highest in the demographically matched, unscreened general population, at 326 per 10,000.
The absolute risk of ESKD per 10,000 patients was 74.7, 32.6, and 22.7 among Black donors, Hispanic donors, and White donors compared with 23.9, 6.7, and 0.0 for Black nondonors, Hispanic nondonors, and White nondonors, respectively.
The risk of ESKD may have been underestimated in the nondonor controls for a variety of reasons [31]. As noted above, the design of the study allowed individual controls to be matched to multiple donors, which may have resulted in the repeated inclusion of long, event-free survival times. In addition, donors may have had a lower competing risk of death for a given comparable decline in kidney function. Finally, whereas donors were identified as having ESKD by virtue of a requirement for dialysis, by transplantation, or by activation to the deceased-donor transplant list, ESKD in controls was identified by requirement for dialysis or elective transplantation. Since the kidney allocation policy prioritizes living donors who develop ESKD and since donors are generally closely scrutinized for decline in kidney function, it is possible that donors were transplanted earlier (ie, at a higher estimated GFR [eGFR]) compared with controls.
●A meta-analysis of three studies, including the two cited above, plus one matched cohort study that compared the risk of acute dialysis among donors versus nondonors [32], showed that kidney donation was associated with a relative risk for ESKD of 8.83 compared with nondonors (95% CI 1.02-20.93) [11]. The absolute risk of ESKD among donors was low with an incident rate of 0.5 cases of ESKD per 1000 person-years. Another systematic review also concluded that moderate-grade evidence reveals an association between living kidney donation and greater risk of ESKD [33].
A number of studies support that the risk of ESKD after kidney donation does not exceed the risk in the general population [21-25,34]. An analysis of living kidney donors in the United States between 1994 and 2003 demonstrated a rate of ESKD among living donors of 0.134 per 1000 years over an average follow-up period of 9.8 years [34], which was not higher than that of the general population.
To improve the evaluation and selection of living donor candidates, a KDIGO work group formulating guidelines for the "Evaluation and Care of Living Kidney Donors" collaborated with the Chronic Kidney Disease-Prognosis Consortium (CKD-PC) to conduct a meta-analysis combined with an analysis of the incidence of ESKD in a low-risk segment of the United States population to produce a comprehensive risk-prediction model for ESKD in the absence of donation based on data for nearly five million healthy persons [35]. For a 40-year-old person with health characteristics similar to those of age-matched donors, 15-year projected ESKD risk in the absence of donation varied according to race and sex: 0.24 percent among Black males, 0.15 percent among Black females, 0.06 percent among White males, and 0.04 percent among White females. Estimated ESKD risk was higher in the presence of a lower eGFR, higher albuminuria, hypertension, current or former smoking, diabetes, and obesity. Projected lifetime ESKD was highest among young adults, especially among young African Americans. The observed incidence of ESKD at 15 years among United States kidney donors was 3.5 to 5.3 times the projected risks for healthy persons in the absence of donation by sex and race.
An online risk tool was developed to project ESKD risk (in the absence of donation) for donor candidates based on simultaneous consideration of baseline demographic and clinical factors. Further research is needed to quantify the impact of donation itself on lifetime risk according to baseline characteristics, to validate the results, and to extend the models to non-US populations and other racial groups.
The impact of some ESKD risk factors may differ in donors compared with nondonors. A retrospective study of 119,769 United States donors found a stronger impact of obesity than reported in the healthy person projection tool, such that each unit increase in BMI among overweight and obese donors increased the risk of ESKD by 7 percent [36]. Another study identified associations of higher BMI at donation with graded increases in the incidence of need for diabetes mellitus medication after donation [37], a possible mediator of postdonation ESKD risk. Future work should seek to develop tools for tailored ESKD risk prediction in both the presence and absence of donation [38].
In the United States, prior living donors receive additional priority points for deceased-donor kidney transplants, which has been associated with higher transplant rates, shorter time to transplant, and receipt of higher-quality allografts compared with candidates with otherwise similar clinical profiles [39-44]. Priority for prior living donors can also be incorporated in kidney-paired donation programs.
Hypertension — A study of 3700 predominantly (95 percent) White donors (mean follow-up 16.6 years) found that hypertension developed in 4, 10, and 51 percent at 5, 10, and 40 years, respectively, and was associated with complications at last follow-up including proteinuria; eGFR <30, 45, and 60 mL/min/1.73 m2; cardiovascular disease; and death [45].
