Health Inequities in Likelihood and Time to Renal Recovery after Living Kidney Donation: Implications for Black American Kidney Health

Abstract

Introduction:

Live donor kidney transplantation has been popularized to help mitigate the organ shortage crisis. At the time of living donor nephrectomy, living donors lose 50% of their kidney function or glomerular filtration rate (GFR). Studies have shown that in healthy living donors, the remaining kidney is able to adapt and recover 10–25% of post-donation lost GFR. GFR recovery is critical to long-term kidney health, particularly for Black Americans who disproportionately suffer from kidney disease with an incidence 2.5-times whites. To date, no study has examined whether health inequities in renal recovery post-donation exist.

Methods:

We retrospectively analyzed 100,121 living kidney donors reported to the Scientific Registry of Transplant Recipients between 1999–2021. We estimated GFR (eGFR) using the CKD-EPI 2021 equation and predicted the likelihood (logistic regression) and time (Cox regression) to recovery of 60% and 75% pre-donation eGFR. Models adjusted for age, sex, race, BMI, and pre-donation eGFR.

Results:

Blacks were 47% (aOR: 0.53, 95%CI: 0.50–0.56, p<0.001) and 43% (aOR: 0.57, 95%CI: 0.54–0.60, p<0.001) less likely to recover 60% and 75% of pre-donation eGFR, respectively, compared to their white counterparts. Moreover, the hazard ratio for time to renal recovery of 60% and 75% of pre-donation eGFR was 22% (aHR: 0.78, 95%CI 0.76–0.80, p<0.001) and 38% (aHR: 0.62, 95%CI 0.60–0.65, p<0.001) lower, respectively, than Whites.

Conclusion:

Black living kidney donors were less likely to recover pre-donation eGFR, and time to renal recovery was significantly longer than their White counterparts. These data highlight the need for enhanced living kidney donor follow-up, particularly for Black living kidney donors who are at greatest future risk of ESKD.

INTRODUCTION

Live donor kidney transplantation is currently the best solution to address the global organ shortage and provides superior outcomes to deceased donor transplantation.¹ However, it is not without risks to the living donor. While the absolute risks of end-stage kidney disease and mortality are low,^2–4 there is conflicting evidence on risk of development of comorbid diseases that are proximal endpoints of end organ damage when compared to non-donor populations. Some have demonstrated increased risk for hypertension,^5–8 particularly in the setting of obesity and post-donation weight gain,⁹ while others have shown no increased risk for hypertension,^10,11 diabetes,^10–12 or cardiovascular disease.^6,10,11 These risks must be balanced in the face of improved recipient outcomes and the benefit that many donors experience from their donation.^13,14

At the time of living donor nephrectomy, donors lose approximately 50% of their kidney function.¹⁵ Reassuringly, in healthy living donors, the remaining kidney is able to adapt and recover 10–25% of lost estimated glomerular filtration rate (eGFR).¹⁶ However, a small reduction in kidney function has been linked to cardiovascular and all-cause mortality in the general population.¹⁷ Studies that have investigated early post-donation eGFR have reported that low eGFR in the early post-donation period is associated with greater risk of renal insufficiency.^18,19 Thus, GFR recovery is critical to long-term kidney health, particularly for Black Americans who disproportionately suffer from kidney disease, with an incidence 2.5 times that of their White counterparts.

Black transplant candidates face disparate access to living kidney donor transplantation,²⁰ which can be partly explained by high racial concordance²¹ and a greater prevalence of comorbid diseases among Black individuals.^22,23 To ameliorate these disparities, it is critical to understand both intermediate and long-term outcomes, as early identification of precursors of organ damage can be slowed or halted.²⁴ Improving our understanding of proximal endpoints of end-stage organ disease will not only identify those who may be at greatest risk of long-term comorbid disease development and allow for intervention early in the disease process but will also enhance informed consent conversations and ensure that donors receive comprehensive follow-up care. To date, only one study has examined racial differences in kidney function in the early post-donation period and found no significant differences in eGFR between Black and White donors.²⁵ However, this study did not analyze post-donation eGFR relative to baseline function and was limited to a median of 52 days of follow-up among Black donors. Thus, our study sought to examine whether Black American donors differ from White donors in their likelihood of recovering kidney function within two years of living donation.

