Renal transplantation in children with emphasis on young patients

We report the results of 41 consecutive renal transplantations performed on 39 children (median age 2.7 years). Twenty-six recipients were less than 5 years old. Twenty-one recipients (13 under the age of 5 years) received cadaver (CAD) grafts. All grafts except 2 were from adult donors and were placed extraperitoneally. Patients were on triple immunosuppression (cyclosporine plus azathioprine plus methylprednisolone). Mean followup time was 2.3 years. No vascular and only one ureteral complication was seen. Acute tubular necrosis occurred in 3 patients (7.3%). No grafts were lost due to acute rejection. Three-year patient survival and 1-year graft survival were 100%. The overall 3-year actuarial graft survival was 86%. Three-year survival of grafts from living-related donors (LRD) was 92% and that of CAD grafts 75%. In recipients younger than 5 years, 3-year LRD graft survival was 89% and CAD graft survival 73%. No significant differences in graft survival between recipients of different age groups or between LRD and CAD grafts were found. We conclude that results of renal transplantation in children under 5 years of age are comparable to those of older children, even using CAD grafts, when adult donors and triple immunosuppression are used.     

Graft function 5-7 years after renal transplantation in early childhood

BACKGROUND: Low recipient age is still a risk factor for graft failure after kidney transplantation (Tx). Detailed prospective reports on long-term graft function in small children after renal Tx are still lacking. METHODS: Forty-nine kidney allograft recipients who received transplants before the age of 5 years were followed prospectively. The most common disease was congenital nephrotic syndrome of the Finnish type. Twenty patients were recipients of living related donors (LRD), and 29 were cadaveric kidney (CAD) recipients. All patients received triple immunosuppression. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), sodium, urate, and potassium handling, and concentrating capacity were studied for up to 7 years after Tx. RESULTS: Patient survival 7 years after Tx was 100% for LRD and 96% for CAD recipients. Graft survival was 94% for LRD and 79% for CAD recipients (P=NS) and 89% and 83% for children >2 years and <2 years of age at Tx, respectively (P=NS). Five years after Tx, GFR was 70 vs. 64 and ERPF was 380 vs. 310 ml/min/1.73 m2 for LRD and CAD recipients, respectively (P=NS). Mean absolute GFR remained stable. GFR was lower in children who received transplants at <2 years than in children who received transplants at >2 years of age, 54 vs. 75 ml/min/1.73 m2 (P=0.02). Sodium handling remained intact, but hyperuricemia was seen in 43-67%; 17-33% showed abnormal handling of potassium; and most patients had a subnormal concentrating capacity. CONCLUSIONS: Excellent long-term graft survival and good graft function can be achieved with triple immunosuppression, even in young CAD kidney recipients.     

Paediatric kidney transplantation in small children – a single centre experience

Kidney transplantation (KTx) remains a challenging procedure in small children. This study presents our centre results. From 1983 to 2004, 40 of 442 paediatric KTx were performed in children with a body weight <11 kg. Median body weight was 9.2 kg (range: 7.2-10.9), median age was 2.7 years (range: 0.9-5.9). Preoperative dialysis was performed in 87.5%. In 24 cases (60%) grafts came from cadaveric (CAD) and in 16 cases (40%) from living related donors (LRD). Median donor age of CAD was 8 years (range: 1-40). The overall 1-, 5-, 10-, 15-year patient survival was 93%, 90%, 90% and 87% respectively. The overall 1-, 5-, 10-, 15-year graft survival was 90%, 80%, 66% and 56% respectively. There was no significant difference in survival of CAD or LRD grafts. Median follow-up was 13.7 years. Initial graft function rate was 100% for LRD and 79% for CAD. The relative glomerular filtration rate (GFR) showed no statistical difference between CAD and LRD. Main reasons for graft loss were chronic transplant nephropathy. Paediatric KTx is the treatment of choice even in very small children. Living donor KTx is the preferable donor source in terms of primary graft function and timing to transplantation.     

