Renal transplantation of the infant and young child and the use of pediatric cadaver kidneys for transplantation in pediatric and adult recipients

Transplantation of infants less than 1 year of age with kidneys from live-related parental donors has recently led to good results, whereas cadaver donor renal transplantation in this recipient age group has led to a high mortality rate (11/13). Similarly, the results of cadaver donor renal transplantation in infants and young children less than 5 years of age has been suboptimal in the past, although recent data are more encouraging. With recent availability of long-term peritoneal dialysis for the infant and young child with end-stage renal disease (ESRD), it is possible to defer transplantation until an optimal donor becomes available. Because of the possible immunologic hyperactivity of such recipients, the immunosuppressive regimen may need to be modified if improved cadaver donor survival rates are to be obtained. The use of anencephalic kidneys for transplantation has been associated with a high incidence of primary nonfunction and few recipients with long-term functioning grafts. Harvesting of kidneys from anencephalic donors declared "brain-dead" at birth may reduce the incidence of primary nonfunction and increase the availability of anencephalic kidneys for transplantation. Reports of the use of pediatric cadaver kidneys for transplantation into pediatric and adult recipients yields discrepant results. Analysis of the data indicates that if pediatric cadaver kidneys from donors less than 6 years of age are used, the potential for decreased graft survival rates and an increased incidence of technical complications exists. However, the use of pediatric cadaver kidneys can provide adequate graft function in both pediatric and adult recipients and the use of such kidneys should increase the number of kidneys available for transplantation.     

The outcome of 304 primary renal transplants in children (1968-1985).

Of 304 children who received primary renal transplants at the University of Minnesota between January 1, 1968, and December 31, 1985, 48 (16%) were under the age of 24 months, 60 (20%) were 2-5 years old, and 196 (64%) were 6-17 years old at transplantation. Currently, 254 (84%) are alive at 2 months to 18 years following their first transplants, 77% with functioning grafts (188 first, 45 retransplants) and 7% on dialysis. Overall, patient and graft survival were not significantly different from the primary graft outcome of nondiabetic adults. The actuarial primary graft function rates at 1, 5, and 10 years were 100, 100, and 90% in 16 HLA-identical sibling kidneys; 84, 64, and 52% in 210 mismatched related kidneys; and 72, 54, and 47% in 78 cadaver kidneys (p less than 0.002). The 1-year patient survival and primary graft function rates in 44 mismatched related recipients under the age of 24 months were 92 and 88%. The use of deliberate, pretransplant random blood transfusion since 1979 has been associated with a decreased rejection rate. Primary graft function of mismatched related kidneys in children receiving standard immunosuppression has significantly improved from 78% at 1 year in the pretransfusion era to 91% (p less than 0.01) in the transfusion era. The overall primary cadaver graft function rate, however, did not improve in the transfusion era. Whether cyclosporine use will improve the cadaver renal allograft function in very young recipients remains to be established. However, with the use of related donors, even very young children can be transplanted safely and with excellent results.     

Improved cadaveric renal transplant outcome in children

We analyzed the results of 165 pediatric cadaver renal transplants performed at the University of California at Los Angeles to identify the factors which are linked to improved allograft survival. Both univariate life-table analysis and the Cox proportional hazard model were used. The use of a sequential immunosuppressive regimen (P<0.001) and kidneys from of more than 6 years of age (P<0.001) were found to be the factors having the most influence on primary graft survival. The sequential regimen was the only factor favorably influencing retransplants. With sequential therapy 1- and 2-year actuarial graft survival rates were 94% and 91% in primary transplants, and 82% and 70% in retransplants. Medication noncompliance exerted a large negative effect on transplant outcome. Of 70 recipients who had been on cyclosporine for at least 6 months, 50% evidenced noncompliance. Sixty-four percent of adolescents were noncompliant. Thirteen percent of the recipients lost their graft because of noncompliance. We conclude that good results can be obtained with cadaver renal transplants in children with a sequential immunosuppressive regimen and the use of kidneys from adolescent and adult donors. Noncompliance is a great barrier to long-term success in pediatric transplantation.     