The risk of hypertension may be increased among kidney donors compared with healthy nondonors:
●The attributable risk of increased blood pressure over time, after kidney donation, was evaluated in a meta-analysis of 48 studies that enrolled 5149 donors, with only six reports being controlled [46]. Analysis of the controlled studies with at least five-year follow-up found that, compared with control participants, systolic and diastolic pressures were 6 and 4 mmHg higher in kidney donors, respectively.
●In a prospective study that was published after the meta-analysis, at three years after nephrectomy, there was no difference in blood pressure determined by 24-hour monitoring between 182 kidney donors (94.6 percent were White donors) and paired control individuals [26]. By contrast, an administrative claims linkage study of 1278 living donors in Ontario, Canada followed for a mean of six years (range 1 to 16 years) found a higher incidence of hypertension diagnoses among living donors compared with healthy controls (16.3 versus 11.9 percent, respectively) [47].
●A small study of 103 African-American donors found higher rates of hypertension at an average of 6.4 years postdonation compared with healthy matched African Americans selected from the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study (40.8 versus 17.9 percent, respectively) [48].
●A retrospective analysis of 1295 living kidney donors with a median of six years of follow-up reported a 19 percent higher risk of hypertension in donors compared with healthy nondonors drawn from two national cohort studies (adjusted HR 1.19, 95% CI 1.01-1.41); this association did not vary by race [49].
Further study is needed to quantify the impact of living kidney donation on hypertension risk, the impact of hypertension on clinical outcomes such as ESKD after donation, and the possible variation in the risk and consequences of hypertension according to race.
Maternal and fetal outcomes — Living kidney donation appears to increase the risk of gestational hypertension and preeclampsia compared with experience among otherwise similar healthy females, and we generally advise females that it is ideal to have completed planned childbearing prior to kidney donation. Consistent with recommendations of a 2015 AST consensus statement [20] and KDIGO clinical practice guidelines [6], OPTN policy requires informing female donor candidates that risks of preeclampsia or gestational hypertension are increased in pregnancies after donation [6,20].
Nevertheless, given the generally good pregnancy outcomes after donation, females should not be excluded based on plans for possible future childbearing alone, and females may value the available information differently in their donation decision. All females who become pregnant after donation should receive regular prenatal care.
Evidence of pregnancy risks among living donors is mostly derived from observational studies [50-52].
Cohort studies have reported higher rates of gestational hypertension and preeclampsia in groups of females with pregnancies after donation versus groups of females with pregnancies before donation:
●Registry data from Norway was used to identify 326 donors (98 percent were White donors) with 726 pregnancies, 106 of which were postdonation in 69 donors [50]. After adjustment for maternal age, birth order, and year of birth, preeclampsia events were more common in postdonation pregnancies than they were in predonation pregnancies (5.7 versus 2.6 percent). The incidence of preeclampsia in donors was also higher than the incidence in the general population (random sample from the Norwegian Birth Registry; 5.7 versus 3.1 percent), although, on average, maternal age was five years older among donors than among nondonors and that comparison did not account for between-group differences in prognostic factors.
●Another study examined 1085 living kidney donors at one center in the United States with 3213 total pregnancies, 490 of which were postdonation in 239 donors [51]. Compared with the group of donors with predonation pregnancies, the group of females with postdonation pregnancies had a higher incidence of fetal loss, gestational diabetes, gestational hypertension, and preeclampsia. Study outcomes were ascertained by donor recall in a survey.
Rates of complications with postdonation pregnancies were similar to those reported in the general population.
An important caveat to interpreting these studies is that, as females age, their risk of pregnancy complications increases, and some females became pregnant for the first time after donation. Comparing the outcomes of predonation to postdonation pregnancies even with statistical adjustment may not clearly delineate the incremental risk attributable to donation.
A retrospective cohort study compared 85 donors (131 pregnancies) with 510 healthy nondonors (788 pregnancies) in Ontario, Canada who, after screening for baseline conditions to simulate donor selection, were matched on characteristics that might be associated with the risk of gestational hypertension or preeclampsia: age, year of cohort entry, urban or rural residency, income, number of pregnancies before cohort entry, number of childbirths prior to cohort entry, and time to first pregnancy after cohort entry [52]. The median follow-up time was 11 years (maximum 20 years). Gestational hypertension or preeclampsia was more common in donors compared with nondonors (11 versus 5 percent; odds ratio [OR] for donors 2.4, 95% CI 1.2-5.0). There were no differences between groups in rate of preterm birth or low birth weight. Most females had uncomplicated pregnancies after kidney donation.