Predictors of graft survival in pediatric living-related kidney transplant recipients

BACKGROUND: A successful kidney transplant from a living-related donor (LRD) remains the most effective renal replacement therapy for children with end-stage renal failure. The use of LRD kidneys results in decreased time on dialysis, increased graft survival, and better function compared with kidneys transplanted from cadaver donors. We retrospectively analyzed data from the United Network of Organ Sharing (UNOS) Scientific Renal Transplant Registry to determine risk factors for graft loss in children who received an LRD kidney. METHODS: Data was obtained from the UNOS Scientific Renal Transplant Registry on 2418 children ranging in age from 0 to 18 years who underwent an LRD kidney transplantation between January 1988 and December 1994. Multivariate analysis of graft survival was performed using Kaplan-Meier and Cox regression models. RESULTS: The effects of age, pretransplantation dialysis, early rejection, and race were found to significantly affect graft survival. Gender, peak panel-reactive antibody, and ABO blood type were not found to be significant risk factors. Infants <2 years of age initially had the worst graft survival; however, over time their results stabilized, and at 7 years estimated graft survival was good (71%). Adolescents ranging in age from 13-18 years had the best initial graft survival, but as time went on graft survival worsened (55%). Patients who underwent pretransplantation dialysis had a relative risk for graft loss of 1.77 (P<0.001), whereas those who had an early rejection had a relative risk for graft loss of 1.41 (P<0.002). African-Americans had a significantly higher relative risk for graft loss than either Caucasians (1.57, P<0.0005) or Hispanics (2.01, P<0.0003). CONCLUSIONS: Predictors of graft survival for children who receive LRD kidney transplants include age at transplantation, pretransplantation dialysis, early rejection, and race. Over time, adolescents and African-Americans seem to have the lowest graft survival.     

Long-term follow-up of pediatric en bloc renal transplantation

We reviewed the outcomes of pediatric en bloc renal transplantation at two Canadian centers in the cyclosporine era. Between 1984 and 2002, 16 patients received pediatric en bloc renal transplants. Mean recipient age and weight were 45 +/- 17 years and 72.2 +/- 14.4 kg, respectively. En bloc kidneys were procured from donors aged 2.1 +/- 0.8 years (range, 0.7 to 4.0), weighing an average of 14.3 +/- 2.0 kg (range, 12 to 17). All en bloc kidneys were successfully transplanted without thrombosis. All patients received calcineurin inhibitors and corticosteroids. Only three patients received antibody-based induction therapy. Rejection episodes occurring in seven grafts were all successfully treated. Mean follow-up was 3.7 years (range 0.4 to 15.0). Mean serum creatinine values at 3 months and 1 and 3 years were 138.8 +/- 54.5 micromol/L, 118.6 +/- 38.1 micromol/L, and 95.1 +/- 24.4 micromol/L, respectively. The mean creatinine value of five patients with at least 5 years follow-up was 96.8 +/- 12.3 micromol/L. Three-year graft and patient survival rates were 94%. Two deaths with functioning grafts occurred secondary to cardiac and infectious etiologies. None of the grafts were lost independent of death. We conclude that en bloc transplantation has excellent short- and long-term results. Improving graft function after 3 years represented by reduced serum creatinine suggests that these kidneys have excellent renal reserve and growth potential.     

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.     

Kidney transplantation in primary oxalosis: data from the EDTA Registry

This paper reports the results of 98 first kidney transplantations in patients with oxalosis as the primary renal disease as recorded by the EDTA Registry. There were 79 patients who received a cadaveric (CAD) graft and 15 patients with a living related donor (LRD) graft; the type of donor was not recorded for four patients. Initial graft survival appeared to be better after LRD as compared to CAD grafts but at 3 years the poor survival was similar with 23% for LRD and 17% for CAD grafts. CAD graft survival did not differ between children and adults and was not affected by the waiting time on dialysis. A slight improvement was observed in grafts performed in the years 1983-1986 as compared to grafts performed in earlier years. The causes of failure reported were mainly rejection (33%) and recurrence of primary renal disease (31%). In view of the poor results related to recurrence of oxalosis in the graft, the potential of combined kidney and liver transplantation is discussed.     

