Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Kidney transplantation among HIV-infected patients with ESRD confers a significant survival benefit over remaining on dialysis. Given the high mortality burden associated with dialysis, understanding access to kidney transplantation after waitlisting among HIV+ candidates is warranted. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:Data from the Scientific Registry of Transplant Recipients were linked to Intercontinental Marketing Statistics pharmacy fills (January 1, 2001 to October 1, 2012) so that we could identify and study 1636 HIV+ (defined as having filled one or more antiretroviral medications unique to HIV treatment) and 72,297 HIV- kidney transplantation candidates. RESULTS:=0.07) compared with in HIV- candidates. CONCLUSIONS:Our findings highlight the need for additional study to better understand disparities in access to kidney transplantation, particularly living donor kidney transplantation, among HIV+ kidney waitlist candidates.

Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End-Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3-month waitlist mortality risk (i.e., concordance-statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P = 0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity (P < 0.001 for each).

Kidney transplantation has become a routine procedure in the treatment of patients with kidney failure, and requires collaboration of experts from different disciplines, such as nephrology, surgery, immunology, pathology, infectious disease medicine, cardiology, and oncology. Grafts can be obtained from deceased or living donors, with different logistical requirements and implications for long-term graft patency. 1-year graft survival rates are greater than 95% in many centres but improvement of long-term function remains a challenge. New developments in molecular immunology and computational biology have increased precision of donor and recipient matching of HLA and non-HLA compatibility. Individual omics-wide molecular diagnostics, extracorporeal therapies, and drug developments allow for precise individual decision making and treatment. Tolerance induction by mixed chimerism without toxic conditioning and with a low risk of graft versus host disease is a visionary but realistic goal. Some of these innovations are already used in modern transplant centres and will allow advancement in long-term allograft preservation.

Kidney Disease: Improving Global Outcomes (KDIGO) engaged an evidence review team and convened a work group to produce a guideline to evaluate and manage candidates for living kidney donation. The evidence for most guideline recommendations is sparse and many "ungraded" expert consensus recommendations were made to guide the donor candidate evaluation and care before, during, and after donation. The guideline advocates for replacing decisions based on assessments of single risk factors in isolation with a comprehensive approach to risk assessment using the best available evidence. The approach to simultaneous consideration of each candidate's profile of demographic and health characteristics advances a new framework for assessing donor candidate risk and for defensible shared decision making.

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.

Nondirected living donors (NDLDs) are an important and growing source of kidneys to help reduce the organ shortage. In its infancy, NDLD transplantation was clustered at a few transplant centers and rarely benefited African American (AA) recipients. However, NDLDs have increased 9.4-fold since 2000, and now are often used to initiate kidney paired donation chains. Therefore, we hypothesized that the initial geographic clustering and racial disparities may have improved. We used Scientific Registry of Transplant Recipients data to compare NDLDs and their recipients between 2008-2015 and 2000-2007. We found that NDLD increased an average of 12% per year, from 20 in 2000 to 188 in 2015 (IRR: 1.12, 95% CI: 1.11-1.13, P < .001). In 2000-2007, 18.3% of recipients of NDLD kidneys were AA; this decreased in 2008-2015 to 15.7%. NDLD transplants initially became more evenly distributed across centers (Gini 0.91 in 2000 to Gini 0.69 in 2011), but then became more clustered at fewer transplant centers (Gini 0.75 in 2015). Despite the increased number of NDLDs, racial disparities have worsened and the center-level distribution of NDLD transplants has narrowed in recent years.