Abstract
Background and objectives: Increasing living kidney donation mandates ongoing assessment of living donors for future health risks and revision of national health policy.
Design, setting, participants, & measurements: Living kidney donors as reported to the Organ Procurement and Transplant Network database from January 1988 through December 2008 were reviewed for minor medical abnormalities, presence of donor health care coverage, and occurrence of surgical complications and death.
Results: At donation in 2008, 19.5% were obese, 2.0% had a history of hypertension, and 3.5% had proteinuria. The median estimated GFR of living donors was 92.2 ml/min. Additionally, 12.2% of donors were reported not to have health insurance at the time of donation. By racial background, 14.9% of black and 17.0% of Hispanic donors did not have insurance at donation. Perioperative complications included blood transfusion (0.4%), reoperation (0.5%), and vascular complications (0.2%). Death occurred within 30 days of donation in 0.03% donating between October 1999 and December 2008. During those same years, overall donor death was 2.8%.
Conclusions: Almost one quarter of living donors have medical conditions that may be associated with future health risk. Close follow-up and a registry of these donors are necessary. Only then will we be able to inform prospective living donors most accurately of the real risk of donation on their health and survival. Additionally, these data speak to the need for a national discussion on the provision of health insurance for living donors.
Living organ donors are the inspiration of transplantation, leading to earlier transplantation and better recipient survival (1–4). This is particularly true for kidney transplantation, where 55,912 (49.5%) of the 112,948 kidney donors between 2000 and 2008 were living donors. Even so, the kidney waiting list continues to grow, and as of December 2009, there are >88,000 kidney patients listed on the United Network for Organ Sharing (UNOS) waiting list (5). Thus, it has been argued that the need for more living donors grows (Figure 1).
The number of waitlisted transplant candidates and living donor and deceased donor transplant recipients by year (1).
Concurrent with the increased need for kidney transplantation has been the recognition of the complex living donor (6). Reese et al. (6) reported that 24% of donors in 2004–2005 reported to the Organ Procurement and Transplant Network (OPTN) were medically complex, defined as the presence of hypertension, obesity, or an estimated GFR (eGFR) <60 ml/min per 1.73 m2. In this cohort, they reported that 12.8% were obese, 10.3% were hypertensive, and 4.2% had low eGFR. Donor characteristics that were associated with medical complexity included spousal relationship to the recipient, low education, older age, and non-U.S. citizenship.
Allaying some fear regarding donor risk was a recent single center study that reported survival of kidney donors was similar to that of controls matched for age, gender, and race (7). Clinical data on a subgroup of donors showed that 85.5% had a GFR of 60 ml/min per 1.73 m2 or higher, 32.1% had hypertension, and 12.7% had albuminuria. Older age and higher body mass index (BMI) were associated with hypertension and a GFR that was <60 ml/min per 1.73 m2.
Also reassuring was a study in which the investigators compared all living donors in Ontario, Canada, from 1993 through 2005 (n = 1278) to a control group (n = 6359) matched for age, gender, income, and use of nonphysician healthcare (8). Living donors did not experience increased cardiovascular events or die more often than the control population over 10 years (1.3% living donors versus 1.7% controls). Donors did, however, experience greater rates of hypertension (16.3%) compared with the control group (11.9%, hazard ratio = 1.4). This corroborates data from a previous meta-analysis of studies of long-term donor follow-up where there was, on average, a 5-mmHg increase in donor BP compared with age- and gender-matched controls by 10 years after donation (9). Although these studies are reassuring, there are two recent reports of increased pre-eclampsia in female living donors when adjusting for maternal age and parity (10,11). Furthermore, it has come to light that up to 50% of donor renal biopsies are not completely normal, with the most common findings being interstitial fibrosis, tubular atrophy, increased mesangial matrix, arteriolar hyalinosis, and glomerulosclerosis (12).
