Cadaveric renal transplantation from a non-heart-beating pediatric donor into adult recipients

INTRODUCTION: The use of cadaveric pediatric kidneys has been suggested as a means to overcome organ shortage, but is debated because of technical complications and an increased incidence of functional allograft impairment. METHODS: We experienced 2 cases of cadaveric renal transplantation from a non-heart-beating pediatric donor. RESULTS: In our cases, transplanted kidneys achieved good graft function and proteinuria due to glomerulosclerosis was not recognized. CONCLUSION: Previous reports indicate that in transplantation from pediatric donors into adults recipients, glomerular sclerosis occurs as the reason for impairment of grafts. Further, cadaveric renal transplantation from a non-heart-beating donor has a warm ischemia time and an increased risk of hyperfiltrated injury and graft failure. If transplantation of pediatric kidneys into adults from a non-heart-beating donor is performed, BMI and BSA must be carefully considered in the selection of recipients in order to avoid imbalance between nephron supply and metabolic demands and to insure successful, healthy grafts.     

Variation in organ donation in northeastern England 1986 to 2003

Renal transplantation is established as the best form of renal replacement therapy, but demand for kidneys exceeds supply from cadaveric donations. It is therefore important to make the best use of the pool of potential cadaveric organ donors. Donation rates are to a large extent dependent on public opinions, which may be influenced by external events. In northeast England from 1986 to 2003, there was a potential pool of 1170 brain stem-dead donors, of whom 190 (16%) could not be retrieved due to relatives' objections. From 1998 to 2003 we were referred 90 potential non-heart-beating donors, of whom relatives refused donation in 10 (11%). A major reason for not retrieving organs from a potential donor has been lack of consent from the relatives. Refusals appear to vary year by year and are consistently lower for non-heart-beating donors. This therefore raises the possibility that negative or positive media publicity plays a role in this variation.     

Agonal period in potential non-heart-beating donors

The shortage of donor kidneys for renal transplantation is becoming more severe as the gap between the number of patients waiting for renal transplantation and the number of cadaveric organs available continues to widen. Therefore, many centres have started using non-heart-beating (NHB) donors. There was no clear plan for maximal duration of agonal period in Maastricht category NHB donors after withdrawal of treatment in Newcastle. This withdrawal has been audited in retrospect. Our current wait time is now a maximum of 5 hours; however, previously there have been some considerably longer periods. Concern has always been expressed about poor quality with protracted periods. Nonuse in this review of 58 kidneys can be expressed against time: 0 to 2 hours 13%, 2 to 5 hours 33%, and >5 hours 45%. Therefore, though the nonuse rate was significantly different between 0 to 2 hours and >5 hours (P < .05, chi-square), there were 16 transplants performed with kidneys >2 hours and 12 transplanted >5 hours. In conclusion, although good usable kidneys can still be used with protracted withdrawal, there are considerable logistical difficulties with our 5-hour cut-off, which means that one third of potential kidneys will not be utilized.     

Outcome of transplantation using kidneys from controlled (Maastricht category 3) non-heart-beating donors

BACKGROUND: Many renal transplant centres are reluctant to use kidneys from non-heart-beating (NHB) donors because of the high incidence of primary non-function and delayed graft function reported in the literature. Here, we report our favourable experience of using kidneys from Maastricht category 3 donors (controlled NHB donors). MATERIALS AND METHODS: From January 1996 to June 2002, 42 renal transplants using kidneys from 25 controlled NHB donors were undertaken at our centre. The rates of primary non-function, delayed graft function (DGF), rejection and long-term graft and patient survival were compared with those of 84 recipients of grafts from heart-beating (HB donors) transplanted contemporaneously. RESULTS: Primary non-function did not occur in recipients of grafts from NHB donors but was seen in two grafts from HB donors. DGF occurred in 21 of 42 (50%) kidneys from NHB donors and 14 of 84 (17%) kidneys from HBD donars (p < 0.001). The acute rejection rates in the two groups were similar (33% for grafts from NHB donors vs. 40% from HB donors). By 1 month after transplantation, there was no significant difference in serum creatinine concentration between the two groups. Over a median follow-up period of 32 months (range 2-75 months), the actuarial graft survival rates at 1, 3 and 5 yr after transplantation were 84, 80 and 74% for recipients of kidneys from NHB donors, compared with 89, 85 and 80% for kidneys from HB donors. CONCLUSION: Controlled NHB donors are a valuable and under-used source of kidneys for renal transplantation. The outcome for recipients of kidney allografts from category 3 NHB donors is similar to that seen in recipients of grafts from conventional HB cadaveric donors.     