The use of double renal transplants from paediatric cadaver donors.

In 224 consecutive kidney transplantations, 3 patients, aged 44, 37 and 13 years received double renal transplants from paediatric cadaver donors aged 1 day, 23 and 19 months respectively. Both adult recipients developed severe hypertension during postoperative rejection crises leading to multiple graft ruptures in the recipient of the neonatal kidneys. 1 patient died from massive gastrointestinal bleeding 4 weeks after transplantation while kidney function was satisfactory. Excellent graft function was achieved in the 3rd patient. The techniques of removal, preservation and transplantation of double renal transplants are described. The significance of increasing the potential number of donor kidneys by the use of paediatric cadaver donors is stressed.     

Outcome of renal transplantation in children less than two years of age.

Twenty-two renal transplants were performed in 21 children less than two years of age at Children's Hospital. Fourteen were from living related donors and eight were from cadaveric donors. The five year patient and graft survivals of these recipients were compared to all other pediatric recipients between two and 18 years of age who received renal transplants over the same time period. Five year graft survival for recipients less than two years of age was 86% following living-related donor transplantation and 38% following cadaver donor transplantation. Older pediatric recipients aged between two and 18 years had a five year graft survival of 73% following living-related donor renal transplantation, which was similar to that for recipients less than two years of age. Although older cadaveric recipients had a comparable five year graft survival to younger recipients, at 42%, the patterns of graft loss were different. Graft failures in young recipients occurred within the first seven months post-transplant, whereas the older recipient's grafts failed more gradually. Actuarial five-year patient survival in recipients less than two years of age was 86% following living-related donor renal transplantation and 70% following cadaver-donor renal transplantation. Recipients less than two years of age had a poorer patient survival than older recipients following both living-related donor renal transplantation (P = 0.06) and cadaver-donor renal transplantation (P less than 0.05). These findings suggest that the graft survival of living-related donor renal transplantation in recipients less than two years of age is better than that of cadaver-donor renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transplantation of pediatric donor kidneys to adult recipients. Is there a critical donor age?

Cadaver kidneys remain a scarce resource, yet single pediatric donor kidneys are underutilized at some centers. Between 1967 and 1984, 133 single pediatric and 318 adult donor cadaver transplants were performed. Patient and graft survival, renal function, and complications in adult recipients grouped by donor age were compared. Recipient age for all groups was similar (34-36 years). Life table analysis revealed no difference in graft survival in recipients of kidneys from donors aged 2, 3, 4, 5-10, and 11-15 when compared with adult donors. Graft survival in these groups improved over time with current 1-year survival over 75%. Recipients from donors less than 24 months of age demonstrated significantly poorer results, with no kidney surviving greater than 2 months. Serum creatinine of grafts functioning greater than 6 months was similar in all groups. It is concluded that single pediatric kidneys from donors greater than 2 years of age can be successfully transplanted to adults with good long-term results.     

Pediatric cadaver kidney transplants into adults

During a 5-year period 77 adults received single kidney cadaver transplants from donors 16 months to 16 years old. Cyclosporin immunosuppression was not used. Three recipients had ischemic ureteral complications, 1 of which resulted in allograft loss. Of the kidney grafts 34 were from donors 8 years old or younger, and comparison of renal function was made with the 43 adult recipients of cadaver kidneys from older children. The mean 1-month serum creatinine nadir was significantly higher in the recipients of kidneys from the younger children (2.6 plus or minus 1.6 versus 1.9 plus or minus 0.8 mg./per dl.). There were no statistically significant differences in 1-week dialysis requirement, 1-month kidney graft function or actuarial kidney graft survivals and serum creatinine levels at 3, 6, 12 and 24 months after grafting. Cadaver kidneys from young donors can be transplanted successfully into adults.     

