Efficient Utilization of the Expanded Criteria Donor (ECD) Deceased Donor Kidney Pool: An Analysis of the Effect of Labeling

We investigated the effect of the expanded criteria donor (ECD) label on (i) recovery of kidneys and (ii) acceptance for transplantation given recovery. An ECD is age ≥ 60, or age 50–59 with ≥ 2 of 3 specified comorbidities. Using data from the Scientific Registry of Transplant Recipients from 1999 to 2005, we modeled recovery rates through linear regression and transplantation probabilities via logistic regression, focusing on organs from donors just‐younger versus just‐older than the ECD age thresholds. We split the sample at July 1, 2002 to determine how decisions changed at the approximate time of implementation of the ECD definition. Before July 2002, the number of recovered kidneys with 0–1 comorbidities dropped at age 60, but transplantation probabilities given recovery did not. After July 2002, the number of recovered kidneys with 0–1 comorbidities rose at age 60, but transplantation probabilities contingent on recovery declined. No similar trends were observed at donor age 50 among donors with ≥ 2 comorbidities. Overall, implementation of the ECD definition coincided with a reversal of an apparent reluctance to recover kidneys from donors over age 59, but increased selectiveness on the part of surgeons/centers with respect to these kidneys.     

Technical Aspects of Unilateral Dual Kidney Transplantation from Expanded Criteria Donors: Experience of 100 Patients

One option for using organs from donors with a suboptimal nephron mass, e.g. expanded criteria donors (ECD) kidneys, is dual kidney transplantation (DKT). In adult recipients, DKT can be carried out by several techniques, but the unilateral placement of both kidneys (UDKT) offers the advantages of single surgical access and shorter operating time. One hundred UDKT were performed using kidneys from ECD donors with a mean age of 72 years (Group 1). The technique consists of transplanting both kidneys extraperitoneally in the same iliac fossa. The results were compared with a cohort of single kidney transplants (SKT) performed with the same selection criteria in the same study period (Group 2, n = 73). Ninety‐five percent of UDKTs were positioned in the right iliac fossa, lengthening the right renal vein with an inferior vena cava patch. In 69% of cases, all anastomoses were to the external iliac vessels end‐to‐side. Surgical complications were comparable in both groups. At 3‐year follow‐up, patient and graft survival rates were 95.6 and 90.9% in Group 1, respectively. UDKT can be carried out with comparable surgical complication rates as SKT, leaving the contralateral iliac fossa untouched and giving elderly recipients a better chance of receiving a transplant, with optimal results up to 3‐years follow‐up.     

Pulsatile Perfusion Reduces the Incidence of Delayed Graft Function in Expanded Criteria Donor Kidney Transplantation

The use of expanded criteria donors (ECD) has been proposed to help combat the discrepancy between organ availability and need. ECD kidneys are associated with delayed graft function (DGF) and worse long-term survival. The aim of this study is to evaluate the impact of pulsatile perfusion (PP) on DGF and graft survival in transplanted ECD kidneys. From January 2000 to December 2003, 4618 ECD kidney-alone transplants were reported to the United Network for Organ Sharing. PP was performed on 912 renal allografts. The prognostic factors of DGF were analyzed using multivariate logistic regression analysis. Risk factors for reduced allograft viability were greater in donors and recipients of PP kidneys. Three-year graft survival of ECD kidneys preserved with PP was similar to cold storage (CS) kidneys. The incidence of DGF in PP kidneys was significantly lower than CS kidneys (26% vs. 36%, p < 0.001). Despite having a greater number of risk factors for reduced graft viability, the ECD-PP kidneys had similar graft survival compared to ECD-CS kidneys. The use of PP, by decreasing the incidence of DGF, may possibly lead to lower overall costs and increased utilization of donor kidneys.     