Use of marginal organs from non-heart-beating cadaveric kidney donors.

BACKGROUND: The severe shortage of cadaver donor kidneys for transplantation has prompted many centers to utilize older donor kidneys, which have been associated with lower graft survival rates. The aim of the present study was to examine the availability and feasibility of considering kidneys from donors over the age of 60. METHOD: We studied 252 cadaveric renal transplant recipients (156 males, 96 females) who received kidneys from uncontrolled non-heart-beating donors between 1987 and 1997. We performed in situ cooling with especially designed double-balloon catheters to minimize warm ischemic kidney damage. Recipients were classified according to donor age (age 60), and we examined graft survival rates. All patients were followed for a minimum of 1 year after transplantation. RESULTS: Graft survival rates for recipients of kidneys from the older donor group at 1, 5, and 10 years after transplantation were 77%, 37%, and 30%, respectively. Corresponding values for the younger donor kidney recipients were 87%, 64%, and 47%, respectively (P=0.0011). Improved survival rates were noted when older kidneys were used for lighter weight recipients (<54 kg). No other significant factors impacted on older donor graft survival rates. CONCLUSION: Older donor kidneys are associated with poorer graft survival rates. However, kidney transplants from older donors can be quite effective in lighter weight recipients (<54 kg).     

Comparison of spousal with other donor groups: Study of a single center

In coping with the shortage of living-related and cadaveric donor groups for renal transplantation, and in the fear of organ marketing, spousal donors are considered an invaluable potential source. Survival rates have been reported to be as high as even some related groups. This study evaluated 1039 renal transplantations up to 2003. Patient survival rates in different donor groups were determined using the Kaplan-Meier method. The 3-year patient survival rates were 93% for kidneys from 61 spouses; 92% for kidneys from 433 living-related donors; 91% for kidneys from 427 living-unrelated (excluding spouses) donors; and 90.5% for 118 cadaveric kidneys. Such results were consistent with many other reports which consistently showed that spousal donors were at least as good as living-related donors, representing a reliable source in cases of organ shortage. The high survival rate of spousal donors is probably related to their strong emotional support.     

Renal transplantation with aged donors

Research indicates that aged heart-beating cadaveric donors cause greater risk factors in kidney transplantation. The influence of age on the outcome of non-heart-beating (NHB) cadaveric renal transplantations has not yet been clarified. From July 1986 to May 1999, 63 patients who received cadaveric renal transplantation at Osaka City University Hospital and Osaka City General Hospital were divided into two groups according to their age. Renal function and graft-survival rates of the two groups were compared. The mean values of nadir donor serum creatinine were significantly worse (P < 0.05) in the aged donor group. In the aged donor group the percentage of immediately functioning grafts was lower and the percentage of non-functioning grafts was higher. During the first 10 years post-transplant, graft survival in the aged donor group was significantly lower than that in the younger donor group. We conclude that cadaveric renal transplantation from NHB aged donors can be to the detriment of renal function and graft survival rates compared to transplantation from younger donors.     

Factors contributing to long graft survival in non-heart-beating cadaveric renal transplantation in Japan: a single-center study at Kitasato University