Effect of increased donor age on kidney transplant outcome

Donors over the age of 50 years provided kidneys for 28 of our 226 recipients (12.4%) transplanted from January 1, 1987 to December 31, 1988. Immediate function following transplantation occurred in 36% of the kidneys from donors both over and under the age of 50. The overall 3-month graft survival rate for transplants from donors over 50 years was 89%, compared with 78% for transplants from donors under 50 years (p greater than 0.05). Thus kidneys from well-selected older donors make an important contribution to the total pool of organs available for transplantation.     

Improvement of kidney transplant regraft results by using trauma death donors

Patients who have lost a transplanted kidney are widely recognized as high-risk patients for retransplantation. We have found a profound difference in cadaver kidney regraft survival associated with the age and sex of the donor. Kidneys from male cadaver donors yielded significantly higher graft survival rates than kidneys from female donors. The difference in graft survival at one year was 7% for all first transplants (n = 2974), 14% if the recipient was sensitized, and 18% in 688 patients being regrafted. The difference was even more striking in regraft recipients of kidneys from young male donors (72% one-year graft survival) as compared with recipients of kidneys from older female donors (44% one-year graft survival). The donor age and sex effects correlated well with the cause of donor death. Young male donors accounted for 59% of trauma deaths whereas older female donors made up only 7%. Nontrauma donors, on the other hand, were 38% older female and 14% younger male. The survival of trauma-death donor kidneys in regrafted patients was 69% at one year and 37% for nontrauma donor kidneys, a 32% difference (P less than 0.001). These results indicate that regraft survival could be significantly increased through the use of cadaver kidneys from trauma death 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).     

A logical basis for age matching in organ transplantation: studies of recipient renal function in relation to donor age

The ever rising demand for renal transplantation has led to an increased use of older (> 50 years) organ donors [9]. Previous studies have shown that donor-to-recipient age difference is an independent risk factor for allograft survival [3]. A recent multicentre study of 6397 first cadaver renal transplants showed that, where donors are more than 5 years older than the recipient, there is significantly impaired graft survival [11]. The mechanism of this effect is unclear, but it has been suggested that age-related donor factors may influence subsequent graft function. Pathological studies have shown that native kidneys acquire specific histological (i. e. glomerulosclerosis, interstitial fibrosis) and functional defects in a linear fashion related to increasing age [1, 5]. Whilst graft loss may be seen as the worst outcome from using older donors, impaired function leading to shortened half-life may also occur. Recipients of kidneys from donors > 50 years of age also have a significantly higher creatinine than those from donors < 50 years of age [3]. A study was therefore undertaken to investigate in greater detail the effect of age on the function of donor kidneys in their respective recipients.     

RENAL TRANSPLANTATION IN VERY YOUNG CHILDREN

Results of renal transplantation in very young children with end-stage chronic renal failure have been poor compared with those in older children and adults. Consequently small children either may not be treated or may be placed on chronic dialysis programmes. Between 1988 and 1992, six children under the age of 5 years received seven renal transplants at the Royal Children's Hospital, Parkville, Victoria, Australia; five from live donors and two from cadaver donors. All children were treated with peritoneal dialysis before transplantation, and immunosuppressed with a standardized regimen of cyclosporine, azathioprine and prednisolone. An extraperitoneal incision was used, and the donor renal vessels were anastomosed to the lower abdominal aorta and inferior vena cava or the common iliac vein. All children received intensive monitoring and fluid replacement during the peri-operative period. Patient survival was 100%. One cadaver graft failed 1 week after transplantation because of irreversible acute rejection. This child subsequently received a successful second transplant. Two children developed postoperative urinary fistulae which were treated successfully by further operation. Current renal function in all children is excellent. The success of this programme has led us to review our attitude towards renal transplantation in this age group and to advocate live donor renal transplantation as the treatment of choice in very young children with end-stage chronic renal failure whenever possible.     

