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Predictors of albumin excretion rate (AER) abnormalities could provide earlier indicators of diabetic nephropathy risk. Data from the Natural History Study, a prospective 5-year observation of renal structure and function in young type 1 diabetic patients, were examined for predictors of AER patterns in normoalbuminuric type 1 diabetic patients. Included were 170 patients (96 females) (aged 16.7 +/- 5.9 years, duration of diabetes 8.0 +/- 4.3 years) with normal blood pressure, normoalbuminuria (AER <20 microg/min), and eight or more follow-up visits over 5 years. AER, blood pressure, and HbA1c (A1C) were determined quarterly and glomerular filtration rate (GFR) annually. Persistent microalbuminuria (PMA) was defined as 20-200 microg/min in two of three consecutive values within 6-12 months. Four different AER patterns were identified. Group 1 (n = 99): all values <20 microg/min. Group 2 (n = 49): intermittent levels >20 microg/min but not meeting microalbuminuria criteria. Group 3 (n = 14): PMA during follow-up but normoalbuminuria at study exit. Group 4 (n = 8): microalbuminuria at study exit. Group 4 (497 +/- 95 nm, P < 0.01) and group 3 (464 +/- 113 nm, P = 0.03) patients had greater baseline glomerular basement membrane (GBM) width versus group 1 (418 +/- 67 nm). Baseline GFR in group 4 (163 +/- 37 ml.min(-1). 1.73 m(-2)) was higher than group 1 (143 +/- 28 ml.min(-1) . 1.73 m(-2), P = 0.04). A1C was higher in group 2 (9.0 +/- 1.2%) than group 1 (8.4 +/- 1.1%, P = 0.008). Thus, greater increases in GBM width and GFR were predictors of PMA. Since 64% of the patients that developed microalbuminuria reverted to normoalbuminuria, the risk of diabetic nephropathy as defined by current microalbuminuria criteria is unclear. [ABSTRACT FROM AUTHOR]

Background: The optimal age of kidney transplantation for infants and toddlers with kidney failure is unclear. We aimed to evaluate the patient survival associated with kidney transplantation before 2 years of age versus remaining on the waitlist until ≥2 years., Method: We used the Scientific Registry of Transplant Recipients to identify all children added to the deceased-donor waitlist before 2 years of age between 1/1/2000 and 4/30/2020. For each case aged <2 years at transplant, we created a control group comprising all candidates on the waitlist on the case's transplant date. Patient survival was evaluated using sequential Cox regression. Dialysis-free time was defined as graft survival time for cases and the sum of dialysis-free time on the waitlist and graft survival time for controls., Results: We observed similar patient survival for posttransplant periods 0-3 and 4-12 months but higher survival for period >12 months for <2-year decreased-donor recipients (aHR: 0.32; 95% CI: 0.13-0.78; p = .01) compared with controls. Similarly, patient survival was higher for <2-year living-donor recipients for posttransplant period >12 months (aHR: 0.21; 95% CI: 0.06-0.73; p = .01). The 5-year dialysis-free survival was higher for <2-year deceased- (difference: 0.59 years; 95% CI: 0.23-0.93) and living-donor (difference: 1.84 years; 95% CI: 1.31-2.25) recipients., Conclusion: Kidney transplantation in children <2 years of age is associated with improved patient survival and reduced dialysis exposure compared with remaining on the waitlist until ≥2 years., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown., Materials and Methods: We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models., Results: The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p < 0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p < 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p < 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p < 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race., Conclusion: We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.

Background: Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking., Methods: We used Scientific Registry of Transplant Recipients to identify 285 pediatric (<18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival., Results: DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P < 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03)., Conclusions: Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients (<18 years). Using propensity scores, we created comparison groups of 375 non-ECD and 357 ≤ 85 KDPI recipients for comparisons with ECD and > 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: En bloc transplantation of small pediatric kidneys in children may help expand the existing deceased donor pool; however, studies examining the long-term outcomes of en bloc transplantation in children are few., Methods: We used the Scientific Registry of Transplant Recipients to identify 149 pediatric en bloc recipients transplanted from October 1, 1987 to December 31, 2017. We used propensity scores to match 148 en bloc with 581 non-en bloc deceased donor recipients (matching variables: transplant age, gender, race, pretransplant dialysis, transplant center, and year). We evaluated patient and graft survival using Kaplan-Meier and Fleming-Harrington weighted log-rank test and examined survival benefit of en bloc transplantation versus remaining on the waiting list using the sequential Cox approach. We divided the study period into three 10-y intervals to assess the effect of era on outcomes., Results: Compared with non-en bloc recipients, en bloc recipients had lower 1-y graft survival (78.9% versus 88.9%; P = 0.007); however, when stratified by transplant era, lower 1-y survival was only observed in the oldest era (1987-1997). En bloc recipients had superior 10-y patient (89.0% versus 80.4%; P = 0.04) and graft survival (51.6% versus 39.9%; P = 0.04) compared with non-en bloc recipients. After multivariate adjustment, en bloc transplantation was associated with superior patient survival compared with remaining on the waiting list (adjusted hazard ratio: 0.58; 95% confidence interval: 0.36-0.95; P = 0.03)., Conclusions: En bloc transplantation of small pediatric kidneys in children is associated with superior long-term patient and graft survival. The increased risk of 1-y graft loss among en bloc recipients only appeared in the oldest era.