Recipient Outcomes for Expanded Criteria Living Kidney Donors: The Disconnect Between Current Evidence and Practice

Older individuals or those with medical complexities are undergoing living donor nephrectomy more than ever before. Transplant outcomes for recipients of kidneys from these living expanded criteria donors are largely uncertain. We systematically reviewed studies from 1980 to June 2008 that described transplant outcomes for recipients of kidneys from expanded criteria living donors. Results were organized by the following criteria: older age, obesity, hypertension, reduced glomerular filtration rate (GFR), proteinuria and hematuria. Pairs of reviewers independently evaluated each citation and abstracted data on study and donor characteristics, recipient survival, graft survival, serum creatinine and GFR. Transplant outcomes for recipients of kidneys from older donors (≥60 years) were described in 31 studies. Recipients of kidneys from older donors had poorer 5-year patient and graft survival than recipients of kidneys from younger donors [meta-analysis of 12 studies, 72% vs. 80%, unadjusted relative risk (RR) of survival 0.89, 95% confidence interval (CI) 0.83–0.95]. In meta-regression, this association diminished over time (1980s RR 0.79, 95% CI 0.65–0.96 vs. 1990s RR 0.91, 95% CI 0.85–0.99). Few transplant outcomes were described for other expanded criteria. This disconnect between donor selection and a lack of knowledge of recipient outcomes should give transplant decision-makers pause and sets an agenda for future research.     

Utilization of Kidneys With Similar Kidney Donor Risk Index Values From Standard Versus Expanded Criteria Donors

With the shortage of standard criteria donor (SCD) kidneys, efficient expanded criteria donor (ECD) kidney utilization has become more vital. We investigated the effects of the ECD label on kidney recovery, utilization and outcomes. Using data from the Scientific Registry of Transplant Recipients from November 2002 to May 2010, we determined recovery and transplant rates, and modeled discard risk, for kidneys within a range of kidney donor risk index (KDRI) 1.4–2.1 that included both SCD and ECD kidneys. To further compare similar quality kidneys, these kidneys were again divided into three KDRI intervals. Overall, ECD kidneys had higher recovery rates, but lower transplant rates. However, within each KDRI interval, SCD and ECD kidneys were transplanted at similar rates. Overall, there was increased risk for discard for biopsied kidneys. SCD kidneys in the lower two KDRI intervals had the highest risk of discard if biopsied. Pumped kidneys had a lower risk of discard, which was modulated by KDRI for SCD kidneys but not ECD kidneys. Although overall ECD graft survival was worse than SCD, there were no differences within individual KDRI intervals. Thus, ECD designation adversely affects neither utilization nor outcomes beyond that predicted by KDRI.     

Evaluation of the Eurotransplant Senior Program. The Results of the First Year

On 4 January 1999, the Eurotransplant Senior Program (ESP) was implemented within the Eurotransplant kidney allocation scheme. PATIENTS AND METHODS: Kidneys obtained from donors aged over 65 years of age (65+) were allocated to a selected group of nonimmunized 65+ patients undergoing their first transplant. All transplants were performed locally to minimize cold-ischemic time. All transplants performed with kidneys from elderly donors that were allocated via ESP (ESP group) were compared to transplants performed with similar kidneys allocated via the standard renal allocation system (control group). Initial kidney function and 1-year graft outcome were assessed. RESULTS: In 1999, 227 ESP and 102 control transplants were performed. The duration of cold-ischemic time was 12 and 19 h for the ESP and control groups, respectively. No rejection episodes occurred in 60% and 67% of the ESP patients and controls, respectively, while a direct kidney function was observed in 59% of ESP and 49% of control patients. The 1-year graft survival rates, censoring for graft losses due to deaths in patients with functioning grafts, were 86% and 79%, respectively. CONCLUSION: An old-for-old renal allocation algorithm can be successful provided that risk factors, such as cold-ischemic time, are reduced.     

