Racial disparity trends for graft failure in the US pediatric kidney transplant population, 1980-2004.

Graft survival among adult African American kidney transplant patients remains low compared to whites, but little information is available for children and adolescents. We examined trends in graft failure among US incident primary kidney transplant patients aged <19 years (n = 13 692), 1980-2004. Trends in 1-year and 2- to 5-year graft failure (for patients whose grafts survived the first year) were analyzed in 5-year intervals. One-year graft failure declined 70% for white and 77% for African American patients over the 25-year period, and 1-year graft failure rates improved at a slightly higher rate for African American compared to white patients (p = 0.02). In contrast, the graft failure rates for years 2-5 declined 53% for white and only 41% for African American patients over the 25 years (p = 0.29). In fully adjusted Cox proportional hazards analysis, the rate of graft failure among African Americans was approximately 2-fold higher than for white patients over the entire study period. Graft survival has improved slightly more for African American than white pediatric patients over the past 25 years. However, graft survival for African American pediatric patients remains poor compared with white patients.

Increased urologic complications in children after kidney transplants for obstructive and reflux uropathy.

In the cyclosporine era, reports on pediatric kidney transplant (KTx) patients with obstructive and reflux uropathy are limited by small numbers, short follow-up, and/or lack of control groups. Our single-center study evaluated long-term outcomes (patient and graft survival, urinary tract infections [UTIs], urologic complications) in a large cohort of KTx recipients (<20 years old). We matched our 117 study patients with obstructive and reflux uropathy with 117 controls whose KTx was needed for other reasons; all 234 underwent their KTx between April 25, 1984, and October 23, 2002. The mean age was 8.0 +/- 6.2 years; mean follow-up, 133 +/- 67 months. The urologic complication rate was higher in study patients (43%) than in controls (11%) (p < 0.0001), as was the UTI rate (45% vs. 2%; p < 0.0001). The metabolic acidosis and UTI rates were higher in study patients who did (vs. did not) undergo bladder augmentation (p < 0.0001). We found no significant difference between study patients and controls in patient or graft survival, acute or chronic rejection, or mean estimated glomerular filtration rates. Unique to our study is the finding of higher metabolic acidosis and UTI rates in study patients who underwent bladder augmentation.

Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative.

The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10-year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients. It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD, but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population. In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients. Evidence from the general population indicates that treatment of dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias. Dyslipidemias are very common in CKD and in transplant patients. However, until recently there have been no adequately powered, randomized, controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD. Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been presented and published. Based on information from randomized trials conducted in the general population and the single study conducted in kidney transplant patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia guidelines, were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients. These guidelines are divided into four sections. The first section (Introduction) provides the rationale for the guidelines, and describes the target population, scope, intended users, and methods. The second section presents guidelines on the assessment of dyslipidemias (guidelines 1-3), while the third section offers guidelines for the treatment of dyslipidemias (guidelines 4-5). The key guideline statements are supported mainly by data from studies in the general population, but there is an urgent need for additional studies in CKD and in transplant patients. Therefore, the last section outlines recommendations for research.

Pretransplant dialysis status and outcome of renal transplantation in North American children: a NAPRTCS Study. North American Pediatric Renal Transplant Cooperative Study.

BACKGROUND: There are no large studies of the effect of pretransplant dialysis status on the outcome of renal transplantation (Tx) in children. This study evaluated the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry data for the outcome of Tx in pediatric patients who either (1) received their transplants preemptively or (2) were maintained on dialysis before receiving their transplants. METHODS: We compared graft survival and patient survival rates, incidence of acute tubular necrosis (ATN), acute rejection episodes, and causes of graft failure in peritoneal dialysis (PD) patients with those maintained on hemodialysis (HD) and those undergoing preemptive Tx (PTx). RESULTS: Primary Tx was performed in 2495 children (59% male; 61% Caucasian; 1090 PD, 780 HD, 625 PTx) between 1/1/1992 and 12/31/1996. The overall graft survival rates of the PD and HD groups were similar, but were less than that of the PTx group (3-year: 82% PD and HD, 89% PTx, overall P = 0.0003). Improved graft survival in the PTx group was present only in recipients of grafts from living donors. There was no difference in the overall patient survival rate at 3 years, or in time to first acute-rejection episodes in the three groups. The incidence of ATN in the first 7 days post-Tx was higher in PD and HD patients than in PTx patients (11% PD and 12% HD vs. 2% PTx, P<0.001; HD vs. PD, P = NS). The major single cause of graft failure in each group was: PD, vascular thrombosis (200%); HD, chronic rejection (27%); PTx, acute and chronic rejection (21% each). CONCLUSION: NAPRTCS data show that graft survival is improved in patients receiving PTx, compared with those receiving PD and HD. Graft loss resulting from vascular thrombosis is more common in children who receive PD than in those receiving HD.

