APOL1 Genotyping in Potential African American Living Kidney Donors: Utility and Cost-Effectiveness

Background: Apolipoprotein L1 gene (APOL1) variants predispose to nondiabetic kidney disease in African American (AA) patients. Here, we share our experience with APOL1 genotyping of AA potential living kidney donors and offer a perspective on its utility and cost-effectiveness in this population. Methods: Since May 2017, all potential AA living kidney donors at our center underwent APOL1 genotyping early in the donor evaluation process. APOL1 high-risk individuals were declined, whereas those with low-risk genotype continued with further evaluation and testing. Results: One out of 26 potential donors had high-risk genotype and was therefore declined. The rest were eligible to continue the donor evaluation process and 7 of them underwent donor nephrectomy without any complications. A crude cost analysis utilizing our sample suggested probable cost-effectiveness of APOL1 genotyping as it can prevent earlier onset of chronic kidney disease in AA donors. Conclusion: We propose a role for systematically incorporating APOL1 genotyping in the evaluation and informed consent process of potential AA donors while acknowledging the controversial considerations associated with it.

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Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors

Annals of Surgery ◽

10.1097/sla.0000000000002174 ◽

2018 ◽

Vol 267 (6) ◽

pp. 1161-1168 ◽

Cited By ~ 21

Author(s):

Jayme E. Locke ◽

Deirdre Sawinski ◽

Rhiannon D. Reed ◽

Brittany Shelton ◽

Paul A. MacLennan ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Disease Risk ◽

Kidney Donors ◽

Living Kidney Donors ◽

Chronic Kidney Disease Risk ◽

Apolipoprotein L1

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APOL1 Genotype and Renal Function of Black Living Donors

Journal of the American Society of Nephrology ◽

10.1681/asn.2017060658 ◽

2018 ◽

Vol 29 (4) ◽

pp. 1309-1316 ◽

Cited By ~ 53

Author(s):

Mona D. Doshi ◽

Mariella Ortigosa-Goggins ◽

Amit X. Garg ◽

Lihua Li ◽

Emilio D. Poggio ◽

...

Keyword(s):

Renal Function ◽

High Risk ◽

Confidence Interval ◽

Kidney Donors ◽

Living Kidney Donors ◽

Risk Genotype ◽

Risk Alleles ◽

Lower Egfr ◽

Developing Kidney ◽

Egfr Decline

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m2; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.

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Kidney Microstructural Features at the Time of Donation Predict Long-term Risk of Chronic Kidney Disease in Living Kidney Donors

Mayo Clinic Proceedings ◽

10.1016/j.mayocp.2020.08.041 ◽

2021 ◽

Vol 96 (1) ◽

pp. 40-51 ◽

Cited By ~ 1

Author(s):

Massini A. Merzkani ◽

Aleksandar Denic ◽

Ramya Narasimhan ◽

Camden L. Lopez ◽

Joseph J. Larson ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Donors ◽

Living Kidney Donors

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Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab035 ◽

2021 ◽

Author(s):

Geir Mjøen ◽

Umberto Maggiore ◽

Nicos Kessaris ◽

Diederik Kimenai ◽

Bruno Watschinger ◽

...

Keyword(s):

Evaluation Process ◽

Kidney Donation ◽

Kidney Donors ◽

Living Kidney Donors ◽

Relative Risks ◽

Written Information ◽

The Difference ◽

Stage Renal Disease ◽

End Stage

Abstract Background Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. Methods All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. Results The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. Conclusions The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

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Application of the 2017 KDIGO Guideline for the Evaluation and Care of Living Kidney Donors to Clinical Practice

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.12141019 ◽

2020 ◽

Vol 15 (6) ◽

pp. 896-905 ◽

Cited By ~ 4

Author(s):

Amit X. Garg ◽

Andrew S. Levey ◽

Bertram L. Kasiske ◽

Michael Cheung ◽

Krista L. Lentine ◽

...

Keyword(s):

Clinical Practice ◽

Work Group ◽

Original Data ◽

Professional Organizations ◽

Living Kidney Donor ◽

Projection Model ◽

Kidney Donors ◽

Living Kidney Donors ◽

Donor Evaluation ◽

Risk Projection

The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 “Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors” was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a “proof-of-concept” risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate’s profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice.

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Yearly Trends of Chronic Kidney Disease III Progressions in Living Kidney Donors

Transplantation Proceedings ◽

10.1016/j.transproceed.2019.03.058 ◽

2019 ◽

Vol 51 (8) ◽

pp. 2539-2542

Author(s):

Hyung Ho Lee ◽

Joon Chae Na ◽

Young Eun Yoon ◽

Hyung Soon Lee ◽

Kyu Ha Huh ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Donors ◽

Living Kidney Donors

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The evaluation of kidney function in living kidney donor candidates

Kidney360 ◽

10.34067/kid.0003052021 ◽

2021 ◽

pp. 10.34067/KID.0003052021

Author(s):

Neetika Garg ◽

Emilio D. Poggio ◽

Didier Mandelbrot

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Creatinine Clearance ◽

Kidney Function ◽

The United States ◽

Estimated Gfr ◽

Kidney Donors ◽

Living Kidney Donors ◽

Increased Risk ◽

Measured Gfr

Living kidney donors incur a small increased risk of end-stage kidney disease (ESKD), of which pre-donation glomerular filtration rate (GFR) is an important determinant. As a result, kidney function assessment is central to the donor candidate evaluation and selection process. This article reviews the different methods of GFR assessment including estimated GFR, creatinine clearance and measured GFR, and the current guidelines on GFR thresholds for donor acceptance. Estimated GFR obtained using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation, while the best of estimating estimations, tends to underestimate and has limited accuracy, especially near normal GFR values. In the United States, the Organ Procurement and Transplantation Network policy on living donation mandates either measured GFR or creatinine clearance as part of evaluation. Measured GFR is considered the gold standard, although there is some variation in performance characteristics depending on the marker and technique used. Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion. GFR declines with healthy aging, and most international guidelines recommend use of age-adapted selection criteria. The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cut-off of <60 ml/min/1.73m2 for exclusion and of ≥90 ml/min/1.73m2 for acceptance, and determination of candidacy with intermediate GFR based on long-term ESKD risk. However, several concerns for this strategy exist, including inappropriate acceptance of younger candidates due to underestimation of risk, and exclusion of older candidates whose kidney function is in fact appropriate for age. Role of cystatin C and other newer biomarkers, as well as data on impact of pre-donation GFR on not just ESKD risk but also advanced chronic kidney disease risk and cardiovascular outcomes are needed.

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