Effect of cold ischemic time and HLA matching in kidneys coming from "young" and "old" donors: do not leave for tomorrow what you can do tonight.

BACKGROUND: Kidneys from older donors are likely to have a lower nephron mass. Nevertheless they constitute a valuable source of kidney allografts. Long cold ischemic time (CIT), with or without delayed graft function (DGF), has been associated with reduced graft survival. The aim of this study was to review the experience of a single UK center to assess the interaction of cold storage time, donor age, organ exchange, and HLA-DR mismatching on short- and long-term survival. METHODS: We analyzed 788 first cadaver kidney transplants that were performed in our center from 1990 to 1997 and had complete data available. A donor age of 55 years was the cutoff age for "old" and "young" donor kidneys. The primary outcome measured was graft failure from any cause. RESULTS: There were 132 grafts from donors 55 years or older (16.7%), with 76.8% of the kidneys implanted after >20 hr of CIT. Kidney grafts from donors older than 55 years had worse graft survival than grafts from donors younger than 55 (87% vs. 78% at 1 year and 80% vs. 58% at 5 years after transplant, P=0.0001). A CIT of >20 hr significantly reduced graft survival (91% vs.74.3% at 5 years after transplant, P=0.0002) in the young donor group and was associated with an overall graft survival in the old donor group of 57.5% at 5 years. In the same group, ignoring the HLA-DR mismatching to achieve shorter CIT, the predicted initial cost on graft survival at 1 year would have been 3.7% but would have increased to 9% 5 years after transplant. For young donors a CIT of >20 hr had a cost of approximately 18% at 5-year graft survival, far higher than a single DR mismatch. Occurrence of DGF decreased survival in both short (P=0.001) and long (P=0.00001) CIT groups. CONCLUSION: Forming local alliances (common recipient lists) and minimizing delays within the hospital might reduce CIT and DGF while achieving excellent HLA matching. This should improve significantly the outcome of both old and young donor kidney grafts.     

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.     

Kidney transplantation using living donors over age 65

Efforts to increase the donor pool of available organs have resulted in some unconventional kidney transplantation procedures. One of these is the use of elderly donors for both living and cadaver kidney transplantations. The aim of this study was to review our experience with kidney transplants from living elderly donors. During a period of 10 years, 70 living renal transplantations were performed. In 32 transplants the age of the donor was above 65 years (mean 69 +/- 4 years, range: 65 to 81 years) and in 10 of these 32 transplants the age of the donor was over 70 years. The survival rate was compared with that of 38 transplants from younger donors (mean age 51 +/- 6 years, range: 24 to 59 years). The time to cold and warm ischemia, the preservation procedure and time to anastomosis of blood vessels were comparable in both groups of donors. Immunosuppression included a sequential quadruple protocol, using thymoglobulin (ATG), prednisolone (PRED), azathioprin (AZA) and cyclosporin A (CsA), which replaced ATG/PRED after day seven. A triple drug maintenance therapy (AZA, PRED, CsA) was used in all recipients. Kaplan-Meier survival curves at 1, 3 and 5 years showed that graft survival was 88%, 79% and 64% respectively for grafts from the advanced age donor group and 92%, 82% and 68% respectively for grafts from the younger donor group. The difference was slightly statistically significant (p < 0.05). Functioning of the graft was delayed in six patients who had received grafts from elderly donors and in one patient who had received a graft from a young donor. Despite worse results in transplantation with grafts from elderly donors, we consider this population as an important source of kidneys, which might help solve the present organ shortage, especially in our region.     

Transplantation of kidneys from pediatric cadaver donors to adult recipients

Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients.     

Immediate graft function positively affects long-term outcome of renal allografts from older but not from younger donors

There is disagreement about the impact of delayed graft function (DGF) on renal allograft outcome. This may depend on several variables including the age of the donor. We evaluated whether DGF could have different effects in recipients of kidneys from donors aged more than 60 years versus well-matched recipients of younger kidney donors. Patients were retrospectively subdivided into 3 groups. Immediate graft function (IGF), DGF without dialysis (DGF-ND), DGF requiring dialysis (DGF-D). DGF-ND and DGF-D occurred more frequently among 198 older than 198 younger donors (P = .016 and P = .044, respectively). The 5-year patient (96% vs 93%) and pure graft (96% vs 89%) survivals were significantly better in younger recipients, while the incidence of acute rejection was similar. After a mean follow-up of 66 +/- 44 months in older donor recipients, the graft survival was significantly better among IGF than patients in the DGF-ND (P = .046) or DGF-D (P = .003) groups. Instead, in younger recipients there was no difference in graft survival between IGD and DGF-ND. Only patients with DGF-D showed a significantly worse outcome. Upon multivariate analysis of older donors, their recipients, showed the pattern of graft function recovery to be the only variable associated with allograft outcome. Instead in younger donor recipients, acute rejection and time on dialysis were the main variables associated with a poor outcome. In older donor recipients, DGF was an independent variable associated with a poor graft outcome. In younger donor recipients, duration of dialysis and rejection were the most important predictors of poor graft outcomes.     