Old-for-Old Kidney Allocation Allows Successful Expansion of the Donor and Recipient Pool

Allocation of kidneys from donors older than 64 years to recipients older than 64 years was started in 1999 to improve use of older donor kidneys. Kidneys are allocated locally without HLA-matching to keep cold ischemia short. We compared survival and rejection rates in elderly patients allocated in the old-for-old program (ESP) to patients aged 60 years and older based on HLA-matching, expected ischemia and waiting time (ETKAS). The 69 ESP patients were older (67.9 +/- 2.5 vs. 63.9 +/- 2.9 years), had older donors (71.2 +/- 3.9 vs. 44.6 +/- 14.5 years) and more HLA-mismatches (4.2 +/- 1.2 vs. 1.6 +/- 1.7) than the 71 ETKAS patients, while ischemia was shorter (7.8 +/- 3.4 vs. 14.2 +/- 5.5 h). ESP and ETKAS had similar graft (1-year: 83.6% vs. 86.9%) and patient survival (85.2% vs. 89.5%). With the introduction of ESP, use of older recipients and donors rose from less than 2% to 16% and 11%, respectively. Incidence of acute rejections was significantly higher in the ESP group (1 year: 43.2% vs. 27.4%) and significantly correlated with the degree of HLA-matching. Introduction of old-for-old allocation allows successful expansion of the donor and recipient pool without affecting patient and graft survival. HLA-matching should not be ignored, as the risk of acute rejection in elderly patients is substantial.     

Comparison of survival outcomes between Expanded Criteria Donor and Standard Criteria Donor kidney transplant recipients: a systematic review and meta‐analysis

In 2002, the United Network for Organ Sharing proposed increasing the pool of donor kidneys to include Expanded Criteria Donor (ECD). Outside the USA, the ECD definition remains the one used without questioning whether such a graft allocation criterion is valid worldwide. We performed a meta‐analysis to quantify the differences between ECD and Standard Criteria Donor (SCD) transplants. We paid particular attention to select studies in which the methodology was appropriate and we took into consideration the geographical area. Thirty‐two publications were included. Only five studies, all from the USA, reported confounder‐adjusted hazard ratios comparing the survival outcomes between ECD and SCD kidney transplant recipients. These five studies confirmed that ECD recipients seemed to have poorer prognosis. From 29 studies reporting appropriate survival curves, we estimated the 5‐year pooled nonadjusted survivals for ECD and SCD recipients. The relative differences between the two groups were lower in Europe than in North America, particularly for death‐censored graft failure. It is of primary importance to propose appropriate studies for external validation of the ECD criteria in non‐US kidney transplant recipients.     

Monolateral placement of both kidneys in dual kidney transplantation: low surgical complication rate and short operating time.

Dual kidney transplantation (DKT) from marginal donors is increasingly used at many centers to help cope with the organ shortage problem. The disadvantages of DKT consist in longer operating times and the risk of surgical complications. DKT can be performed in two ways, i.e. using monolateral or bilateral procedures. From October 1999 to June 2005, 58 DKTs were performed at our unit. In 29 cases (group I), the kidneys were extraperitoneally placed bilaterally in the iliac fossae via two separate incisions; as of June 2003, monolateral kidney placement was preferred in 29 cases, whenever compatible with the recipient's morphological status (group II). After a mean follow-up of 51 +/- 19 months for group I and 15 +/- 7 months for group II, all patients are alive with 1-year graft survival rates of 93% and 96%, respectively. Mean operating times were 351 +/- 76 min in group I and 261 +/- 31 min in group II (P = 0.0001). The mean S-creatinine levels in groups I and II were 132 +/- 47 and 119 +/- 36 mumol/l, respectively, at 1 year. We observed eight surgical complications in group I and seven in group II. Both techniques proved safe, with no differences in surgical complication rates. The monolateral procedure has the advantage of a shorter operating time and the contralateral iliac fossa remains available for further retransplantation procedures.     

Transplanting Kidneys Without Points for HLA‐B Matching: Consequences of the Policy Change

In 2003, the US kidney allocation system was changed to eliminate priority for HLA‐B similarity. We report outcomes from before and after this change using data from the Scientific Registry of Transplant Recipients (SRTR). Analyses were based on 108 701 solitary deceased donor kidney recipients during the 6 years before and after the policy change. Racial/ethnic distributions of recipients in the two periods were compared (chi‐square); graft failures were analyzed using Cox models. In the 6 years before and after the policy change, the overall number of deceased donor transplants rose 23%, with a larger increase for minorities (40%) and a smaller increase for non‐Hispanic whites (whites) (8%). The increase in the proportion of transplants for non‐whites versus whites was highly significant (p < 0.0001). Two‐year graft survival improved for all racial/ethnic groups after implementation of this new policy. Findings confirmed prior SRTR predictions. Following elimination of allocation priority for HLA‐B similarity, the deficit in transplantation rates among minorities compared with that for whites was reduced but not eliminated; furthermore, there was no adverse effect on graft survival.     

