Changes in kidney function follow living donor nephrectomy
Authors: Ngan N. Lam, Anita Lloyd, Krista L. Lentine, Robert R. Quinn, Pietro Ravani, Brenda R. Hemmelgarn, Scott Klarenbach, Amit X. Garg
Journal: Kidney International (2020)

Better understanding of kidney function after living donor nephrectomy and how it differs by donor characteristics can inform patient selection, counselling, and follow-up care. To evaluate this, we conducted a retrospective matched cohort study of living kidney donors in Alberta, Canada between 2002-2016, using linked healthcare administrative databases. We matched 604 donors to 2,414 healthy non-donors from the general population based on age, sex, year of cohort entry, urban residence and the estimated glomerular filtration rate (eGFR) before cohort entry (nephrectomy date for donors and randomly assigned date for non-donors). The primary outcome was the rate of eGFR change over time (median follow-up seven years; maximum 15 years). The median age of the cohort was 43 years, 64% women, and the baseline (pre-donation) eGFR was 100 mL/min/1.73 m2. Overall, from six weeks onwards, the eGFR increased by +0.35 mL/min/1.73 m2 per year (95% confidence interval +0.21 to +0.48) in donors and significantly decreased by -0.85 mL/min/1.73 m2 per year (-0.94 to -0.75) in the matched healthy non-donors. The change in eGFR between six weeks to two years, two to five years, and over five years among donors was +1.06, +0.64, and -0.06 mL/min/1.73 m2 per year, respectively. In contrast to the steady age-related decline in kidney function in non-donors, post-donation kidney function on average initially increased by 1 mL/min/1.73 m2 per year attributable to glomerular hyperfiltration, which began to plateau by five years post-donation. Thus, the average change in eGFR over time is significantly different between donors and non-donors. Better understanding of kidney function after living donor nephrectomy and how it differs by donor characteristics can inform patient selection, counselling, and follow-up care. To evaluate this, we conducted a retrospective matched cohort study of living kidney donors in Alberta, Canada between 2002-2016, using linked healthcare administrative databases. We matched 604 donors to 2,414 healthy non-donors from the general population based on age, sex, year of cohort entry, urban residence and the estimated glomerular filtration rate (eGFR) before cohort entry (nephrectomy date for donors and randomly assigned date for non-donors). The primary outcome was the rate of eGFR change over time (median follow-up seven years; maximum 15 years). The median age of the cohort was 43 years, 64% women, and the baseline (pre-donation) eGFR was 100 mL/min/1.73 m2. Overall, from six weeks onwards, the eGFR increased by +0.35 mL/min/1.73 m2 per year (95% confidence interval +0.21 to +0.48) in donors and significantly decreased by -0.85 mL/min/1.73 m2 per year (-0.94 to -0.75) in the matched healthy non-donors. The change in eGFR between six weeks to two years, two to five years, and over five years among donors was +1.06, +0.64, and -0.06 mL/min/1.73 m2 per year, respectively. In contrast to the steady age-related decline in kidney function in non-donors, post-donation kidney function on average initially increased by 1 mL/min/1.73 m2 per year attributable to glomerular hyperfiltration, which began to plateau by five years post-donation. Thus, the average change in eGFR over time is significantly different between donors and non-donors. see commentary on page 57 see commentary on page 57 Following donor nephrectomy, there is a 25%–40% early reduction in glomerular filtration rate (GFR), rather than a 