The influence of donor age on graft survival in renal transplantation

The current supply of kidneys from cadaver and living related donor sources is not sufficient to meet the demand. As a result, alternative sources of renal allografts are being explored, including very young donors and anencephalic newborns. However, data on the success of transplanting kidneys from very young donors are limited and conflicting. The purpose of this study was to determine whether the function and survival of renal grafts obtained from newborns and very young donors is different from that for grafts obtained from older donors. Thirty-six cadaveric donors under the age of 3 years, including seven anencephalic newborns, were evaluated. Allograft recipients ranged in age from 12 months to 57 years. The clinical outcome for these donor organs was compared with the graft survival for 136 kidneys transplanted from cadaver donors over age 3 years at our institution. There was a 65% 6-month and 64% 1-year graft survival in recipients of kidneys from donors greater than or equal to 3 years. Survival of grafts from donors under 12 months of age (n = 16) was significantly decreased compared with donors age 3 years and older, with a 31% 6-month (P less than .01) and 19% 12-month survival (P less than .001). Grafts obtained from anencephalic donors did not differ in survival or function from kidneys obtained from other donors less than 12 months of age. Survival for renal allografts from donors age 13 months to 3 years was also decreased relative to older donors: 55% at 6 months (P greater than .1) and 40% at 1 year (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Kidney transplantation from living related donors with multiple vessels. A problem revisited

Thirty-one renal transplantations were performed using kidneys from living donors with known bilateral double renal arteries. In twenty-one patients both vessels were anastomosed but in ten patients a tiny polar vessel was sacrificed resulting in a small infarct in the grafted kidney. Results of transplantation in these patients were compared with those in recipients of related and cadaver kidneys matched for time of transplant, sex, and age of recipient. There is an increased incidence of acute tubular necrosis in recipients of transplants from living donors with double renal arteries. By several weeks after transplantation, however, renal function is identical to that in recipients of related donor organs with single arteries. Hypertension that is more common in patients with double renal arterial anastomoses is relatively easy to control with increased antihypertensive medications. Two patients had loss of the kidney transplants because of stenosis of one or both renal arterial anastomoses. Despite these losses, the results of renal transplantation from living related donors with double renal arteries are almost as successful as those from a related donor with single renal arteries.In contrast, recipients of kidneys with polar infarcts appear to undergo more episodes of rejection, infection, or both, than do recipients of related transplants with single renal arteries. In one patient with a polar infarct, delayed total ureteral necrosis developed.Living related donors with bilateral double renal arteries should be accepted as donors in preference to cadaver donors if both vessels can easily be anastomosed. If, however, a polar vessel must be sacrificed, it is suggested that a cadaver donor be utilized in preference to a related donor.     

Influence of cadaver donor age on posttransplant renal function and graft outcome

To assess the impact of cadaver donor age on posttransplant renal function and graft survival, we analyzed our clinical results in 17 recipients of younger donor kidneys (less than 10 years) and 48 recipients of older donor kidneys (greater than 50 years) and compared them with a control group of 598 patients who received kidneys from donors between 11 and 50 years of age. The 3 groups were comparable with respect to recipient age, duration of dialysis, prior transfusions, previous transplants, cold ischemia time, HLA AB mismatches, cytotoxic antibody profile, posttransplant ATN, and prophylactic ALG treatment. The cumulative patient survival at 1, 2, and 3 years was not significantly different among the 3 groups, but the graft survival in recipients of older donor kidneys was significantly lower than the control (71% vs. 62% at 2 years, P = .09 and 66% vs. 55% at 3 years, P = .0003. The short-term renal function assessed at 1 month posttransplant was significantly lower in the older donor group compared with the control (creatinine clearance 45 mL/min vs. 59 mL/min, P = .0003). Likewise, the long-term renal function assessed at the last follow-up was also lower in the older donor group than the control (creatinine clearance 40 mL/min vs. 49 mL/min, P = .07). There were no significant differences in graft survival or short- or long-term renal function between the younger donor group and the control group. These observations suggest that transplantation of a kidney from an older cadaver donor is associated with an inferior posttransplant outcome. The practical decision whether or not to use an older donor kidney should be individualized taking this as well as other factors into account.     