METHODS

This study used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donor, wait-listed candidates, and transplant recipients in the U.S., submitted by members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA) U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors.

Study population

Initially we selected 102,965 living kidney donors aged 18 years or older who donated from January 1, 1999 to December 31, 2021 and had both pre- and post-operative serum creatinine measurements. Donor eGFR was calculated using the 2021 eGFR formula at baseline, 6, 12, and 24 months if patients had measured serum creatinine. Percent eGFR recovery was subsequently calculated at each time relative to the donor’s baseline eGFR. Patients were excluded if they had pre-operative eGFR values less than 60 ml/min/1.73m² (n=1540). An additional 1304 donors were excluded after dropping postop records where eGFR recovery exceeded 99.4%. Our final cohort consisted of 100,121 kidney donors with 1 to 3 post donation eGFR measurements.

Outcomes and exposures

Recovery of pre-donation kidney function was assessed using two thresholds (60% and 75%) for eGFR recovery. Observation time was set as either the time to first exceeding the relevant eGFR threshold or, if the threshold was not achieved, to the donors last available measurement time. We generated descriptive statistics for our cohort using means and standard deviations for continuous variables and counts and percentages for categorical variables. Bivariate analyses utilized Chi-square, t-test, and Kaplan-Meier analysis, as appropriate. Multivariable logistic regression was utilized to estimate odds of eGFR recovery greater than both 60% and 75% within 24 months. Cox proportional hazards models were also fit to evaluate factors associated with time to eGFR recovery to > 60% and > 75%, Multivariable models accounted for patient characteristics including gender, age at donation, race, preoperative body mass index (BMI), preoperative mean arterial pressure (MAP), preoperative eGFR, and transplant year. Preoperative BMI was operationalized as a binary factor indicating pre-donation obesity (BMI ≥30 kg/m²). Similarly, preoperative eGFR was categorized into groups consisting of 60–80, 80–90, 90–100, and 100 or greater ml/min/1.73m². Models utilized 94,333 (93%) patients due to missing values in preoperative MAP (n=4230) and BMI (n=3049). The proportional hazards assumption was confirmed by Schoenfeld residual plots, which showed constant hazards over time. We also explored one-way interaction terms to test for the presence of effect modification. Statistical analyses were performed using R (version 4.2.1, 2022), and all statistical tests were two sided, with p <0.05 considered significant.

RESULTS

Among the 100,121 living donors from 1999–2021, 62.4% were female, 10.3% were Black, 3.7% were Asian, 84.6% were White, and 1.4% were of another race (Table 1). The majority were female (62.4%), with a mean age of 42.4 years (SD: 11.9). Mean pre-operative BMI, MAP, and eGFR were 26.9 kg/m² (SD: 4.3), 89.8 mmHg (SD: 9.5), and 99.6 ml/min/1.73m² (SD: 16.0), respectively. Overall, 30.5% had postop eGFR records indicating recovery of at least 75% of their pre-donation eGFR within 2 years of donation. When stratifying by recovery of 75% of pre-donation eGFR within 2 years, a higher proportion of females achieved the threshold compared to males (33.3% vs. 25.8%, p < 0.001). Donors of Asian race comprised the largest group who attained 75% pre-donation eGFR (35.5%), followed by White (31.0%), other race (29.5%), and Black donors (24.8%, p < 0.001). A lower proportion of those with obesity achieved 75% pre-donation eGFR compared to non-obese donors (28.8% vs. 30.9%, p < 0.001), and donors who recovered were younger (40.3 vs. 43.3 years, p < 0.001). We also explored a threshold of 60% recovery of pre-donation eGFR, with similar findings, although the percentage achieving at least 60% was greater at 83.3% (Table S1).

Table 1.

Demographics for living donors with post-donation creatinine measurements.