Does cytomegalovirus cause glomerular injury in renal allograft recipients?

The case of a 16-yr-old woman who received an ABO-incompatible renal allograft for end-stage renal disease due to membranoproliferative glomerulonephritis type I is presented. The patient's posttransplant course was complicated by cytomegalovirus (CMV) infection and the rare finding of glomerular CMV inclusions on renal biopsy. This article focuses on the pathology and pathogenesis of glomerular injury associated with CMV infection in renal allograft recipients and also reviews the epidemiology, clinical implications, diagnosis and management of CMV infection in these patients.

Delayed acute renal failure in post-transplant period in young children from unexplained etiology.

This report describes six young children (5 male) who developed delayed acute renal failure (DARF) in the early post-kidney-transplant (Tx) period in the absence of acute rejection (AR) or other diagnosable conditions. These young children, aged 16.5 +/- 3.1 (12-21) months [mean +/- SD, (range)] and weighing 8.5 +/- 1.7 (7.1-11.4) kg received a primary renal Tx (5 living-related donor, 1 cadaver) between 1984 and 1992. Immunosuppression included prednisone, azathioprine, and Minnesota antilymphocyte globulin (MALG, n = 5); one patient received cyclosporine and no MALG. Initially, all patients had good urine output (UO). They became systemically ill and abruptly developed diminished UO on post-operative day (POD) 6.5 +/- 1 (4-8). DARF was accompanied by fever (39.1-40.4 degrees C, n = 6), thrombocytopenia (platelets < 100,000/mm3, n = 6), leukocytosis, or leukopenia (white cell count > 20,000/mm3, n = 4 or < 1,000/mm3, n = 1). Four patients had diarrhea. Three had ascites and one was surgically explored for suspected urinary leak. None showed significant urinary obstruction by renal ultrasound. Renograms showed intact blood flow. Renal biopsy showed tubular ectasia (n = 6), vascular congestion (n = 5), focal glomerular endothelial swelling (n = 4), and capillary thrombi (n = 3). None showed AR. Five patients required dialysis for 11 +/- 4 (7-15) days. All patients survived. One patient, treated for suspected AR with the monoclonal antibody OKT3, developed shock and lost her graft on POD 12 due to vascular thrombosis. Renal functional recovery in the remaining five patients took 14 +/- 5 (6-20) days and their serum creatinine at discharge was 0.7 +/- 0.5 (0.3-1.6) mg/dl. We report DARF from undetermined etiology occurring in the first 2 weeks of renal Tx in young children. Treatment is supportive care including dialysis. Recognition of this complication will help avoid risky investigations or unnecessary treatment for rejection.

Risk factors for chronic rejection in pediatric renal transplant recipients--a single-center experience.