A meta-analysis of two studies cited above [50,52] identified an increased relative risk for preeclampsia (RR 2.12, 95% CI 1.06-4.27) but no significant differences in risk of gestational hypertension, low birthweight, or preterm birth [11]. A systematic review concluded that consistent evidence from three studies reveals that donors are at higher risk for preeclampsia and gestational hypertension with postdonation pregnancies [33].
There is a need for more research on pregnancy outcomes among donors, including assessment of differential risk among donor subgroups; notably, African Americans were not represented in the three major studies to date. Better understanding of clinical sequelae of gestational hypertension and preeclampsia, including on long-term renal outcomes, is also needed. The Ontario study observed trends towards more cesarean sections and low-birth-weight deliveries in both donors and nondonors with gestational hypertension, but statistical power was low, and replication is needed.
Gout — Kidney donors may be at higher risk for developing gout compared with equally healthy nondonors. This was suggested by a study of 1988 living kidney donors from Ontario, Canada who were followed for a median of 8.8 years (maximum 20.8 years) [53]. Living kidney donors were more likely to be diagnosed with gout compared with healthy, matched nondonors (3.5 versus 2.1 events per 1000 person-years; HR 1.6, 95% CI 1.2-2.1). The absolute risk difference over the follow-up time was modest, at 1.4 percent, and the number needed to harm was 71. At 20 years, the cumulative incidence of gout was 2 percent higher in donors compared with nondonors (6.8 versus 4.9 percent).
The risk of gout after kidney donation may vary based on race. A study of 4650 kidney donors from the United States, including 13.1 percent African Americans, found that, by seven years, African Americans were almost twice as likely to develop gout as White donors (4.4 versus 2.4 percent; aHR 1.8, 95% CI 1.0-3.2) [54]. Postdonation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in males (aHR 2.80). Compared with matched donors without gout, donors with gout had more frequent diagnoses for renal conditions including acute kidney failure, chronic kidney disease (CKD), and other disorders of the kidney. Future studies should examine whether the direct impacts of donation on the risk and consequences of gout differ according to demographic traits.
Mineral and bone disease — The effect of the modest decrease in GFR on the development of metabolic bone disease among kidney donors is not clear. One study showed that kidney donors had higher serum concentrations of fibroblast growth factor 23 (FGF-23) and greater fractional excretion of inorganic phosphate compared with nondonor controls [55]. The ALTOLD prospective, controlled cohort study found a 23 percent higher parathyroid hormone (PTH) concentration among 206 donors assessed at six months postdonation compared with levels among 198 healthy controls (52.7 versus 42.8 pg/mL, respectively); serum phosphate was also lower among donors compared with controls (3.3 versus 3.5 mg/dL, respectively) [56]. Other differences reported in this study included a lower hemoglobin among donors (13.1 versus 13.6 g/dL in controls), greater uric acid (5.3 versus 4.9 in controls), higher homocysteine (1.5 versus 1.2 mg/L), and lower high-density lipoprotein (HDL) cholesterol (54.1 versus 54.9 in controls).
A three-year follow-up of the ALTOLD cohort that included 182 of the original donors and 173 of the original controls showed a persistent increase in PTH, uric acid, homocysteine, and potassium and a decrease in hemoglobin among donors compared with control individuals [26]. Similarly, the CRIB-Donor Study cited above reported larger increases in serum FGF-23, PTH, and uric acid at 12 months postdonation versus predonation compared with prospective changes in these parameters among healthy nondonors [17].
A matched cohort study showed no increase in the risk of nontrauma-related upper- or lower-extremity fractures and no difference in the proportion of adults receiving prescriptions for bisphosphonates among 2015 kidney donors in Ontario, Canada compared with healthy controls [57].
Malignancy — The overall risk of developing cancer does not appear to be increased among donors. In one study that examined administrative data from a private health insurer linked to the OPTN registry, the frequency of non-skin cancer was lower among donors compared with age- and sex-matched nondonors [58]. This observation likely reflects the impact of predonation screening since it was limited to donors who enrolled in the insurance plan within 4.9 years of donation. However, this study also showed an increase in incidence of prostate cancer among donors compared with nondonors that did not appear to be explained by increased prostate screening among donors. Further study of the incidence of cancer and of prostate cancer, in particular, after donation is warranted.
