Urologic care and progression to end-stage kidney disease: a Chronic Kidney Disease in Children (CKiD) nested case-control study.

INTRODUCTION: Children with chronic kidney disease (CKD) risk progressing to end-stage kidney disease (ESKD). The majority of CKD causes in children are related to congenital anomalies of the kidney and urinary tract, which may be treated by urologic care. OBJECTIVE: To examine the association of ESKD with urologic care in children with CKD. STUDY DESIGN: This was a nested case-control study within the Chronic Kidney Disease in Children (CKiD) prospective cohort study that included children aged 1-16 years with non-glomerular causes of CKD. The primary exposure was prior urologic referral with or without surgical intervention. Incidence density sampling matched each case of ESKD to up to three controls on duration of time from CKD onset, sex, race, age at baseline visit, and history of low birth weight. Conditional logistic regression analysis was performed to estimate rate ratios (RRs) for the incidence of ESKD. RESULTS: Sixty-six cases of ESKD were matched to 153 controls. Median age at baseline study visit was 12 years; 67% were male, and 7% were black. Median follow-up time from CKD onset was 14.9 years. Seventy percent received urologic care, including 100% of obstructive uropathy and 96% of reflux nephropathy diagnoses. Cases had worse renal function at their baseline visit and were less likely to have received prior urologic care. After adjusting for income, education, and insurance status, urology referral with surgery was associated with 50% lower risk of ESKD (RR 0.50 [95% confidence interval [CI] 0.26-0.997), compared to no prior urologic care (Figure). After excluding obstructive uropathy and reflux nephropathy diagnoses, which were highly correlated with urologic surgery, the association was attenuated (RR 0.72, 95% CI 0.24-2.18). DISCUSSION: In this study, urologic care was commonly but not uniformly provided to children with non-glomerular causes of CKD. Underlying specific diagnoses play an important role in both the risk of ESKD and potential benefits of urologic surgery. CONCLUSION: Within the CKiD cohort, children with non-glomerular causes of CKD often received urologic care. Urology referral with surgery was associated with lower risk of ESKD compared to no prior urologic care but depended on specific underlying diagnoses.

Computer-aided diagnosis of congenital abnormalities of the kidney and urinary tract in children based on ultrasound imaging data by integrating texture image features and deep transfer learning image features.

INTRODUCTION: Anatomic characteristics of kidneys derived from ultrasound images are potential biomarkers of children with congenital abnormalities of the kidney and urinary tract (CAKUT), but current methods are limited by the lack of automated processes that accurately classify diseased and normal kidneys. OBJECTIVE: The objective of the study was to evaluate the diagnostic performance of deep transfer learning techniques to classify kidneys of normal children and those with CAKUT. STUDY DESIGN: A transfer learning method was developed to extract features of kidneys from ultrasound images obtained during routine clinical care of 50 children with CAKUT and 50 controls. To classify diseased and normal kidneys, support vector machine classifiers were built on the extracted features using (1) transfer learning imaging features from a pretrained deep learning model, (2) conventional imaging features, and (3) their combination. These classifiers were compared, and their diagnosis performance was measured using area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. RESULTS: The AUC for classifiers built on the combination features were 0.92, 0.88, and 0.92 for discriminating the left, right, and bilateral abnormal kidney scans from controls with classification rates of 84%, 81%, and 87%; specificity of 84%, 74%, and 88%; and sensitivity of 85%, 88%, and 86%, respectively. These classifiers performed better than classifiers built on either the transfer learning features or the conventional features alone (p < 0.001). DISCUSSION: The present study validated transfer learning techniques for imaging feature extraction of ultrasound images to build classifiers for distinguishing children with CAKUT from controls. The experiments have demonstrated that the classifiers built on the transfer learning features and conventional image features could distinguish abnormal kidney images from controls with AUCs greater than 0.88, indicating that classification of ultrasound kidney scans has a great potential to aid kidney disease diagnosis. A limitation of the present study is the moderate number of patients that contributed data to the transfer learning approach. CONCLUSIONS: The combination of transfer learning and conventional imaging features yielded the best classification performance for distinguishing children with CAKUT from controls based on ultrasound images of kidneys.