Chronic rejection (CR) is the most common cause of graft loss beyond the 1st posttransplant year. The aim of this analysis was to identify the risk factors for the development of CR in pediatric renal transplant recipients. Between June 1984 and March 1994, 217 renal transplants were performed in children at our center. Immunosuppression included prednisone, azathioprine, cyclosporine (CsA), and prophylactic antibody. Using multivariate analysis, we studied the impact of the following variables on the development of biopsy-proven CR: age at transplant (< or = 5 years, > 5 years), gender, race, transplant number (primary, retransplant), donor source (cadaver, living donor), donor age (< 20 years, 20-49 years, > 49 years), number of ABDR mismatches (0, 1-2, 3-4, 5-6), number of DR mismatches (0, 1, 2), percentage peak panel reactive antibody (PRA) (< or = 50%, > 50%), percentage PRA at transplantation (< or = 50%, > 50%), dialysis pretransplant, preservation time > 24 h, acute tubular necrosis requiring dialysis, initial CsA dosage (< or = 5 mg/kg per day, > 5 mg/kg per day), CsA dosage at 1 year posttransplant (< or = 5 mg/kg per day, > 5 mg/kg per day), acute rejection (AR), number of AR episodes (ARE) (1, > 1), timing of AR (< or = 6 months, > 6 months), reversibility of AR (complete, partial), and infection [cytomegalovirus (CMV), non-CMV viral, bacterial]. Risk factors for the development of CR in pediatric renal transplant recipients were: AR (P < 0.0001, odds ratio 19.4), multiple ARE (> 1 vs. 1) (P < 0.0001, odds ratio 30.1), and high percentage peak PRA (> 50%) (P < 0.03, odds ratio 3.6).

Complications by age in primary pediatric renal transplant recipients.

We asked whether pediatric renal transplant recipients, subgrouped by age, differed in the percentage and number of hospital readmissions and in the incidence of infectious complications post transplant. Between 1 August 1985 and 31 October 1993, a total of 164 patients < 18 years of age underwent primary transplants, with cyclosporine-based immunosuppression, at the University of Minnesota. The percentage of readmissions (P = NS), the mean number of readmissions (P = NS), and the length of hospital stay during readmissions (P = NS) did not differ significantly among age groups. The overall incidence of acute rejection was greater in those > or = 2 years than those < 2 years (P = 0.002), and in living donor recipients > or = 2 years versus those < 2 years (P = 0.02). The incidence of bacterial infection (< 2 years, 87%; 2-5 years, 72%; 6-12 years, 51%; 13-17 years, 40%) was greater in younger recipients (P = 0.0001). The most common bacterial infection in recipients < or = 5 years was Clostridium difficile-associated diarrhea; in those > 5 years, urinary tract infection. The overall incidence of viral infection did not differ among groups (P = NS). The most common viral infection in recipients < or = 5 years was varicella and those > 5 years, cytomegalovirus infection. Risk factors for infection in the first 6 months post transplant included age < 2 years and Solu-Medrol treatment for acute rejection. In conclusion, young recipients < 2 years of age at the time of transplant are at a higher risk for bacterial infection post transplant.

Simultaneous pancreas-kidney transplant in two children with hemolytic-uremic syndrome.

Simultaneous pancreas-kidney (SPK) transplantation has rarely been performed in the pediatric population. This report describes successful SPK transplantation in a 12-year-old girl and a 14-year-old boy with renal and pancreatic insufficiency secondary to postdiarrheal hemolytic-uremic syndrome. All reported cases of pediatric SPK transplantation are reviewed. SPK transplantation is a feasible option in selected pediatric patients with combined pancreatic and renal insufficiency.

Pre-transplant blood transfusion and renal allograft outcome: 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 pre-transplant blood transfusions on graft survival and acute rejection for pediatric renal transplant recipients. Between January 1, 1987 and November 11, 1995, 4015 renal transplants in children <18 years of age (2007 living donor, 2008 cadaver) were registered in the study. Recipients were grouped by number of pre-transplant blood transfusions (0, n=1171; 1-5, n=1796; >5, n=1048). The risks of graft failure and acute rejection were related to number of pre-transplant transfusions by proportional hazards regression analysis. Models were adjusted for recipient age, sex, race, induction therapy, prior dialysis, prior transplant, HLA-DR mismatching, and transplant year. Additionally, the living donor (LD) model was adjusted for the use of donor-specific blood transfusion, and the cadaver donor (CAD) model was adjusted for donor age and cold storage time. The risk of graft failure was increased in LD (p<0.001) and CAD (p=0.001) recipients who received >5 pre-transplant transfusions. There was no significant difference in the causes of graft loss between groups. The risk of a first acute rejection decreased in LD recipients who received 1-5 blood transfusions compared with 0 (p=0.04) or >5 (p=0.003) and in CAD recipients who received 1-5 compared with 0 (p=0.05). We conclude that multiple (>5) pre-transplant blood transfusions are a risk factor for graft failure in pediatric recipients and should be avoided. However, limited blood transfusions (1-5) are associated with a decreased risk of acute rejection. Our data show that for pediatric recipients the number of pre-transplant blood transfusions is an important factor in transplant outcome.