Comparable renal graft survival in African-American and Caucasian recipients

In past years, many pediatric transplant centers found African-American renal transplant recipients to have poor graft survival. Since 1991 anti-lymphocyte induction therapy has been routinely used for pediatric cadaveric (CAD) and living-related donor (LRD) renal allograft recipients at the University of Tennessee, Memphis. Sixteen African-American first renal allograft recipients received induction therapy: 11 CAD allografts (10 OKT3, 1 ATGAM) and five LRD (all ATGAM). Sixteen Caucasian recipients received induction therapy; 3 CAD (all OKT3), 1 living-unrelated donor (OKT3), and 12 LRD (9 ATGAM, 3 OKT3). Mean age at renal transplantation was 11.8 and 10.5 years for African-American and Caucasian recipients, respectively. Predicted graft survival (PGS) estimated by the Kaplan-Meier method for the African-American patients was 94% at both 1 and 3 years, and for Caucasian patients was 94% and 85% at 1 and 3 years, respectively. Eleven African-American CAD recipients had a PGS of 91% at 1 and 3 years. Renal allograft survival for African-American and Caucasian pediatric recipients at our center appears to be comparable. This could be due, in part, to the use of anti-lymphocyte induction therapy. However, other factors, such as improved compliance or better immunological and pharmacological monitoring, may also have contributed. Received April 18, 1997; received in revised form January 14, 1998; accepted January 19, 1998     

Adult-size kidneys without acute tubular necrosis provide exceedingly superior long-term graft outcomes for infants and small children: a single center and UNOS analysis. United Network for Organ Sharing

BACKGROUND: Infants with end-stage renal disease are at highest risk for early graft loss and mortality of any subgroup undergoing renal transplantation. This study evaluates the influence of donor tissue mass and acute tubular necrosis (ATN) on graft survival and incidence of acute rejection episodes in infant and small child recipients of living donor (LD) and cadaver (CAD) adult-size kidneys (ASKs), pediatric CAD kidneys and combined kidney-liver transplants. Methods. Kidney transplants in infants and small children at a single center and those reported to the UNOS Scientific Renal Transplant Registry were analyzed. At Stanford, multi-variate analysis was conducted on 45 consecutive renal allograft recipients weighing < or = 15 kg, mean weight 11.2 +/- 2.6 kg. The UNOS Registry results in age groups 0-2.5 (n=548) and 2.5-5 years (n=743) were compared with age groups 6-12, 13-18, and the lowest risk adult group of 19-45 years. STANFORD RESULTS. Graft survival was 97.8 +/- 0.0 at 2 years and 84.6 +/- 0.1% at 8 years. The incidence of biopsy proven rejection was 8.8% in the first 3 months and 15.5% over the 8-year follow-up. None of the pediatric CAD kidneys had ATN. Rejection episodes were restricted to the pediatric CAD kidneys alone (3/3), with no kidney rejections in the combined pediatric CAD kidney-liver transplants (0/6; P=0.003). Four ASK transplants had ATN (1 postoperative and 3 late), and all predisposed to subsequent acute rejection episodes (4/4), whereas there were no rejection episodes in ASK transplants without ATN (0/32; P<0.001). At 3 years posttransplantation, mean serum creatinines were worse in ASKs with ATN (1.5 vs. 0.9 mg/dL; P<0.001) and in all grafts with rejection episodes (1.2 vs. 0.9 mg/dL; P<0.05). UNOS RESULTS: Among the 5 age groups studied, significantly better (P<0.001) long-term graft survival rates were observed in allograft recipients in the 2 youngest age groups with ASKs without ATN: 82 +/- 3% and 81 +/- 3% for LD and 70 +/- 7% and 78 +/- 4% for CAD recipients in the 0-2.5 and 2.5- to 5-year age groups, respectively, at 6 years after transplantation. Moreover, the projected graft half-lives after the 1st year in the LD groups without ATN were at least equivalent to those of HLA-identical sibling recipients ages 19-45 years: 26.3 +/- 5 and 29.3 +/- 6 years for the 0- to 2.5- and 2.5- to 5-year age groups, respectively, and 23.3 +/- 1 years for HLA-identical transplants. The graft half-lives for CAD recipients without ATN ages 0-2.5 and 2.5-5 yearswere equivalent or better than those for LD transplants without ATN in recipients aged 19-45 years: 15.4+/- 7 and 23.7 +/- 8 years versus 15.0 +/- 0.3 years. Mean serum creatinines were superior in the 2 younger recipient age groups compared with older age groups. CONCLUSIONS: Increased donor tissue mass of the ASK or kidney-liver transplants, in the absence of ATN, seems to confer a protective effect to infant and small child recipients of these allografts. This is manifested by a prolonged rejection-free state in the single center experience and enhanced graft survival and function in the UNOS analysis, comparable to HLA identical sibling transplants for LD infant and small child recipients and to LD adult results for CAD infant and small child recipients. To optimize this protective effect by whatever mechanism, absolute avoidance of ATN is essential in infant recipients of ASK or combined kidney-liver transplants.     