Obesity and kidney disease: hidden consequences of the epidemic.

Obesity has become a worldwide epidemic and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day will promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

Predictors of arthritis in pediatric patients with lupus.

BACKGROUND: Arthritis is one of the most common manifestations of systemic lupus erythematosus (SLE). Although typically non-erosive and non-deforming, children with SLE arthritis can have significant morbidity with decreased quality of life. Our goal was to identify potential clinical and laboratory predictors of arthritis in a cohort of pediatric patients with SLE. METHODS: We performed a cohort study of incident and prevalent patients with SLE aged ≤ 19 years. In cross sectional analysis, we compared demographic and clinical characteristics at initial clinic presentation between patients with arthritis noted at any time during follow-up and those without arthritis. We performed time to event analysis using Cox proportional hazard ratios to identify predictors of arthritis, clustering for repeated measures. RESULTS: Forty seven children and adolescents with SLE were followed in the cohort, 91 % female and 68 % Black. In cross-sectional analyses, presence of malar rash was associated with arthritis. In longitudinal analyses, controlling for gender and race, increased age (HR: 1.4, 95 % CI: 1.1-1.7), malar rash (HR: 2.1, 95 % CI: 1.1-3.6), and presence of RNP antibodies (HR: 1.9, 95 % CI: 1.1-3.4) were predictive of arthritis. When controlling for gender, race, and medication use, anemia (HR: 8.5, 95 % CI: 2.9-24.2) and thrombocytopenia (HR: 6.1, 95 % CI: 2.4-15.6) were associated with increased risk of arthritis. CONCLUSIONS: We identified markers predictive of arthritis in a longitudinal cohort of children with SLE. The recognition of these markers may help clinicians identify patients at risk for arthritis before its onset thus improving quality of life in children with SLE.

Predictors of kidney disease in a cohort of pediatric patients with lupus.

INTRODUCTION: Children with systemic lupus erythematosus (SLE) have an increased prevalence of kidney disease compared to their adult counterparts. Our goal was to identify potential clinical and laboratory predictors of renal disease. METHODS: We performed a cohort study of incident and prevalent patients with SLE aged ≤19 years. Retrospective data from initial presentation until study enrollment was also collected. Laboratory and clinic data were recorded from each clinic visit including disease activity indices, autoantibodies, urinalyses, blood counts, and metabolic profile. Kidney disease was defined as the presence of abnormal renal biopsy or by American College of Rheumatology case definition for lupus nephritis. Logistic regression analyses were used to determine the association between clinical and laboratory data with kidney disease in those who had renal involvement within 30 days of SLE diagnosis. We also performed a time to event analysis to identify antecedents of renal disease. RESULTS: Forty-seven children and adolescents with SLE were followed in the cohort, 91% female and 68% black. All of the males in the cohort developed renal disease, and all within one month of the diagnosis of SLE. In logistic regression, low serum albumin (odds ratio (OR): 4.8, 95% CI: 1.9-12.5) and positive dsDNA antibodies (OR: 3.2, 95% CI: 1.7-5.9) were associated with kidney disease. In longitudinal analyses, isolated sterile pyuria (hazard ratio (HR): 3, 95% CI: 1.1-6.4) and low serum albumin (HR: 3.4, 95% CI: 1.7-6.9) were predictors of future kidney disease. The presence of antibodies against Ro were protective against renal disease (HR: 0.2, 95% CI: 0.05-0.5). CONCLUSION: We identified variables associated with kidney disease, both at initial diagnosis of SLE and in longitudinal follow-up in a cohort of children with SLE. The recognition of these abnormal laboratory values may help clinicians identify patients at risk for kidney disease before its onset thus preventing long-term complications.

Risk factors for end-stage kidney disease after pediatric liver transplantation.