50% reduction, due to the compensatory hyperfiltration of the remaining kidney.1Garg A.X. Muirhead N. Knoll G. et al.Proteinuria and reduced kidney function in living kidney donors: a systematic review, meta-analysis, and meta-regression.Kidney Int. 2006; 70: 1801-1810Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar, 2Kasiske B.L. Anderson-Haag T. Israni A.K. et al.A prospective controlled study of living kidney donors: three-year follow-up.Am J Kidney Dis. 2015; 66: 114-124Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 3Gourishankar S. Courtney M. Jhangri G.S. et al.Serum cystatin C performs similarly to traditional markers of kidney function in the evaluation of donor kidney function prior to and following unilateral nephrectomy.Nephrol Dial Transplant. 2008; 23: 3004-3009Crossref PubMed Scopus (23) Google Scholar A systematic review of 8 studies reported that 12% of donors developed a GFR between 30 and 59 ml/min per 1.73 m2, and 0.2% had a GFR <30 ml/min per 1.73 m2 over a mean follow-up that ranged between 3 and 20 years.1Garg A.X. Muirhead N. Knoll G. et al.Proteinuria and reduced kidney function in living kidney donors: a systematic review, meta-analysis, and meta-regression.Kidney Int. 2006; 70: 1801-1810Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar However, many studies that assessed postdonation renal function are limited by small sample sizes, lack of appropriate nondonor control groups, and significant loss to follow-up.1Garg A.X. Muirhead N. Knoll G. et al.Proteinuria and reduced kidney function in living kidney donors: a systematic review, meta-analysis, and meta-regression.Kidney Int. 2006; 70: 1801-1810Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar,4Li S.S. Huang Y.M. Wang M. et al.A meta-analysis of renal outcomes in living kidney donors.Medicine (Baltimore). 2016; 95: e3847Crossref PubMed Scopus (15) Google Scholar,5Waterman A.D. Dew M.A. Davis C.L. et al.Living-donor follow-up attitudes and practices in U.S. kidney and liver donor programs.Transplant J. 2013; 95: 883-888Crossref Scopus (34) Google Scholar Studies with more donors lost to follow-up demonstrate a larger decrement in GFR after donation.1Garg A.X. Muirhead N. Knoll G. et al.Proteinuria and reduced kidney function in living kidney donors: a systematic review, meta-analysis, and meta-regression.Kidney Int. 2006; 70: 1801-1810Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar A prospective study with excellent follow-up reported renal function at 6 months, and 1, 2, and 3 years after donation for 182 living kidney donors and 173 nondonor controls.2Kasiske B.L. Anderson-Haag T. Israni A.K. et al.A prospective controlled study of living kidney donors: three-year follow-up.Am J Kidney Dis. 2015; 66: 114-124Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar At 3 years of follow-up, the average measured GFR by plasma iohexol clearance for donors was 78 versus 104 ml/min for nondonor controls. From months 6 to 36, the measured GFR for all donors increased at an annual rate of +1.5 ml/min, whereas it decreased at an annual rate of –0.4 ml/min for nondonor controls. In this study, age did not have an effect on the rate of change in measured GFR; however, this study was limited by the relatively short observation period. A better understanding of the trends in postdonation GFR, and how this varies by donor characteristics, can inform the evaluation, selection, and counseling of living kidney donor candidates. Recognizing the risk factors associated with a greater ongoing loss of postdonation GFR may also enable physicians to identify donors who could benefit from closer monitoring and surveillance. We performed a retrospective cohort