Kidney transplant in children weighing less than 15 kg: donor selection and technical considerations

BACKGROUND: Small children represent a challenging patient group in kidney transplantation (KTx). The aim of this study was to analyze patient and donor data influencing outcome in children that weighed <15 kg. METHODS: Sixty-eight kidneys were transplanted in 64 children that weighed <15 kg. In 44 cases, kidneys came from cadaveric donors (CAD) and in 24 cases from living-related donors (LRD). Grafts were placed transperitoneally via midline incision (n=16) or extraperitoneally to the iliac fossa (n=52). Vascular anastomoses were routinely performed to the aorta and vena cava even when the extraperitoneal approach was used. RESULTS: Vascular thrombosis was observed in two (3%), urinary leaks in five (7%), and stenosis in four (6%) patients. In six children receiving organs from adults to the iliac fossa, wound closure was performed using an absorbable mesh to avoid organ compression. Initial graft function occurred in 60 cases (88%). Frequency of initial graft function was significantly higher after KTx from LRD (100%) compared with CAD (82%). The 1-, 5-, and 10-year patient survival was 93%, 91%, and 91%, respectively, and the 1-, 5-, and 10-year graft survival was 92%, 85%, and 85%, respectively. There was no significant difference in patient and graft survival when KTx from LRD and CAD were compared. Within the CAD group, graft survival was improved using kidneys from donors >12 years compared with younger donors. CONCLUSION: Despite size discrepancy between recipients and grafts, KTx is feasible in children that weigh <15 kg by using an improved surgical technique even when adult organs are placed to the iliac fossa.     

Renal Allograft Survival in Transplant Recipients with Focal Segmental Glomerulosclerosis

Previous literature suggests that the recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is more common in recipients who have received an HLA-identical living-related (LRD) transplant. To address the question if FSGS patients can safely receive a 6-antigen match LRD kidney transplant, we analyzed death-censored renal allograft survival data of FSGS patients from the United States Renal Data System database (USRDS). Using the USRDS and the U.S. Scientific Renal Transplant Registry between the years 1988-97, we found 19259 adult primary renal transplant recipients, of which 2414 patients had FSGS as their primary diagnosis as compared to 16845 patients who had other types of glomerulonephritis (GN). A Cox proportional hazard model was used to estimate death-censored graft survival among FSGS patients with a zero mismatch LRD kidney transplant. The model included a triple interaction term comparing FSGS vs. GN vs. living donation (LD) vs. cadaveric donation (CAD) vs. zero mismatch (six antigen or HLA-identical) vs. mismatch. Annually adjusted death censored graft loss rates per 1000 patients (ADGL) were calculated. Focal segmental glomerulosclerosis patients receiving a zero mismatch LRD kidney transplant had the lowest ADGL rate, losing 10.5 grafts per 1000 patients per year. Not significantly different but higher (14.3) was the ADGL rate for LD, zero mismatch GN recipients. The ADGL rate was significantly higher in FSGS recipients who received a LD, mismatched transplant (36.5). Focal segmental glomerulosclerosis patients who received a CAD, zero mismatched graft (44.1), or CAD, mismatched graft (63.2), had significantly higher ADGL rates. Zero mismatch LRD kidney transplants are not a risk factor for graft loss in FSGS patients but are associated with significantly better death-censored graft survival as compared to CAD 6-antigen match or mismatched donations.     