Last, there is ongoing discussion whether the mere act of donation causes chronic kidney disease (CKD) and/or increases the risk for ESRD (13,14). The level of postdonation kidney function may put some donors numerically into CKD stages 2 to 4; however, does this level of kidney function carry the same other risks as two diseased kidneys? The answer is likely no; however, the real answer is unknown. It is known that renal reserve capacity is maintained except in those with a high BMI and old age (15), and proteinuria or albuminuria may increase over time from surgery (7,16–20). It is also known that in mostly white donor populations, between 0.1 to 1.1% develop ESRD, roughly the same as the general population (5,7,21–23). This information comes from identification of donors added to the UNOS transplant waitlist and does not include those starting dialysis but not listed for transplant. Recently analyses of the OPTN data showed that 148 previous living kidney donors were on the kidney waiting list between January 1, 1996 and March 31, 2007 (24). Most of the waitlisted donors had donated between the ages of 18 and 34 years and had donated to a full sibling. The median time from donation to listing was 21 years for white donors and 16 years for African-American donors; 43% of such donors were African Americans, who made up and do make up ∼12% of living kidney donors. These data suggest that the risk of postdonation ESRD is not equal among ethnic/racial groups and mirrors the increased risk of ERSD that these groups experience in the general population (25–27). For instance, focal sclerosis and hypertensive renal disease in African Americans has recently been tied to genetic variations in nonmuscle myosin heavy chain 9, perhaps making changes in intrarenal hemodynamics more problematic in certain African-American donors (28–31).
To understand if these findings indicate increasing risks for present living donors, it is important to re-examine the face of our current living donors and compare it to those, where possible, of the past. What characteristics do they have that may be predictive for kidney disease, other medical illnesses, and mortality and lack of access to health care? Furthermore, what are the current postoperative complications experienced by living donors in this era of laproscopic nephrectomy? This review of OPTN data aims to keep donors and practitioners updated as to their short and longer-term risks and show where there is room for policy change and research.
Materials and Methods
Cohort
We analyzed the OPTN database for information on living donor demographics, physical and medical characteristics, and insurance coverage during 1988, 1991, 1995, 2000, 2005, and 2008. These years were chosen because they represented the first full year of data after major changes were made to the OPTN Living Donor Registration (LDR) and Living Donor Follow-up (LDF) forms. Because of the changes made over time to these forms, data for some metrics are not available for all years.
Forms
In October 1987, the OPTN began to collect information regarding living organ donors (name, gender, age, and relationship to the recipient) on the OPTN Donor Histocompatibility Form. The LDR form was created in October 1990 and added serology data and basic demographic information. In April 1994, the donor social security number was added to the LDR. The 6-month and 1-year LDF forms were implemented in October 1999, and the LDR was expanded at that time to include BP, height, weight, predischarge complications, donor education level, donor status (alive, dead, lost to follow-up), re-hospitalizations, complications such as dialysis, laboratory values such as serum creatinine, and cause of death, where appropriate. A June 2004 update included additional data about the donor's predonation insurance and functional status, employment status, clinical data such as hypertension, diabetes, and the presence of proteinuria, and more details on complications after donation. Additional changes to the LDR and LDF, which were implemented in March 2008, captured more information about the center's attempts to contact the donor and extended the follow-up period for living donors to 2 years after donation.
Clinical Metrics
Clinical data on the LDR form, which is submitted by transplant programs at 6 weeks after donation or at discharge from surgical care after donation, whichever comes first, were analyzed as pre- and postdonation metrics. Hypertension was defined as a report of history of hypertension. Predonation obesity was defined as a BMI >30 kg/m2. Proteinuria was defined as a positive urine protein by dipstick. eGFR was calculated with the Modification of Diet in Renal Disease 4 equation, using gender, ethnicity, age, and serum creatinine (32). Insurance coverage at donation was reported to be present, not present, or unknown. Date and cause of donor death was determined by evaluating the causes reported to UNOS and matching the UNOS living donor data with the Social Security Death Master file.
Results
Donor Demographics
The gender breakdown of living donors has not changed drastically over time, with the majority being female throughout the years and a moderate increase in the percent of female donors between 1988 (54.7% female) and 2008 (60.6% female) (5). The median age of donors has increased from 35 years old in 1988 to 41 years old in 2008 (Table 1) (5). The number of living donors over the age of 65 has increased: 0.7% in 1988 and 1.5% in 2008. A more drastic increase is seen in the 50- to 64-year-old group. Although some ethnic groups are over-represented in the ESRD population, the ethnicity of living donors is approximately equivalent to that of the general population (Table 2) (5,21). There has, however, been a gradual shift over the years such that the proportion of nonwhite donors has increased from 23.9% in 1988 to 30.9% in 2008.
Percent in each age range of living donors over time (5)
Ethnicity of living kidney donors over time as percentage of the living donor population (5)
Relationships between Donors and Recipients
The relationship between living donors and their recipients has changed over time (5). Today, donors are less likely to be blood relatives of the recipient and instead are spouses and friends (Figure 2) (5). This change in the relationship between donors and recipients is important because the changes in donor characteristics are often based on their relationship to the recipient. For example, in 2008, spousal/life partner donors (median age = 48 years) were older than other donors (median age = 40 years). Parental donors (median age = 48 years) were also older than nonparental donors (median age = 40 years). Another trend is increased donation by adult offspring to their parents, from 8.7% of living kidney donors in 1988 to 18.4% in 2005 and 16.8% in 2008 (5). More recent times have seen an increase in emotionally uninvolved donors (altruistic, or the preferred term, nondirected donors). However, nondirected donors still make up a small proportion of all living donors (1.1% in 2005; 1.8% in 2008).