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.     

The use of pediatric cadaver kidneys in renal transplantation (Experience with 97 cases and comparison with adult kidneys)

Pediatric cadaver donors are an important pool of kidneys for human allotransplantation. Experiences with 97 transplantations of pediatric cadaveric kidneys (age: 4 months to 15 years) and comparison with 230 transplantations of adult kidneys (age: 16–25 and 40–68 years) are presented. The cumulative patient survival was similar in both groups, however, the graft survival was significantly lower in the pediatric donor group (p<0.05). This difference was established almost exclusively within the first 3 months after transplantation. In this group the percentage of technical complications in the first month was higher (13.4%) than in the adult kidney group (6.5%). The analysis of the whole pool of harvested kidneys shows a significantly higher rate of transplanted kidneys in the pediatric group (61%) as compared with the adult group (44.7%). In both groups the mode of arterial vascular anastomosis (end-to-end or end-to-side) does not influence the graft survival.Further investigations on pediatric donor kidneys are necessary. The utilization of pediatric cadaveric kidneys for transplantation should be increased because 20–25% of all potential kidney donors are younger than 15 years.     

Histological Assessment of Preimplantation Biopsies May Improve Selection of Kidneys from Old Donors After Cardiac Death

Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.     

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.     

Living related renal transplantation--the use of advanced age donors

AIM: Efforts to increase the donor pool and available organs included some unconventional kidney transplantation. One of these was including elderly donors for both, living and cadaver kidney transplantation. The aim of the study was to review our single centre experience with living donor transplants from elderly advanced age donors. PATIENTS AND METHODS: During a period of 7 years, 71 living related renal transplantations were performed. Twenty-six of them were over 65 (mean 69+/-4, range 65 to 81), but 10 were over 70 years of age. The survival rate was compared with 45 transplants from younger donors (mean age 51+/-6, range 24 to 59). The cold and warm ischemia time, the preservation procedure and blood vessels anastomosis time were comparable in both donor groups. The immunosuppression included sequental quadruple protocol with ATG, PRED, AZA and CyA replacing ATG after 7 days. The triple drug (AZA, PRED, CyA) maintenance therapy was applied to all recipients. RESULTS: Kaplan-Meier 1-, 3- and 5-year graft survival was 88.0%, 79.2% and 68%, respectively, for advanced donor age group and 90.2%, 82.4% and 74%, respectively, for younger donor group. The difference was slightly statistically significant (p < 0.05). In 6 patients who received graft from elderly donors, a delayed graft function was observed, whereas only in one in the younger donor group. CONCLUSION: Despite the worse results in the elderly donors' transplants, we consider the advanced age donors as an important source of kidneys contributing to solving the actual organ shortage, especially in our region.     

Effect of donor–recipient age difference on long-term graft survival in living kidney transplantation

Purpose

We aimed to examine the influence of donor age on living-donor kidney transplantation (KTx), particularly with regard to long-term graft survival in young recipients with aged kidney grafts.

Methods

Between 1988 and 2012, 287 living-donor KTxs were performed in our center. The recipients were divided into 3 groups according to age in years: under 30 (young), 30–49 (middle-aged), and over 50 (old). The data regarding the influence of kidneys from donors aged over 50 years were retrospectively analyzed.

Results

Graft survival at 1, 5, 10, and 15 years was 94.7, 94.7, 90.2, and 75.2 %, respectively, in young recipients who received grafts from donors aged under 50 years, and 96.4, 91.9, 65.4, and 41.4 %, respectively, in young recipients who received grafts from donors aged over 50 years (P = 0.023). In contrast, there were no significant differences regarding graft survival and donor age in the middle-aged and old recipient groups. Multivariate analysis revealed that young recipient and rejection episode were significant predictors of graft loss in transplantation from older donors. Histological examination revealed significant age-related changes in the grafts before transplant and a significant higher rate of glomerular hypertrophy at the 1-month protocol biopsy in young recipients with aged kidney grafts.