Pediatric renal transplantation from related living donor

Living related donor (LRD) provides significant advantages when compared with cadaveric donor (CAD) in term of improved patient and graft survival and shorten waiting time. From 1985, 176 kidney transplants were performed at our Center. Of these, 156 (89%) were from CAD and 20 (11%) were from LRD, first degree. The purpose of this paper is to show our experience at 5 years with use of LRD. All donors underwent standardized metabolic workup, angiography assessed and renal function test. Twelve children received their first transplant and 8 were retransplant (6-second, 1-third and 1-fourth). Immunosuppressive therapy consisted of globulin antithymocyte, azathioprine, cyclosporine and prednisolone, using FK506 and mycophenolate mofetil in some of them. Four kidneys with multiple renal arteries were reconstructed ex vivo with microsurgical technique before transplantation. The most significant morbidity was due to FK506-associated thrombotic microangiopathy (TMA) with graft lost. All patients (donor and recipient) survived. Five years graft survival rate is 95% and mean glomerular filtration rate is 81.33 ml/min/1.73 m2.     

Pancreas transplantation. A new program

Sixteen pancreatico-duodenal transplants were performed on 15 insulin-dependent diabetics, aged 25-46, during a 20-month period beginning May 1, 1988. Fourteen patients received a combined cadaveric pancreas/renal transplant with bladder drainage. One patient received a second pancreas transplant 24 hours after the first pancreas graft failed due to portal vein thrombosis. One patient received a pancreas graft 3 years after kidney transplantation. Complications included five cases of hematuria, two bladder leaks, two wound infections, one cytomegalovirus pneumonia, three cases of graft pancreatitis, one pseudocyst, one urine reflux pancreatitis requiring conversion to pancreatico-enterostomy, and two late deaths. Average time to discharge was 17 days following transplant, with 2.9 re-hospitalizations per patient and an average of 38 in-hospital days during the first 6-12 months. Seventeen rejection episodes occurred in 12 patients, diagnosed by declining urine amylase and pH and/or finding of rejection on kidney biopsy. Patient and kidney graft survival is 87 per cent. Pancreas graft survival is 81 per cent (1-20 months follow-up). All patients are insulin-independent and normoglycemic. Mean glycosylated hemoglobin concentration is 4.0 +/- 0.9 post-transplant vs. 7.5 +/- 0.6 pretransplant. Mean serum creatinine is 1.4 +/- 0.7 mg/dl. A new program of pancreas transplantation can be successful in carefully selected diabetic patients, with special attention to avoidance of preservation injury to the pancreas during multiorgan donor procurement. Combined pancreatic/renal transplantation is believed to be the therapeutic treatment of choice in Type I diabetic patients who have impaired renal function and have no significant cardiovascular disease.     

Spousal renal donor transplantation in Chinese subjects: a 10 year experience from a single centre.

BACKGROUND: The shortage of cadaveric kidneys for renal transplantation is a particularly problematic situation in the locality of Hong Kong. Kidneys from spousal donors are therefore increasingly being used for transplantation. This study was undertaken to evaluate the outcome of spousal donor transplant recipients in comparison with that of genetically related living donor (LRD) allograft recipients. METHODS: From 1988, we have transplanted 22 spousal kidney recipients (group 1). All donors must demonstrate a genuine spousal relationship. Their outcome was compared with that of 24 LRD allograft recipients (group 2) transplanted in the same period with similar demographics, pre-transplant dialysis duration, immunosuppressive protocol and length of post-transplant follow-up. RESULTS: The mean (+/-SD) age was 36.5 +/- 8 and 32.5 +/- 6 years for groups 1 and 2, who were followed for 56.6 +/- 35 and 59.1 +/- 38 months, respectively. There was no difference in the incidence of delayed graft function, acute rejection and serum creatinine level at 5 years. Graft survival rates were 86.4 and 79.2% (P = 0.56), while patient survival rates were 100 and 91.7% (P = 0.171) at 5 years for groups 1 and 2, respectively. CONCLUSIONS: Spousal kidney transplantation shares comparable results with LRD transplantation and should be encouraged in places where cadaveric organs remain scarce. Stringent measures must be implemented to prevent the possible emergence of kidney bartering and to protect the interests of living donors. The ethical and social issues regarding the spousal donor in Hong Kong and other countries are discussed.     