study using healthcare administrative databases in Alberta, Canada to describe the trends in postdonation GFR in living kidney donors. We matched 604 living kidney donors to 2414 healthy nondonors from the general population. The baseline characteristics for the cohort are presented in Table 1. The median age was 43 years (interquartile range [IQR], 33–51) and 64% were women. As expected, living kidney donors had more physician visits in the year prior to the index date compared to nondonors, likely related to their evaluation process (11 vs. 2). The median predonation estimated GFR (eGFR) was 100 ml/min per 1.73 m2 (IQR, 88–112), and 12% of donors had pre-existing hypertension.Table 1Baseline characteristics of living kidney donors and matched, healthy, nondonor controlsCharacteristicLiving kidney donors (n = 604)Healthy nondonors (n = 2414)Standardized difference (%)aStandardized difference provides a measure of difference between groups divided by pooled SD. A value of >10% is interpreted as a meaningful difference between groups.Age, yr42.6 [33.4, 51.0]43.1 [33.4, 51.3]0.7 18–30102 (16.9)416 (17.2)2.7 31–40149 (24.7)569 (23.6) 41–50175 (29.0)717 (29.7) >50178 (29.5)712 (29.5)Women389 (64.4)1554 (64.4)0Socioeconomic statusbIncome was categorized according to fifths of average neighborhood income. Lowest (level = 1)102 (17.2)456 (19.3)8.5 Middle (level = 3)138 (23.2)484 (20.5) Highest (level = 5)125 (21.0)516 (21.8) Missing10 (1.7)47 (1.9)NAUrban residencecUrban indicates a population >10,000 or a population >1000 with population density >400/km2.535 (88.6)2140 (88.6)0Distance to transplant center,dFor distance from the transplant center, >500 km was imputed as 500 km. km35 [20, 225]30 [15, 120]20.8 <50348 (57.7)1593 (66.1)21.4 50.1–15077 (12.8)280 (11.6) 150.1–30099 (16.4)357 (14.8) >30079 (13.1)179 (7.4) Missing1 (0.2)5 (0.2)NAYear of cohort entry 2002–2006169 (28.0)679 (28.1)1.2 2007–2011198 (32.8)801 (33.2) 2012–2016237 (39.2)934 (38.7)Transplant center Southern Alberta255 (42.2)NANA Northern Alberta349 (57.8)NANAPhysician visits in the prior yreIncludes all visits/measurements, even if multiple visits/measurements occurred on the same day.11 [8.5, 15]2 [1, 2]294Serum creatinine measurements in the prior yreIncludes all visits/measurements, even if multiple visits/measurements occurred on the same day.3 [3, 4]1 [0, 1]314eGFR category in the prior yr,fLaboratory values were based on the most recent measurement (inpatient, outpatient, or emergency room) in the 1 yr prior to the index date. eGFR was calculated using the Chronic Kidney Disease–Epidemiology Collaboration equation.6,7 Albuminuria was defined by ACR, PCR, or urine dipstick result and categorized based on the Kidney Disease: Improving Global Outcomes definition as none/mild (A1: dipstick negative or trace, PCR <15 mg/mmol, or ACR <30 mg/g), moderate (A2: dipstick 1+, PCR 15–50 mg/mmol, or ACR 30–300 mg/g), and severe (A3: dipstick ≥2+, PCR ≥51 mg/mmol, or ACR ≥301 mg/g).8–11 ml/min per 1.73 m2100.0 [88.2, 112.2]99.8 [87.3, 112.8]2.4 ≥90432 (71.5)950 (71.3)7.2 80–89103 (17.1)221 (16.6) 70–7949 (8.1)130 (9.8) 60–6920 (3.3)31 (2.3) Missing0 (0)1082 (44.8)NAAlbuminuria measurements in the prior yreIncludes all visits/measurements, even if multiple visits/measurements occurred on the same day.5 [4, 7]0 [0, 1]313Albuminuria category in the prior yrfLaboratory values were based on the most recent measurement (inpatient, outpatient, or emergency room) in the 1 yr prior to the index date. eGFR was calculated using the Chronic Kidney Disease–Epidemiology Collaboration equation.6,7 Albuminuria was defined by ACR, PCR, or urine dipstick result and categorized based on the Kidney Disease: Improving Global Outcomes definition as none/mild (A1: dipstick negative or trace, PCR <15 mg/mmol, or ACR <30 mg/g), moderate (A2: dipstick 1+, PCR 15–50 mg/mmol, or ACR 30–300 mg/g), and severe (A3: dipstick ≥2+, PCR ≥51 mg/mmol, or ACR ≥301 mg/g).8–11 None/mild586 (97.8)900 (96.2)9.6 Moderate13 (2.2)36 (3.9) Severe0 (0)0 (0) Missing5 (0.8)1478 (61.2)NAComorbid conditionsgComorbid conditions were based on algorithms of diagnostic or procedural codes in the 3 yr prior to donation for which the validations are presented in Supplementary Table S1, where available. Hypertension73 (12.1)0 (0)52.4 Asthma11 (1.8)0 (0)19.3 Chronic pulmonary disease11 (1.8)0 (0)19.3ACR, albumin–creatinine ratio; eGFR, estimated glomerular filtration rate; NA, not applicable; PCR, protein–creatinine ratio.Data are presented as median [interquartile range] or count (percent). Time of cohort entry (index date) was the nephrectomy date for donors and was randomly assigned to nondonors.a Standardized difference provides a measure of difference between groups divided by pooled SD. A value of >10% is interpreted as a meaningful difference between groups.b Income was categorized according to fifths of average neighborhood income.c Urban indicates a population >10,000 or a population >1000 with population density >400/km2.d For distance from the transplant center, >500 km was imputed as 500 km.e Includes all visits/measurements, even if multiple visits/measurements occurred on the same day.f Laboratory values were based on the most recent measurement (inpatient, outpatient, or emergency room) in the 1 yr prior to the index date. eGFR was calculated using the Chronic Kidney Disease–Epidemiology Collaboration equation.6Huang N. Foster M.C. Lentine K.L. et al.Estimated GFR for living kidney donor evaluation.Am J Transplant. 2016; 16: 171-180Crossref PubMed Scopus (31) Google Scholar,7Levey A.S. Inker L.A. GFR evaluation in living kidney donor candidates.J Am Soc Nephrol. 2017; 28: 1062-1071Crossref PubMed Scopus (28) Google Scholar Albuminuria was defined by ACR, PCR, or urine dipstick result and categorized based on the Kidney Disease: Improving Global Outcomes definition as none/mild (A1: dipstick negative or trace, PCR <15 mg/mmol, or ACR <30 mg/g), moderate (A2: dipstick 1+, PCR 15–50 mg/mmol, or ACR 30–300 mg/g), and severe (A3: dipstick ≥2+, PCR ≥51 mg/mmol, or ACR ≥301 mg/g).8Lamb E.J. MacKenzie F. Stevens P.E. How should proteinuria be detected and measured?.Ann Clin Biochem. 2009; 46: 205-217Crossref PubMed Scopus (173) Google Scholar, 9Hemmelgarn B.R. Clement F. Manns B.J. et al.Overview of the Alberta Kidney Disease Network.BMC Nephrol. 2009; 10: 30Crossref PubMed Scopus (182) Google Scholar, 10Tonelli M. Muntner P. Lloyd A. et al.Impact of age on the association between CKD and the risk of future coronary events.Am J Kidney Dis. 2014; 64: 1-8Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 11Andrassy K.M. Comments on 'KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.'.Kidney Int. 2013; 84: 622-623Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholarg Comorbid conditions were based on algorithms of diagnostic or procedural codes in the 3 yr prior to donation for which the validations are presented in Supplementary Table S1, where available. Open table in a new tab ACR, albumin–creatinine ratio; eGFR, estimated glomerular filtration rate; NA, not applicable; PCR, protein–creatinine ratio. Data are presented as median [interquartile range] or count (percent). Time of cohort entry (index date) was the nephrectomy date for donors and was randomly assigned to nondonors. The median follow-up was 6.6 years (IQR, 3.4–10.4) for donors and 6.8 years (IQR, 3.8–10.7) for nondonors, with a maximum follow-up of 14.7 years. By the end of study follow-up (March 31, 2017), the observed follow-up time was censored for the following reasons: 6 (1.0%) donors and 31 (1.3%) nondonors at the time of death, 0 (0%) donors and 3 (0.1%) nondonors at the time of developing end-stage renal disease, and 21 (3.5%) donors and 20 (0.8%) nondonors at the time they emigrated from the province. Based on the last available serum creatinine measurement, the majority of donors (60%) had an eGFR between 60 and 89 ml/min per 1.73 m2, whereas 29%, 1.7%, and 0.2% had an eGFR of 45–59, 30–44, and 15–29 ml/min per 1.73 m2, respectively (Table 2).Table 2eGFR (ml/min per 1.73 m2) category for donors and matched nondonor controls based on last available measurementeGFR categoryDonors (%)Controls (%)≥909.656.860–8959.941.545–5928.61.430–441.70.215–290.20.1<1500.1eGFR, estimated glomerular filtration rate. Open table in a new tab eGFR, estimated glomerular filtration rate. The 604 living kidney donors had a total of 7106 serum creatinine measurements after the index date, compared to 15,970 serum creatinine measurements for the 2414 nondonors. For both groups, most serum creatinine measurements were done in the outpatient setting (62% for donors and 76% for nondonors). From 6 weeks onward, donors had a median of 7 (IQR, 3–11) serum creatinine measurements compared to 4 (IQR, 3–7) for nondonors during follow-up. The median time between measurements was 214 days (IQR, 133–359) for donors versus 359 days (IQR, 183–500). The median number of measurements per year was 1.1 (IQR, 0.7–1.6) for donors and 0.8 (IQR, 0.5–1.2) for nondonors. The mean eGFRs at various timepoints, for donors and nondonors, are presented in Figure 1, whereas the median eGFR values are presented in Supplementary Table S2. Overall, the eGFR on average increased by +0.35 ml/min per 1.73 m2 per year (95% confidence interval [CI], +0.21 to +0.48) in donors and decreased by –0.85 ml/min/1.73 m2 per year (95% CI, –0.94 to –0.75) in nondonors (P < 0.001; Table 3). Based on the linear spline model, the average change in eGFR between 6 weeks to <2 years, 2 to <5 years, and ≥5 years onward in donors was +1.06 (95% CI, +0.41 to +1.72), +0.64 (95% CI, +0.30 to +0.98), and –0.06 (95% CI, –0.31 to +0.19) ml/min per 1.73 m2 per year, respectively. Among nondonors, the rate of change in eGFR during these time periods did not differ substantially and remained consistently negative over time (Table 3).Table 3Change in eGFR (ml/min per 1.73 m2 per year) in donors and matched nondonor controls from 6 wk onwardModelDonors (n = 566)aA total of 38 living kidney donors did not have serum creatinine measurements beyond the 6 wk following donation, so their matched controls were also excluded from this analysis.Controls (n = 2259)aA total of 38 living kidney donors did not have serum creatinine measurements beyond the 6 wk following donation, so their matched controls were also excluded from this analysis.P valueOverall+0.35 (+0.21, +0.48)–0.85 (–0.94, –0.75)<0.001Linear spline model 6 wk to <2 yr+1.06 (+0.41, +1.72)–0.89 (–1.41, –0.37)<0.001 2 to <5 yr+0.64 (+0.30, +0.98)–0.64 (–0.93, –0.35)<0.001 ≥5 yr–0.06 (–0.31, +0.19)–0.97 (–1.13, –0.81)<0.001eGFR, estimated glomerular filtration rate.Change in eGFR is presented as mean (95% confidence interval).Results are from both the primary model (overall, where the change in eGFR over time is represented as a single slope) and the secondary model (linear spline model, where the change in eGFR over time is allowed to change).a A total of 38 living kidney donors did not have serum creatinine measurements beyond the 6 wk following donation, so