Patricia L. Adams

The APOL1 Gene and Allograft Survival after Kidney Transplantation

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. The 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.

The Report of a National Conference on the Wait List for Kidney Transplantation

In March, 2002, over 100 members of the transplant community assembled in Philadelphia for a meeting designed to address problems associated with the growing number of patients seeking kidney transplantation and added to the waiting list each year. The meeting included representatives of nine US organizations with interests in these issues. Participants divided into work groups addressing access to the waiting list, assigning priority on the list, list management, and identifying appropriate candidates for expanded criteria donor kidneys. Each work group outlined problems and potential remedies within each area. This report summarized the issues and recommendations regarding the waiting list for kidney transplantation addressed in the Philadelphia meeting.

The nondirected live-kidney donor: ethical considerations and practice guidelines: A National Conference Report.

Background. The success of kidney transplantation from a genetically unrelated living spouse or friend has influenced transplant physicians to consider the requests of individuals wishing to volunteer to be a kidney donor who have no intended recipient specified. Representatives of the transplant community gathered in Boston, MA, on May 31, 2001, to deliberate on the experience of live kidney donation from such volunteers, currently termed nondirected donors (NDD). Objective of Conference Participants. The objective of the conference was to recommend ethical and practice guidelines for health care professionals considering the transplantation of a kidney from a live NDD. Conference Participants. This conference was convened under the sponsorship of The National Kidney Foundation, with representation from The American Society of Transplantation and The American Society of Transplant Surgeons, The American Society of Nephrology, The United Resource Networks, The United Network for Organ Sharing, The Association of Organ Procurement Organizations, The National Institutes of Health, and The Division of Transplantation of the Health Resources and Services Administration (see Appendix). Conference Report. The suggested content of screening interviews, which provide information regarding the donation process, elicits pertinent medical and psychosocial history, and assesses NDD motivation are presented in this report. Approaches to identifying the center that would evaluate the suitability of the NDD, to performing the kidney recovery, and to selecting the NDD recipient are also proposed. Other ethical issues such as the use of prisoners as an NDD, compensation for the NDD, media involvement, and communication between the NDD and recipient are discussed. Conclusion. 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.

A Randomized Trial of Alemtuzumab Versus Antithymocyte Globulin Induction in Renal and Pancreas Transplantation

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.

Increased Kidney Transplantation Utilizing Expanded Criteria Deceased Organ Donors with Results Comparable to Standard Criteria Donor Transplant

Objective:To compare outcomes in recipients of expanded criteria donor (ECD) versus standard criteria donor (SCD) kidneys at a single center using a standardized approach with similar immunosuppression. Summary Background Data:Expanded criteria deceased organ donors (ECD) are a source of kidneys that permit more patients to benefit from transplantation. ECD is defined as all deceased donors older than 60 years and donors older than 50 years with 2 of the following: hypertension, stroke as the cause of death, or preretrieval serum creatinine (SCr) greater than 1.5 mg/dl. Methods:We retrospectively studied 90 recipients of adult deceased donor kidneys transplanted from October 1, 2001 to February 17, 2003, including 37 (41%) from ECDs and 53 (59%) from SCDs. ECD kidneys were used by matching estimated renal functional mass to recipient need, including the use of dual kidney transplants (n = 7). ECD kidney recipients were further selected on the basis of older age, HLA-matching, low allosensitization, and low body mass index. All patients received a similar immunosuppressive regimen. Minimum follow up was 9 months. Results:There were significant differences in donor and recipient characteristics between ECD and SCD transplants. Patient (99%) and kidney graft survival (88%) rates and morbidity were similar between the 2 groups, with a mean follow-up of 16 months. Initial graft function and the mean 1-week and 1-, 3-, 6-, 12-, and 18-month SCr levels were similar among groups. Conclusions:The use of ECD kidneys at our center effectively doubled our transplant volume within 1 year. A systematic approach to ECD kidneys based on nephron mass matching and nephron sparing measures may provide optimal utilization with short-term outcomes and renal function comparable to SCD kidneys.

Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation: A Spectrum or Specter of Quality?

Objective:To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data:Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods:Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results:ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. Conclusions:By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants.

Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post-transplant outcomes.

Singh RP, Farney AC, Rogers J, Zuckerman J, Reeves‐Daniel A, Hartmann E, Iskandar S, Adams P, Stratta RJ. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes. 
Clin Transplant 2011: 25: 255–264.

A report of the Lisbon Conference on the care of the kidney transplant recipient

An International Conference on the Care of the Kidney Transplant Recipient was convened in Lisbon, Portugal from February 2– 4, 2006 under the auspices of the National Kidney Foundation and Kidney Disease: Improving Global Outcomes (KDIGO), and in cooperation with The Transplantation Society. Conference participants included over 100 experts and leaders in kidney transplantation, representing more than 40 countries from around the world, including participants from Africa, Asia, Australia, Europe, North American, and South America (Appendix). The goal of the conference was to develop recommendations to improve the outcomes of kidney transplant recipients worldwide with regard to the following basic medical issues: cardiovascular disease (Work Group I), cancer and infection (Work Group II), and anemia, bone disease, reproductive issues, growth and development (Work Group III). Work Groups I, II, and III addressed the preand posttransplant care of kidney transplant recipients by the following components: timelines of preand posttransplantation, immunosuppression, level of kidney allograft function, and burden of disease (prior history of dialysis or preemptive transplant and how that history affects outcome). A graft maintenance section (Work Group IV) addressed: 1) recipient (and donor) selection; 2) surgical aspects and immediate posttransplant care of recipients including consideration of minimal surgical infrastructure; 3) immunosuppression including an assessment of the incremental expected value of more complex and expensive regimens in comparison to simpler and less expensive regimens, generics, midand long-term immunosuppression; 4) living donor versus deceased donor transplantation; and 5) midand long-term posttransplant care and monitoring of allograft function. In addition, conference participants were asked to examine the issue of applicability of the recently published Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for chronic kidney disease (CKD) in kidney allograft recipients (1). Specifically, Work Group V addressed the role of estimated glomerular filtration rate (eGFR) in monitoring kidney function after transplantation, as well as the stratification for intervention according to eGFR values.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure

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 effect of the American heart association step one diet on hyperlipidemia following renal transplantation

Cardiovascular disease is a frequent cause of morbidity and mortality following renal transplantation. The percentage of deaths due to ischemic cardiovascular disease and cerebrovascular accidents nearly equals that caused by infection among patients receiving their first transplant, according to data from the European Dialysis and Transplant Association Registry. Hypercholesterolemia is a risk factor for cardiovascular disease frequently identified following renal transplantation, and diets low in fat and cholesterol have been suggested as treatment. Previous studies have not reported the response of LDL cholesterol to dietary treatment, and it is this form of cholesterol that is most closely related to cardiovascular disease. The American Heart Association has provided nutritionists with guidelines for the treatment of hyperlipidemic patients which include the Step One Diet. Previous dietary studies of renal transplant recipients have allowed a slightly higher intake of fat than that currently recommended by the AHA. We wondered if an easily reproducible diet well known to nutritionists such as the AHA Step One Diet would be effective in lowering cholesterol levels in hyperlipidemic renal transplant recipients. The purpose of our study was not to define the mechanisms of posttransplant hyperlipidemia, but rather to assess the effectiveness of dietary intervention on hyperlipidemia following renal transplantation.