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S R Alexander

Publications and source records attributed to S R Alexander.

At least 37 records · Page 2Linked to original sources

Glomerular filtration rate in children following renal transplantation.

Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.

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ABO-mismatched renal transplantation in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) and the Midwest Organ Bank (MOB).

Successful ABO-mismatched renal transplantation (RT) (blood group A2 donor to blood group B or O recipient) has occurred in adults in the setting of a low titer (< or =4) natural isoagglutinin (anti-A) level in the recipient of the mismatched organ. Similar experiences have rarely occurred in children. Between 1986-1996, 11 pediatric patients (6 male and 5 female) received 11 ABO-mismatched kidneys [7 cadaveric (CAD) and 4 living related donor (LRD)]. There were 8 O recipients/A2 donor pairs, 2 B recipients/A2 donor pairs and 1 B recipient/A2B donor pair. Recipient age at the time of RT was 14.7+/-3.0 yr (mean +/- SD). Prior to RT, 2 recipients underwent splenectomy and none received donor-specific transfusions. Induction and early maintenance immunosuppression consisted of corticosteroids (11 pts), ALG/ATG (6 pts), OKT3 (3 pts), azathioprine (11 pts) and cyclosporine (8 pts). The mean 30-d cyclosporine dosage was 10.6+/-4.0 mg/kg/d. Eight patients suffered > or =1 acute rejection episodes, the initial episode occurring within the first 31 d post-transplant in 7 of them. Five grafts (45.4%) failed secondary to vascular thrombosis (1), acute rejection (2) and chronic rejection (2). The remaining grafts (54.5%) all functioned for >1000 d (range: 1023-3746 d). The pre-transplant anti-A titer was determined in 6 pts; in 4 it was low (2) and in 2 it was high (8). Graft survival in all but one of these patients (whose titer was 8 and who suffered a non-rejection-related vascular thrombosis) was > or =2 yr. In summary, ABO-mismatched RT in pediatric patients is an uncommon practice. However, the adult experience and our preliminary pediatric experience suggests that evaluation of recipient isoagglutinin levels in this setting may be helpful in the selection of donor/recipient pairs in whom mismatched transplantation can be successful.

ABO Blood-Group System↗

Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study summarizes data voluntarily collected from 123 centers on 5,197 children and adolescents grouped into three cohorts: (1) patients who received renal transplants on or after 1 January 1987 (n = 3,066), (2) patients who were maintained on peritoneal dialysis (PD) or hemodialysis (HD) on or after 1 January 1992 (n = 1,488), and (3) patients treated for chronic renal insufficiency (CRI) on or after 1 January 1994 (n = 643). The transplant and dialysis information update previous registry data whereas the CRI information reflects 1st-year registry data. Three-year graft survival rates were 83% and 66% for living donor grafts and cadaver donor (CD) grafts, respectively. Triple drug maintenance therapy with prednisone, cyclosporine, and azathioprine was used by > 70% of all transplant recipients through 5 years of follow-up. The 2-year CD survival has steadily improved from 65% in 1987 to 82% in 1992. Fifty malignancies have been reported, the majority of which are lymphoproliferative disorders. The 2-year patient survival posttransplantation is 95%. Mortality rates for the youngest patients have drastically improved over the past 2 years. Approximately two-thirds of patients in the dialysis cohort are maintained on PD; automated PD remains the preferred modality. Overall, the peritonitis rate is one infection every 13.3 patient months, the frequency of infection being greatest in the youngest patients. Whereas the primary reason for dialysis modality termination is transplantation approximately 40% of the entire dialysis cohort (PD at HD) were not considered active transplant candidate Baseline CRI data revealed the most common primary diagnoses to be obstructive uropathy (24%) and aplastic/hypoplastic/dysplastic kidneys (19%). The standardized height deficit in the CRI cohort was greatest in the younger patients and those with the most impaired renal function.

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Growth rates in pediatric dialysis patients and renal transplant recipients.