Living donors' relationship to their recipient in (A) 1988 and (B) 2008 (1).
Predonation Health Status of the Living Donor
A key consideration in the evaluation of prospective kidney donors is their predonation renal function. The most common method of determining kidney function captured by the OPTN donor database is serum creatinine (33–35). The median serum creatinine values and eGFR by year of donation for 2000, 2005, and 2008 were, respectively, 0.9 mg/dl and 90.5 ml/min per 1.73 m2, 0.9 mg/dl and 88.7 ml/min per 1.73 m2, and 0.8 mg/dl and 92.2 ml/min per 1.73 m2. Median/mean eGFR for 2008 was 90.3/90.9 ml/min per 1.73 m2 for spousal/partner donors, 89.4/94.1 ml/min per 1.73 m2 for parents who donated to their children, 96.2/97.7 ml/min per 1.73 m2 for children who donated to their parents, 85.5/90.6 ml/min per 1.73 m2 for nondirected donors, and 87.4/89.2 ml/min per 1.73 m2 in paired exchange donors (5). These results are not significantly different between groups.
Because proteinuria is the single largest risk factor for the development of kidney disease, protein excretion is an important component of the living kidney donor evaluation (33–35). A protein excretion rate of >150–200 mg/day is abnormal in most laboratories, and dipstick proteinuria is tightly correlated with the long-term risk for the development of kidney disease (36–40). Mandelbrot et al. (35) reported that transplant programs usually evaluate protein excretion in living donor candidates by 24-hour urine collection (76% of programs), dipstick urinalysis (55% of programs), the protein:creatinine ratio in a spot urine (27% of programs), and/or by measurement of albuminuria (44% of programs). The OPTN collects data on dipstick protein and timed collections; however, only the urine dipstick is reported for 2008, and no 24-h urine data were reported. Of 5968 living kidney donors in 2008, 211 (3.5%) tested positive for urine protein by dipstick. This is an increase from 2.0% reported as positive in 2005, but the data must be interpreted with caution because of the high level of missing data for this field: 575 (9.6%) were reported as not done or unknown in 2008. The data on urine protein:creatinine ratio is too sparse and inaccurate to be dependable (n = 94/5968; range, 0 to 64.0; with 49/94 with ratios >0.2).
Donor Physical Characteristics and Metabolic Syndrome 2008 Data
Obesity.
The literature suggests that transplant programs generally exclude as donors individuals with a BMI > 35 kg/m2, and 10% of programs exclude donors with a BMI >30 kg/m2 (35). Obesity is, however, now prevalent in living donors, with 19.5% of living donors reported as having a BMI >30 kg/m2 in 2008 (n = 5968 donors, n = 1165 obese, n = 478 missing data) (1) compared with over a third of adults in the general population (33.3% of men and 35.3% of women) (41,42). There has been a small but important increase in donor BMI from 2000, when 14.4% of living donors were obese (n = 5494 donors, n = 791 obese, n = 1457 missing data). Obesity was present in 18.1% of spousal/partner donors and 16.9% nonspousal donors and 13.2% of nondirected donors. Obesity varied by donor ethnicity in 2008: 18.1% of white donors were obese, 25.6% of black donors were obese, 22.8% of Hispanic donors were obese, 10.7% of Asian donors were obese, 34.2% of American Indian/Alaska Native donors were obese, and 23.1% of Native Hawaiian/Pacific Islander donors were obese. BMI was >35 kg/m2 in 2.5, 2.4, and 2.1% in 2000, 2005, and 2008, respectively.
Hypertension.
The changing definition of hypertension makes comparison of yesterday's donors with today's donors somewhat difficult. In the past, hypertension was a BP of >150 to 160/90 to 100 mmHg, whereas today it often is defined as a BP of >140/90 mmHg (prehypertension, 120 to 139/80 to 89) or treatment for hypertension (43,44). Despite this limitation, some trends can be examined. About 2.0% of living donors in 2008 had a reported history of hypertension, with another 1.5% reported as unknown. Using predonation BP as recorded by the transplant center, 1.8% of donors had a BP of 140/90 or higher, and 6.2% had a BP of 130/85 or higher. There were differences in history of hypertension based on ethnicity of donors. Hypertension was reported by 5.3% (2 of 38) of Native Americans, 2.5% of whites, 1.4% of blacks, 0.4% of Hispanics, and 0.5% of Asians. About 0.4% of donors in 2008 were reported on the LDR to have developed hypertension within 6 weeks of donation (5). Looking more closely at the connection between predonation BP and postdonation medication treated hypertension, 0.34% of those with a BP <130/85 (17/5063) and 2.2% of those (8/360) with a BP ≥130/85 predonation developed medication requiring hypertension after donation.
