As of December 31, 2007, a total of 3404 of the 3698 donors were documented as being alive, 268 were documented as having died, and 26 were foreign nationals whose vital status was unknown. A total of 196 donors died before the initiation of this study, and 72 died during the study period (December 2003 through December 2007). The cause of death was unknown for 162 donors; among the remaining 106, cardiovascular disease accounted for 30% of all deaths. Excluding donors who were foreign nationals, the survival of donors appeared to be similar to that of the controls in the general population, but survival could not be formally compared, since life tables from the National Center for Health Statistics do not provide confidence intervals for the probability of survival in the general population ().
Survival of Kidney Donors and Controls from the General Population
RISK OF ESRD
ESRD that necessitated dialysis or transplantation developed in 11 donors 22.5±10.4 years after donation; 7 of the donors were women and 8 were white. All of the donors had donated kidneys to relatives, 7 of whom were siblings. The causes of ESRD in the recipients of kidneys from these 11 donors were type 1 diabetes (4 recipients), hypertension (2), glomerulonephritis (2), obstructive uropathy (1), hemolytic–uremic syndrome (1), and interstitial nephritis (1). Three of the 11 donors had the same cause of ESRD as their sibling recipients: hemolytic–uremic syndrome (1 donor), hypertension (1) and glomerulonephritis (1). The causes of ESRD in the other 8 donors were hypertension (2 donors), renal-cell carcinoma (1), scleroderma (1), and unknown (4).
A measurement of the serum creatinine level for 232 donors who had died was available 1 to 10 years before their death. The mean level was 1.2±0.2 mg per deciliter (107±18 µmol per liter). No donors who had died had reported needing dialysis or a transplantation in our multiple contacts with them. Therefore, the estimated incidence of ESRD in donors would appear to be 180 per million persons per year, as compared with the overall adjusted incidence rate of 268 per million persons per year in the white population of the United States.
GFR AND URINARY PROTEIN EXCRETION
We were able to contact 2949 of the 3404 donors who were known to be alive as of December 31, 2007. At the beginning of this effort in 2003, a total of 3162 kidney donations from living donors had been performed; 2199 of the donors consented to give health status updates and report laboratory results. Of these 2199 donors, 255 (who represented 6.9% of the entire donor pool, 11.6% of those contacted, and 14.3% of the 1785 donors who were invited to undergo measurement of iohexol GFR) agreed to return for formal measurement of GFR.
The mean age of donors who underwent formal evaluation was 41.1±11.0 years at the time of donation and 53.2±10.0 years at the time that measurement of iohexol GFR was performed; 61.6% of the donors were women, and 98.8% were white. From the time of donation, 12.2±9.2 years had elapsed; 43.1% of the donations had occurred more than 10 years before. The 255 donors who returned for measurement of the iohexol GFR were older than the 3443 donors who did not (41.1±11.0 vs. 38.4±11.7 years, P<0.001), and they had donated more recently (13.7±9.2 vs. 16.3±11.0 years earlier, P<0.001); the two groups were otherwise similar.
The mean serum creatinine level at the time of donation was 0.9±0.2 mg per deciliter (88±74 µmol per liter); the GFR (as estimated from the MDRD study equation) was 84.0±13.8 ml per minute per 1.73 m2. At the time, the iohexol GFR was measured (12.2±9.2 years after donation), the mean serum creatinine level was 1.1±0.2 mg per deciliter (98±19 µmol per liter), and the estimated GFR was 63.7±11.9 ml per minute per 1.73 m2. The estimated GFR at the time of the measurement of the iohexol GFR was 76±12% of the estimated GFR at the time of donation. A younger age at the time of donation, a longer time since donation, and a higher estimated GFR at the time of donation were associated with a greater compensatory increase in the estimated GFR in the remaining kidney.
The majority of the donors in whom the GFR was measured (85.5%) had an iohexol GFR that was greater than 60 ml per minute per 1.73 m2; none had a rate that was less than 30 ml per minute per 1.73 m2. A longer time since donation was associated with a higher iohexol GFR but also with a higher albumin excretion rate (). The slope for the relationship between the iohexol GFR and the time since donation was 0.20 (95% confidence interval [CI], 0.05 to 0.36; P = 0.01), indicating that each year after donation was associated with an increase in the iohexol GFR of 0.20 ml per minute per 1.73 m2. Among the 255 donors, 87.3% had normoalbuminuria, 11.5% had microalbuminuria, and only 1.2% had macroalbuminuria. None of the 255 donors had both an iohexol GFR under 45 ml per minute per 1.73 m2 and albuminuria. Since albuminuria is the hallmark of hyperfiltration damage, we compared the estimated GFR at donation and at the last visit among donors with and those without albuminuria (microalbuminuria or macroalbuminuria). At the time of donation, those in whom albuminuria developed later had a higher baseline estimated GFR, as compared with those in whom albuminuria did not develop, although the difference was not significant (88.4±13.4 vs. 82.6±15.9 ml per minute per 1.73 m2, P = 0.08). Among donors in whom iohexol GFR was measured, the rate was 75.7±13.0 ml per minute per 1.73 m2 in those with albuminuria, as compared with 71.2±11.5 ml per minute per 1.73 m2 in those without albuminuria (P = 0.04).
Glomerular Filtration Rate (GFR) and Urinary Albumin Excretion According to Time since Donation
The measured iohexol GFR was inversely related to age; there was a decline of 0.49 ml per minute per 1.73 m2 per year (95% CI, 0.34 to 0.62) in the GFR. Among men, the decline was 0.34 ml per minute per 1.73 m2 per year (95% CI, 0.14 to 0.55), and in women, 0.60 (95% CI, 0.43 to 0.78).