Adult liver transplant (LT) recipients commonly develop advanced kidney disease. However, burden of end-stage kidney disease (ESKD) after pediatric LT has not been well-described. We performed a retrospective cohort study of pediatric LTs in the United States from 1990 to 2010. Multivariable Cox regression models were fit to determine risk factors for ESKD and death. Eight thousand nine hundred seventy six children received LTs. During median follow-up of 7.8 years, 2005 (22%) subjects died (mortality rate 26.1 cases/1000 person-years); 167 (2%) developed ESKD (incidence rate 2.2 cases/1000 person-years). Risk factors for ESKD included older age at LT (highest risk age >15 vs. < 5 years, HR = 4.94, p < 0.001), hepatitis C (HR 2.79, p = 0.004), liver re-transplant (HR 2.67, p < 0.001), eGFR pre-LT < 60 versus ≥ 60 (HR 2.37, p < 0.001), hepatitis B (HR 2.25, p = 0.027), black race (HR 1.46, p = 0.046), and male sex (HR 1.44, p = 0.022). LT recipients with ESKD had increased risk of mortality (HR 2.37, p < 0.001). Among pediatric LT recipients, rate of ESKD was lower than among adults and far exceeded by rate of death, however follow-up time in this study may underestimate lifetime burden of ESKD. Although uncommon, ESKD was highly associated with mortality. Pediatric LT recipients should be routinely monitored for kidney disease, particularly those at highest risk of ESKD.

Assessing associations between medication adherence and potentially modifiable psychosocial variables in pediatric kidney transplant recipients and their families.

Post-transplant immunosuppressant (IS) medication adherence is essential for long-term graft survival and relatively little is known about psychosocial barriers that interfere with optimum medication adherence in pediatric kidney transplant patients. The objective of this prospective observational cohort study was to assess the impact of modifiable psychosocial variables on medication adherence. Our hypothesis was that parental stress, dysfunctional parent-child interactions and child behavior problems would be associated with poorer medication adherence. Thirteen pediatric kidney transplant patients and their caregivers were enrolled. Transplant recipients who were able to read and caregivers of all the transplant recipients completed behavioral and attitudinal surveys. A subgroup of seven families dispensed their primary IS medication from an electronic monitoring vial (MEMS Smart Cap). For these patients, medication adherence was calculated by computing a ratio of the medication taken divided by the prescribed dose. In addition, for the entire group, serial IS levels were reviewed by two board certified pediatric nephrologists who categorized all 13 transplant recipient families as either 'probably adherent (PA)' or 'possibly non-adherent (PNA)'. Pearson correlation coefficients and independent samples Student t-tests were used to assess the association between medication adherence and psychosocial variables measured by standardized questionnaires. In this study, elevated parental stress, dysfunctional parent-child interactions, and child behavior problems were associated with poorer medication adherence. In addition, we found evidence to support the relationship between subjective dissatisfaction with appearance and poorer medication adherence. These findings suggest that pre-transplant recipient evaluations of risk factors for poor adherence are warranted.

The impact of dialysis and transplantation on children.

Effective methods to treat end stage renal disease (ESRD) in children have become available in the United States during the last 3 decades. Since the United States Congress created the Medicare ESRD Program in 1972, most children with ESRD have the option of Medicare insurance. Medicare expenditures for children with ESRD range from $14,000 for transplant recipients to $43,000 for dialysis patients per year. The tremendous expense of ESRD treatment has led to research to determine which treatment options are associated with the best health outcomes and the best value (quality/cost) for the money spent treating ESRD. The National Kidney Foundation's Dialysis Outcomes Quality Initiative recommends the use of quality of life and health status measures to gauge the impact of renal replacement therapy on quality of life in the ESRD population. In adult patients with renal failure, several generic and disease-specific quality of life measures have been validated and tested for reliability. In contrast, little research using validated and reliable health status measures has been performed in pediatric patients to measure the impact of ESRD. This article summarizes existing literature on how we currently measure the impact of dialysis and transplantation on children, discusses existing health status measures for children and adolescents, and describes how these measures might be used to improve our care of patients and long-term outcomes for children with kidney failure.

Does growth retardation indicate suboptimal clinical care in children with chronic renal disease and those undergoing dialysis?