Outcome of chickenpox in 66 pediatric renal transplant recipients.

Although chickenpox can cause severe morbidity and mortality in pediatric renal transplant recipients, published reports describing treatment of these patients are few, especially in the cyclosporine era. Sixty-nine episodes of chickenpox occurring in 66 patients were diagnosed in our transplant population between January 1984 and May 1996. Immunosuppression consisted of prednisone and azathioprine (30 cases); prednisone, azathioprine, and cyclosporine (38 cases); or prednisone alone (1 case). Azathioprine was temporarily discontinued in 66 of 68 cases. Cyclosporine was continued at the preexisting dose in 36 of 38 cases. Acyclovir was administered parenterally in 62 of 69 cases. Sixty-five of 66 patients survived. Cyclosporine use did not increase the incidence of severe disease (p > 0.1). Acute allograft rejection occurred in three patients and responded to prednisone. Chickenpox in children with renal transplants can be successfully treated with intravenous acyclovir and temporary withdrawal of azathioprine. Allograft rejection is uncommon with this approach. Patients receiving cyclosporine do not appear to experience increased morbidity or mortality with chickenpox.

The importance of early cyclosporine levels in pediatric kidney transplantation.

We studied the impact of early cyclosporine (CSA) levels on the incidence of rejection in pediatric transplant recipients. Between 1 January 1984 and 31 December 1994, a total of 234 pediatric patients underwent kidney transplants and received CSA immunosuppression. We analyzed the impact of CSA levels (at 1 wk, 2 wk, 1 month, 2 months, and 3 months) on the incidence of rejection in the first 3 and the first 6 months post-transplant. We found that CSA levels at all timepoints correlated, i.e. recipients with low levels in the early post-transplant period tended to have low levels throughout the first 12 months. Multivariate analysis for risk factors by biopsy-proven rejection in the first 3 months revealed that the CSA trough level was the critical factor (p < 0.05). Recipients with CSA trough levels < 100 ng/ml had 2.24 times the risk of rejections vs. those with blood levels > 100 ng/ml. Similarly, the CSA trough level at 1 month was the critical risk factor for biopsy-proven rejection within the first 6 months (p < 0.05). The major risk factor for graft loss within the first 12 months was a biopsy-proven rejection episode. We conclude that in pediatric kidney transplant recipients, early CSA trough levels < 100 ng/ml are associated with a significantly increased incidence of rejection in the first 6 months post-transplant.

Impact of age on renal graft survival in children after the first rejection episode.

Infants are thought to be more immunoreactive and at a greater risk for developing irreversible rejection compared with older children. We investigated this by analyzing patient and graft survival rates, incidence of acute rejection, reversibility of acute rejection, development of a subsequent acute rejection, and incidence of graft loss due to rejection in 154 children (< 18 years of age) after primary renal transplantation. Most patients (n = 139) were treated with quadruple immunosuppression (antibody, azathioprine, prednisone, cyclosporine). Treatment of the first acute rejection episode (ARE) consisted of antibody and increased prednisone (68%) or increased prednisone alone (30%), and was not significantly different between the age groups. Transplants were from living donors (LRD) in 80% of cases. Patients were followed for at least 1 year (mean 58 +/- 30 months); 68% (105/154) of recipients experienced 1 or more ARE. The incidence of ARE was significantly lower in patients < 2 years of age (45%) compared with patients 2-5 (76%, P = 0.01), 6-12 (78%, P = 0.005), and 13-17 (76%, P = 0.009) years of age. There was no significant difference in the 1-, 2- and 5-year patient or graft survival rates, the development of a subsequent acute rejection, or the incidence of graft loss due to acute rejection when analyzed by age group. These data suggest that the impact of an ARE is similar for younger and older children in our population receiving predominantly LRD transplants and quadruple immuno-suppression.

