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.
Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox proportional-hazard models tested for association between time to graft failure and donor APOL1 genotypes. Mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT, and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p=0.008) and higher HLA mismatch (HR 1.52; p=0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long term renal allograft survival.
BACKGROUND.: Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction of immunsuppression for kidney and pancreas transplantation, but the two agents have not been compared directly. METHODS.: We conducted a prospective randomized single-center trial comparing alemtuzumab and rATG induction in adult kidney and pancreas transplantation in patients treated with similar maintenance immunosuppression. RESULTS.: Between February 1, 2005, and September 1, 2007, 222 patients randomly received either alemtuzumab (n=113) or rATG (n=109) induction; 180 (81%) underwent kidney alone, 38 (17%) simultaneous pancreas-kidney, and 4 (2%) pancreas after kidney transplants. Of 180 kidney-alone transplants, 152 (84%) were from deceased donors, including 61 (34%) from expanded criteria donors. Retransplantation, human leukocyte antigen match, antibody titer, expanded criteria donors, race, cytomegalovirus status, delayed graft function, and immunologic risks were similar between the two induction groups. With a median follow-up of 2 years (minimum 1 year), overall patient, kidney, and pancreas graft survival rates were 96%, 89%, and 90%, respectively. Survival, initial length of stay, and maintenance immunosuppression (including early steroid elimination) were similar between alemtuzumab and rATG groups, but biopsy-proven acute rejection (BPAR) episodes occurred in 16 (14%) alemtuzumab patients compared with 28 (26%) rATG patients (P=0.02). Late BPAR (>12 months after transplant) occurred in 1 (8%) alemtuzumab patient and 3 (11%) rATG patients (P=NS). Infections and malignancy were similar between the two induction arms. CONCLUSION.: Alemtuzumab and rATG induction therapies were equally safe, but alemtuzumab was associated with less BPAR.
Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p=0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p=0.001) and African American recipient race/ethnicity (HR 1.60; p=0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.
The willingness of health care professionals to consider NDD volunteers is driven by the compelling need to provide organs for an ever-expanding list of patients awaiting a kidney transplant. However, the psychological impact and emotional reward of donation has yet to be determined for NDD who may not have any relationship to the recipient or knowledge of the recipient's outcome. Transplant centers that accept NDD should document an informed consent process that details donor risks, assures donor safety, and determines that the goals and expectations of the NDD and the recipient can be realized.
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