	Overall (N=100,121)	eGFR recovered 75% (N=30,515)	eGFR did not recover 75% (N=69,606)	p
Age, mean (SD)	42.4 (11.9)	40.3 (11.8)	43.3 (11.8)	< 0.001
Pre-donation BMI, mean (SD)	26.9 (4.3)	26.5 (4.3)	27.0 (4.2)	< 0.001
BMI ≥ 30, N(%)	22,070 (22.0)	6,365 (28.8)	15,705 (71.2)	< 0.001
Pre-donation eGFR, mean (SD)	99.6 (16.0)	98.1 (17.9)	100.3 (15.1)	< 0.001
Mean arterial pressure, mean (SD)	89.8 (9.5)	89.1 (9.4)	90.2 (9.5)	< 0.001
Sex, N(%)
Male	37,667 (37.6)	9,728 (25.8)	27,939 (74.2)	< 0.001
Female	62,454 (62.4)	20,787 (33.3)	41,667 (66.7)
Race
Asian	3,730 (3.7)	1,323 (35.5)	2,407 (64.5)	< 0.001
Black	10,297 (10.3)	2,555 (24.8)	7,742 (75.2)
White	84,698 (84.6)	26,225 (31.0)	58,473 (69.0)
Other	1,396 (1.4)	412 (29.5)	984 (70.5)

In a logistic regression model adjusting for age at donation, sex, and race along with pre-operative BMI, MAP, and eGFR; Black donors had a significantly lower odds than White donors of an observed eGFR within 2 years of donation that was greater than 75% of pre-donation eGFR [odds ratio (OR): 0.57, 95% confidence interval (CI): 0.54–0.60, p< 0.001] (Figure 1). Those of Asian race had a higher odds of observed recovery vs. Whites (OR: 1.27, 95% CI: 1.18–1.37, p < 0.001). Male sex, older age, greater pre-donation BMI, and higher pre-donation eGFR were associated with lower odds of recovery.

Figure 1.

Multivariable logistic regression for observed recovery of 60% and 75% preoperative eGFR within 2 years by race

In time to event analyses, Black donors recovered 75% of pre-donation eGFR more slowly than White and Asian donors (log-rank p-value < 0.001) (Figure 2). In a multivariable model adjusting for donor age, sex, MAP, pre-operative BMI, pre-donation eGFR, and transplant year, the likelihood of recovering 60% or 75% was lower for Blacks compared to Whites (hazard ratio (HR): 0.78, 95% CI: 0.76–0.80, p < 0.001; HR: 0.62, 95% CI: 0.60–0.65, p < 0.001) (Table 2). Male sex, older age, higher pre-operative BMI, and higher pre-donation eGFR were all associated with lower likelihood of recovery at either threshold (all p<0.01). Higher MAP was significantly associated with inhibited recovery to > 75% pre-operative eGFR (p=0.001), but not > 60% (p=0.30). We then explored one-way multiplicative interaction terms. There was a significant interaction between age and obesity, with older obese donors having the lowest likelihood of recovery compared to younger non-obese donors. We also observed a significant interaction between eGFR and both obesity and race, with obese donors and Black donors with greater pre-operative eGFR having lower likelihood of recovery than non-obese donors and White donors with lower eGFR, respectively. Finally, we observed a significant interaction between race and gender, with Black males having the lowest likelihood of recovery compared to White females. (Table S2 and Figure S1)

Figure 2.

Kaplan-Meier failure curve for time to observed recovery of 60% and 75% preoperative eGFR within 2 years by race

Table 2.

