Hypertension and Kidney Function After Living Kidney Donation

Abstract

ImportanceRecent guidelines call for better evidence on health outcomes after living kidney donation.ObjectiveTo determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared.Design, Setting, and ParticipantsProspective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics.ExposureLiving kidney donation.Main Outcomes and MeasuresHypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g]).ResultsAmong the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors’ eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19).Conclusions and RelevanceIn this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up.Trial RegistrationClinicalTrials.gov Identifier: NCT00936078

Donation-Attributable Risk—A Call to Action

“…Over a median of 7 years of follow-up with more than 100 000 blood pressure measurements, the authors found no difference in hypertension or albuminuria between donors and nondonor control participants, and as expected with aging, donors and nondonors had a similar average increase in systolic blood pressure. Moreover, they demonstrated that at 12 months postdonation, donors had a slower rate of decline in estimated glomerular filtration rate (eGFR) compared to nondonors . These results are encouraging and provide real-world evidence that uninephrectomy does not increase a living donor’s future risk for hypertension.…”

“…The gap addressed, however, is much smaller than we hoped. While impressive in duration, follow-up, and robustness of nondonor controls, the Garg et al study is hampered by an ethnically and racially homogenous donor population, with only 14 of 954 donors identifying as Black, that no longer reflects modern-day living kidney donor populations as the study cohort had a median BMI (calculated as weight in kilograms divided by height in meters squared) of 26 and 25 among donors and nondonor controls, respectively . This lack of generalizability is poignant as hypertension has been recognized as a precursor and cause of future kidney failure .…”

“…The needle on our understanding of donation-attributable risk for hypertension has definitively moved as Garg and colleagues report results from their prospective cohort study that included the most rigorous and robust cohort of nondonor controls ever reported for assessing donation-attributable risk that achieved the highest score for methodological quality on the Newcastle-Ottawa Quality Assessment Scale. Nondonor control participants included individuals who were evaluated and approved for living donation but did not go on to donate and who underwent follow-up measurements and testing with the same frequency and intervals as the living donors.…”