Hypertension was seen in 2.8% of donors with a BMI >30 kg/m2 compared with 1.7% in those with a BMI <30 kg/m2, 1.6% of those with BMI >35 kg/m2, and 1.9% of those with BMI <35 kg/m2. Hypertension was seen in 1.6% of living related compared with 2.5% of living unrelated donors and 1.9% of nondirected donors. Unrelated donors are often spouses; 4.42% of spousal donors were hypertensive.
Postdonation Complications
Acute Complications.
Acute postoperative complications reported by programs to the OPTN include bleeding, gastrointestinal injury and dysfunction, venous embolism, and re-operation. Short-term (6 weeks after donation or to discharge from postsurgical care, whichever comes first) outcomes show that of donors who donated in 2007 and 2008 (n = 12,010), 0.4% (n = 47) needed intra- or postoperative blood transfusions, 2.1% (n = 250) readmission after initial discharge, 0.9% (n = 113) needed an interventional procedure, 0.5% (n = 59) needed re-operation, 0.2% (n = 29) had vascular complications, and 2.1% (n = 252) had other complications. Reasons for re-operation included bleeding (n = 25), bowel obstruction (n = 8), and hernia repair (n = 7). The most common reason for donor readmission was an abdominal problem (n = 105; e.g., nausea, vomiting, gastroenteritis, abdominal pain, ileus, constipation, or bowel obstruction). Less frequent reasons included chylous ascites, pancreatitis, shortness of breath, pulmonary embolism, subphrenic fluid, and infection (e.g., wound, pneumonia, or urinary tract). Because >50% of LDR forms were submitted by transplant centers <6 weeks after donation, all complication rates were considered minimum estimates. Furthermore, reporting by centers rather than living donors themselves likely resulted in fewer complications being reported (45).
Donor Mortality
Death after living donation is reported in 0.02 to 0.04% within 90 days of donation (16,46,47). From October 1999 through December 2008, 14 living kidney donor deaths (of 51,153 donors, 0.03%) occurring within 30 d of donation were reported to the OPTN or identified by examination of the Social Security Death Master File (5). During the same time period, 39 donors (0.08%) died by 12 months after donation. The most common reasons for death at any time (range = 0 to 2688 days; (n = 146 for the cohort, plus 1 donor whose cause of death is recorded as predonation coma; Table 3) were cancer (n = 15; 10.3%), motor vehicle accident (n = 9; 6.2%), cardiovascular disease (cerebral hemorrhage, heart attack, aneurysm) (n = 9; 6.2%), accidental other than motor vehicle accident (n = 8; 5.5%), homicide (n = 4; 2.7%), suicide (n = 7; 4.8%), and unknown (n = 82; 56%). This translates into a homicide rate of 8 per 100,000 living donors and suicide rate of 14 per 100,000. Nationally for the general population in 2006 the National Center for Injury Prevention reported that homicide and suicide occurred in 6.34/100,000 persons and suicide in 10.96/100,000. The rates vary tremendously depending on age, location, and race. More specific analysis for donors, however, has not been performed.
Living donor causes of death for donors donating from October 25, 1999 through December 31, 2008
Health Insurance Coverage.
Donors without health insurance comprised 11.8% of donors in 2005 and 12.2% of donors in 2008. By age, donors without health insurance comprised 17.4% of donors aged 18 to 34, 11.2% aged 35 to 49, 7.6% age 50 to 64, and 5.6% over age 65. About 25% of donors in each of the age categories had insurance status reported as unknown. In 2008, obesity was reported in 19.0% of donors who had health insurance and 20.7% without insurance, with more obese donors having unreported health insurance status (26.7 versus 24.12%). Of 2008 donors with a history of hypertension, 5.1% did not have health insurance; 8.9% of donors with BP over 140/90 mmHg were without insurance. Of donors with proteinuria (n = 211), 9.5% had no insurance; insurance status was unknown in 20.4%. By race, 14.9% of black, 17.0% of Hispanic, 15.2% of Asian, 18.4% of American Indian/Alaska Native, and 10.3% of white donors did not have insurance at donation.
