Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors.

BACKGROUND: The purpose of this study was to perform a case-matched cohort analysis of dual kidney transplantation (DKT) from expanded criteria donors (ECDs) compared to single kidney transplantation (SKT) from concurrent ECDs and standard criteria donors (SCDs, defined as non-ECD). METHODS: Deceased donor (DD) kidney transplants (KTs) performed at a single center between October 2001 and February 2006 were reviewed retrospectively. If the calculated DD creatinine clearance (CrCl) was <65 mL/min, then the kidneys were transplanted dually into a single patient. In the case of DKT and SKT from ECDs, low risk patients were chosen and informed consent was obtained. Patients in each group were matched for age, gender, race, transplant number, and time of transplant. RESULTS: Of 294 adult DD KTs performed, 16 (5%) were DKTs, which were matched with 16 concurrent SCD and 16 ECD SKT patients. Mean donor age in years (65 DKT vs. 33 SCD vs. 61 ECD; P<0.0001) and mean donor CrCl in ml/min (54 DKT vs. 91 SCD vs. 76 ECD; P=0.002) were different between groups. Patient survival was 100% in the DKT and SCD SKT groups and 94% in the ECD SKT group (mean follow up 23-28 months); graft survival rates in the DKT, SCD, and ECD groups were 81%, 81%, and 94%, respectively (P=NS). Graft function, rejection, and morbidity were similar between groups. CONCLUSIONS: DKT using kidneys from marginal ECDs is a viable option to counteract the growing shortage of available organs. Excellent short-term results and renal function can be achieved with older, low nephron mass donors provided that both kidneys are transplanted into a single recipient.

Experience with dual kidney transplants from donors at the extremes of age.

BACKGROUND: Dual kidney transplantation (DKT) from donors at the extremes of age represents one approach to expanding the organ donor pool. The purpose of this study was to review our experience with DKT from older donors and en bloc KT (EBKT) from small pediatric donors. METHODS: Deceased donor KTs performed at our center between October 2001 and November 2005, were reviewed retrospectively. If the calculated creatinine clearance in an expanded criteria donor was <65 mL/min, then the kidneys were transplanted dually into a single adult recipient. If a pediatric donor weighed <15 kg, then the kidneys were transplanted en bloc. In both instances, low-risk recipients were chosen (primary transplant, low sensitization, body mass index <25 kg/m(2), human leukocyte antigen matching). Donor, recipient, and transplant characteristics, waiting time, and outcomes were examined. RESULTS: Of a total of 279 deceased donor KTs during the 49-month study period, 15 (5%) recipients underwent DKT and 5 (2%) underwent EBKT. Mean donor age was 65.4 years and 21.4 months in the DKT and EBKT groups, respectively. Patient survival rates in both groups were 100% with a mean follow-up of 22 months (minimum, 6 months). Kidney graft survival rates were 80% (12/15) and 60% (3/5) in the DKT and EBKT groups, respectively. The combined incidence of delayed graft function was 10%. Mean 12-month glomerular filtration rates were 46 mL/min and 66 mL/min in the DKT and EBKT groups, respectively. CONCLUSIONS: DKT using kidneys from marginal elderly donors and EBKT from small pediatric donors appear to offer a viable option to counteract the shortage of acceptable kidney donors.

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.

Optimal use of older donors and recipients in kidney transplantation.