A total of 107 cadaveric kidneys from non-heart-beating donors (NHBDs) have been transplanted between 1974 and 2000 at Kitasato University Hospital, Sagamihara, Japan. The patient survival of the 107 recipients of cadaveric renal transplants at 1, 5 and 10 yr was 0.857, 0.770 and 0.746, respectively. The 50% graft survival was 3.8 yr. The 5 and 10-yr graft survival was 0.457 and 0.337, respectively. Twenty of the 107 recipients of non-heart-beating cadaveric renal transplantation had graft survival longer than 10 yr. Of these 20 patients, 14 survivors still maintain functioning renal grafts and two died with functioning graft, although the remaining four reverted to dialysis because of chronic rejection and nephropathy. The average graft survival of these 20 patients at the time of study was 13.3 yr and the longest was 21.4 yr. The average serum creatinine level at 10 yr after transplantation was 1.63 mg/dL, almost identical to that at 5 yr post-transplant. The donors aged on average 40.2 yr; 13 were male and seven were female. The youngest donor was 9-yr-old and the oldest was 66. The graft survival was significantly better in the group with donor age younger than 55 yr (Log-rank: p=0.007). The average weight of the renal graft was not different between the long and shorter graft survival groups. The average warm ischemic time and total ischemic time were 9.7 and 539.7 min, respectively. The duration of post-transplant acute tubular necrosis averaged 9.2 days. These parameters tended to be shorter than those in recipients with graft survival >10 yr, but with no statistical significance. The mean numbers of acute rejection (AR) episode within 3 months after transplantation were 0.25 +/- 0.66 and 0.92 +/- 0.90 (p=0.020) in long survival and shorter survival groups, respectively. Long survivors had a significantly lower incidence of AR. Two of 20 cases received conventional immunosuppression with prednisolone, azathioprine and mizoribin, and 18 had prednisolone and calcineurin inhibitor (CNI). Kaplan-Meier analysis showed a significant contribution of CNI to graft survival (p=0.036). However, the graft survival reduction rate after 1 yr post-transplant did not differ between conventional and CNI immunosuppression. These data suggest that renal grafts retrieved with proper organ procurement procedures from NHBDs may survive long-term and help to overcome donor shortage.     

Optimizing outcomes by preconditioning the donor

The criteria that define a so-called “marginal donor” kidney have been standardized since 2002. However, every transplant center must establish its own guidelines on organ acceptability. An expanded criteria donor (ECD) kidney is age at least 60 years, or 50 to 59 years with at least two of three specified comorbidities. Cadaveric kidneys have shown worse functional and survival outcomes compared with those from living donors. Thus, all efforts should be made to minimize the effects of ischemia on standard, non-heart-beating or ECD cadaveric donor kidneys. Because of an increasing shortfall between the diminishing number of deceased donor organs available and the increasing waiting lists, an increasing number of living donor transplantations are being performed in Europe. Among deceased donor kidneys, the largest percentage corresponds to ECD—aged or comorbidity donors—and donors after cardiac death. The results of transplants with kidneys from donors over 65 years are 10% to 15% lower than those from younger donors. Older donors present more comorbidities; however, acceptable results may be obtained with careful selection and shortened cold ischemic times. If the transplant center uses these donors to expand the pool of available organs, the donor must be evaluated according to age, vascular condition, renal function, and comorbidity. If the donor is accepted, suitable questions are: Has the potential donor undergone maneuvers to improve the quality of the kidneys? Which kind of approaches should we perform? Should we only use the biopsy information for a decision?     

Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors

BACKGROUND: Availability of cadaveric kidneys for transplantation is far below the growing need, leading to longer waiting time and more deaths while waiting. METHODS: Using national data from 1995 to 2000, we evaluated graft survival by donor characteristics and the rate of discard of retrieved organs, with the goal of increasing use of kidneys that are associated with increased risk of graft failure, that is, expanded donor kidneys. RESULTS: Cox models identified four donor factors that independently predicted significantly higher relative risk of graft loss compared with a low-risk group. These factors included donor age, cerebrovascular accident as the cause of death, renal insufficiency (serum creatinine >1.5 mg/dL), and history of hypertension. Expanded donor kidneys were defined as those with relative risk of graft loss greater than 1.70 and included all donors aged 60 years and older and those aged 50 to 59 years with at least two of the other three conditions (cerebrovascular cause of death, renal insufficiency, hypertension). The expanded donor group accounted for 14.8% of transplanted kidneys. Among organs procured from expanded donors, 38% were discarded versus 9% for all other kidneys. The risk of graft loss of expanded donor kidneys was increased in both older and younger recipients but to a greater extent in those recipients older than 50 years. CONCLUSION: By identifying donor factors associated with graft failure, these analyses may help to expand the number of transplanted kidneys by increasing the utilization of retrieved cadaveric kidneys.     

