Changes in kidney function follow living donor nephrectomy

Abstract

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 on the rate of change in measured this study was limited by the A understanding of the in postdonation and how this by donor can inform the selection, and of living kidney donor the with a loss of postdonation GFR to donors from and We a retrospective cohort study using healthcare administrative in Alberta, Canada to the in postdonation GFR in living kidney We matched 604 living kidney donors to healthy from the general The baseline characteristics for the cohort are in The median age was 43 years and 64% living kidney donors had more in the year prior to the date to to evaluation The median estimated GFR (eGFR) was 100 ml/min per 1.73 m2 and 12% of donors had characteristics of living kidney donors and nondonor kidney donors a of between by A of is a between was to of average a population a population with population to from the was of cohort entry in the prior all on the in the prior all on the in the prior based on the in the 1 prior to the eGFR was using the Kidney was by and based on the Kidney <30 and ml/min per 1.73 in the prior all on the in the prior based on the in the 1 prior to the eGFR was using the Kidney was by and based on the Kidney <30 and based on of in the 3 prior to donation for which the are in estimated glomerular filtration not are median of cohort entry was the nephrectomy date for donors and was randomly assigned to a of between by A of is a between was to of average a population a population with population from the was all on the based on the in the 1 prior to the eGFR was using the Kidney N. et GFR for living kidney donor J Transplant. 2016; PubMed Scopus Google GFR evaluation in living kidney donor PubMed Scopus Google Scholar was by and based on the Kidney <30 and and PubMed Scopus Google Scholar, et of the Kidney PubMed Scopus Google Scholar, M. et of age on the between and the of J Kidney Dis. Full Text Full Text PDF PubMed Scopus Google Scholar, on for the evaluation and of kidney Int. 2013; Full Text Full Text PDF PubMed Scopus Google based on of in the 3 prior to donation for which the are in in a estimated glomerular filtration not are median of cohort entry was the nephrectomy date for donors and was randomly assigned to The median follow-up was years for donors and years for with a maximum follow-up of the of study follow-up the follow-up time was for the following 6 donors and at the time of donors and 3 at the time of renal and donors and 20 at the time from the on the the of donors had an eGFR between and ml/min per 1.73 m2, whereas and 0.2% had an eGFR of and ml/min per 1.73 m2, per 1.73 for donors and matched nondonor based on estimated glomerular filtration in a estimated glomerular filtration The 604 living kidney donors had a of after the to for the groups, in the for donors and for From 6 weeks donors had a median of to for The median time between was for donors versus The median of per year was for donors and for The mean at for donors and are in 1, whereas the median eGFR are in Overall, the eGFR on average increased by +0.35 ml/min per 1.73 m2 per year (95% confidence interval +0.21 to +0.48) in donors and decreased by m2 per year (95% to in on the the average change in eGFR between 6 weeks to years, to years, and years in donors was (95% to (95% to and (95% to ml/min per 1.73 m2 per year, respectively. the rate of change in eGFR time did not and over time in eGFR per 1.73 m2 per in donors and matched nondonor from 6 of living kidney donors did not have the 6 following matched from this of living kidney donors did not have the 6 following matched from this 6 to to estimated glomerular filtration in eGFR is mean (95% confidence are from the primary the change in eGFR over time is a and the the change in eGFR over time is to A of living kidney donors did not have the 6 following matched from this in a estimated glomerular filtration in eGFR is mean (95% confidence are from the primary the change in eGFR over time is a and the the change in eGFR over time is to The mean eGFR at for the donor are in The average eGFR was in donors to donors ml/min per 1.73 m2 for donors years ml/min per 1.73 m2 for donors years; donors years a decline in eGFR in the 6 weeks after to a decline in From 6 weeks there was significant in the average change in eGFR over time based on age for of glomerular filtration rate in ml/min per 1.73 in living kidney donors by age eGFR per 1.73 eGFR reduction in the 6 eGFR per at 1 and to the eGFR per 1.73 in living kidney donors by eGFR per 1.73 reduction in the 6 per at 1 to estimated glomerular filtration not are mean eGFR on Kidney was using the in the 1 prior for and all for 6 and for 1, 2, and in a in eGFR per 1.73 m2 per in living kidney donors by over different time follow-up from 6 weeks of living kidney donors did not have the 6 following donation and from this to to eGFR per 1.73 reduction in the 6 per at 1 to estimated glomerular filtration are change in eGFR (95% confidence A of living kidney donors did not have the 6 following donation and from this in a estimated glomerular filtration not are mean eGFR on Kidney was using the in the 1 prior for and all for 6 and for 1, 2, and estimated glomerular filtration are change in eGFR (95% confidence the eGFR was between and donors the in eGFR over time was on average in donors to donors ml/min per 1.73 m2 per with a of had a eGFR than donors ml/min per 1.73 a average postdonation in eGFR over time +0.35 ml/min per 1.73 m2 per significant in the change in eGFR over time based on the eGFR for of The change in eGFR over time was by the decline in baseline eGFR the 6 weeks for of a decline in baseline eGFR after donation on average had of an in eGFR over time to donors a decline from baseline the did not ml/min per 1.73 m2 per eGFR over time increased for donors in the eGFR at 1 year ml/min per 1.73 eGFR over time in donors in the eGFR at 1 year ml/min per 1.73 did not significantly change and ml/min per 1.73 m2 per year, The change in eGFR over time was significantly different in donors with an eGFR ml/min per 1.73 m2 at postdonation versus donors in of the for eGFR ml/min per 1.73 m2 and for eGFR ml/min per 1.73 m2, The change in eGFR over time was not by for of In this retrospective study, we the postdonation in eGFR for 604 living kidney donors with matched in Alberta, We that the eGFR increased by +0.35 ml/min per 1.73 m2 per year from 6 weeks postdonation was in contrast to that for a steady decline of ml/min per 1.73 m2 per The renal in living kidney donors was in the years ml/min per 1.73 m2 per and began to plateau by year ml/min per 1.73 m2 per in eGFR over time after donation by sex, decline in eGFR the 6 weeks after and eGFR at 1 year, not by age at eGFR to studies have that the of kidney is in living kidney donors than in the general G. et of renal among kidney 2006; 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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 follow-up we to the change in eGFR over time postdonation weeks to years, to years, and and that the in kidney function of the remaining kidney to plateau after in a study from living kidney donors and matched healthy nondonor with a mean follow-up of et and renal outcomes of kidney donors to with excellent kidney PubMed Scopus Google Scholar In that study, the eGFR was in the 3 years and in the years et and renal outcomes of kidney donors to with excellent kidney PubMed Scopus Google Scholar follow-up is to not the change in eGFR to decline in donors to the of age-related decline in the general B.L. Anderson-Haag T. 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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 studies have that did not the postdonation in N. et and renal function after kidney donation from living PubMed Scopus Google M. et of on and renal function after donor PubMed Scopus Google Scholar In that baseline based on the of the of kidney for living kidney donor in the of et for the living J 2016; PubMed Scopus Google Scholar are was a study, and the of and study was to had a of in follow-up, which that follow-up not and However, the from of a lack of follow-up was small 6 We did lack on baseline and of renal and and that have on the of renal we had on all in the and we did not have cystatin C measured GFR based on study of living kidney donors from the of that cystatin C did not with to postdonation the year to of kidney S. Courtney M. 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