Respiratory syncytial virus infections in pediatric renal transplant recipients.

Immunocompromised patients are considered at increased risk from respiratory syncytial virus (RSV) infection. We examined the incidence and outcome of RSV infection in pediatric renal transplant (Tx) recipients on chronic immunosuppressive therapy. Of 173 recipients transplanted between November 1985 and April 1993, 5 (3%) developed RSV infection (age range 11-39 months). Initial immunosuppression included prednisone, azathioprine, cyclosporine, and polyclonal antibody therapy. Time from Tx to onset of RSV infection was 1 day to 7 months. Symptoms included rhinorrhea, cough, tachypnea, retractions, fever, wheezing, and abnormal chest X-ray. Treatment included bronchodilator therapy, bronchial drainage, ribavirin, and mist tent. Azathioprine was transiently withheld for leukopenia during treatment in 2 recipients. Three recipients developed biopsy-proven acute rejection during (n = 2) or immediately following (n = 1) RSV infection; all responded to corticosteroid treatment. RSV infection is not commonly diagnosed in pediatric renal Tx recipients. The course of RSV infection in our patients did not differ from that reported in normal children. The possible association between RSV and acute rejection warrants further observation. When diagnosed early, RSV infection does not appear to be associated with increased mortality in pediatric renal Tx recipients. Larger numbers of recipients need to be studied to confirm these results.

Recipient evaluation, preparation, and care in pediatric transplantation: the University of Minnesota protocols.

At the University of Minnesota, outcome of renal transplants for infants and young children is the same as outcome for older children and adults. We reviewed our decision-making process in the pre-, peri-, and postoperative care of these recipients.

Chronic renal allograft rejection in the first 6 months posttransplant.

Between May 1, 1986 and May 31, 1992 at the University of Minnesota, we interpreted 129 renal allograft biopsy specimens (done in 48 grafts during the first 6 months posttransplant) as showing changes consistent with chronic rejection. For this retrospective analysis, we reexamined these biopsies together with clinical information to determine: (a) whether a diagnosis other than chronic rejection would have been more appropriate, (b) how early posttransplant any chronic rejection changes occurred, and (c) if the diagnosis correlated with outcome. We found that (1) chronic rejection is uncommon in the first 6 months posttransplant; it was documented in only 27 (2.4%) of 1117 renal allografts and was preceded by acute rejection in all but 3 recipients (for these 3, the first biopsy specimen showed both acute and chronic rejection). (2) Chronic vascular rejection was seen in 1 recipient as early as 1 month posttransplant; the incidence increased over time and was associated with an actual graft survival rate of only 35%. (3) The most frequent cause of arterial intimal fibrosis in the first 6 months posttransplant was arteriosclerotic nephrosclerosis (ASNS) of donor origin. Long-term graft function for recipients with ASNS was 67%. (4) Early-onset ischemia or thrombosis was seen in 14 recipients and predicted poor outcome: only 35.7% of these recipients had long-term graft function. (5) Cyclosporine (CsA) toxicity was implicated in only 3 recipients, who had mild diffuse interstitial fibrosis in association with elevated CsA levels. Other variables (including systemic hypertension, urinary tract infection, obstructive uropathy, neurogenic bladder, cobalt therapy, and recurrent disease) were not significantly associated with chronic renal lesions in the first 6 months posttransplant. A significant number of biopsies were originally interpreted as showing chronic rejection, but the diagnosis was changed upon reevaluation in conjunction with clinical data. We conclude that many factors coexist to produce chronic lesions in biopsies during the first 6 months posttransplant, so clinical correlation is needed before establishing a diagnosis of chronic rejection.

Effects of growth hormone on kidney function in pediatric transplant recipients.