Multiple organ donation: its impact on the recovery of cadaver kidneys

Cyclosporin A not only has improved renal allograft survival but it also has caused a renewed interest in cardiac and hepatic transplantation. The South Texas Organ Bank was sensitive to the need for multiple organ donors and also concerned that the recovery of multiple organs could have a negative impact on the quantity or quality of kidneys recovered. From July 1983 through March 1985 cadaveric kidneys were obtained from 43 renal donors and multiple vital organs were obtained from 11 additional donors. There was no statistical difference between the renal and multiple organ donors in the incidence of renal contamination, post-transplant acute renal failure or renal discard rate (p greater than 0.3 in each comparison). No donor family rescinded permission for renal donation because other vital organs were requested. Urologists involved in cadaveric renal recovery are encouraged to view every cadaver donor as a potential multiple organ donor.     

Transplantation of pediatric kidneys to adult recipients: an analysis of 13 cases

INTRODUCTION: The shortage of cadaveric donors for kidney transplantation has prompted many centers to expand the criteria used for donor selection to increase the organ supply. The use of cadaveric pediatric kidneys has been suggested as a means to overcome the shortage. However, some studies indicate that kidneys from pediatric donors show inferior results to those from adult donors. In this retrospective study we examined the outcome of kidney transplantation using cadaveric pediatric donors. MATERIALS AND METHODS: From October 1990 to May 2002, 13 adult patients received pediatric renal transplants including two that were transplanted en bloc. The patients were divided into two groups based upon donor age: group I donors were 18 months to 6 years old; the seven recipients were of mean age 47.3 years. Group II donors were 7 to 15 years old; the six recipients were of mean age 43.6 years old. Cyclosporine-based immunosuppressive regimens were used in both groups. RESULTS: The patient survival rate was 85.7% in group I and 100% in group II. The graft survival rates at the first and third posttransplant year in group I were 71.4% (5/7) and 57.1% (4/7) and in group II, 66.7% and 50%, respectively. The frequency of urinary complications in group I was 28.5% (2/7) and in group II 33.3% (2/6). There was one case of venous thrombosis in group II. CONCLUSION: Pediatric renal grafts may be used with reasonable safety. However, surgical complications remain a significant problem especially with younger pediatric grafts.     

Allotransplanting donor kidneys after resection of a small renal cancer or contralateral healthy kidneys from cadaveric donors with unilateral renal cancer: a systematic review

This systematic review summarizes evidence on allotransplantation of donor kidneys after resection of a small renal cancer or contralateral healthy kidneys from cadaveric donors with unilateral renal cancer. Eligible studies were identified by screening four bibliographic databases, contacting key authors, and analyzing the bibliographies of included studies. Two reviewers independently assessed the reports for inclusion and extracted data, which were summarized as a narrative review. In the 20 case report or case series studies included in the analysis, there were 97 documented cases of donor kidney transplantation after resection of small renal cancer without pathologically confirmed recurrence, whereas 22 cases used contralateral healthy kidneys from cadaveric donors with unilateral renal cancer with one case of cancer recurrence. These results suggest that the use of donor kidneys after resection of small renal cancer is associated with a relatively low cancer recurrence rate.     

Effect of machine perfusion preservation on delayed graft function in non-heart-beating donor kidneys – early results

The functioning of non-heart-beating (NHB) donor kidneys upon transplantation is often delayed. To evaluate the effect of preservation by machine perfusion (MP) on early post-transplant function, 37 NHB donor kidneys were compared to 74 matched heart-beating (HB) donor kidneys preserved by cold storage (CS). The NHB donor kidneys were subject to 49 ± 34 min of warm ischemia. Delayed function (DF) and primary nonfunction (PNF) rates were significantly higher for NHB than for HB donor kidneys (49 % and 19 % vs 34 % and 7 %, respectively). Consequently, renal function was impaired but recovered within 6 months. MP could not eliminate the differences in DF rate between NHB and HB donor kidneys. However, NHB donor kidneys preserved by MP showed less DF than that reported in kidneys preserved by CS. This suggests that MP has a beneficial effect on ischemically damaged kidneys. The similar results observed with category 2 and category 3 NHB donors also suggest this effect. The high PNF rate emphasizes the need for viability tests that prevent the transplantation of nonviable organs. We conclude that MP alone is not sufficient to reduce DF and PNF rates in NHB donor kidneys. Received: 16 January 1997 Received after revision: 7 April 1997 Accepted: 11 April 1997     