Growth failure is an important problem for children with end-stage renal disease (ESRD). Patients receiving replacement therapy for longstanding renal failure since childhood are likely to report dissatisfaction with certain aspects of their lives, especially with final adult height. Additionally, recent data suggest that growth failure in children with ESRD is associated with adverse clinical outcomes, including more frequent hospitalizations, and increased mortality. Although poor growth is unlikely to be the cause of this increased morbidity, growth failure may be a marker for a group of patients at high risk of adverse events. In this review, the authors describe the prevalence of growth retardation in children in the US with chronic renal disease, and present recent data on morbidity associated with growth failure. After reviewing published reports documenting available strategies to optimize growth, the authors conclude that despite vigilance and aggressive clinical management, a subset of children with long-term renal insufficiency and ESRD may still have poor linear growth. A discussion of "optimal care" leads one to consider evidence of current variability in the management of growth retardation in ESRD, and the strengths and limitations of developing practice guidelines to optimize growth in this population.

Relation between pediatric experience and treatment recommendations for children and adolescents with kidney failure.

CONTEXT: Children and adolescent patients with renal failure are frequently cared for by adult subspecialists. While peritoneal dialysis is used in less than 17% of adults with kidney failure, it is the preferred dialysis treatment for children. National data show that 45% of children receiving dialysis are treated with peritoneal dialysis and pediatric nephrologists report its use in 65% of patients receiving dialysis. Whether differences in peritoneal dialysis use among children are due to the pediatric experience of the clinician has not been examined. OBJECTIVE: To assess whether the pediatric experience of nephrologists directly affects treatment recommendations for children with kidney failure. DESIGN: Cross-sectional survey using 10 case vignettes per survey based on random combinations of 8 patient characteristics (age, sex, race, distance from facility, cause of renal failure, family structure, education, and compliance). SETTING AND PARTICIPANTS: National random sample of office-, hospital-, and academic medical center-based adult and pediatric nephrologists, stratified by geographic region and conducted June to November 1999. Of 519 eligible physicians, 316 (61%) responded, including 191 adult and 125 pediatric nephrologists. MAIN OUTCOME MEASURE: Treatment recommendations for peritoneal dialysis vs hemodialysis, compared based on nephrologists' pediatric experience. RESULTS: After controlling for patient characteristics, pediatric nephrologists were 60% more likely than adult nephrologists to recommend peritoneal dialysis for identical patients (odds ratio, 1.61; 95% confidence interval, 1.35-1.92). This was true regardless of dialysis training, years in practice, practice setting, geography, or patient characteristics. CONCLUSIONS: Our data indicate that pediatric specialization of clinicians influences treatment recommendations for children and adolescents with end-stage renal disease. Referring children to adult subspecialists may lead to differences in treatment choices and processes of care.

Risk factors for urolithiasis in children on the ketogenic diet.

Kidney stones have been associated with use of the ketogenic diet in children with refractory seizure disorders. We performed a case-control study examining risk factors for the development of stones on the ketogenic diet, and prospectively followed children initiating the ketogenic diet to evaluate the incidence of urolithiasis. Clinical characteristics of 18 children presenting with stones (8 uric acid stones, 6 mixed calcium/uric acid stones, 1 calcium oxalate/phosphate stone, 3 stones not evaluated) were compared with characteristics of non-stone-forming children initiating the ketogenic diet at Johns Hopkins since July 1996. Since July 1996, 112 children initiating the ketogenic diet have been followed for development of stones. Follow-up times on the diet range from 2 months to 2.5 years. Of 112 children, 6 have developed stones (3 uric acid, 3 mixed calcium/uric acid stones) (0.8 children developing stones/ 100 patient-months at risk). Comparisons of children presenting with stones on the ketogenic diet with characteristics of the entire cohort initiating the ketogenic diet suggest younger age at diet initiation and hypercalciuria are risk factors for the development of stones. Prospective evaluation of children initiating the ketogenic diet revealed that almost 40% of patients had elevated fasting urine calcium: creatinine ratios at baseline; this increased to 75% after 6 months on the diet. Median urine pH was 5.5 at diet initiation, and remained at 6.0 thereafter. In a subset of patients tested, urinary citrate excretion fell from a mean of 252 mg/24 h pre diet initiation to 52 mg/24 h while on the diet. Uric acid excretion remained normal. Patients maintained on the ketogenic diet often have evidence of hypercalciuria, acid urine, and low urinary citrate excretion. In conjunction with low fluid intake, these patients are at high risk for both uric acid and calcium stone formation.