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.     

The effect of cyclosporine on early graft function in human renal transplantation

The effect of cyclosporine and steroids on early renal allograft function and eventual graft outcome was analyzed in 100 recipients; 33 recipients of living related donor (LRD) and 67 recipients of cadaveric donor (CAD) allografts were studied. A concurrent population of 47 CAD recipients treated with azathioprine and steroids was used for comparison. Recipients received oral cyclosporine (14 mg/kg) 48 hours (LRD) or 6-12 hours (CAD) pretransplant. No cases of acute tubular necrosis (ATN) were observed in the LRD recipients. The incidence of posttransplant ATN was similar in the cyclosporine-treated (41%) and in the azathioprine-treated (45%) CAD recipients (P = ns). Cyclosporine-treated CAD kidneys preserved less than 24 hr experienced a lower rate of ATN (P less than .01) using simple cold storage (31%), as compared with hypothermic pulsatile perfusion (57%). One-month creatinine nadirs were higher in cyclosporine-treated than in azathioprine-treated recipients, using median values for each group. One-year actuarial patient survival for cyclosporine-treated LRD recipients was 97%; CAD recipients, 94%, and azathioprine-treated CAD recipients, 91%. Graft survival rates in the same groups were 91%, 76%, and 55%, respectively. The major causes of graft loss in cyclosporine-treated patients were nonimmunologic. It is concluded that cyclosporine and prednisone are a safe, efficacious combination for LRD and CAD renal transplantation. The possibility of nephrotoxicity leading to impaired graft function in the early posttransplant period should not preclude the administration of cyclosporine prior to alloantigen presentation.     

Living donor nephrectomy--no impact of genetic relationship

PURPOSE: A retrospective, single-center analysis was conducted to compare the results of living donor kidney transplantation between living unrelated (LURD) and living related (LRD) donors. PATIENTS AND METHODS: One hundred forty-seven consecutive living renal transplantations were performed at our institution, starting in 1983. Graft and patient survival were assessed as well as transplant function, including a subgroup analysis for the period of kidney transplantation. RESULTS: Mean follow up for the LRD group was 88.5 months and for the LURD cohort 34.4 months. One- and 3-year graft survival (censored for death with functioning graft) for LRD versus LURD was 97.5% versus 94.4% (P =.4) and 95.3% versus 88.8% (P =.35). Patient survival at 1 and 3 years was 95.1% versus 94.7% (P =.91) and 87.8% versus 90.0% (P =.79). Of the related recipients, 37% experienced at least one episode of rejection in the first year following renal transplantation, compared to 34% in the LURD group (P =.80). Mean serum creatinine for LRD versus LURD after 1, 3, and 12 months () was 1.52 +/- 0.81 versus 1.59 +/- 1.17 mg/dL (P =.98), 1.41 +/- 0.55 versus 1.30 +/- 0.40 mg/dL (P =.51), and 1.44 +/- 0.39 versus 1.40 +/- 0.40 mg/dL (P =.75). Mean creatinine clearance after 1 year was 82.2 versus 71.7 mL/min (P =.26). Subgroup analysis for the time between 1996 and 2002 revealed no difference between LURD and LRD. Multivariate analysis could exclude an impact of the significantly different recipient age and of first/second warm ischemic time on the endpoints described above. CONCLUSION: LURD is a good way to meet the growing organ shortage and should be encouraged.     