CMV Infection in the Donor and Increased Kidney Graft Loss: Impact of Full HLA‐I Mismatch and Posttransplantation CD8+ Cell Reduction

Despite a large body of literature, the impact of chronic cytomegalovirus (CMV) infection in donor on long‐term graft survival remains unclear, and factors modulating the effect of CMV infection on graft survival are presently unknown. In this retrospective study of 1279 kidney transplant patients, we analyzed long‐term graft survival and evolution of CD8⁺ cell population in donors and recipients by CMV serology and antigenemia status. A positive CMV serology in the donor was an independent risk factor for graft loss, especially among CMV‐positive recipients (R⁺). Antigenemia was not a risk factor for graft loss and kidneys from CMV‐positive donors remained associated with poor graft survival among antigenemia‐free recipients. Detrimental impact of donor's CMV seropositivity on graft survival was restricted to patients with full HLA‐I mismatch, suggesting a role of CD8⁺ cells. In R⁺ patients with positive CMV antigenemia during the first year, CD8⁺ cell count did not increase at 2 years posttransplantation, in contrast to R^? recipients. In addition, marked CD8⁺‐cell decrease was a risk factor of graft failure in these patients. This study identifies HLA‐I full mismatch and a decrease of CD8⁺ cell count at 2 years as important determinants of CMV‐associated graft loss.

     

Donor nephrectomy: A comparison of techniques and results of open, hand assisted and full laparoscopic nephrectomy

PURPOSE: Laparoscopic donor nephrectomy (LAP) has been gaining more popularity among kidney donors and transplant surgeons. There have been some concerns about the function of kidney grafts harvested by laparoscopic procedures. We report our results of LAP. MATERIALS AND METHODS: Prospective data were collected for our donor nephrectomy operations. A telephone survey was done by an independent investigator on the impact of surgery on quality of life. Graft function was also evaluated by serial serum creatinine and mercaptoacetyltriglycine renal nuclear scans. RESULTS: A total of 100 patients were included in the study; of whom 55 underwent open donor nephrectomy (OD), 28 underwent LAP and 17 underwent hand assisted donor nephrectomy (HAL). Mean patient age was 39 +/- 12 years and it was similar in all groups. Mean operative time was 306 +/- 40 minutes for LAP, 294 +/- 42 minutes for HAL and 163 +/- 24 minutes for OD (p = 0.001). Laparoscopic operative time was decreased to 180 +/- 56 minutes for LAP and 155 +/- 40 minutes for HAL in the last 10 patients. Mean estimated blood loss was 200 +/- 107 cc for LAP, 167 +/- 70 cc for HAL and 320 +/- 99 cc for OD (p = 0.0001). Mean warm ischemia time was 3 +/- 2 minutes for LAP, 2 +/- 2 minutes for HAL and 2 +/- 1 minutes for OD (p = 0.002). Postoperative hospitalization was 2 +/- 2 days for LAP and 3 +/- 2 days for OD (p = 0.01). LAP required 30% less narcotic medicine than OD postoperatively (p = 0.04). There were no major complications in LAP cases and no complete or partial graft loss was noted. Mean followup was 7 months. Recipient creatinine was not significantly different for kidneys harvested by LAP or OD (p = 0.5). Diuretic mercaptoacetyltriglycine renograms were performed in all recipients 1 to 3 days after surgery and mean effective renal plasma flow was similar for the 3 groups (p = 0.9). According to telephone survey results 85% of LAP, 71% of HAL and 43% of OD patients reported a return to normal physical activity within 4 weeks after surgery. Similarly 74% of LAP, 62% of HAL and 26% of OD patients were able to return to work within 4 weeks after surgery. CONCLUSIONS: Our data show no significant difference in graft function between LAP and OD. LAP and HAL were safe and complications were minimal. The main difference was that patients treated with LAP and HAL returned to normal physical activity and work significantly earlier than those who underwent OD.     