Kidneys from Deceased Donors: Maximizing the Value of a Scarce Resource

Donor age is a significant risk factor for graft loss after kidney transplantation. We investigated the question whether significant graft years were being lost through transplantation of younger donor kidneys into older recipients with potentially shorter lifespans than the organs they receive. We examined patient and graft survival for deceased donor kidney transplants performed in the United States between the years 1990 and 2002 by Kaplan-Meier plots. We categorized the distribution of deceased donor kidneys by donor and recipient age. Subsequently, we calculated the actual and projected graft survival of transplanted kidneys from younger donors with the patient survival of transplant recipients of varying ages. Over the study period, 16.4% (9250) transplants from donors aged 15-50 were transplanted to recipients over the age of 60. At the same time, 73.6% of donors above the age of 50 were allocated to recipients under the age of 60. The graft survival of grafts from younger donors significantly exceeded the patient survival of recipients over the age of 60. The overall projected improvement in graft survival, by excluding transplantation of younger kidneys to older recipients, was approximately 3 years per transplant. Avoiding the allocation of young donor kidneys to elderly recipients, could have significantly increased the overall graft life, by a total 27,500 graft years, between 1990 and 2002, with projected cost savings of about 1.5 billion dollars.     

Transplantation of kidneys from children

During an 11-year period from 1978 to 1988, 720 cadaver kidneys were transplanted at the University Hospital of Zurich. 103 of the kidney grafts were from donors 16 years old or younger. The mean age of these donors was 11 years (range 2 1/3 to 16 years). There were 3 donors under 5 years, where we preserved and transplanted both kidneys en bloc. Only 3 recipients were less than 16 years old. After 1 year, 67 out of 103 recipients had a functioning pediatric graft. In the cyclosporine-treated group, the 1-year graft survival was even 80%, similar to kidney transplants from adult donors. Graft loss was observed in 48 cases. 33 patients rejected the transplant and 10 grafts were lost after recurrence of the primary renal disease. Only 5 grafts had a vascular complication. We conclude that kidneys from pediatric donors can successfully be transplanted into adults.     

The effect of donor age on graft survival in pediatric cadaver renal transplant recipients--a report of the North American Pediatric Renal Transplant Cooperative Study.

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of donor age on graft survival for pediatric recipients of cadaver donor renal transplants. Between January 1, 1987, and November 16, 1990, 787 cadaver donor renal transplants in children less than 18 years of age were registered in the study. The ages of the donors were less than or equal to 5 years in 203 transplants, between 6 and 9 years in 87, between 10 and 39 in 389, and greater than or equal to 40 years in 108. The risk of graft loss was related to donor age by a proportional hazards analysis. The ideal donor age was 20-25 years. The risk of graft loss was increased by both young and old donor age. The risk of graft loss from a neonate donor was 2.7-fold that of the ideal donor, and the risk from a 50-year-old donor was 1.8-fold that of the ideal donor. The relationship between donor age and graft survival was not affected by the age of the recipient. Cold storage time had an added impact on graft survival: grafts with cold storage time greater than 24 hr were 1.5 times more likely to fail than grafts with shorter cold storage time for all donor ages. Analysis of the causes of graft failure revealed that 9.9% of grafts from donors less than or equal to 5 years of age were lost due to vascular thrombosis, primary nonfunction, and other technical causes, compared with 4.6% in 6-9, 4.4% in 10-39, and 2.8% in greater than or equal to 40-year-old donors. We conclude that kidneys from both young and old donors are at increased risk for graft loss, and this increased risk is seen in all recipient age groups. Many of the losses from the young donors--but not older donors--may be due to technical causes. Knowledge of these risks can be used to develop strategies for optimal utilization of kidneys from young and old donors.     