Competing Interests: All authors have nothing to disclose.

Temporal changes in kidney transplant outcomes for cystinosis are unknown. We used the SRTR to identify all kidney transplants performed for cystinosis in patients younger than 31 years between 1987 and 2017. We divided time into three equal eras (1987-1997, 1998-2007, and 2008-2017) to assess changes in outcomes using Cox proportional and linear regression models. We examined 441 transplants in 362 patients. Age at ESRD progressively increased (12.1 vs 13.3 vs 13.4; P = .046). Eras 2 and 3 had lower risk of acute rejection (aHR 2 vs 1:0.45; P < .001) (aHR 3 vs 1:0.26; P < .001) and higher 5-year mean GFR (difference 2 vs 1:9.2 mL/min/1.73 m 2 ; P = .005) (difference 3 vs 1:12.9 mL/min/1.73 m 2 ; P = .002) compared with era 1. Five-year graft survival was similar across eras, but 5-year patient survival was higher for era 2 (aHR: 0.25; P = .01). Seventy-nine patients underwent retransplantation. Five-year patient (94.2% vs 92.5%; P = .57) and graft survival (79.1% vs 74.1%; P = .52) were similar between primary and subsequent transplants. Age at ESRD, acute rejection, GFR at 5 years, and patient survival improved over time. Kidney retransplantation is associated with excellent outcomes in children and young adults with cystinosis., (© 2019 Wiley Periodicals, Inc.)

Increased risk donors (IRDs) may inadvertently transmit blood-borne viruses to organ recipients through transplant. Rates of IRD kidney transplants in children and the associated outcomes are unknown. We used the Scientific Registry of Transplant Recipients to identify pediatric deceased donor kidney transplants that were performed in the United States between January 1, 2005 and December 31, 2015. We used the Cox regression analysis to compare patient and graft survival between IRD and non-IRD recipients, and a sequential Cox approach to evaluate survival benefit after IRD transplants compared with remaining on the waitlist and never accepting an IRD kidney. We studied 328 recipients with and 4850 without IRD transplants. The annual IRD transplant rates ranged from 3.4% to 13.2%. IRDs were more likely to be male (P = .04), black (P < .001), and die from head trauma (P = .006). IRD recipients had higher mean cPRA (0.085 vs 0.065, P = .02). After multivariate adjustment, patient survival after IRD transplants was significantly higher compared with remaining on the waitlist (adjusted hazard ratio [aHR]: 0.48, 95% CI: 0.26-0.88, P = .018); however, patient (aHR: 0.93, 95% CI: 0.54-1.59, P = .79) and graft survival (aHR: 0.89, 95% CI: 0.70-1.13, P = .32) were similar between IRD and non-IRD recipients. We recommend that IRDs be considered for transplant in children., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Infants (age, < 2 years) with end-stage renal disease (ESRD) have increased morbidity and mortality. We evaluated our long-term outcomes of kidney transplants (KTx) in infants., Methods: Between 1984 and 2014, 136 infants underwent KTx. We examined trends in survival rates and complications by era (1984-1993 [era 1], 1994-2003 [era 2], 2004-2014 [era 3])., Results: Patients were 92.6% white and 70.6% males. Posttransplant (Tx) initial length of hospital stay declined 37% over the 30-year period (P <0.01). Ten-year death-censored graft survival improved from 60% (era 1) to 80% (era 2) (P = 0.04). The incidence of acute rejection, graft thrombosis, cytomegalovirus, and urine leaks did not significantly change across eras. Frequency of Epstein-Barr virus diagnosis (era 2 vs era 3, P < 0.01) increased. Post-Tx lymphoproliferative disorder incidence was increased in era 2 compared with eras 1 and 3 (P = 0.03)., Conclusions: Infants deserve earlier consideration for KTx. Length of initial hospital stay and patient and graft survival rates after KTx have improved in infants since 1984.