Risk among African-American and Hispanic donors — African Americans are generally at higher risk than White persons for the development of hypertension and CKD in the general population, and this increased risk has been observed among kidney donors [34,59,60]. The risk may be increased further by kidney donation. As examples:
●In a retrospective cohort study from the University of Minnesota, drug-treated hypertension was reported in 25 percent of 255 White donors assessed at an average of 12 years after donation [61]. By comparison, hypertension was identified in 41 percent of 39 African-American donors at one center at an earlier average assessment time of seven years postdonation [62].
●One study compared 103 African-American kidney donors with 235 matched, healthy participants selected from the CARDIA study [48]. At a mean follow-up of approximately 6.6 years, the frequency of hypertension was higher among kidney donors compared with nondonors (41 versus 18 percent, respectively; RR 2.4, 95% CI 1.7-3.4). The study identified a high proportion of previously undiagnosed hypertension through study encounters.
●Linkage of OPTN living-donor registry with administrative billing claims from a private health insurer found that, as compared with White donors, African-American donors had increased risk of postdonation diagnoses of hypertension (aHR 1.52, 95% CI 1.23-1.88), diabetes mellitus requiring drug therapy (aHR 2.31, 95% CI 1.33-3.98), and CKD (aHR 2.32, 95% CI 1.48-3.62) [59]. Consistent patterns of racial variation were observed for use of antihypertensive medications [63] and for diagnoses of postdonation medical conditions among Medicare beneficiaries [64].
Subsequent analysis of the linked OPTN registry and private payer data found that, by seven years after donation, after adjustment for age and sex, greater proportions of African-American compared with White donors had renal condition diagnoses: CKD (12.6 versus 5.6 percent; aHR 2.32, 95% CI 1.48–3.62), proteinuria (5.7 versus 2.6 percent; aHR 2.27, 95% CI 1.32–3.89), nephrotic syndrome (1.3 versus 0.1 percent; aHR 15.7, 95% CI 2.97–83.0), and any kidney diagnosis (14.9 versus 9 percent; aHR 1.71, 95% CI 1.23–2.41) [65].
●In the United States registry study that compared ESKD among 96,217 donors and matched healthy nondonors, African-American donors had the highest incidence of ESKD and highest absolute risk increase at 15 years compared with their own healthy controls [19]. The absolute 15-year incidence per 10,000 was 74.7, 32.6, and 22.7 among Black donors, Hispanic donors, and White donors compared with 23.9, 6.7, and 0.0 per 10,000 for Black nondonors, Hispanic nondonors, and White nondonors, respectively [19]. Thus, donation-attributable risk by race was 50.8, 25.9, and 22.7 ESKD events per 10,000 at 15 years, respectively, among Black donors, Hispanic donors, and White donors.
Racial variation in the risk of post-donation ESKD may relate to the incidence of hypertension and diabetes [64,66], access to care and other unmeasured environmental factors, and the presence of kidney-disease risk alleles such as apolipoprotein L1 (APOL1) [67]. In the general (ie, nondonor) population, studies suggest that at least a portion of kidney failure previously attributed to hypertensive nephrosclerosis in persons of African descent may be genetically mediated by coding variants in APOL1 and not modifiable by antihypertensive therapy. (See "Focal segmental glomerulosclerosis: Genetic causes", section on 'APOL1' and "Epidemiology of chronic kidney disease".)
Some have suggested that potential donors who self-identify as African Americans undergo APOL1 genotyping [60,67,68]. The presence of two kidney risk variants (compound heterozygote or homozygous variant) may be a prudent relative contraindication to donation, especially among younger donors. In a case-control study published from the 1000 Genomes Project, homozygosity or compound heterozygosity for APOL1 variants (G1 and G2) was associated with a higher risk for ESKD in African Americans compared with zero risk alleles (OR 7.3). A single copy of a kidney risk allele is present in approximately 37 percent of the African-American population, only conferred a very modest risk (OR 1.26) for ESKD, and is not considered as an exclusion criterion for donor candidates [60].