Discussion
Today, 22.4% of new living kidney donors in the United States have some form of medical abnormality or condition that puts them squarely at risk for developing cardiovascular or renal disease (5,6). These characteristics include obesity, hypertension, and proteinuria (48–56). These conditions are being seen at younger ages in the United States than when living donation began in 1954, thus extending the time of donor health risk. Obesity rates in the general U.S. population have increased from 22.9% during 1988 to 1994 to 32.2% during 2003 to 2004 (57). Obesity is now seen in 19.5% of living kidney donors. Hypertension is noted in 30% of the general population, increasing with age. Hypertension is seen in 2.0% of living donors at donation and develops in up to 40% of donors over time (17,58,59) with the most recent paper by Garg (8) reporting a 10-year rate of 16%, which is ∼5% above the control population. Furthermore, the U.S. and potential donor population is aging. Such changes result in a pool of possible living donors that may be less healthy than the donor pool of previous years, making the results of prior follow-up studies less applicable to today's donors and less applicable for the donor consent process. Donor death caused by cardiovascular disease, cancer, and psychosocial events should be continually reviewed not only in the context of the general population but also in the context of the medical evaluation performed. To clarify, although this article may seem to suggest that living donation in those with potential risk should be curtailed, the true purpose of this article is to increase awareness of changing donor characteristics and to assist the effort to enhance living donor follow-up to be able to most accurately inform future living donors as to their potential risks.
In addition to risky medical characteristics, a significant number of donors have no medical insurance at the time they donate (10 to 18%) (5,60). Lack of insurance is more pronounced in the young and donors of color. This fact should be included in the accumulating list of disparities in the category of access to health care. Along these lines, a recent study of African-American donors (n = 39 of 107) on average 7.1 years after donation revealed that 41% had hypertension (undiagnosed in 20.5% of donors), 2.6% had diabetes, 15.4% had microalbuminuria, 2.6% had macroalbuminuria, 17.9% had CKD stage 3, and a decline in the eGFR was the greatest in those with a BMI ≥35 kg/m2 (59). Although not all programs have observed this outcome and eGFR is not the best method for determining donor GFR (61), the combination of increased basic health risk with lack of insurance could be a recipe for future ESRD and death. Improved national information capture, at a minimum from complex and non-white donors, is needed. Health insurance covering complications related to living donation should be guaranteed.
Short-term surgical complications reported here mirror the results of prior publications (45,46). To assure continued safety and optimize informed consent for prospective living donors, there is a need to continue to track these short-term donor complications and to begin to assess donor perspective. Additionally, the noticeable number of donor deaths caused by motor vehicle accident, homicide, and suicide point to a need to re-examine the psychologic evaluations and follow-up of living donors.
The strength of our report is the sheer number of living donors evaluated from multiple ethnic and geographic backgrounds. The OPTN database represents the largest database in the world on living donors. One serious limitation, however, to this report is the amount of missing donor data in the OPTN/Scientific Registry of Transplant Recipients database. When 25% of some data fields are missing data, this clearly impacts the level of conclusions that may be made using the database. Although missing donor data is a current problem, processes are being established to educate programs on how to improve donor follow-up. Longer-term OPTN donor follow-up is also being considered. At a minimum, the current data now allow a portrayal of contemporary living kidney donors and an overview of the most common short-term complications.
Conclusions
Living donor transplantation shows the best of the human spirit. The current living donor is changed compared with the past. Although the OPTN data show that the health risks presently encountered by living donors mirror those of the changing U.S. population, this information is not enough. Living donors need more precise information about their short- and long-term risks. If society and the transplant community are going to encourage living donation, we must modify policies to accomplish this task. Thus, the debate on national healthcare should include provisions to take care of these national heroes, as it has chosen to care for those who serve our country in other ways.
Disclosures
The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Acknowledgments
We thank Jennifer Wainright, PhD, and Lee Bolton MSN, ACNP, for their technical help and guidance and the living donors for their amazing courage. This work was supported in part by Health Resources and Services Administration Contract 234-2005-370011C.
Footnotes
Published online ahead of print. Publication date available at www.cjasn.org.
See related editorial, “Profiling Live Kidney Donors in America: Cause for Optimism and for Concern,” on pages 1732–1733.
Access to UpToDate on-line is available for additional clinical information at http://www.cjasn.org/
- Received February 16, 2010.
- Accepted June 15, 2010.
- Copyright © 2010 by the American Society of Nephrology
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Renal Transplantation
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