Background: Post-transplant malignancy (PTM) remains a concern among pediatric kidney transplant (PKT) recipients., Study Design: Between 1963 and 2015, 884 pediatric (age 0 to 17 years old) patients received 1,055 PKTs at our institution. Cox proportional hazards models were constructed to identify risk factors for PTM after PKT with time-to-first-PTM as a primary outcome. Secondly, the hazard of death or graft loss was calculated in patients who developed PTM., Results: Median patient survival was 33 years (interquartile range [IQR] 18.7 to 47 years); 260 patients died during the study period and 47 had been diagnosed with PTM. There were 235 PTMs that occurred in 136 (15.4%) recipients at a median age of 29 years (IQR 17.8 to 37 years). The percentages of patients with PTM were 13% at 20 years post-PKT and 26% at 30 years post-PKT. Of PTM patients who died, 63.8% died of PTM. Among those who developed PTM, there was a higher hazard of death or graft loss (hazard ratio [HR] 1.62; 95% CI 1.11 to 2.38). In multivariable proportional hazards models, factors associated with PTM were increasing age at PKT (adjusted HR [AHR] 3.14; 95% CI 1.80 to 5.48 for 14 to 17 year-olds compared with children less than 3 years), having a living unrelated donor (LURD; AHR 3.25; 95% CI 1.27 to 8.35 compared with a living related donor), or implanting an Epstein-Barr virus (EBV)-positive allograft in an EBV-negative recipient (AHR 5.66; 95% CI 1.11 to 29.0). Compared with the general population, the cancer rate for PKT recipients was 6 times higher (126 vs 21 per 100,000 person-years)., Conclusions: Pediatric kidney transplant recipients are at increased risk of PTM, which adversely affects survival. Children receiving transplants at an older age, from a LURD, or who receive an EBV-positive organ, should be monitored closely for the development of PTM., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

AR is lower in pKTx recipients on Tac vs CsA. Data comparing infection outcomes for children treated with these agents are limited. We retrospectively studied infection outcomes in 96 pKTx recipients on a RDP. PS, DCGS, AR, and infection-free survival were assessed using Kaplan-Meier/log-rank tests and proportional hazards models. There were no differences in 1-year PS, DCGS, or AR between Tac and CsA recipients. After adjusting for AR, the hazard of CMV viremia was 4.0 times higher (95%CI: 1.04, 15.5; P = .044) and that of BK viremia was 3.8 times higher (95%CI: 1.5, 10.2; P = .007) in Tac recipients. The incidence of EBV viremia was similar between the groups (P = .56). PostTx lymphoproliferative disease was only observed in Tac recipients (3%). There was no difference in the incidence of pneumonia, urinary tract, or Clostridium difficile infections between Tac and CsA recipients. Among KTx recipients on RDP, the hazards of CMV and BK viremia within 1 year post-KTx were significantly higher in Tac recipients compared to CsA. Regular assessment for infections and lower Tac trough levels may be warranted in Tac recipients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In adults on chronic hemodialysis, achieving a hemoglobin concentration of 12g/dl and above with erythropoiesis stimulating agents leads to increased cardiovascular events and mortality, but this may not be true in children. Therefore, we conducted a retrospective cohort study of pediatric patients (under 18) from the Centers for Medicare and Medicaid Services End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project (2000 to 2008) merged with the United States Renal Data System. Hemoglobin was determined from the Clinical Performance Measures data, and beginning annually on January 1st of the next year, patients were followed for up to 1 year. We determined the outcomes (mortality, hospitalization, and cardiovascular events) during follow-up by hemoglobin group at baseline. Models were adjusted for demographic and clinical characteristics of 1569 children studied. The hemoglobin 12 g/dl and above group was older, had fewer years of ESRD, and was more often transplanted. Inpatient and outpatient visits for congestive heart failure, cardiomyopathy, and valvular heart disease were most common in the hemoglobin under 10g/dl group and the frequency of these diagnoses decreased with increasing hemoglobin. The hazard ratio of all-cause mortality (0.33, 95% confidence interval 0.14-0.81) and the adjusted relative rate of all-cause hospitalizations (0.81, 0.74-0.89) were significantly lower in the hemoglobin 12 g/dl and above group. Cardiovascular hospitalizations were significantly higher in the hemoglobin under 10g/dl group (1.31, 1.05-1.64). Thus, in children on hemodialysis, hemoglobin 12g/dl and above is not associated with increased cardiovascular visits, mortality, or all-cause and cardiovascular-related hospitalizations., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is a well-documented complication of pediatric hematopoietic stem cell transplantation (HSCT). Dialysis after HSCT is associated with a lower overall survival (OS); however, the association between less severe AKI and OS is unclear. We retrospectively studied 205 consecutive pediatric HSCT patients to determine the incidence and impact of all stages of AKI on OS in pediatric HSCT recipients. We used the peak pRIFLE grade during the first 100 days to classify AKI (ie, R = risk, I = injury, F = failure, L = loss of function, E = end-stage renal disease) and used the modified Schwartz formula to estimate glomerular filtration rate. AKI was observed in 173 of 205 patients (84%). The 1-year OS rate decreased significantly with an increasing severity of pRIFLE grades (P < .01). There was no difference in the OS between patients without AKI and the R/I group. Regardless of the dialysis status, stages F/L/E had significantly lower rates of OS compared with patients without AKI or R/I (P < .01). There was no difference in OS among patients with dialysis and F/L/E without dialysis (P = .65). Stages F/L/E predicted mortality independent of acute graft-versus-host disease, gender, and malignancy. The OS of children after HSCT decreases significantly with an increasing severity of AKI within the first 100 days post-transplant. Although our data did not show an increased risk of mortality with stages R/I, stages F/L/E predicted mortality regardless of dialysis. Prevention and minimization of AKI may improve survival after pediatric HSCT., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background/aims: Few published data describe survival rates for pediatric end-stage renal disease (ESRD) patients. We aimed to describe one-year mortality rates for US pediatric ESRD patients over a 15-year period., Methods: In this retrospective cohort study, we used the US Renal Data System database to identify period-prevalent cohorts of patients aged younger than 19 for each year during the period 1995-2010. Yearly cohorts averaged approximately 1,200 maintenance dialysis patients (60% hemodialysis, 40% peritoneal dialysis) and 1,100 transplant recipients. Patients were followed for up to 1 year and censored at change in modality, loss to follow-up, or death. We calculated the unadjusted model-based mortality rates per time at risk, within each cohort year, by treatment modality (hemodialysis, peritoneal dialysis, transplant) and patient characteristics; percentage of deaths by cause; and overall adjusted odds of mortality by characteristics and modality., Results: Approximately 50% of patients were in the age group 15-18, 55% were male, and 45% were female. The most common causes of ESRD were congenital/reflux/obstructive causes (55%) and glomerulonephritis (30%). One-year mortality rates showed evidence of a decrease in the number of peritoneal dialysis patients (6.03 per 100 patient-years, 1995; 2.43, 2010; p = 0.0263). Mortality rates for transplant recipients (average 0.68 per 100 patient-years) were consistently lower than the rates for all dialysis patients (average 4.36 per 100 patient-years)., Conclusions: One-year mortality rates differ by treatment modality in pediatric ESRD patients.