Activation of mitochondrial apoptotic pathways in human renal allografts after ischemiareperfusion injury

BACKGROUND: Ischemia-reperfusion injury in cadaveric (CAD) kidney allografts is associated with tubular cell injury, delayed graft function, and an increased incidence of acute and chronic rejection. We tested the hypothesis that activation of specific apoptotic pathways represents a mechanism for tubular cell death after CAD kidney transplantation. METHODS: Serial tissue sections from paraffin-embedded needle biopsy specimens obtained at approximately 1 hr of reperfusion after transplantation of 13 CAD and 12 living-related donor (LRD) renal allografts were examined by using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay to detect apoptosis and by immunohistochemistry for expression of key pro-apoptotic molecules (Bax, Bak, tumor necrosis factor receptor [TNFR]-1, Fas, and cytochrome c). RESULTS: Apoptosis was detected primarily in tubular cells, with a mean+/-standard deviation of 6.8+/-2.2 apoptotic cells per 100 cells examined in CAD renal allografts compared with 1.8+/-2.7 cells per 100 in LRD (P<0.001) renal allografts. There was a significant correlation between apoptosis rate and cold ischemia time in CAD (r=0.86, P<0.001) renal allografts. Bax was expressed in 100% of CAD versus 17% of LRD renal allografts (P<0.001), Bak in 92% of CAD versus 17% of LRD renal allografts (P<0.001), and TNFR-1 in 100% of CAD versus 58% of LRD renal allografts (P<0.05). Fas was expressed in only a small number of samples (23% of CAD and 17% of LRD renal allografts, P=not significant). Bax and Bak were expressed predominantly in apoptotic cells. Cytochrome c was detected as a mitochondrial pattern in LRD renal allografts, but in a diffuse cytosolic distribution in CAD renal allografts. CONCLUSIONS: Ischemia-reperfusion injury in CAD kidney transplants is associated with a duration-dependent increase in tubular cell apoptosis, mediated at least in part by activation of mitochondrial pathways.     

Ten-year experience with cyclosporine as primary immunosuppression in recipients of renal allografts.

Cyclosporine has been used as primary immunosuppression in renal allograft recipients in our unit for the past decade. The overall clinical experience and long-term effects of the agent are reviewed. There were 461 consecutive recipients of kidney grafts; 379 received grafts from cadaver donors (CAD) and 82 from living related donors (LRD). Four separate clinical protocols were used sequentially using progressively decreasing doses of CyA; azathioprine was added in group 4 recipients of LRD grafts, and in patients receiving secondary CAD grafts (group 5). The patient mortality rate was less than 5%, with sepsis being the prime contributor. The majority of kidney grafts were lost within the first 2 months after operation; those that never functioned were found almost invariably to have been irreversibly rejected. During the subsequent years of follow-up, attrition of CAD grafts was significantly greater than LRD grafts. In contrast, the attrition rate of primary and secondary CAD grafts was the same after the first 3 months, emphasizing the importance of early immunologic graft destruction. Primary nonfunction occurred in 49% of CAD kidneys and 17% of LRD grafts; however 71% of initially nonfunctioning LRD grafts never functioned at all compared to 34% of CAD grafts, the majority of such organs undergoing fulminate rejection. Individual graft loss after 1 year was almost inevitably due to chronic rejection; there were no differences in long-term allograft function among the treatment groups. Although CyA has improved overall results of kidney transplantation, chronic rejection remains a major unresolved problem.     

Renal transplantation in Alport's syndrome

Nineteen patients (3 women and 16 men) with Alport's Syndrome and endstage renal failure received 23 allograft kidneys at two medical centers between 1972 and 1983. Ten patients had pretransplant splenectomies, and four patients had pretransplant thoracic duct drainage. After a mean follow-up time of 49 months, analysis revealed total allograft survival was 65 per cent at 1 year, 50 per cent at 2 years, and 57 per cent at 5 years. Pretransplant splenectomy resulted in 60 per cent allograft survival at 24 months mean follow-up. Pretransplant thoracic duct drainage resulted in 100 per cent allograft survival at 15.6 months mean follow-up. The overall allograft survival was greatest for three and four antigen-matched kidneys and for living related donor kidneys. Data indicated that 50 per cent of all allografts in men were functional at 50.8 months mean follow-up. All allografts in women were functional at 48.3 months mean follow-up. Three of four patients who expired had pretransplant splenectomies. From this study, the authors conclude that renal transplantation is the preferred method of treatment for patients with Alport's Syndrome.