We compared growth rates by modality over a 6- to 14-month period in 1,302 US pediatric end-stage renal disese (ESRD) patients treated during 1990. Modality comparisons were adjusted for age, sex, race, ethnicity, and ESRD duration using linear regression models by age group (0.5 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 18 years). Growth rates were higher in young children receiving a transplant compared with those receiving dialysis (ages 0.5 to 4 years, delta = 3.1 cm/yr v continuous cycling peritoneal dialysis [CCPD], P < 0.01; ages 5 to 9 years, delta = 2.0 to 2.6 cm/yr v CCPD, chronic ambulatory peritoneal dialysis (CAPD), and hemodialysis, P < 0.01). In contrast, growth rates in older children were not statistically different when comparing transplantation with each dialysis modality. For most age groups of transplant recipients, we observed faster growth with alternate-day versus daily steroids that was not fully explained by differences in allograft function. Younger patients (<15 years) grew at comparable rates with each dialysis modality, while older CAPD patients grew faster compared with hemodialysis or CCPD patients (P < 0.02). There was no substantial pubertal growth spurt in transplant or dialysis patients. This national US study of pediatric growth rates with dialysis and transplantation shows differences in growth by modality that vary by age group.

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Pediatric renal transplantation--the NAPRTCS experience.

The NAPRTCS has enrolled 4,329 children who have received an index renal transplant since 1987. Seventy-three percent of the transplant recipients were children above 6 years of age. In the age group below 6 years rejection episodes are not more frequent, however the first acute rejection episode is frequently irreversible leading to graft failure. Many of the renal disorders that lead to ESRD and transplantation in adults, such as diabetes and hypertension, are less often observed in the pediatric population. Developmental disorders, such as renal dysplasia and obstructive uropathy, are frequent diagnostic entities, and the most common glomerular disorder leading to transplantation in children is focal segmental glomerulosclerosis. In an attempt to overcome dialysis-associated growth retardation many pediatric renal centers resort to preemptive transplantation, thus 24% of the children receiving a transplant have never undergone dialysis. Graft survival in these children is similar to that observed in children receiving maintenance dialysis, however accelerated growth is not noted. Catch-up growth, defined as gain of 1 SDS, is observed in 47% of children below the age of 6 years and in only 22% of children over the age of 6 years. Infants (below 2 years) have a higher mortality rate following transplantation compared to older children. Long-term (5-year) graft survival for children receiving a cadaver donor graft is 60%, and for living donor kidney recipients the graft survival is 76%. Due to changes in practice patterns, such as a judicious use of cadaver donors, increased use of prophylactic T-cell antibody, and better maintenance immunosuppression, cadaver donor graft survival has improved each year since 1987. The cohorts of children with a cadaver donor transplant in the years 1991 and 1992 have a 2-year graft survival which is 10% better than that observed in the earlier years.

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125Iodine-iothalamate clearance in children. A simple method to measure glomerular filtration.

Glomerular filtration rate (GFR) is the most widely used test to evaluate renal function. Several clearance markers have been used to measure GFR in adults. In children, however, a simple and reliable method to measure GFR is not available. Renal 125iodine (I)-iothalamate clearance, after a single subcutaneous injection, is a simple and accurate test to measure GFR in adults. The validity of unlabelled iothalamate, as a marker for measurement of GFR in children, was reported recently. Unfortunately, the unlabelled iothalamate assay is arduous. We report our experience with a single subcutaneous injection of 125I-iothalamate to measure GFR in normal children and those with renal disease. A weight-adjusted dosing regimen was adopted. This regimen resulted in sufficient above-background radioactivity in both blood and urine for reproducible measurement of GFR. Intra-test variability for GFR was not affected by the degree of renal insufficiency. The test was well tolerated with only 2 patients developing mild headache during the procedure. Our study showed that renal clearance of 125I-iothalamate is reproducible, simple, and practical in healthy children and those with mild and advanced renal disease.

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Peritoneal membrane transport function in children receiving long-term dialysis.