Background: Lecitin cholesterol acyltransferase (LCAT) deficiency comprises a group of rare disorders related to HDL metabolism. These disorders are characterized by ophthalmologic, hematologic, and renal findings. Case diagnosis/treatment: A 15-year-old female who presented with nephrotic syndrome and hypertension was diagnosed with LCAT deficiency by renal biopsy and LCAT enzyme activity. Her edema and hypertension improved with diuretic and antihypertensive therapies. Continued care of her LCAT deficiency is ongoing., Conclusion: Although rare, LCAT deficiency should be in the differential diagnosis of nephrotic syndrome in the setting of abnormally low HDL cholesterol levels.

Hypertension (HTN) is common in pediatric recipients following kidney transplantation (KT). We retrospectively assessed the impact of HTN on long-term (>10-yr) outcomes in pediatric KT recipients (aged < 18 yr) at our center. Two hundred and ninety-three pediatric KT recipients (83% living donor [LD]) with graft survival (GS) for ≥5 yr were studied. HTN was defined by antihypertensive medication use at five yr post-KT. One hundred and sixty (55%) recipients did not have HTN, and 133 (45%) had HTN at five yr post-KT. There were no differences in actuarial patient survival between cohorts. Actuarial GS at 15 and 20 yr was 68% and 53% for recipients without HTN, and 53% and 33% for recipients with HTN (p = 0.006). Among LD recipients using one antihypertensive, GS at 15 yr was 100% for those using an angiotensin-converting enzyme inhibitor (ACEI) and 44% for those not using an ACEI (p = 0.04). Among these recipients, HTN treated with no ACEI was a significant risk factor for graft failure at >5 yr (hazard ratio [HR] = 2.5, p = 0.02), but HTN treated with an ACEI was not (HR = 0.6, p = 0.7). HTN at five yr post-KT is associated with poorer long-term GS in pediatric recipients, but ACEI therapy may enable better outcomes and should be studied further., (© 2013 John Wiley & Sons A/S.)

Recurrent disease is the fourth most common cause of graft loss (GL) in pediatric KTx recipients. We studied the incidence of recurrent disease and GL due to recurrent disease in pediatric KTx recipients on a RDP protocol. Between 2002 and 2010, we performed 74 KTxs in patients aged 5-18 yr using an RDP protocol, 25 (34%) were at risk of recurrence of primary disease. Outcomes were compared to 69 historical controls (18 [26%] at risk of recurrence), KTx between 1996 and 2000. Follow-up period was 39 ± 25 months in RDP and 124 ± 38 months in controls. The incidence of recurrent disease at three yr post-KTx was 16% in RDP and 28% in controls (p = NS). Mean time to recurrent disease was 22 ± 26 months in RDP and 46 ± 48 months in controls (p = 0.54). Nine (12%) grafts were lost in the RDP group (1-recurrence) and 32 (46%) in the control group (4-recurrence). Time to GL was 85 months in the RDP recipient and 46 ± 21 months in controls. An RDP protocol in pediatric KTx recipients may not be associated with increased risk of graft loss due to recurrent disease., (© 2012 John Wiley & Sons A/S.)