Transplantation of Kidneys from Deceased Adult Polycystic Donors

Renal transplantation is the best treatment for end-stage renal disease. The discrepancy between donor organ supply and demand continues to widen. Maximum efforts should be made to make use of donor kidneys and we suggest that polycystic kidneys can be suitable marginal donor organs. Five polycystic cadaveric donor kidneys were transplanted in four recipients at our institution between year 2000 and 2004. The donor kidneys were either of normal size or moderately enlarged (less than 15 x 10 cm). Donor ages were 24, 46 and 55 years. All donors had normal serum creatinine at the time of organ retrieval. Recipients gave informed consent to be transplanted with the polycystic kidneys. Three of four recipients had primary graft function. The patient with primary nonfunction required graft nephrectomy 8 weeks post-transplantation. One patient died due to cardiovascular causes with a functioning graft 18 months after transplantation. Two patients remain well, 26 and 58 months after transplantation, with normal graft function. Our experience and the limited evidence from the literature suggest that, with careful selection of both donor and recipient, transplantation of cadaveric polycystic donor kidneys should be considered given the current organ shortage.     

Cadaveric renal transplantation: our experience at the Institute of Kidney Diseases & Research Centre, Institute of Transplantation Sciences, Ahmedabad

In a developing country such as India, cadaveric renal transplantation accounts for only less than 1% of total renal transplantations. The reasons for such a low rate of cadaveric transplantation are many, ranging from lack of awareness to socioeconomic reasons. Our institute conducted a statewide public awareness program and initiated an intercity organ harvesting program. This doubled the cadaveric renal transplantations in the last 2 years. We performed 38 cadaveric transplantations among 190 renal transplantations in the last year (August 2005 to July 2006). We retrieved kidneys from 21 donors, of whom 9 were outside our city. From 21 donors we transplanted 38 recipients; out of whom 3 received dual kidneys and one kidney was discarded. The Mean age of the donors was 41.4 +/- 18.2 years with a mean cold ischemia time of 6.9 +/- 3.8 hours. Sixty-eight percent had delayed graft function. At the last follow-up, which was 190 +/- 98 days, patient survival rate was 90%: 4 patients died, including 2 due to bacterial sepsis and 2 due to cytomegalovirus (CMV) disease. The Graft survival rate was 85%, and the death-censored graft survival rate was 90%. Mean serum creatinine value at the last follow-up was 1.2 +/- 0.3 mg%. There were 5 episodes of acute rejection in 31 patients during first 3 months (16% acute rejection rate). The increase in cadaveric transplantations was associated with satisfactory patient and graft survival despite the high incidence of delayed graft function.     

Diabetic donors as a source of non-heart-beating renal transplants

Due to the organ shortage, many renal transplantation centers attempt to increase the donor pool by using non-heart-beating donors (NHBDs). These kidneys are generally regarded as "marginal" grafts. Many centers do not consider transplantation from an NHBD with a history of diabetes as it is a more suboptimal donor. We began our NHBD program in 1998 and have performed 5 renal transplants from diabetic NHBDs. Viability testing identified kidneys suitable for single or dual transplantation. Although kidneys from brain stem dead donors with diabetes have been used successfully, our data suggested that kidneys from diabetic NHBDs can also be used although we still need long-term results.     