Determinants of Discard of Expanded Criteria Donor Kidneys: Impact of Biopsy and Machine Perfusion

We examined factors associated with expanded criteria donor (ECD) kidney discard. Scientific Registry of Transplant Recipients (SRTR)/Organ Procurement and Transplantation Network (OPTN) data were examined for donor factors using logistic regression to determine the adjusted odds ratio (AOR) of discard of kidneys recovered between October 1999 and June 2005. Logistic and Cox regression models were used to determine associations with delayed graft function (DGF) and graft failure. Of the 12 536 recovered ECD kidneys, 5139 (41%) were discarded. Both the performance of a biopsy (AOR = 1.21, p = 0.02) and the degree of glomerulosclerosis (GS) on biopsy were significantly associated with increased odds of discard. GS was not consistently associated with DGF or graft failure. The discard rate of pumped ECD kidneys was 29.7% versus 43.6% for unpumped (AOR = 0.52, p < 0.0001). Among pumped kidneys, those with resistances of 0.26–0.38 and >0.38 mmHg/mL/min were discarded more than those with resistances of 0.18–0.25 mmHg/mL/min (AOR = 2.5 and 7.9, respectively). Among ECD kidneys, pumped kidneys were less likely to have DGF (AOR = 0.59, p < 0.0001) but not graft failure (RR = 0.9, p = 0.27). Biopsy findings and machine perfusion are important correlates of ECD kidney discard; corresponding associations with graft failure require further study.     

The Nondirected Living Donor Program: A Model for Cooperative Donation, Recovery and Allocation of Living Donor Kidneys

We describe an altruistic nondirected (ND) and live donor/deceased donor list exchange (LE) donor program administered by an organ procurement organization (OPO) in the Washington, DC area. Screening eliminated 25 donors (17 NE; 8 LE) from the 97 donor applications (62 ND; 35 LE) completed. Twenty-one donors (16 ND; 5 LE) failed to follow through with the psychiatric evaluation, which eliminated 13 donors (9 ND; 4 LE). Two donors dropped out and 12 (9 ND; 3 LE) were medically unsuitable after final clinical evaluation. Twenty donor procedures were performed (10 ND; 10 LE) with four pending (2 ND; 2 LE). This resulted in a modest 3-5% increase in the OPO-procured kidney organ pool. The average cold ischemia time of the grafts not transported between transplant centers was 205 +/- 66 min compared with 243 +/- 48 min for transported grafts. With no documented adverse outcomes, donors had a hospital stay of length 2.9 days and at home recuperation of 12.3 days. Three- and 6-month creatinines were 1.44 +/- 1.36 and 1.68 +/- 0.61 for grafts not transported between transplant centers, and 1.6 +/- 0.27 and 1.6 +/- 0.44 for transported grafts. An OPO-administered altruistic donor program can serve as a model for cooperative donation, recovery and allocation of living donor kidneys.     

Current status of kidney and pancreas transplantation in the United States, 1994–2003

This article reviews the OPTN/SRTR data collected on kidney and pancreas transplantation during 2003 in the context of trends over the past decade. Overall, the transplant community continued to struggle to meet the increasing demand for kidney and pancreas transplantation. The number of new wait-listed kidney registrants under the age of 50 has remained relatively stable since 1994, but the number of new registrants aged 50 to 64 has doubled. However, there was only a 2.3% increase in the total number of kidney transplants performed in 2003. Expanded criteria donor kidneys made up 20% of all recovered kidneys and 16% of all transplants performed, compared with 15% in the prior year. In May 2003, new rules were implemented to promote equity in kidney organ allocation. These changes seem to have improved access for historically disadvantaged groups, though they have reduced the quality of HLA matching. The effects on long-term outcomes have yet to be measured. Although the majority of SPK recipients are white (82%), the percentage of simultaneous kidney-pancreas recipients who are African-American has increased from 9% in 2000 to 16% in 2003. The percentage of Hispanic/Latino recipients increased from 5% to 9% over the same period.     