Background and Objectives: Few data are available on kidney function in normal US adolescents. This study characterizes the distribution of kidney function measures and associated factors., Design, Setting, Participants, & Measurements: Serum creatinine, cystatin C, and urinary albumin-to-creatinine ratios were measured in US adolescents (aged 12 to 17 years; n = 5575) in the cross-sectional National Health and Nutrition Examination Survey 1999-2008. The reference population was defined as healthy adolescents with BP <120/80 mmHg and a Z-score for weight-to-height ≤1.645, without self-reported diabetes or hypertension, not using prescription medications in the preceding 30 days, not pregnant or currently menstruating., Results: were analyzed by age, gender, race, ethnicity, body mass index, and BP; estimated GFR (eGFR) was calculated using the original and revised Schwartz formulas. Results Mean values for eGFR(Schwartz original formula), serum creatinine, and serum cystatin C were 147 ml/min/1.73 m(2), 0.71 mg/dl, 0.82 mg/L, respectively. The median urinary albumin-to-creatinine ratio was 6.8 mg/g creatinine. In the reference population (n = 2881), eGFR differed significantly using the two Schwartz formulas; values were higher using the original formula (median values 143 versus 96 ml/min/1.73 m(2)). Serum creatinine level (0.7 versus 0.72 mg/dl), but not cystatin C level (0.82 versus 0.82 mg/L), was lower in the reference population than in a nonreference population of adolescents., Conclusions: These findings provide important demographic information and highlight the need for confirmatory testing of the revised Schwartz formula by comparison to measured GFR in healthy US adolescents.

Background: Cardiac disease is a significant cause of morbidity and mortality in children with end-stage renal disease (ESRD). This study aimed to report the frequency of cardiac disease diagnostic methods used in US pediatric maintenance hemodialysis patients., Methods: A cross-sectional analysis of all US pediatric (ages 0.7-18 years, n = 656) maintenance hemodialysis patients was performed using data from the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project. Clinical and laboratory information was collected in 2001. Results were analysed by age, sex, race, Hispanic ethnicity, dialysis duration, body mass index (BMI), primary ESRD cause and laboratory data., Results: Ninety-two percent of the patients had a cardiovascular risk factor (63% hypertension, 38% anemia, 11% BMI > 94th percentile, 63% serum phosphorus > 5.5 mg/dL and 55% calcium-phosphorus product ≥ 55 mg(2)/dL(2)). A diagnosis of cardiac disease was reported in 24% (n = 155) of all patients: left ventricular hypertrophy/enlargement 17%, congestive heart failure/pulmonary edema 8%, cardiomyopathy 2% and decreased left ventricular function 2%. Thirty-one percent of patients were not tested. Of those tested, the diagnostic methods used were chest X-rays in 60%, echocardiograms in 35% and electrocardiograms in 33%; left ventricular hypertrophy/enlargement was diagnosed using echocardiogram (72%), chest X-ray (20%) and electrocardiogram (15%)., Conclusions: Although 92% of patients had cardiovascular risk factors, an echocardiography was performed in only one-third of the patients. Our study raises the question of why echocardiography, considered the gold standard for cardiac disease diagnosis, has been infrequently used in pediatric maintenance dialysis patients, a high-risk patient population.

Background and Objectives: Data are limited regarding BP distribution and the prevalence of hypertension in pediatric long-term dialysis patients. This study aimed to examine BP distribution in U.S. pediatric long-term hemodialysis patients., Design, Setting, Participants, & Measurements: This cross-sectional study of all U.S. pediatric (aged 0-< 18 yr, n = 624) long-term hemodialysis patients was performed as part of the Centers for Medicare & Medicaid Services End-Stage Renal Disease (ESRD) Clinical Performance Measures Project. BP and clinical information were collected monthly in October, November, and December 2001. Hypertension was defined as the mean of pre- and postdialysis systolic or diastolic BP above the 95th percentile for age, height, and sex, or antihypertensive medication use. Results were calculated by age, sex, race, ethnicity, ESRD duration, body mass index percentile, primary cause of ESRD, and laboratory data., Results: Hypertension was present in 79% of patients; 62% used antihypertensive medication. Five percent of patients were prehypertensive (mean BP at 90th to 95th percentile). Hypertension was uncontrolled in 74% of treated patients. Characteristics associated with hypertension included acquired kidney disease, shorter duration of ESRD, and lower mean hemoglobin and calcium values. Characteristics associated with uncontrolled hypertension were younger age and shorter duration of ESRD., Conclusions: Hypertension is common in U.S. pediatric long-term hemodialysis patients, uncontrolled in 74% of treated patients, and untreated in 21% of hypertensive patients. It is concluded that a more aggressive approach to treatment of hypertension is warranted in pediatric long-term hemodialysis patients.