The presence of two APOL1 kidney risk variants in deceased donors has been correlated with two to four times the risk of allograft loss compared with zero or one risk alleles [69,70]. Carrying two APOL1 risk variant alleles has been associated with increased risks of focal segmental glomerulosclerosis and human immunodeficiency virus (HIV)-associated nephropathy histopathologies, proteinuria, reduced GFR, younger age at dialysis, and more rapid progression of kidney disease among African Americans in the general population [71-74], although functional decline may require a "second hit" or progress only after onset of albuminuria [75,76]. (See "Focal segmental glomerulosclerosis: Genetic causes", section on 'FSGS in Black patients' and "Epidemiology of chronic kidney disease".)
A cohort study of 136 African-American living kidney donors reported that those with APOL1 high-risk genotypes had lower predonation kidney function and faster rates of decline in postdonation eGFR; 11 percent (2/19) subsequently developed ESKD after an average 12 years of follow-up [77]. While recommending that APOL1 genotyping may be considered in the living-donor candidate evaluation, the 2017 KDIGO guideline identified the need to define the role of APOL1 genotyping in the evaluation of donor candidates with recent African ancestry as a key research priority [6]. Importantly, 2018 will mark the launch of the National Institutes of Health (NIH)-sponsored collaborative APOL1 Long-term Kidney Transplantation Outcomes (APOLLO) Consortium, charged with prospectively assessing the effects of kidney risk variants in the APOL1 on outcomes for kidneys from donors with recent African ancestry and the impact of APOL1 kidney risk variants on the health of living kidney donors [78].
African-American donor candidates should be counseled regarding higher risks of ESKD and medical conditions compared with White donors as well as current knowledge of donation-attributable risks. Among all African-American donor candidates, we use conservative acceptance criteria for baseline GFR, blood pressure, BMI, and glucose tolerance. APOL1 genotyping may be of benefit. (See "Kidney transplantation in adults: Evaluation of the living kidney donor candidate", section on 'Kidney function'.)
Estimation of projected lifetime ESKD risk in the donor evaluation [35] may demonstrate baseline risk exceeding a center's acceptance threshold, even in the absence of donation, for some young African-American candidates.
Risk among older donors — Outcomes are generally acceptable among carefully selected older living donors. In a study of 3368 older donors (≥55 years) in the United States (1996 to 2006), all-cause mortality over a median eight years follow-up did not differ significantly from that of healthy, demographically matched nondonors selected from the Health and Retirement Study (4.9 versus 5.6 deaths per 1000 person-years, HR 0.90, 95% CI 0.71-1.15) [13]. There was also no difference in a composite outcome of death or cardiovascular disease (defined as ischemic cardiac disease, congestive heart failure, stroke, peripheral vascular disease; HR 1.02, 95% CI 0.87-1.20).
A review of 219 living kidney donors over the age of 70 years demonstrated donor survival of 99.5, 95.8, and 90 percent at 1, 5, and 10 years [79]. Donor survival was higher than that of a matched cohort from the NHANES-III (HR 0.37, 95% CI 0.21-0.65). However, the graft survival in the recipients was only comparable with deceased donors aged 50 to 59 years and significantly lower compared with allografts from living donors aged 50 to 59 years.
In addition, patients >60 years are more likely to have a GFR <60 mL/min after donation [61,80]. This was best demonstrated in a retrospective study that compared outcomes of 422 donors <60 years with those of 117 donors ≥60 years [80]. At a median follow-up of 5.5 years, significantly more older donors had an eGFR <60 mL/min compared with younger donors (80 versus 31 percent). However, there was no difference between groups in the mean maximal decline in GFR (38±9 percent), which, in both groups, remained stable out to 13 years; however, the starting GFR was lower among older patients (80 versus 96 mL/min/1.73 m2 among younger individuals).
In a United States registry-based study, cumulative incidence of ESKD at 15 years per 10,000 individuals was 29 for donors 18 to 39 years, 17 for those 40 to 49 years, 55 for those 50 to 59 years, and 70 for those over 60 years of age [19]. Importantly, however, patterns of ESKD risk according to age change when considered on a lifetime horizon. Based on United States Renal Data System (USRDS) and cohort data for nearly five million healthy persons, the projected lifetime risk of ESKD for older adults, even those with hypertension or isolated medical abnormalities, may be lower than for young persons, especially young African Americans [50].