Cox proportional hazards regression for time to recovery

	Cox Model: Time to eGFR recovery >75%			Cox Model: Time to eGFR recovery >60%
Predictors	HR	CI	p	HR	CI	p
Age at donation (yr)	0.97	0.96 – 0.97	<0.001	0.98	0.98 – 0.98	<0.001
Male sex (ref=Female)	0.71	0.69 – 0.73	<0.001	0.88	0.87 – 0.89	<0.001
Race (ref=White)	1
Asian	1.24	1.17 – 1.32	<0.001	1.09	1.05 – 1.13	<0.001
Black	0.62	0.60 – 0.65	<0.001	0.78	0.76 – 0.80	<0.001
Other	0.88	0.80 – 0.98	0.015	0.91	0.86 – 0.97	0.002
Mean arterial blood pressure (per 10 mmHg)	0.98	0.97 – 0.99	0.001	1	0.99 – 1.00	0.299
Pre-operative obesity (BMI≥30)	0.95	0.92 – 0.98	<0.001	0.93	0.91 – 0.94	<0.001
Preop eGFR (ref=60 – 80)	1
80 – 90	0.64	0.61 – 0.66	<0.001	0.84	0.81 – 0.86	<0.001
90 – 100	0.46	0.44 – 0.48	<0.001	0.72	0.70 – 0.74	<0.001
100 – 200	0.36	0.35 – 0.37	<0.001	0.61	0.59 – 0.62	<0.001
Transplant year	0.99	0.99 – 1.00	<0.001	1.02	1.01 – 1.02	<0.001
Observations	94,333			94,333
R2Nagelkerke	0.062			0.062

DISCUSSION

In this retrospective cohort study using national data on 100,121 prior living kidney donors, we assessed racial differences in post-donation eGFR recovery and found that Black donors, in particular males were less likely and took longer than their White counterparts to recover 75%, or even 60%, of their pre-donation kidney function. We also found that older age, male sex, higher pre-donation eGFR, and higher pre-donation BMI were associated were lower likelihood of recovery at either threshold.

Previous studies have looked at kidney function early in the post-donation period. In a prospective cohort study, Kasiske et al. reported that eGFR declines immediately after donation and continues to recover for up to three years post-donation.²⁶ However, this study did not report recovery of eGFR relative to baseline eGFR, nor did it differentiate eGFR recovery by race, with the authors acknowledging the homogeneity of their study cohort. A study of time-zero biopsies from living donors showed that presence of chronic histologic changes at baseline was associated with suboptimal recovery of post-donation function.²⁷ While single center studies benefit from more granular data and internal validity, national registry studies permit generalizations to the larger donor population, as they represent the entirety and diversity of the donation experience. Others like Massie et al. have utilized national data linked to other data sources to show that for every 10 ml/min/1.73m² reduction in 6 month post-donation eGFR, the risk of ESKD increased by 28%, and that the immediate 50% reduction in nephron mass may not be endured equally for donors with similar pre-donation eGFRs.¹⁸ Our finding that Black males have the lowest likelihood of recovery provides additional insight into donors who might be particularly vulnerable to increased ESKD risk and may benefit from earlier and longer-term follow-up.

The estimated attributable risk of donation on ESKD depends largely on the selected control group. In comparison to the general population, living donors have no increased or decreased risk of ESKD.^2,4 However, when comparing to well-matched healthy non-donors there is an increased risk of ESKD among the donor group,^2,28 with Black donors at the highest risk of all groups studied.² It is important to remember that not all Black donors develop kidney failure, and the absolute risk of ESKD among donors is very low. Taken together with these studies, our findings suggest that these donors should have access to intensive follow-up and interventions aimed at reducing or even removing modifiable factors that enhance baseline risk, including obesity and metabolic dysfunction. Hence, the study of precursors of kidney disease, such as hypertension, diabetes, and early evidence of low eGFR is both timely and informative.

As with any analysis of national registry data, our study is not without limitations. There may be residual confounding from variables not captured in the SRTR database, but we attempted to control for factors known to be associated with kidney function in the literature. The value used for eGFR was based on the 2021 CKD-EPI race-free equation, which is known to underestimate kidney function in Black patients. However, estimation of kidney function can still offer a valuable tool for general practitioners with whom donors resume their care post-donation, allowing for early identification of underlying disease and potential slowing of the disease process.

In this retrospective cohort analysis of living donors in the US, we found that Black living donors were less likely to recover pre-donation eGFR, and time to renal recovery was significantly longer than their White counterparts. These data highlight the need for enhanced living kidney donor follow-up, particularly for Black living donors who are at greatest future risk of ESKD.