All 255 donors were invited to return in 3 years for a second measurement of the iohexol GFR, and thus far, none have refused. To date, 38 donors who had donated a kidney 11.7±7.7 years previously have undergone two measurements of the iohexol GFR. As compared with those with a single measurement, these donors were older at the time of the first measurement (57.9±11.1 vs. 52.4±9.6 years, P<0.001) and older at the time of donation (43.8±8.4 vs. 41.1±11.0 years, P = 0.04). However, these 38 donors had creatinine levels and estimated GFRs at the time of donation that were similar to those in the rest of the 255 donors (serum creatinine level, 0.9±0.19 and 1.00±0.90 mg per deciliter [79.6±16.8 and 88.4±79.6 µmol per liter], respectively [P = 0.20]; estimated GFR, 82.6± 15.4 and 83.4±15.8 ml per minute per 1.73 m2, respectively [P = 0.80]). The iohexol GFR remained stable in the donors with two serial GFR measurements (69.4±12.7 and 67.7±8.5 ml per minute per 1.73 m2), with a decline of only 0.6±3.8 ml per minute per 1.73 m2 per year. Blood pressure, as well as the albumin-to-creatinine ratio, remained essentially unchanged in the donors with two serial GFR measurements (systolic pressure, 124.3±15.0 and 124.0±16.6 mm Hg; diastolic pressure, 71.5±6.7 and 72.5±7.0 mm Hg; albumin-tocreatinine ratio, 0.01±0.01 and 0.07±0.37). None of the differences were significant.
The mean systolic blood pressure was 122.2±14.9 mm Hg, and the mean diastolic blood pressure was 73.3±9.0 mm Hg. Sixty-three donors (24.7% of those who underwent measurement of the GFR) required antihypertensive medication, and 19 (7.5%) had newly diagnosed hypertension, which was defined as blood pressure higher than 140/90 mm Hg. Among those receiving antihypertensive medications, 19.4% had poorly controlled hypertension. Since higher blood-pressure levels within the normal range are associated with increased cardiovascular risk,16
we further characterized blood pressure in the 173 donors who were not receiving antihypertensive treatment: 54.6% had a systolic pressure lower than 120 mm Hg, 35.4% a systolic pressure between 120 and 140 mm Hg, and 9.9% a systolic blood pressure higher than 140 mm Hg.
RISK OF REDUCED GFR, ALBUMINURIA, AND HYPERTENSION
The risk of having a GFR lower than 60 ml per minute per 1.73 m2 was associated with age (odds ratio, 1.15; 95% CI, 1.08 to 1.21; P<0.001), body-mass index (odds ratio, 1.12; 95% CI, 1.02 to 1.23; P = 0.02), and female sex (odds ratio, 3.11; 95% CI, 1.11 to 8.67; P = 0.03). The time since donation and, surprisingly, smoking status were not associated with this risk (). However, the time since donation was significantly associated with the development of albuminuria (odds ratio, 1.12, 95% CI, 1.05 to 1.20; P<0.001). Albuminuria was less likely to develop in women. The risk of hypertension increased with age (odds ratio, 1.09; 95% CI, 1.04 to 1.13; P<0.001) and with a higher body-mass index (odds ratio, 1.12; 95% CI, 1.04 to 1.21; P = 0.003).
Multivariable Risk of Reduced Iohexol Glomerular Filtration Rate (GFR), Albuminuria, and Hypertension in 255 Kidney Donors.*
HEALTH STATUS AND QUALITY OF LIFE
The current health status of the 255 donors who underwent measurement of iohexol GFR was compared with that of 255 controls from NHANES who were matched for age, sex, race or ethnic group, and body-mass index.15
Donors had a lower estimated GFR, lower systolic blood pressure, and a lower urinary albumin excretion rate (). Hemoglobin, glucose, cholesterol, triglyceride and high-density lipoprotein cholesterol levels were lower in the donors than in the controls. Donors were less likely than controls to be smokers and were less likely to report having received a diagnosis of cancer. Self-reported diabetes and use of antihypertensive medications were similar in the two groups. These patterns in self-reported conditions and laboratory measurements persisted beyond the first 20 years after kidney donation. In 55 donors who had a measured iohexol GFR and had donated a kidney more than 20 years before, the serum creatinine level was 1.1±0.2 mg per deciliter (93±20 µmol per liter), and the iohexol GFR was 74.0±13.8 ml per minute per 1.73 m2
. As compared with the NHANES controls, these 55 donors had a lower GFR but similar urinary albumin excretion. There was no significant difference in the prevalence of diabetes, use of antihypertensive medications, or cancer between the donors and the controls (). To strengthen this comparison, we used data that we obtained from the pool of donors who had donated a kidney more than 20 years before. There are 1445 such donors, and 1035 responded to our health survey, provided laboratory results, or did both. The findings in this larger group were similar to those in the two other groups ().
Current Health Status of Kidney Donors with Measured Glomerular Filtration Rate (GFR).*
Health Status of Kidney Donors More Than 20 Years after Donation.*
The physical-health summary score (53.6±7.4) and the mental-health summary score (52.6±7.7) for the 255 donors were significantly above the U.S. population norms (P<0.001 for both comparisons) (). To determine whether donors, who were considered very healthy at the time of donation in order to donate, were “losing ground” over time, age- and sex-adjusted difference scores were plotted according to the time since donation (). The bivariate correlations were small and not significant (physical-health summary score, r = −0.11 [P = 0.10]; mental-health summary score, r = 0.03 [P = 0.69]).
Quality-of-Life Scores for Kidney Donors