Psychosocial outcomes — In general, donors demonstrate good quality of life and have a low rate of donation-related regret. The following studies illustrate the range of findings:
●A multicenter study reported that average postdonation health-related quality-of-life (HRQoL) scores at a median of six years after donation were similar to scores among healthy nondonors and general population norms [81].
●The Renal and Lung Living Donors Evaluation Study (RELIVE) study of 2455 living donors from three large United States centers (93 percent were White donors, 72 percent were biologically related to recipient) determined that HRQoL scores in living donors in the decades following donation were similar or better than the general United States population [82].
●Two systematic reviews found that, on average, donors experienced increased self-esteem, empowerment, and community awareness; however, some also described a lack of emotional support [83,84]. A subsequent systematic review of 34 prospective studies of postdonation HRQoL (1990 to 2014) found that, after mild reductions early after nephrectomy, HRQoL returned to baseline or was slightly reduced by 3 to 12 months, particularly for fatigue, but was still comparable with general population norms [85]. Among nine studies examining risk factors for impaired HRQoL, low psychological functioning before donation was the most common predictor.
Living donors may experience clinical fatigue in the postoperative period. A survey of fatigue symptoms among 193 living donors in the Kidney Donor Outcome Consortium found higher fatigue scores at one month postdonation compared with scores among 20 healthy controls [86]. While there were no differences in fatigue scores between donors and controls at later time points, of the 155 donors who completed one- and six-month postdonation assessments, 50 (32 percent) had persistent clinical fatigue (ie, at both time points following surgery).
With regard to measures of pain beyond the perioperative period, a study of pharmacy claims data among a sample of privately insured United States donors found that, while prescription narcotic use was more common among females than males in the intermediate term after donation, total narcotic exposure was lower than among nondonors from the general population [87].
Some donors have experienced psychosocial difficulties (eg, depression, anxiety, stress, worries about health) that may impact their function and capability to return to work. Among respondents in the RELIVE study, 9 percent reported one or more of the following poor psychosocial outcomes: "fair" or "poor" overall donor experience, financial burden, regret or discomfort with decision to donate, or psychological difficulties since donation [88]. Recipient graft failure was the only identified predictor of reporting one or more of these poor psychosocial outcomes and was associated with 77 percent higher risk (OR 1.77, 95% CI 1.33-2.34). In a study of 4650 United States donors, postdonation depression rates did not exceed that of general population nondonors [66]. However, recipient graft failure and death were associated with increased risk of subsequent depression diagnoses and use of antidepressant medications in donors, and most of the failure events occurred beyond the first year [66]. These data support a need to assess the psychological health of donors after adverse recipient events, even if event are late after donation.
Economic considerations — Donor candidates and actual donors incur personal direct and indirect expenses as part of the evaluation and donation procedure, even in countries where the donor's medical expenses are paid by the recipient's insurance or the health care system. Major costs include transportation, accommodation, child care, and lost income (or vacation time) from missed work [89,90]. In a multicenter cohort study of 194 living donors, most reported one or more direct costs, including ground transportation (80 percent), health care (24 percent), lodging (17 percent), and air transportation (14 percent), totaling USD $101,484 (mean $523±942) [89]. Excluding paid vacation or sick leave, donor and companion lost wages totaled USD $35,918 (mean $187±556) and $14,378 (mean $76±311), respectively. One-third of living kidney donors used paid vacation or sick leave to avoid incurring lost wages. Few living kidney donors reported receiving financial support from the transplant candidate (6 percent), transplant candidate's family (3 percent), a nonprofit organization (3 percent), the National Living Donor Assistance Center (7 percent), or transplant center (3 percent). Higher total costs were significantly associated with longer distance traveled to the transplant center.
In the United States, some states have enacted legislation to offer tax deductions or credits, or other benefits, to living organ donors [91,92]. These programs vary state by state, are underused, and have not been studied with regard to impacts on financial burdens of donation.
Coordinating the timing of the donor candidate evaluation with work and dependent care schedules may minimize indirect costs. An earlier return to work may be facilitated by the use of laparoscopic compared with open donor nephrectomy [93]. By 2013, almost all living donations in the United States are performed laparoscopically, and, with increasing experience with the laparoscopic procedure, few are converted to open procedures [94].