their matched controls were also excluded from this analysis. Open table in a new tab eGFR, estimated glomerular filtration rate. Change in eGFR is presented as mean (95% confidence interval). Results are from both the primary model (overall, where the change in eGFR over time is represented as a single slope) and the secondary model (linear spline model, where the change in eGFR over time is allowed to change). The mean eGFR at various timepoints for the donor subgroup analyses are presented in Figure 2. The average predonation eGFR was higher in younger donors compared to older donors (115 ml/min per 1.73 m2 for donors aged 18–30 years vs. 89 ml/min per 1.73 m2 for donors aged >50 years; Table 4). Younger donors (18–30 years old) experienced a 33% decline in eGFR in the first 6 weeks after donation, compared to a 35%–37% decline in older donors. From 6 weeks onward, there was no significant difference in the average change in eGFR over time based on age category (P > 0.05 for omnibus test of interaction terms; Table 5).Figure 2Estimated glomerular filtration rate (eGFR in ml/min per 1.73 m2) in living kidney donors by subgroup during follow-up: (a) age (yr); (b) sex; (c) predonation hypertension; (d) predonation eGFR category (ml/min per 1.73 m2); (e) eGFR reduction (%) in the first 6 weeks; (f) eGFR category (ml/min per 1.732) at 1 year; (g) socioeconomic status; and (h) distance to the transplant center (km).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table 4Mean eGFR (ml/min per 1.73 m2) in living kidney donors by subgroup during follow-upCharacteristicPredonation6 wk1 yr2 yr4 yr6 yr8 yr10 yrAge (yr) 18–30115.4 (13.5)77.4 (13.4)80.6 (15.7)82.3 (14.5)85.2 (18.0)82.8 (14.2)79.4 (11.6)81.0 (19.1) 31–40106.3 (13.2)69.2 (13.5)72.6 (13.2)73.0 (12.0)75.1 (14.0)73.8 (13.9)74.7 (13.7)70.5 (11.0) 41–5097.2 (13.5)61.4 (10.9)63.3 (10.6)65.0 (10.3)64.9 (10.0)67.0 (11.1)65.2 (10.3)63.2 (10.0) >5088.7 (11.1)57.5 (9.1)57.7 (9.8)58.4 (9.8)58.4 (8.9)61.5 (10.7)62.4 (10.0)62.2 (10.3)Sex Female100.6 (16.0)66.1 (13.9)67.0 (14.8)68.0 (14.6)65.5 (13.5)69.7 (14.1)69.4 (13.2)67.7 (13.1) Male98.9 (15.7)61.8 (12.0)64.3 (13.4)64.9 (12.1)68.6 (15.9)66.0 (12.6)66.2 (11.7)65.1 (12.8)Predonation hypertension Yes95.0 (15.3)61.6 (14.8)62.1 (13.7)63.0 (12.5)69.0 (17.7)66.3 (14.5)69.3 (14.9)65.2 (13.2) No100.7 (15.8)65.1 (13.1)66.7 (14.3)67.6 (14.0)67.4 (14.7)69.0 (13.6)68.1 (12.4)67.1 (13.0)Predonation eGFR category (ml/min per 1.73 m2) ≥90107.8 (10.9)69.1 (12.6)71.1 (13.7)71.6 (13.1)72.9 (15.0)73.3 (12.6)71.7 (12.9)69.6 (12.7) 80–8985.3 (2.8)56.8 (8.4)56.3 (7.4)58.9 (9.0)58.9 (7.6)58.4 (7.2)59.3 (7.1)55.8 (7.6) <8073.1 (4.5)50.3 (6.4)52.2 (6.6)53.0 (7.3)52.4 (5.9)52.1 (6.7)58.7 (5.9)56.8 (8.3)eGFR reduction (%) in the first 6 wk ≤30105.9 (18.7)79.1 (17.9)73.3 (15.2)75.5 (14.6)85.6 (21.4)82.3 (16.8)78.1 (18.1)72.8 (11.9) 31–4099.9 (17.8)67.8 (15.4)70.3 (17.4)70.9 (15.9)70.7 (18.5)70.1 (15.7)71.0 (11.9)68.1 (14.1) >4099.7 (15.1)62.9 (11.9)64.4 (12.9)65.3 (12.7)66.6 (13.8)67.5 (12.6)66.5 (12.2)65.7 (12.9) Missing101.0 (14.8)48.1 (N/A)68.0 (13.1)63.6 (15.7)61.7 (15.6)63.8 (10.6)67.0 (16.1)66.2 (11.5)eGFR category (ml/min per 1.732) at 1 yr ≥90120.4 (10.3)90.1 (14.7)100.0 (9.3)92.2 (8.5)95.2 (14.8)92.9 (6.0)90.7 (8.6)100.2 (N/A) 80–89115.5 (9.3)82.4 (12.1)84.3 (2.7)83.7 (9.3)87.1 (11.4)89.1 (7.5)86.3 (12.9)80.5 (7.1) 60–79103.5 (11.5)66.4 (8.4)68.7 (5.5)69.7 (9.6)69.6 (9.9)72.0 (9.3)69.0 (8.5)70.1 (9.6) <6086.2 (10.9)54.0 (7.0)53.1 (4.7)55.4 (6.8)56.9 (7.9)57.7 (8.1)60.7 (7.9)58.2 (10.2) Missing102.8 (15.9)65.3 (12.4)N/A70.0 (14.7)69.3 (18.5)70.2 (16.4)69.4 (14.2)68.2 (14.6)Socioeconomic status Lowest (level = 1)105.9 (15.1)70.5 (15.0)72.1 (15.7)73.2 (14.6)74.2 (17.0)71.9 (15.9)71.0 (12.4)71.1 (18.5) Middle (level = 3)97.8 (16.2)61.8 (11.7)64.5 (14.3)64.7 (14.1)65.6 (14.2)67.3 (14.2)68.6 (12.5)65.0 (10.5) Highest (level = 5)98.3 (15.9)63.7 (12.5)63.8 (13.4)64.5 (12.5)63.9 (13.5)64.0 (10.0)66.6 (14.4)63.1 (8.9) Missing93.9 (19.8)55.1 (7.4)66.0 (8.6)74.7 (25.6)62.7 (N/A)N/AN/AN/ADistance to transplant center (km) <50100.0 (16.2)65.2 (14.2)66.0 (15.0)66.7 (14.5)67.1 (15.7)67.7 (13.2)66.1 (12.3)66.2 (13.1) 50.1–15098.5 (17.0)62.9 (12.0)64.7 (13.2)65.0 (12.8)65.5 (13.4)67.7 (13.3)68.3 (10.4)69.8 (9.3) 150.1–300101.5 (14.8)66.5 (14.3)67.3 (12.3)69.1 (12.8)69.8 (13.9)72.7 (15.4)72.8 (14.9)68.7 (12.7) >30099.4 (14.8)61.9 (9.5)66.3 (14.2)67.5 (12.6)69.8 (16.2)68.0 (14.5)70.9 (13.9)63.3 (17.0)eGFR, estimated glomerular filtration rate; N/A, not available/applicable.Data are presented as mean ± SD. Mean eGFR (based on Chronic Kidney Disease-Epidemiology Collaboration equation) was calculated using the most recent measurement in the 1 yr prior for predonation, and all measurements (i.e., inpatient, outpatient, or emergency room) ±3 wk for 6 wk, and ±6 mos for 1, 2, 4, 6, 8, and 10 yr. Open table in a new tab Table 5Changes in eGFR (ml/min per 1.73 m2 per year) in living kidney donors by subgroup over different time periods during follow-up from 6 weeks onwardaA total of 38 living kidney donors did not have serum creatinine measurements beyond the 6 wk following donation and were excluded from this analysis.CharacteristicPrimary modelSecondary modelOverall6 wk to <2 yr2 to <5 yr≥5 yrAge (yr) 18–300.42 (0.07, 0.77)2.11 (0.31, 3.91)0.73 (–0.21, 1.67)–0.51 (–1.17, 0.15) 31–400.22 (0.18, 0.67)1.73 (0.38, 3.09)0.13 (–0.57, 0.83)–0.20 (–0.68, 0.29) 41–500.43 (0.18, 0.67)1.49 (0.31, 2.67)0.65 (0.05, 1.26)–0.11 (–0.55, 0.34) >500.39 (0.14, 0.64)–0.01 (–1.07, 1.06)0.83 (0.27, 1.38)0.44 (–0.03, 0.92)Sex Female0.27 (0.10, 0.44)1.04 (0.23, 1.84)0.54 (0.12, 0.95)–0.08 (–0.39, 0.23) Male0.56 (0.33, 0.79)1.40 (0.29, 2.50)0.79 (0.23, 1.35)0.06 (–0.37, 0.49)Predonation hypertension Yes0.48 (0.12, 0.83)1.40 (–0.24, 3.03)0.77 (–0.04, 1.58)0.31 (–0.34, 0.95) No0.35 (0.20, 0.50)1.11 (0.40, 1.82)0.60 (0.23, 0.96)–0.09 (–0.36, 0.19)Predonation eGFR category (ml/min per 1.73 m2) ≥900.39 (0.23, 0.54)1.05 (0.27, 1.83)0.79 (0.39, 1.18)–0.12 (–0.40, 0.16) 80–890.16 (–0.17, 0.49)1.58 (0.003, 3.17)0.33 (–0.46, 1.12)–0.35 (–0.96, 0.26) <800.45 (0.01, 0.89)1.02 (–0.66, 2.69)–0.07 (–1.01, 0.87)1.13 (0.06, 2.20)eGFR reduction (%) in the first 6 wk ≤300.78 (0.18, 1.38)1.95 (–1.69, 5.59)0.09 (–1.90, 2.09)0.76 (–0.39, 1.91) 31–400.01 (–0.27, 0.29)0.85 (–0.49, 2.18)0.43 (–0.25, 1.12)–0.51 (–1.01, –0.01) >400.47 (0.30, 0.64)1.16 (0.39, 1.92)0.75 (0.35, 1.14)0.06 (–0.26, 0.37)eGFR category (ml/min per 1.732) at 1 yr ≥90–0.46 (–1.04, 0.12)–1.06 (–4.10, 1.98)–0.89 (–2.40, 0.62)0.14 (–0.95, 1.24) 80–890.09 (–0.44, 0.63)1.40 (–1.25, 4.05)0.86 (–0.51, 2.22)–0.93 (–1.93, 0.07) 60–790.44 (0.22, 0.65)0.69 (–0.31, 1.69)0.81 (0.30, 1.31)0.03 (–0.39, 0.45) <600.56 (0.32, 0.81)1.65 (0.61, 2.69)0.61 (0.06, 1.16)0.29 (–0.15, 0.73)Socioeconomic status Lowest (level = 1)0.31 (–0.01, 0.63)2.42 (0.78, 4.06)0.79 (0.02, 1.57)–0.59 (–1.15, –0.03) Middle (level = 3)0.48 (0.20, 0.76)1.43 (0.11, 2.75)0.60 (–0.09, 1.28)0.03 (–0.50, 0.56) Highest (level = 5)0.43 (0.13, 0.73)1.58 (0.22, 2.94)0.34 (–0.38, 1.07)0.11 (–0.45, 0.67)Distance to transplant center (km) <500.27 (0.09, 0.45)1.12 (0.29, 1.95)0.38 (–0.05, 0.81)–0.01 (–0.35, 0.33) 50.1–1500.60 (0.25, 0.95)0.93 (–0.86, 2.72)1.35 (0.52, 2.17)0.01 (–0.60, 0.63) 150.1–3000.60 (0.26, 0.93)1.00 (–0.74, 2.73)0.93 (0.05, 1.81)0.19 (–0.41, 0.79) >3000.25 (–0.14, 0.63)1.81 (0.00, 3.62)0.52 (–0.47, 1.50)–0.55 (–1.27, 