Accurate characterization of peritoneal solute transport capacity in children has been hampered by a lack of standardized test mechanics and small patient numbers. A standardized peritoneal equilibration test was used to study 95 pediatric patients (mean age, 9.9 +/- 5.6 yr) receiving chronic peritoneal dialysis at 14 centers. Patients were divided into four age groups (< 1, 1 to 3, 4 to 11, 12 to 19 yr) for analysis. Each patient received a 4-h peritoneal equilibration test with an exchange volume of 1100 mL/m2 per body surface area. Dialysate to plasma (D/P) ratios for creatinine (C) and urea (U) and the ratio of dialysate glucose (G) to initial dialysate glucose concentration (D/D0) were determined. Mass transfer area coefficients (MTAC) were calculated for the three solutes and potassium (P). The mean (+/- SD) 4-h D/P ratios for C and U were 0.64 +/- 0.13 and 0.82 +/- 0.09, respectively. The mean 4-h D/D0 for G was 0.33 +/- 0.10. D/P and D/D0 ratio results were similar across age groups. Normalized (for body surface area) mean MTAC (+/- SD) values were as follows: C, 10.66 +/- 3.74; G, 12.93 +/- 5.02; U, 18.43 +/- 4.02; and P, 14.02 +/- 3.94. Whereas a comparison of the normalized MTAC values across age groups with an analysis of variance showed significant age group differences only for glucose (P = 0.001) and potassium (P = 0.036), analysis by quadratic regression demonstrated a nonlinear decrease with age for C (P = 0.016), G (P < 0.001), and P (P = 0.034). In summary, evaluation of D/P and D/D0 ratios obtained from a large group of children in a standardized manner reveals values that are similar across the pediatric age range and not unlike the results obtained in adults. In contrast, normalized MTAC values of young children are greater than the values of older children, possibly as a result of maturational changes in the peritoneal membrane or differences in the effective peritoneal membrane surface area.

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Lessons from the peritoneal dialysis patient database: a report of the North American Pediatric Renal Transplant Cooperative Study.

Data derived from 1383 independent courses of peritoneal dialysis have been recorded in the database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Automated peritoneal dialysis (APD) continues to be the preferred modality. Peritoneal access is most commonly achieved with a Tenckhoff curled catheter with a single-cuff and straight tunnel. Overall, the peritonitis rate is 1 infection every 13.3 months, the frequency of infection being greatest in the youngest patients. Two-cuffed catheters and exit-sites directed down positively influence this rate. Excessive infection is the primary reason for modality termination in surviving patients not transplanted. A total of 64 deaths have occurred in the peritoneal dialysis population. The 12-month and 24-month mortality probabilities in children < two years of age are significantly greater than comparable data in the older children.

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Chylous ascites complicating neonatal peritoneal dialysis.

We report the development of chylous ascites in a neonate as an uncommon complication during continuous peritoneal dialysis. Cloudy dialysis fluid containing many white blood cells might confuse the diagnosis of chylous ascites with infective peritonitis and result in inappropriate use of antibiotics. Resolution may be critical, since chyle removal during dialysis may result in profound immunosuppression and malnutrition due to lymphocyte and fat losses. After 4 weeks on a modified diet, the chyle leak resolved. The patient returned to breast milk and continues nighttime continuous-cycle peritoneal dialysis without further chyle leak.

Acute Kidney Injury↗

The evaluation of candidates for renal transplantation. The current practice of U.S. transplant centers.

The criteria for acceptance of candidates for renal transplantation varies throughout the United States. The Patient Care and Education Committee of the American Society of Transplant Physicians conducted a survey of all U.S. centers that participate in the United Network for Organ Sharing (UNOS) concerning their evaluation of adult candidates for kidney transplantation. The response to each question was examined according to the specialty of the individual who filled out the questionnaire, as well as the type of transplant center (university or private) and the size of the center. The response rate to the survey was 81% (147/182). We found the following: (1) university-based and larger centers accepted more medically complicated patients; (2) 83% noted that attendance to dialysis was an important indicator of compliance after transplantation; (3) 79% did not require preoperative blood transfusions for cadaver kidney recipients; (4) 66% set no specific upper age limit for transplantation; (5) 56% excluded patients with chronic active hepatitis in the setting of hepatitis B antigenemia; (6) 50% had no specific policy for evaluating hepatitis C antibody-positive patients, while 54% excluded the use of hepatitis C antibody-positive donors, and (7) 15% obtained coronary angiography on all diabetic patients. U.S. transplant centers have a heterogeneous approach to the evaluation of patients for renal transplantation, particularly in the areas of viral hepatitis, cardiovascular disease, and noncompliance. University-based centers and centers that perform a larger number of transplants accept more medically complicated patients.