Conclusions

Kidney grafts from older living donors affected long-term graft survival in young recipients. In addition to the damage from rejection, aged kidney grafts, which have less nephron mass, may have a limited capacity to appropriately respond to increases in physiological or metabolic demands of young recipients, leading to a greater reduction in renal function.     

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.     

Survival of cadaveric renal transplant grafts from young donors and in young recipients

Evidence from multicenter registries has suggested that cadaveric renal graft survival is poorer when either the recipient or the donor is very young. We therefore analyzed our results from a single pediatric center. There was a significant correlation between greater recipient age and improved cadaveric graft (P=0.002) and patient (P=0.0009) survival. The age of the donor also appeared important, particularly in very young children, but became less so as donor age rose. Forty-four percent of recipients under 3 years old who received cadaveric kidneys from donors less than 4 years old lost their grafts as a result of renal thrombosis, ischemia, or technical problems, compared with only 3% of recipients over 9 years of age, whose grafts came from donors who were also over 9 years. The 1-year first cadaveric graft survival rates for these two age groups were 33% and 82% respectively. Our experience confirms the poor findings reported in very young recipients and with very young donors.     

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.     

Transplantation of pediatric en bloc cadaver kidneys into adult recipients: a single-center experience

Faced with an extreme shortage of organs transplant professionals continue to explore various strategies to expand the donor pool. Transplantation of kidneys from older and very young donors are two such options. Although kidneys from young donors (less than 5 years of age) have been associated with a high rate of technical complications and suboptimal results, use of these kidneys en bloc has been advocated to improve the outcomes. We reviewed our experience with en bloc kidney transplantation at the University of Kentucky over the past 10 years. Between 1991 and 2000 ten patients underwent kidney transplantation using kidneys en bloc from donors <5 years age. The mean age of the donors was 2.8 years with a mean weight of 16 kg (range 13-21). Mean age of the recipients was 42 years. One patient lost the graft on day one from venous thrombosis. One patient lost the graft 7 years post-transplant from chronic rejection. All of the remaining patients are doing well with functioning grafts (mean follow-up 4.5 years; range 6 months to 10 years). Both one-year and five-year graft survival rates are 89 per cent. The present study confirms that excellent results can be achieved with kidney transplantation using kidney transplantation using kidneys en bloc from donors younger than 5 years of age.     

Prognostic factors in a transplantation center with good results

In a homogeneous group of 299 first cadaver kidney allograft recipients transplanted within one single center between 1973 and 1983, we analyzed the influence of several factors on graft survival. All recipients received at least one blood transfusion before transplantation. Criteria of donor-recipient selection as well as immunosuppressive treatment policy have never changed significantly within the studied period. In contrast to matching for HLA-A and B antigens, DR-matching has a significant influence on early graft survival. Kidneys with zero DR-mismatches have a one year graft survival of 96.2% versus 75.6% for kidneys with 2 DR-mismatches (P less than 0.05). The presence or absence of DRW6 in the recipient as well as in the donor has no effect on graft survival. A preservation time less than 12 hours is accompanied by a decreased early graft survival. The long-term survival of kidneys from donors older than 30 years is significantly reduced. At 5 years graft survival of kidneys from donors younger than 30 years is 75% versus 53% for kidneys from donors older than 30 years.     

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.     

Influence of recipient and donor age in pediatric renal transplantation

Abstract. The influence of recipient and donor age on the outcome of first cadaver kidney transplants was analyzed in a series of 1325 pediatric recipients and in 4230 transplants from pediatric kidney donors. Graft survival improved significantly with increasing recipient age ( P < 0.0001) and donor age ( P < 0.0001). Combined analysis of recipient and donor age groups revealed an overriding effect of donor age on graft outcome. Kidneys from donors younger than 3 years old consistently yielded poor results regardless of recipient age. Kidneys from adult donors gave the best results even in young recipients 0–5 years of age. With adult donor kidneys in cyclosporin-treated patients, high 1-year graft survival rates of 86 9% (SE) in 15 0-to 5-year-old recipients, 85 3% in 137 6-to 12-year-old recipients, and 83 1% in 6027 13-to 40-year-old recipients were observed.     

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.     

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).