Background: There are few prospective studies of prednisone-free immunosuppression (IS) in pediatric kidney transplant (KTx) recipients. We studied the outcomes of a protocol using rapid discontinuation of prednisone (RDP, <1 week) and thymoglobulin induction., Methods: Twenty-one RDP recipients (mean age 14+/-3 years) received KTx between May 2002 and December 2005 and were matched with controls (n=39) for age, race, and donor source. For the RDP group, IS consisted of prednisone tapered off over 6 days, thymoglobulin, mycophenolate mofetil, and cyclosporine A (CsA). In controls, IS consisted of thymoglobulin, maintenance prednisone, azathioprine, and CsA., Results: For the RDP group, graft survival at 1 and 2 years was 90% and 86%; for the controls, graft survival at 1 and 2 years was 92%, and 90% (P=0.86). For the RDP group, the incidence of acute rejection at 1 and 2 years was 14% and 19%; for controls, the incidence of acute rejection at 1 and 2 years was 23%, and 31% (P=0.17). Of the 18 RDP recipients with functioning grafts, 89% remain prednisone-free at follow-up. There was no significant difference between groups in recipient survival rates, incidence of hypertension, chronic allograft nephropathy, or cytomegalovirus disease., Conclusions: RDP using thymoglobulin, mycophenolate mofetil, and CsA in selected pediatric KTx recipients is associated with recipient and graft survival rates and acute rejection incidence comparable with quadruple drug therapy.

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.

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.

Infection is a common cause of morbidity and mortality in patients with ESRD. Infection-related hospitalization (IH) incidence among US Medicare incident pediatric and adult dialysis and transplant patients within 3 yr of presentation was compared from 1996 to 2001: Hemodialysis (HD) patients (pediatric n = 1469; adult n = 305,323); peritoneal dialysis (PD) patients (pediatric n=982; adult n=27,119), and kidney transplant (KTx) patients (pediatric n=1108; adult n=31,663). IH were identified from principal diagnosis codes; IH cumulative incidence and rates were calculated from claims data. Cumulative incidence of IH at 36 mo for incident pediatric patients with ESRD during 1996 to 2001 was 39.9% in HD, 51.2% in PD, and 47.4% in KTx patients (HD or PD versus KTx, P<0.0001). Cumulative incidence for adults was 52.6% in HD, 51.8% in PD, and 39.8% in KTx patients (HD or PD versus KTx, P<0.0001). IH rates per 1000 patient-months were highest for pediatric KTx patients (adjusted rate ratio 1.53 versus HD and 1.90 versus PD, P<0.001 for each) and adult HD patients (adjusted rate ratio 1.20 versus KTx and 1.11 versus PD, P < 0.001 for each). Within the first 36 mo of incidence, IH rates are highest for incident pediatric KTx patients compared with HD and PD patients, in contrast to findings for adult patients with ESRD. Pediatric KTx patients require infection surveillance after transplantation.

Cat-scratch disease, an infectious illness infrequently reported in kidney transplant patients, is caused by the organism Bartonella henselae and is transmitted through contact with cats or kittens. It is a self-limited disorder in the general pediatric population. Here we present a case of unsuspected cat-scratch disease in a pediatric kidney transplant patient who presented with fever and lymphadenopathy. Eight months after treatment with a short course of azithromycin, the patient developed a recurrence of cat-scratch disease. We emphasize that the evaluation of a young immunocompromised kidney transplant patient presenting with fever and lymphadenopathy should include unusual infections such as cat-scratch disease. We review the diagnosis and treatment of this uncommon infection in the organ transplant population.

Background: Induction immunosuppressive therapy with the anti-T-cell antibody Thymoglobulin decreases the incidence of acute rejection in adult kidney transplant (KTx) recipients, but limited data are available for pediatric KTx recipients., Methods: We conducted a historical cohort study to compare rates of survival, rejection, and infection in pediatric (age <19 years) KTx recipients who received induction therapy with polyclonal antibody, ATGAM (n=127) or Thymoglobulin (n=71), from December 1, 1992, to January 31, 2003. Maintenance immunosuppression included cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Mean follow-up was 90+/-25 months for ATGAM recipients and 32+/-15 months for Thymoglobulin recipients., Results: Overall, the incidence of acute rejection was lower in Thymoglobulin recipients versus ATGAM recipients (33% vs. 50%, P=0.02). Epstein-Barr virus (EBV) infection was higher in Thymoglobulin recipients versus ATGAM recipients (8% vs. 3%, P=0.002). But the two groups did not significantly differ in patient and graft survival rates, incidence of chronic rejection, EBV lymphoma, or other infection., Conclusions: Thus, Thymoglobulin induction was associated with a decreased incidence of acute rejection and an increased incidence of EBV infection in pediatric KTx recipients. EBV monitoring should be performed in EBV-naive recipients receiving Thymoglobulin.