Racial differences in access to the kidney transplant waiting list for children and adolescents with end-stage renal disease.

CONTEXT: Renal transplantation is the treatment of choice for pediatric patients with end-stage renal disease (ESRD). Black patients wait longer for kidney transplants than do white patients. OBJECTIVE: To determine whether the increased time to transplantation for black pediatric patients is attributable not only to a shortage of suitable donor organs, but also to racial differences in the time from a child's first treatment for ESRD until activation on the cadaveric kidney transplant waitlist. DESIGN: National longitudinal cohort study. SETTING: US Medicare-eligible, pediatric ESRD population. PATIENTS: Children and adolescents

Septicemia in diabetic hemodialysis patients: comparison of incidence, risk factors, and mortality with nondiabetic hemodialysis patients.

Diabetes mellitus is the most common cause of treated end-stage renal disease (ESRD), and diabetic hemodialysis patients have a high mortality rate. To identify differences in risk of septicemia among diabetic and nondiabetic hemodialysis patients, we examined the incidence, risk factors, and mortality for septicemia in a large sample of the US hemodialysis population. We performed a longitudinal cohort study of the incidence and risk factors for hospitalized cases of septicemia in diabetic and nondiabetic hemodialysis patients using baseline data from the US Renal Data System case-mix severity study with 7-year follow-up from hospitalization and death records. Independent risk factors for septicemia were assessed using Poisson regression. Independent effect of septicemia on mortality was assessed using Cox proportional hazards analysis. Over 7 years, 11.1% of nondiabetic patients and 12.5% of diabetic patients experienced at least one episode of septicemia. Older age and low serum albumin were independent risk factors for septicemia in all patients. In diabetics, white race, peripheral vascular disease, and hemodialyzer reuse, particularly in type 1, were independent risk factors. In nondiabetics, coronary artery disease, cerebrovascular disease, and temporary and permanent catheters were associated with an increased risk. In both groups, patients who experienced an episode of septicemia had twice the risk of death from any cause and an eightfold risk of death from septicemia. Septicemia occurs equally frequently and carries a marked increased risk of death in both nondiabetic and diabetic hemodialysis patients. Improving nutritional status and minimizing the use of catheters might help ameliorate the risk of septicemia. In diabetics, aggressive treatment of peripheral vascular disease might help reduce the risk of septicemia. Further research to elucidate potential mechanisms for variations in risk for septicemia according to race and hemodialyzer reuse practices are warranted in diabetic patients.

Peritoneal dialysis catheter infections and peritonitis in children: a report of the North American Pediatric Renal Transplant Cooperative Study.

Peritonitis and catheter-related infections remain the two most-common causes of peritoneal dialysis (PD) treatment failure. To define the frequency and risks associated with exit site/tunnel infections (ESI/TI), as well as peritonitis, in pediatric patients on PD, we undertook a retrospective cohort study of patients initiated on PD in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). We examined demographic data and PD catheter characteristics of 1,258 patients, aged < or = 21 years, initiated on PD from 1992 to 1997. We examined the frequency and complications of ESI/TI occurring within 30 days, 6 months, and 1 year of follow-up. For peritonitis episodes, we examined patient risk factors for peritonitis. Almost 11% of patients had an ESI/TI at 30 days, 26% between 30 days and 6 months, and 30% between 6 months and 1 year of follow-up. There was no increased risk of ESI/TI associated with patient age, race, or catheter characteristics. Peritonitis occurred in dialysis patients at a rate of 1 episode per 13.2 patient months. Proportional hazards regression analysis demonstrated that black race, single-cuffed catheters, and upward pointing exit sites were independent risk factors for peritonitis in the pediatric PD population. Patients with ESI/TI had twice the risk of those without these infections of developing peritonitis or needing access revision, and an almost threefold increased risk of hospitalization for access complications/malfunction. ESI/TI occurs commonly in pediatric PD patients. These infections cause significant morbidity, through risk of peritonitis, access revision, and hospitalization for catheter complications. Further study of potentially modifiable risk factors for ESI/TI in pediatric end-stage renal disease patients is warranted.