Living organ donors may encounter difficulties with insurance after donation. This was shown in a systematic review of 23 studies including 2076 living organ donors, 385 potential donors, and 239 responses from insurance companies [95]. Three to 11 percent of donors stated that they had problems obtaining insurance. In a more recent study that included 395 individuals in the United States who either changed or initiated health insurance after kidney donation, 27 (7 percent) reported difficulty; of these, 15 were denied health insurance, and 12 were charged a higher premium [96]. Eight individuals were told they had a pre-existing condition because of kidney donation. Among 186 individuals who changed or initiated life insurance after kidney donation, 46 (25 percent) had difficulty obtaining life insurance; of these, 23 were denied insurance, and 27 were charged a higher premium. Seventeen were told they had a pre-existing condition because of kidney donation.
The economic impacts of donation may extend beyond direct costs to longer-term impacts on employment and socioeconomic status, although data on these outcomes are limited. A retrospective analysis of 1285 living kidney donors who donated at seven university-affiliated hospitals in South Korea found that donors had a higher likelihood of employment loss in years 1 to 2 after enrollment compared with healthy non-donor controls (22 versus 11 percent; adjusted odds ratio [aOR] 2.27) [97]. Living donors also had an increased likelihood of worsened household economic quartiles (22 versus 16 percent; aOR 1.54) and parallel decreases in likelihood of economic improvement (31 versus 43 percent; aOR 0.57) in years 1 to 2. While more work is needed to understand the mechanisms of these findings, there is a clear call for robust efforts to prioritize financial health along with medical health in protecting the safety of living donation [98].
Living-donor candidates should receive counseling about financial costs prior to donation, education on how to access available financial supports, and the limitations of available resources. Recommendations to advance financial neutrality for donors and donor candidates include allocation of resources for standardized system of reimbursement of donation-related costs, improved tax credits, and legislation to standardize employment and insurability protections [99,100]. The American Society of Transplantation Live Donor Community of practice developed a toolkit to help living-donor candidates and donors prepare for financial impacts of donation and links to resources including state tax credits and assistance-ships that may be available for cost mitigation [101].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)
SUMMARY AND RECOMMENDATIONS
●Overview – The complications from kidney donation can be divided into perioperative risks and risks that may arise many years after donation. (See 'Introduction' above.)
●Perioperative risks – Perioperative mortality after living-donor nephrectomy is 1 in 3000 at 90 days. In addition to death, the most important perioperative risks of donor nephrectomy include hemorrhage, pneumothorax, pneumonia, urinary tract infection, wound complications, and deep vein thrombosis with or without pulmonary embolism. (See 'Perioperative risks' above.)
●Long-term risks – Living donation may cause small increases in the long-term risks of end-stage kidney disease (ESKD), preeclampsia, hypertension, and metabolic diseases such as gout. These risks should be discussed with all donor candidates. (See 'Long-term risks' above.)
•ESKD – The risk of ESKD among donors is low but appears to be higher than among healthy nondonors. Estimation of projected risk of ESKD in the absence of donation according to a donor candidate's predonation demographic and health characteristics may improve consistency and transparency in the evaluation and selection of donor candidates. The overall incidence and donation-related risks of ESKD and hypertension after kidney donation are higher among African-American compared with White donors. (See 'End-stage kidney disease' above and 'Risk among African-American and Hispanic donors' above.)
•Maternal and fetal outcomes – We generally advise females that it is ideal to have completed planned childbearing prior to kidney donation. Living kidney donation appears to increase the risk of gestational hypertension and preeclampsia compared with experience among otherwise similar healthy females. Nevertheless, given the generally good pregnancy outcomes after donation, females should not be excluded based on plans for possible future childbearing alone, and females may value the available information differently in their donation decision. (See 'Maternal and fetal outcomes' above.)
•Psychosocial outcomes – Donor candidates can be informed that, in general, donors demonstrate good quality of life and have a low rate of donation-related regret. However, some do experience psychosocial difficulties after donation (eg, depression, anxiety, a negative change in their relationships, or more pain or slower recovery than expected). (See 'Psychosocial outcomes' above.)
●Economic considerations – Donor candidates and actual donors incur personal direct and indirect expenses as part of the evaluation and donation procedure, even in countries where the donor's medical expenses are paid by the recipient's insurance or the health care system. Major costs include transportation, accommodation, child care, and lost income (or vacation time) from missed work. (See 'Economic considerations' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Emilio Ramos, MD, FACP and Anitha Vijayan, MD, who contributed to earlier versions of this topic review.