Idiopathic intracranial hypertension, characterized by headache, visual disturbance, papilledema, and increased intracranial pressure in the absence of space-occupying lesions, has been reported in pediatric recipients several months to years following kidney transplantation (KTx). We describe the development of idiopathic intracranial hypertension in a 10-year-old girl in the first few hours after KTx. We hypothesize that this event was associated with thymoglobulin administration, perhaps on the background of growth hormone therapy. Awareness of this possibility could lead to earlier diagnosis and treatment of children with similar risk factors.

Background: Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx., Methods: We reviewed the medical records of 399 children who received KTx at our center between September 1986 and January 2003. Transplant outcomes were compared in stone formers and controls., Results: Twenty (5%) patients, age 9+/-5 (X +/- SD) years, developed stones over the follow-up period (74+/-53 months). Time to stone presentation was 19+/-22 months post-KTx. Presenting features were urinary tract infection (UTI), 8; gross hematuria, 5; microscopic hematuria, 2; dysuria without infection, 6; difficulty voiding, 3; and silent stones, 2. Stones were removed by cystoscopy in 11 (55%) patients. Stone composition was determined in 11 patients: calcium phosphate (55%), calcium oxalate (18%), mixed calcium phosphate and oxalate (9%), and struvite (18%). Factors predisposing to stones in study patients included suture retention (n = 4), elevated urinary calcium excretion (n = 2), recurrent UTI (n = 2), and urinary stasis (n = 2). The incidence of UTI was higher (P = 0.003) and of acute rejection was lower (P = 0.02) in stone patients compared with controls. Patient and graft survival rates and the incidence of chronic rejection did not significantly differ between study patients and controls (P = NS)., Conclusions: Urolithiasis is not uncommon in pediatric KTx patients. Factors associated with post-KTx urolithiasis include retention of suture material, recurrent UTI, hypercalciuria, and urinary stasis. Treatment is associated with excellent outcome and low recurrence rate.

Cardiovascular disease is the major cause of mortality in adults and children on chronic dialysis and in adults after kidney transplantation. Cardiovascular disease burden and cardiovascular mortality are high in adults with chronic kidney disease. The early development of cardiovascular disease risk factors, some of which are modifiable, largely explain this phenomenon. Limited data are available on the prevalence of chronic kidney disease in children, the prevalence of cardiovascular disease in children with chronic kidney disease, and the prevalence of cardiovascular disease risk factors in these patients. This article summarizes the current knowledge of the prevalence of cardiovascular disease and of cardiovascular disease risk factors in pediatric patients with predialysis chronic kidney disease. Long-term prospective studies are needed to determine the impact of early identification and treatment of cardiovascular disease and its risk factors on the natural history of cardiovascular disease in children with chronic kidney disease.

Background: Recent guidelines recommend a target hemoglobin range of 11 to 12 g/dL in pediatric and adult dialysis patients. We compared anemia prevalence in United States Medicare pediatric and adult dialysis patients., Methods: Prevalent hemodialysis patients (0 to 19 years, pediatric: N= 1692; adult: N= 352,291) and peritoneal dialysis patients (pediatric: N= 597; adult: N= 39,136) treated with recombinant human erythropoietin (rHuEPO) from 1996 to 2000 were selected. Mean annual hemoglobin values were calculated by modality, age, sex, and race., Results: Among hemodialysis patients, mean annual hemoglobin values less than 11 g/dL were present in pediatric and adult patients during 54.1% versus 39.8% patient years, respectively (P < 0.0001); for peritoneal dialysis patients, 69.5% versus 55.1% (P < 0.0001). Mean hemoglobin values increased over time and were 11.2, 11.5, 10.8, and 11.2 g/dL for pediatric and adult hemodialysis and peritoneal dialysis patients, respectively, in 2000. Pediatric hemodialysis patients received intravenous iron less frequently than adults (66.3% vs. 82.5% patient years; P < 0.0001)., Conclusion: Hemoglobin values in rHuEPO-treated pediatric dialysis patients lagged behind those of adult patients, with pediatric patients achieving target hemoglobin values only a minority of the time (45.9% and 30.5% patient years, respectively, for hemodialysis and peritoneal dialysis). Trends show recent improvement in anemia treatment of children on dialysis. Still, further attention to and analysis of rHuEPO and iron therapy in pediatric dialysis patients is warranted.

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.