BACKGROUND: The aging donor and recipient population have led to new challenges in kidney transplantation. The purpose of this study was to review retrospectively our single center experience in deceased-donor kidney transplantation, with respect to donor and recipient age. METHODS: From October 1, 2001, through February 20, 2004, we performed 144 deceased-donor kidney transplantations, which included 37 procedures (26%) in recipients > or =60 years old and 107 procedures (74%) in recipients 19 to 59 years old. The deceased-donor pool included 57 expanded criteria donors (ECD) and 87 standard criteria donors (defined as not ECD). ECD kidneys were used by matching estimated renal functional mass to recipient size (body mass index, <25 kg/m(2)), which included the use of dual kidney transplantations (n = 9). ECD kidney recipients were further selected on the basis of age >40 years and low immunologic risk. Recipients received rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The mean age differed between recipient groups (65 vs 46 years; P < .001). In recipients > or =60 years old, 23 recipients (62%) received kidney transplants from ECDs compared with 34 kidney transplants from ECDs (32%; P < .001) in recipients who were <60 years old. Patient survival was 89% in recipients who were > or =60 years old, compared with 95% in recipients who were <60 years old (P = .11), with a mean follow-up time of 27 months. Kidney graft survival rates were 84% in both recipient groups. Initial and subsequent graft function, rejection, infection, reoperation, length of stay, readmission, and resource use were similar among groups. CONCLUSION: By the matching of nephron mass with recipient size and avoiding the use of ECD kidneys in recipients with a high immunologic risk, short-term outcomes that are comparable with standard criteria donor kidneys in younger patients can be achieved with either older donors or recipients, regardless of age.

The role of Fis1p-Mdv1p interactions in mitochondrial fission complex assembly.

Mitochondrial division requires coordinated interactions among Fis1p, Mdv1p, and the Dnm1p GTPase, which assemble into fission complexes on the outer mitochondrial membrane. The integral outer membrane protein Fis1p contains a cytoplasmic domain consisting of a tetratricopeptide repeat (TPR)-like fold and a short NH(2)-terminal helix. Although it is known that the cytoplasmic domain is necessary for assembly of Mdv1p and Dnm1p into fission complexes, the molecular details of this assembly are not clear. In this study, we provide new evidence that the Fis1p-Mdv1p interaction is direct. Furthermore, we show that conditional mutations in the Fis1p TPR-like domain cause fission complex assembly defects that are suppressed by mutations in the Mdv1p-predicted coiled coil. We also define separable functions for the Fis1p NH(2)-terminal arm and TPR-like fold. These studies suggest that the concave binding surface of the Fis1p TPR-like fold interacts with Mdv1p during mitochondrial fission and that Mdv1p facilitates Dnm1p recruitment into functional fission complexes.

Kidney and pancreas transplantation at Wake Forest University Baptist Medical Center.

More than 1,100 transplants have been performed at WFUBMC, including 60 pediatric transplants and 40 pancreas transplants. The one-year living donor kidney graft survival rate exceeds 90% and the 2 year deceased donor kidney graft survival rate exceeds 80%. The current active waiting list includes more than 300 candidates. Despite more transplants being performed, we continue to under-serve our referral area, which has among the highest rates of hypertension, diabetes, and end stage renal disease in the country. The AOTP has experienced a period of rapid growth over the past 2 years based upon sharing of zero HLA antigen-mismatched kidneys, use of ECD kidneys, liberalization of donor and recipient selection criteria, and the continued development of the pancreas transplant and laparoscopic donor nephrectomy programs. The pancreas transplant program will continue to grow as the waiting list enlarges and matures, with a 200% increase in activity expected within the next few years. The LDKT program will expand as more emphasis is placed on our pretransplant practice, including the more liberal application of laparoscopic donor nephrectomy, which has now become a standard procedure at our WFUBMC is involved in a number of clinical research projects studying new immunosuppressive agents and regimens. In this chapter, we have presented our recent experience with KTX in the elderly, ECD kidneys, alternate day Thymoglobulin administration, valganciclovir prophylaxis, SRL conversion using daclizumab bridge therapy, and pancreas transplantation with portal-enteric drainage. We plan to initiate a number of new protocols in the immediate future, including desensitization of the highly sensitized patient, ABO incompatible transplantation, transplantation of the HIV-positive patient, steroid withdrawal and avoidance regimens, living kidney donation from the anonymous altruistic donor, paired kidney exchanges from living donors, and islet transplantation. WFUBMC remains the most active donor hospital in North Carolina, and a non-heart beating donor protocol has been successfully initiated at our facility. Although much has been accomplished, a number of challenges remain. We look forward to building on our accomplishments, confronting the challenges, and achieving a level of excellence that could only be attained by mutual commitment from a dedicated, multidisciplinary team.