The Impact of the New Kidney Allocation System on Prior Living Kidney Donors’ Access to Deceased Donor Kidney Transplants: An Early Look

This study investigated the early effects of the new kidney allocation system (KAS) on the access of prior living kidney donors (PLDs) to deceased donor kidney transplants. Using data from the Organ Procurement and Transplantation Network, we compared prevalent and incident cohorts of PLDs in the 1‐year periods before and after KAS implementation (pre‐KAS group: December 4, 2013, to December 3, 2014, n = 50 [newly listed PLDs]; post‐KAS group: December 4, 2014, to December 3, 2015, n = 39). We assessed transplant rates per active patient‐year, waiting times, and Kidney Donor Profile Index (KDPI) of transplanted kidneys. Transplant rates were not statistically different before and after KAS implementation for either prevalent (2.37 vs. 2.29, relative risk [RR] 0.96; 95% confidence interval [CI] 0.62–1.49) or incident (4.76 vs. 4.36, RR 0.92; 95% CI 0.53–1.60) candidates. Median waiting time (MWT) to deceased donor kidney transplant for prevalent PLDs in the post‐KAS cohort was 102.6 days compared with 82.3 days in the pre‐KAS cohort (p = 0.98). The median KDPI for PLD recipients was 31% with KAS versus 23% before KAS (p = 0.02). Despite a sharp decrease in the MWT for highly prioritized candidates with calculated panel reactive antibodies of 98–100% (from >7000 to 1164 days), PLDs still had much shorter waiting times (MWT 102.6 days). The new system continues to provide quick access to high‐quality organs for PLDs.     

Kidney and Pancreas Transplantation in the United States, 1998–2007: Access for Patients with Diabetes and End-Stage Renal Disease

Although the number of candidates on the kidney transplant waiting list at year-end rose from 40 825 to 76 070 (86%) between 1998 and 2007, recent growth principally reflects increases in the number of patients in inactive status. The number of active patients increased by 'only' 4510 between 2002 and 2007, from 44 263 to 48 773. There were 6037 living donor and 10 082 deceased donor kidney transplants in 2007. Patient and allograft survival was best for recipients of living donor kidneys, least for expanded criteria donor (ECD) deceased donor kidneys, and intermediate for non-ECD deceased donor kidneys. The total number of pancreas transplants peaked at 1484 in 2004 and has since declined to 1331. Among pancreas recipients, those with simultaneous pancreas-kidney (SPK) transplants experienced the best pancreas graft survival rates: 86% at 1 year and 53% at 10 years. Between 1998 and 2006, among diabetic patients with end-stage renal disease (ESRD) who were under the age of 50 years, 23% of all and 62% of those waitlisted received a kidney-alone or SPK transplant. In contrast, 6% of diabetic patients aged 50–75 years with ESRD were transplanted, representing 46% of those waitlisted from this cohort. Access to kidney-alone or SPK transplantation varies widely by state.     

The Effects of Donor and Recipient Practices on Transplant Center Finances

Over the past several years we have noted a marked decrease in this profitability of our kidney transplant program. Our hypothesis is that this reduction in kidney transplant institutional profitability is related to aggressive donor and recipient practices. The study population included all adults with Medicare insurance who received a kidney transplant at our center between 1999 and 2005. Adopting the hospital perspective, multi-variate linear regression models to determine the independent effects of donor and recipient characteristics and era effects on total reimbursements and total hospital margin. We note statistically significant decreased medical center incremental margins in cases with ECDs (−$5887) and in cases of DGF (−4937). We also note an annual change in the medical center margin is independently associated with year and changes at a rate of −$5278 per year, related to both increasing costs and decreasing Medicare reimbursements. The financial loss associated with patient DGF and the use of ECD kidneys may resonate with other centers, and could hinder efforts to expand kidney transplantation within the United States. The Centers for Medicare and Medicaid Services (CMS) should consider risk-adjusted reimbursement for kidney transplantation.