Increasing the supply of kidneys for transplantation

Kidney transplantation confers a survival advantage for patients with end-stage renal disease (ESRD) when compared to dialysis and improves the quality of life in a cost-effective manner. Currently there are more than 60,000 patients on the U.S. waiting list for kidney transplantation. In 2004, 16,879 kidney transplants, including 880 simultaneous kidney and pancreas transplants, were performed in this country. Recent strategies for increasing the supply of kidneys hold promise, such as systematic programs designed to improve consent rates for deceased donor organ procurement. Efforts to increase donation after cardiac death (DCD) have been highly successful and now account for more than 5% of all deceased organ donors. Transplantation of kidneys from DCD donors yields 1-year graft and patient survival rates equivalent to kidneys from brain-dead donors. Expanded criteria donor (ECD) kidneys from donors > or = 60 years of age (or donors age 50-59 years with certain comorbidities) confer a survival benefit for end-stage renal disease (ESRD) patients compared to remaining on dialysis on the waiting list. The number of live donor kidney transplants, both from biologically related and unrelated donors, is increasing. Paired live donor kidney transplants provide yet another transplantation opportunity for ESRD patients with willing but incompatible (by ABO or direct antibody) living donors.     

Intermediate outcomes of dual renal allografts: the University of Washington experience

PURPOSE: The increased survival advantage of renal transplantation with end stage renal disease combined with an increasing incidence of renal disease fuel an increasing disparity between supply and demand for transplantable kidneys. Despite efforts to increase cadaveric organ donation through education and publicity, the number of cadaveric kidneys transplanted has not increased and in the last year was surpassed by kidneys transplanted from living donors. In an effort to maximize cadaver organ donors use of kidneys from expanded criteria donors has been investigated. In select cases both donor kidneys have been transplanted into a single recipient, which is called dual renal transplant. We report on the 4-year dual renal transplant graft and patient outcomes and compare these to age matched single cadaver kidney transplants. MATERIALS AND METHODS: A retrospective review of 10 dual renal transplant recipients and 10 age matched single cadaver kidney recipients was performed. All patients underwent transplantation at our university between January 1996 and February 1998. Mean followup was 4.1 years (range 2.5 to 5.1) for the dual kidney recipients and 3.6 (0.0 to 5.5) years for the control group. RESULTS: Of the 10 dual renal transplant recipients 7 remain alive and 3 died of nontransplant related causes. Of the 10 single recipients 8 are alive, 1 died of postoperative complications and 1 died of nontransplant related causes. When censored for death with a functioning graft, 7 of 10 dual grafts are functioning at followup with a mean creatinine clearance of 39.4 ml. per minute (range 16.1 to 65.9) and mean serum creatinine of 2.0 mg./dl. (1.1 to 3.9). If not censored for death with a functioning graft, 50% of dual grafts are functioning. Of the 3 graft losses 2 were due to recurrent disease and 1 was attributed to chronic rejection. In the control group 8 of 10 grafts are functioning at current followup (regardless of censoring for death with a functioning graft) with a mean creatinine clearance of 48.7 ml. per minute (range 23.4 to 66.5) and mean serum creatinine of 1.6 mg./dl. (1.2 to 2.4). Of the 2 graft losses 1 resulted from postoperative complications and 1 was due to chronic rejection. CONCLUSIONS At the 4-year followup patients undergoing dual renal transplant have comparable graft function, incidence of graft loss and survival compared to the control group. However, because of our small sample size, differences in the 2 groups may be significant in a larger study. Additional studies need to be conducted to determine if this practice represents an acceptable use of kidneys from expanded criteria donors.