Adult↗

Renal transplantation in children and adolescents: the 1992 annual report of the North American Pediatric Renal Transplant Cooperative Study.

From January 1987 to January 1992 the North American Pediatric Renal Transplant Cooperative Study registered and followed 2,037 children and adolescents 17 years of age or less who received 2,197 renal transplants at 75 participating centers in the United States and Canada. The cumulative experience over 5 years of data collection demonstrated trends in renal transplantation practice for pediatric patients. The percentage of live donor organ recipients receiving donor-specific blood transfusions decreased from 40% in 1987 to less than 12% in 1991; random blood transfusions also were used less frequently during the most recent 2 years of the study. Immunosuppressive therapy on posttransplant day 0 or 1 with polyclonal and monoclonal antilymphocyte agents was used in over 40% of transplants. There was also a notable preference for the combined use of prednisone, azathioprine and cyclosporine as maintenance immunosuppression. The percentage of live donor source graft recipients receiving cyclosporine increased from 78% in 1987 to 90% in the most recent year, and considered together, nearly 90% of live donor and cadaver organ recipients received cyclosporine. The observed graft survival probabilities for live donor grafts were 88%, 83%, 81% and 76% at years 1-4 post transplantation, respectively. The 1st through 4th year graft survival probabilities for cadaver grafts were 74%, 68%, 63% and 58%, respectively. The five most common causes of pediatric end-stage renal disease have remained as: hypoplastic-dysplastic kidney, obstructive uropathy, focal segmental glomerulosclerosis, reflux nephropathy and systemic immunological diseases throughout the 5 years of this study. There has been a decrease in children 2 years of age or less undergoing transplant surgery. On average, 50% of graft failures were due to the various forms of rejection. Vascular thrombosis (14%) and recurrence of primary renal disease (7%) were the next most frequently encountered causes of graft failure. Poor linear growth was identified as a problem affecting the majority of children both before and after transplantation. Post transplant linear growth was best among recipients less than 6 years of age at transplantation and recipients of all ages who received alternate-day prednisone. A total of 16 malignancies were reported during the 5 years of study. A total of 105 deaths were reported, with infection (41%) the most common primary cause of death. The 2-year patient survival probabilities were 95.5% and 93% for recipients of live donor and cadaver grafts, respectively.

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Mandibular condyle position: comparison of articulator mountings and magnetic resonance imaging.

This study evaluated the reliability of jaw positions, the existence of distinct jaw positions, and condyle-disk-fossa relationships in a symptom-free population by using articulator mountings and magnetic resonance imaging (MRI). The subjects examined included 28 men, 22 to 35 years of age, all having Angle Class I molar relationships and no discernible TMJ dysfunction. Records taken included the following: an axiographic face-bow to locate retruded hinge axis position, an interocclusal registration of retruded position (RE), a series of interocclusal registrations for centric occlusion (CO), a leaf gauge-generated centric relation (CR), a series of interocclusal registrations for CR, and MRI. The mandibular position indicator of the SAM articulator (Great Lakes Orthodontics, Ltd., Tonawanda, N.Y.) was used to determine reliability and existence of distinct jaw positions. Magnetic resonance imaging also evaluated jaw positions and anatomic relationships. The results indicate: (1) The articulator analysis of CO and CR is statistically replicable. (2) A distinct jaw position could be demonstrated for CO that was separate from RE and CR. It was not possible to discriminate between RE and CR. (3) Condylar concentricity was observed in half of the sample and remained consistent in RE, CO, and CR. (4) Of the sample 13% demonstrated anteriorly displaced disks that were not influenced by posterior condyle placement. (5) The clinical concept of treating to CR as a preventive measure to improve disk-to-condyle relationships was not supported by this study.