Recent evidence suggests that treatment with recombinant human growth hormone (rhGH) after a successful kidney transplant improves the growth rate of children with short stature. We prospectively investigated eight children (6 boys, 2 girls), focusing on acute rejection episodes and changes in serum creatinine levels during rhGH treatment. The children (mean age 11.6 +/- 3.4 years) received rhGH daily (0.04-0.05 mg/kg subcutaneously). Seven patients completed at least 12 months (20 +/- 8 months) of rhGH treatment. Their mean serum creatinine level was 1.3 +/- 0.7 mg/dl 12 months before, and increased to 3.4 +/- 4.2 mg/dl after 12 months of rhGH treatment, but did not achieve statistical significance (P = 0.06). Their mean calculated glomerular filtration rate was 58 +/- 20 ml/min per 1.73 m2 12 months before, and decreased to 38 +/- 21 ml/min per 1.73 m2 after 12 months of rhGH treatment, but did not achieve statistical significance (P = 0.08). Of the seven patients, two developed acute rejection after 5 and 6 rejection-free years; three lost their grafts and returned to dialysis. These preliminary observations describe untoward renal events in children receiving rhGH treatment after a kidney transplant.

Relationship between retinal and glomerular lesions in IDDM patients.

Current knowledge regarding the concordance and discordance of the eye and kidney complications of diabetes is based on observations by ophthalmoscopy of retinal structural changes, which may be present at early stages of the disorder, and renal functional changes, which only become apparent at the later stages of the disease. For this reason we investigated the relationship between retinal structural lesions and quantitative measures of glomerular structure in patients with insulin-dependent diabetes mellitus (IDDM). Renal biopsies were evaluated using morphometric techniques, and retinopathy classification was determined by retinal fundus photography in 86 patients with IDDM: age 30.4 +/- 7.3 years and duration of IDDM 18.9 +/- 6.3 years (mean +/- SD). Retinopathy score correlated with glomerular basement membrane width (r = 0.39, P = 0.0002), mesangial volume fraction (VvMes/Glom) (r = 0.35, P = 0.0009), surface density of the peripheral capillary wall (SvPGBM/Glom) (r = 0.34, P = 0.0013), and index of arteriolar hyalinosis (r = 0.36, P = 0.0008). Abnormalities in VvMes/Glom and SvPGBM/Glom were more pronounced in patients with both retinopathy and hypertension. Four of the 15 patients (27%) with either normal urinary albumin excretion (UAE) or low-level microalbuminuria had advanced retinopathy but normal VvMes/Glom. In conclusion, the presence of advanced retinal disease with or without hypertension in patients with IDDM indicates a greater likelihood of advanced nephropathy as evidenced by increased VvMes/Glom and decreased SvPGBM/Glom. However, marked discordance between retinopathy and nephropathy occurs, as illustrated by patients with normal UAE or low-level microalbuminuria, normal glomerular structural measures, and advanced retinopathy.

Causes of kidney allograft loss in a large pediatric population at a single center.

At our institution, 521 kidney transplants were performed in 429 children (mean age 8.7 +/- 5.6-years) between 1969 and 1991. Of these transplants, 408 were primary, 113 were retransplants, 347 were living related, 171 were cadaver, and 3 were living nonrelated. Immunosuppression consisted of prednisone, azathioprine, and Minnesota antilymphocyte globulin (non-CSA) in 339 patients, total lymphoid irradiation in 8, and, more recently, cyclosporine (CSA) in addition in 168 patients. Average follow-up was 8.8 +/- 6.0 years. Actuarial graft survival in the non-CSA versus CSA groups at 1 year was 77.0% versus 85.7%; at 5 years, 59.6% versus 71.9%. Of 136 non-CSA patients, causes of graft loss at 5 years included: chronic rejection in 55 (40.4%), acute rejection in 27 (19.9%), recurrent disease in 16 (11.8%), technical complications in 8 (5.9%), infectious complications in 4 (2.9%), other causes in 5 (3.7%), and death with a functioning graft in 21 (15.4%). Of 40 CSA patients, causes of graft loss at 5 years included: chronic rejection in 16 (40.0%), acute rejection in 8 (20.0%), recurrent disease in 6 (15.0%), technical complications in 3 (7.5%), other causes in 2 (5.0%), and death with a functioning graft in 5 (12.5%). The causes of graft loss did not significantly differ in the non-CSA and CSA groups. Chronic rejection was the most common cause of graft loss in both groups. Research focusing on chronic rejection is needed to improve graft outcome in pediatric kidney transplantation.