0.17)eGFR, estimated glomerular filtration rate.Data are presented as change in eGFR (95% confidence interval).a A total of 38 living kidney donors did not have serum creatinine measurements beyond the 6 wk following donation and were excluded from this analysis. Open table in a new tab eGFR, estimated glomerular filtration rate; N/A, not available/applicable. Data are presented as mean ± SD. Mean eGFR (based on Chronic Kidney Disease-Epidemiology Collaboration equation) was calculated using the most recent measurement in the 1 yr prior for predonation, and all measurements (i.e., inpatient, outpatient, or emergency room) ±3 wk for 6 wk, and ±6 mos for 1, 2, 4, 6, 8, and 10 yr. eGFR, estimated glomerular filtration rate. Data are presented as change in eGFR (95% confidence interval). Although the predonation eGFR was similar between male and female donors (Table 4), the increase in eGFR over time was on average higher in male donors compared to female donors (+0.56 vs. +0.27 ml/min per 1.73 m2 per year; P = 0.045; Table 5). Donors with a history of hypertension had a lower predonation eGFR than donors without hypertension (95 vs. 101 ml/min per 1.73 m2; P = 0.004; Table 4), but a similar average postdonation increase in eGFR over time (+0.48 vs. +0.35 ml/min per 1.73 m2 per year; P = 0.53; Table 5). There were also no statistically significant differences in the change in eGFR over time based on the predonation eGFR category (P > 0.05 for omnibus test of interaction terms). The change in eGFR over time was modified by the initial percent decline in baseline eGFR within the first 6 weeks (P < 0.05 for omnibus test of interaction terms). Donors who experienced a >40% decline in baseline eGFR after donation on average had less of an increase in eGFR over time compared to donors who experienced a ≤30% decline from their baseline eGFR, although the results did not reach statistical significance (+0.47 vs. +0.78 ml/min per 1.73 m2 per year; P = 0.33; Table 5). Although eGFR over time increased for donors in the lower eGFR categories at 1 year (60–79 or <60 ml/min per 1.73 m2), eGFR over time in donors in the upper eGFR categories at 1 year (80–89 or ≥90 ml/min per 1.73 m2) did not significantly change (+0.09 and –0.46 ml/min per 1.73 m2 per year, respectively). The change in eGFR over time was significantly different in donors with an eGFR ≥90 ml/min per 1.73 m2 at 1-year postdonation versus donors in each of the lower 2 categories (P = 0.005 for eGFR 60–79 ml/min per 1.73 m2 and P = 0.001 for eGFR <60 ml/min per 1.73 m2, respectively; Table 5). The change in eGFR over time was not modified by either income category or distance-to-transplant-center category (P > 0.05 for omnibus test of interaction terms). In this retrospective study, we describe the postdonation trends in eGFR for 604 living kidney donors compared with 2414 healthy, matched nondonors in Alberta, Canada. We found that the eGFR increased by +0.35 ml/min per 1.73 m2 per year from 6 weeks postdonation onward. This finding was in contrast to that for nondonors, who showed a steady decline of –0.85 ml/min per 1.73 m2 per year. The renal compensation in living kidney donors was greatest in the first 2 years (+1.06 ml/min per 1.73 m2 per year) and began to plateau by year 5 (–0.06 ml/min per 1.73 m2 per year). Changes in eGFR over time after donation varied by sex, percent decline in eGFR within the first 6 weeks after donation, and eGFR category at 1 year, but not by age category at donation, predonation hypertension, predonation eGFR category, socioeconomic status, or distance to transplant center. Although previous studies have shown that the risk of kidney failure is lower in living kidne