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Maintenance dialysis in North American children and adolescents: a preliminary report. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

During 1992 the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) began to develop a pediatric Dialysis Patient Data Base by collecting data on pediatric patients who had received either hemodialysis (HD) or peritoneal dialysis (PD), or both, at a participating NAPRTCS center. This preliminary report describes study methods and contains detailed, though short-term observations reported by 64 of 87 NAPRTCS centers on 762 patients who were < 21 years of age at enrollment and who received treatment between January 1, 1992 and September 15, 1992. In these 762 patients, a total of 810 independent courses of dialysis therapy were identified (PD = 534 [65.9%]; HD = 276 [34.1%]). Patients age groupings showed a significantly greater proportion of PD patients among younger age groups. Automated peritoneal dialysis was used by about 75% of registered PD patients at one and six months after registration. A total of 196 peritonitis episodes were reported, yielding a peritonitis rate of one episode every 7.1 patient-months. Ten percent of PD catheters were replaced, primarily for mechanical malfunction and leaks. Percutaneous catheters were used for vascular access in about one-half of the HD patients, with the remainder almost equally divided between arteriovenous fistulae and grafts. Vascular access revision was reported in 28% of HD patients, with about one-third of these revisions performed to create a more permanent access. Recombinant human erythropoietin therapy was used in 89% of PD and 94% of HD patients at six months. Recombinant human growth hormone therapy was used in 9% of PD and 5% of HD patients at six months.(ABSTRACT TRUNCATED AT 250 WORDS)

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Continuous peritoneal dialysis for children: a decade of worldwide growth and development.

This review surveys the dramatic worldwide expansion of the use of continuous peritoneal dialysis as maintenance renal replacement therapy for children with end-stage renal disease that has occurred during the past decade. Before 1982, fewer than 100 pediatric patients had been treated with continuous ambulatory peritoneal dialysis (CAPD), and continuous cycler peritoneal dialysis (CCPD) for children was virtually unknown. By the end of 1989 CAPD/CCPD was accounting for 50% of pediatric dialysis patients (less than 15 years old) in the United States, 65% in Canada, and 75% in Australia/New Zealand. Growth of CAPD/CCPD for children in Europe overall has been less spectacular, but there is wide variability from country to country, with CAPD/CCPD concentrated in eight member countries of the European Dialysis and Transplant Association. Several of these countries (notably the United Kingdom, Israel, the Netherlands and the former Federal Republic of Germany) were treating 46% to 70% of pediatric patients with CAPD/CCPD by the end of 1987. Other European countries such as France and Spain showed little growth of CAPD/CCPD over the decade (10% to 20% of patients treated with CAPD/CCPD). In Japan, CAPD for children has just begun, but because Japanese children are likely to spend longer periods on dialysis awaiting transplantation, information on long-term use of CAPD/CCPD in children may be forthcoming from Japan in the future. No effort is made to compare CAPD/CCPD to hemodialysis as a maintenance therapy for children. The advantages of CAPD/CCPD for the young patient, especially the infant and very young child are noted, and from the past decade of dramatic worldwide growth of CAPD/CCPD in pediatric patients it is inferred that the majority of children, (from 50% to 75%) can be successfully treated with these modalities, at least for the short-term (that is, several years), while awaiting transplantation.

Adolescent↗

Those cheating rats: male and female rats use odor trails in a water-escape "working memory" task.

Three-month-old Sprague-Dawley rats were trained on a working memory win-stay (spatial delayed matching-to-sample) water-escape task with the escape platform location the same for all subjects on a given trial, a procedure that maximizes the buildup of an odor trail to the escape platform. In subsequent tests during which the location of the escape platform varied randomly between subjects, the rats, especially the females, while continuing to perform above chance level, made increased errors. Varying the platform location between subjects eliminated odor trail as a nonambiguous cue for locating the escape platform. In a second experiment females performed better than males on a reference memory odor trail discrimination task which involved following the path of like-gender "pathmaker" rats to the escape platform. The relatively poor use of odor trails by the males was associated with a high frequency of choosing a preferred choice section or returning to the choice section selected first on the immediately preceding trial (perseveration). Collectively, the two experiments demonstrate that rats can use either working memory or odor trails to locate an escape platform in a water maze, and that they, especially females, will use odor trails in a working memory task if odor trails are available. Clearly, the location of the escape platform should be varied randomly between subjects in tests of working memory.

Analysis of Variance↗

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.

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