KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors

Abstract

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1-S109.

FIGURE 1

Perspectives of risk in living kidney donation. These perspectives provide a framework for assessment of donor outcomes, interpretation of observations, patient communication, and future research design. LKD, living kidney donors. Adapted with permission from Lentine KL, Segev DL. Understanding and communicating medical risks for living kidney donors: a matter of perspective. J Am Soc Nephrol. 2017;28:12-24.

FIGURE 2

Literature flow diagram. SR, systematic review.

FIGURE 3

Framework to accept or decline donor candidates based on a transplant program’s threshold of acceptable postdonation risk. The decision by the transplant program to accept or decline a donor candidate is grounded on whether an individual’s estimated postdonation risk is above or below the threshold set (dotted line) by the transplant program. The threshold may vary across transplant programs, but the same threshold should apply to all donor candidates at each program. For example, candidate A (green) would be acceptable because the estimated projected postdonation risk is far below the threshold. Candidate B (yellow) could be accepted with caution because the estimated projected postdonation risk is close but below the threshold, and candidate C (red) would be unacceptable because the estimated postdonation projected risk is far above the threshold.

FIGURE 4

Framework to accept or decline donor candidates based on a transplant program’s threshold of acceptable projected lifetime risk of kidney failure, quantified as the aggregate of risk related to demographic and health profile and donation-attributable risks. The decision by the transplant program whether to accept or decline a donor candidate is grounded on the candidate's estimated postdonation lifetime risk, including estimated risk in the absence of donation (risk related to demographic and health characteristics as denoted in blue and beige, respectively) and estimated risk attributable to donation (brown). BMI, body mass index; GFR, glomerular filtration rate.

FIGURE 5

Performance of the CKD-EPI equation in estimating measured GFR. The figure shows the difference between measured and estimated GFR (bias) versus estimated GFR in an external validation dataset (N = 3896). A smoothed regression line is shown with the 95% CI. CI, confidence interval; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; GFR, glomerular filtration rate. Copyright © 2009 American College of Physicians and reprinted with permission from Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604-612.

FIGURE 6

Complications of CKD according to baseline eGFR and albuminuria. The data above were derived using creatinine-based eGFR (eGFR_cr) estimated with the MDRD Study equation. Comparable data are not available for mGFR. However, studies using more accurate GFR estimates confirm these results. For the outcomes of ESKD, all-cause mortality and cardiovascular mortality, any given reduced level of eGFR is associated with a greater increase in the risk of these outcomes if the 2009 CKD-EPI equation is used to estimate eGFR_cr. The increase in risk is even greater if cystatin C is used to estimate GFR, either with or without creatinine (eGFR_cr-cys or eGFR_cys), compared with eGFR_cr The 3 lines represent severe, moderate, and normal/mild albuminuria (top to bottom, respectively). CKD, chronic kidney disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; GFR, glomerular filtration rate. MDRD, Modification of Diet in Renal Disease. Reprinted with permission from Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2011;80:17-28.

FIGURE 7

Estimated 15-year incidence (%) of ESKD in the United States according to baseline eGFR and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 8

Estimated lifetime incidence (%) of ESKD in the United States according to baseline eGFR and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. Lifetime risk projections are based on 15 years of follow-up data and calibrated to the incidence of ESKD in the low-risk population, and thus are likely imprecise. ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 9

Estimated 15-year incidence (%) of ESKD in the United States according to baseline albumin-to-creatinine ratio (ACR, mg/g) and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 10

Estimated lifetime incidence (%) of ESKD in the United States according to baseline albumin-to-creatinine ratio (ACR, mg/g) and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. Lifetime risk projections are based on 15 years of follow-up data and calibrated to the incidence of ESKD in the low-risk population, and thus are likely imprecise. BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 11

Proteinuria after kidney donation. Solid line, regression line; dotted line: 95% confidence interval. Reprinted with permission of the Massachusetts Medical Society from Ibrahim HN, Foley R, Tan L, et al. Long-term consequences of kidney donation. N Engl J Med. 2009;360:459-469.

FIGURE 12

Meta-analysis of proteinuria after kidney donation. Controlled studies of proteinuria after kidney donation. The size of each square is inversely proportional to the variability of the study estimate. *Studies are arranged by the average number of years after donation. ‡Microalbuminuria was assessed by 24-hour urine. †Mathematically pooled results are not presented graphically because of statistical heterogeneity between studies. CI, confidence interval. Reprinted with permission from Garg AX, 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;70:1801-1810.

FIGURE 13

Sequential evaluation of microscopic hematuria in living kidney donor candidates. In general, lower risk and less expensive tests should be performed first, and at each step additional testing should only be performed if necessary. Boxes indicate stopping points in the donor candidate hematuria evaluation. AER, albumin excretion rate; GFR, glomerular filtration rate; hpf, high-power field; RBC, red blood cell.

FIGURE 14

Estimated 15-year incidence (%) of ESKD in the United States according to baseline systolic blood pressure (SBP) and demographic profile from the CKD-PC. SBP mm Hg without (black) and with (red) antihypertension medication. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 15

Estimated lifetime incidence (%) of ESKD in the United States according to baseline systolic blood pressure (SBP) and demographic profile from the CKD-PC. SBP mm Hg without (black) and with (red) antihypertension medication. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. Lifetime risk projections are based on 15 years of follow-up data and calibrated to the incidence of ESKD in the low-risk population, and thus are likely imprecise. ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 16

Estimated 15-year incidence (%) of ESKD in the United States according to baseline body mass index (BMI) and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. ACR, albumin-to-creatinine ratio; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 17

Estimated lifetime incidence (%) of ESKD in the United States according to baseline body mass index (BMI) and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. Lifetime risk projections are based on 15 years of follow-up data and calibrated to the incidence of ESKD in the low-risk population, and thus are likely imprecise. ACR, albumin-to-creatinine ratio; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 18

Estimated 15-year incidence (%) of ESKD in the United States according to non–insulin-dependent diabetes mellitus status and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 19

Estimated lifetime incidence (%) of ESKD in the United States according to non–insulin-dependent diabetes mellitus status and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. Lifetime risk projections are based on 15 years of follow-up data and calibrated to the incidence of ESKD in the low-risk population, and thus are likely imprecise. ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 20

Estimated 15-year incidence (%) of ESKD in the United States according to baseline smoking status and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI, 26 kg/m²; and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. Smoking status, current (Cur), former (For), and Never (Nev). ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.

FIGURE 21

Estimated lifetime incidence (%) of ESKD in the United States according to baseline smoking status and demographic profile from the CKD-PC. *The base-case scenario is defined as: age-specific eGFR (114, 106, 98, 90, 82, 74, and 66 mL/min per 1.73 m² for ages 20, 30, 40, 50, 60, 70, and 80 years, respectively), SBP 120 mm Hg, urine ACR 4 mg/g [0.4 mg/mmol], BMI 26 kg/m², and no diabetes mellitus or antihypertensive medication use. These were selected as being representative of recent US living kidney donors where, with the exception of eGFR, there was little variation in health characteristics by age. Lifetime risk projections are based on 15 years of follow-up data and calibrated to the incidence of ESKD in the low-risk population, and thus are likely imprecise. Smoking status, current (Cur), former (For), and Never (Nev). ACR, albumin-to-creatinine ratio; BMI, body mass index; CKD-PC, Chronic Kidney Disease-Prognosis Consortium, eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SBP, systolic blood pressure. Reprinted from Grams ME, Sang Y, Levey AS, et al. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016;374:411-421.