Evaluation of pediatric cadaver kidneys transplanted into adult recipients receiving cyclosporine

The major problem in clinical transplantation is the imbalance between the need for cadaveric organs and the available numbers of donors. If pediatric kidneys were transplanted into adult recipients when no pediatric recipient was available, the potential number of renal donors would be increased by 15 to 20%. Some centers are reluctant to use pediatric kidneys for adult recipients because of recent reports indicating poorer patient and allograft survival, increased delayed graft function, increased post-transplant hypertension and increased technical complication. (There also has been concern that the nephrotoxic effect of cyclosporine A would retard the organ growth that is necessary to provide normal renal function in adults.) A retrospective analysis was performed on 18 adult recipients who received kidneys from cadaver donors 14 months to 12 years old (group 1). These patients were compared to 106 adult recipients who received kidneys from donors greater than 12 years old (group 2). Actuarial patient survival at 1 year was 85% for group 1 and 95.8% for group 2 (p equals 0.13), while 1-year actuarial allograft survival was 83.1% for group 1 and 81.1% for group 2 (p equals 0.87). There was no significant difference between groups 1 and 2 in the frequency of delayed graft function, serum creatinine at 1, 3 and 6 months after transplantation, incidence of post-transplant hypertension or frequency of surgical complications. It is of interest that the pediatric kidneys had significant growth during the initial post-transplant month. Sonographic examination at postoperative days 1 and 30 demonstrated a mean increase in size from 80.7 to 143.5 cm. (p less than 0.001). In this series pediatric kidneys were safe and effective donor organs in adult recipients, and increased the available number of organs by 15%.     

Living donor kidney transplantation in a Veterans Administration medical center

BACKGROUND: A shortage of organ donors remains the major limiting factor in kidney transplantation. Living donor renal transplantation, especially living-unrelated donors, may expand the donor pool by providing another source of excellent grafts. METHODS: Between 1983 and 2003, 109 living donor kidney transplants were performed. Potential donors were assessed with a standardized routine. Antithymocyte serum (N-ATS) and Basiliximab were used as induction agents. Sandimmune, Gengraf, Neoral, and Prograf were the main immunosuppressants with Immuran, Mycophenolate Mofetil, and steroids. Eighty-two percent of the recipients were from out of state. RESULTS: Seventy-eight percent of the living donors were from living-related donors and 22% were from living-unrelated donors. One- and three-year patient survival rates were 97.6% and 93.2% with 1- and 3-year graft survival rates of 93.2% and 88.3%, respectively. There were 6 delayed graft functions (5.5%), 16 acute cellular rejections (10%), and 10 chronic rejections (9%). Twelve patients died, 7 of them with a functioning graft. In the past 6 years (1997-2003), the number of living donor kidney transplants surpassed deceased donor kidney transplants. CONCLUSIONS: Because of the limited number of cadaveric kidneys available for transplant, living donors represent a valuable source, and the use of living-unrelated donors has produced an additional supply of organs. In our program, the proportion of living donors used for kidney transplant is comparable with other non-Veterans Administration programs and the survival of these allografts appears to be superior to deceased donor kidney transplants.     

Primum non nocere: avoiding harm to vulnerable wait list candidates in an indirect kidney exchange.

BACKGROUND: One proposal to increase kidney transplantation is to exchange kidneys between pairs of ABO-incompatible (or cross-match-incompatible) living donors and their recipients. One variation that has greater potential exchanges living donor kidneys for cadaveric donor kidneys (indirect exchanges). A primary concern with indirect exchanges is the potential to disadvantage blood group O wait list candidates. Using wait list modeling, we examine whether this proposal would disadvantage cadaveric kidney blood group O wait list candidates, and present an approach for neutralizing these negative effects. METHODS: A probability model estimated the total number and blood type frequencies of donor-recipient pairs that would participate in indirect exchanges. A supply-to-demand model for the cadaveric kidney wait list estimated the mean wait time under different allocation policies and donor selection mechanisms for candidates on the wait list classified according to the candidates' race and blood type. RESULTS: Indirect exchanges will reduce the mean wait time for cadaveric kidney wait list candidates. The mean wait time of blood group O cadaveric kidney wait list candidates increases when the participating living donors self-select and when kidney allocation is determined by efficiency. This is neutralized when the transplant team preferentially selects blood group O living donors and cadaveric kidney allocation is determined by need. CONCLUSION: Indirect exchange programs will significantly shorten the wait times for cadaveric kidney wait list candidates. The wait times of blood group O candidates will not be affected adversely if blood group O living donors are selected preferentially and if allocation is based on need.