Hyperlipidemia is a risk factor for cardiovascular disease in adult kidney transplant (Tx) recipients. We sought to determine the prevalence of, and the risk factors associated with, hyperlipidemia in pediatric kidney Tx recipients on cyclosporine (CsA). We identified 59 patients (mean age 8.2+/-5.7 years) transplanted between 1 January 1991 and 31 December 1993. Pre Tx, 34% had elevated total cholesterol [TC >200 mg/dl (5.17 mmol/l)]; 54% had elevated triglycerides [TG >200 mg/dl (2.26 mmol/L)]. Mean TG was higher pre Tx in dialysis (versus nondialysis) patients: 306 mg/dl (3.46 mmol/l) versus 228 mg/dl (2.58 mmol/l) ( P=0.04). Mean TC was higher in peritoneal dialysis than hemodialysis patients: 222 mg/dl (5.74 mmol/l) versus 169 mg/dl (4.37 mmol/l) ( P=0.03). Pre Tx and 3-year values correlated (TC, r=0.49, P=0.0008; TG, r=0.41, P=0.001); 3- and 5-year TC values correlated ( r=0.57, P=0.003). At 5 years post Tx, 41% of the recipients had elevated TC; 14% had elevated TG. Recipients with elevated TC had higher mean CsA concentrations at 1 year post Tx ( P=0.03). Recipients with elevated TG tended to receive more prednisone ( P=0.06). At 5 years post Tx, recipients had a high prevalence of hyperlipidemia. The identification and treatment of hyperlipidemia should be included in pediatric kidney Tx protocols.

Background: Little information is available regarding cardiac morbidity and mortality in children with end-stage renal disease. We sought to determine the incidence of cardiac morbidity and mortality in pediatric chronic dialysis patients., Methods: Medicare incident pediatric (0 to 19 years) dialysis patients from 1991 to 1996 were identified from the United States Renal Data System. Study endpoints included development of arrhythmia, valvular heart disease, cardiomyopathy, or cardiac arrest, all causes of death, and cardiac-related death. Statistical analyses were performed using the Poisson regression model and chi-square test., Results: A total of 1454 children were eligible for inclusion, 452 (31.1%) of whom developed a cardiac-related event. Arrhythmia was the most common event (19.6%) compared with valvular disease (11.7%), cardiomyopathy (9.6%), and cardiac arrest (3%). Arrhythmia and valvular heart disease incidence were increased in 15- to 19-year-olds (P < 0.0001 for both), females (P = 0.004, P = 0.03) and blacks (P < 0.0001, P = 0.002). Cardiomyopathy incidence was increased in blacks (P = 0.001) and tended to be increased in females (P = 0.053). The adjusted annual cardiomyopathy rate during the first 3 years increased between 1991 and 1996 (P = 0.003). Death occurred in 107 patients, and 41 (38%) were cardiac deaths., Conclusions: Cardiovascular disease is a significant cause of morbidity and mortality in pediatric chronic dialysis patients. Cardiomyopathy incidence is increasing. Black, female, and adolescent children have increased risk for cardiovascular disease.

Presentation of autosomal recessive polycystic kidney disease (ARPKD) ranges from severe renal impairment and a high mortality rate in infancy to older children and adolescents with minimal renal disease and complications of congenital hepatic fibrosis (CHF), cholangitis and portal hypertension. Renal transplantation improves prognosis but it is unclear whether CHF in transplanted children follows the same clinical course as in older children with less severe renal disease. The aim of this study was to evaluate morbidity from CHF in ARPKD post renal transplantation. Data were analyzed for six males and eight females, transplanted for ARPKD (mean age 8.3 years, range 1-22.3 years) at the University of Minnesota between 1972 and 1998. Follow-up was for a mean of 14.5 years (range 3.1-33.6 years). One and 5 years patient survival rates were 93% and 86%, respectively. Overall five patients (36%) died; 4/5 deaths were related to CHF. Causes of death were hepatic failure immediately post transplant (n = 1), septicemia related to bile duct dilatation (n = 3) and multiorgan failure (n = 1). One and 5years graft survival rates were 87% and 70%, respectively. One patient had a combined liver-kidney transplant and two were re-transplanted. Initial signs of CHF were splenomegaly (n = 5), hepatosplenomegaly (n = 4) and gastrointestinal bleed (n = 2). Progression of CHF through childhood included hypersplenism (n = 7), esophageal varices with gastrointestinal bleeding (n = 5) and bile duct dilatation (n = 5). Portal hypertension was treated with portosystemic shunt (n = 3), sclerotherapy (n = 2), banding of varices (n = 1) and transjugular intrahepatic portosystemic shunt (n = 1). Of the nine survivors (mean age 12.8 years) 78% have functioning grafts (one liver-kidney transplant), 63% have portal hypertension and 22% have asymptomatic biliary dilatation. Complications of CHF developed in 79% of children who received a renal transplant for ARPKD. Mortality related to CHF occurred in 29% and accounted for 80% (4/5) of the deaths.

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.

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 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.

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.

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.

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).

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.

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.

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.

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.