For-profit versus not-for-profit dialysis care for children with end stage renal disease.

OBJECTIVE: Over the last 2 decades, for-profit dialysis units have become the most common providers of renal replacement therapy for adults with end stage renal disease (ESRD) and have had an increasing role in the dialysis of children. We undertook a study to determine whether dialysis facility profit status influences the choice of dialysis therapy in the pediatric population. DESIGN: Cross-sectional study of national data from the Health Care Financing Administration. SETTING: Free-standing and hospital-based outpatient dialysis facilities in the United States. PATIENTS: A total of 1568 children and adolescents (

Septicemia in dialysis patients: incidence, risk factors, and prognosis.

BACKGROUND: Infection is second to cardiovascular disease as a cause of death in patients with end-stage renal disease (ESRD), and septicemia causes a majority of these infectious deaths. To identify patients at high risk and to characterize modifiable risk factors for septicemia, we examined the incidence, risk factors, and prognosis for septicemia in a large, representative group of U.S. dialysis patients. METHODS: We conducted a longitudinal cohort study of incident ESRD patients in the case-mix study of the U.S. Renal Data System with seven years of follow-up from hospitalization and death records. Poisson regression was used to examine independent risk factors for hospital-managed septicemia. Cox proportional hazards analysis was used to assess the independent effect of septicemia on all-cause mortality and on death from septicemia. Separate analyses were performed for patients on peritoneal dialysis (PD) and hemodialysis (HD). RESULTS: Over seven years of follow-up, 11.7% of 4005 HD patients and 9.4% of 913 PD patients had at least one episode of septicemia. Older age and diabetes were independent risk factors for septicemia in all patients. Among HD patients, low serum albumin, temporary vascular access, and dialyzer reuse were also associated with increased risk. Among PD patients, white race and having no health insurance at dialysis initiation were also risk factors. Patients with septicemia had twice the risk of death from any cause and a fivefold to ninefold increased risk of death from septicemia. CONCLUSIONS: Septicemia, which carries a marked increased risk of death, occurs frequently in patients on PD as well as HD. Early referral to a nephrologist, improving nutrition, and avoiding temporary vascular access may decrease the incidence of septicemia. Further study of how race, insurance status, and dialyzer reuse can contribute to the risk of septicemia among ESRD patients is indicated.

Effect of parental donor sex on rejection in pediatric renal transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study.

Using the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database, we performed a retrospective cohort study of 1,552 pediatric renal transplant patients who had received a graft from a biological parent to determine if parental donor sex influences the development of rejection. There were 102/675 (15.1%) graft failures in paternal grafts compared to 144/877 (16.4%) graft failures in maternal grafts. Overall graft survival (p=0.48) and time to first rejection (p>0.9) were not different in patients receiving paternal versus maternal grafts. The overall frequency of graft loss to rejection was also not different. However, maternal donation was associated with a significantly longer time to first rejection in patients less than one year of age at the time of transplantation (p=0.01). Time to first rejection was not different between maternal and paternal grafts in older recipients. In summary, the present study did not demonstrate a difference in graft survival between maternal and paternal donations, but the youngest patients may experience a longer time to first rejection with maternal donation. The number of young patients is small, however, and further data are necessary to confirm this observation.

Evaluation of neurotoxicity in pediatric renal transplant recipients treated with tacrolimus (FK506).

The presence of severe and mild neurotoxicity in our pediatric renal transplant recipients treated with tacrolimus was determined by chart review (severe neurotoxicity) and patient survey (mild neurotoxicity). 14 patients were studied (mean age 15 yr, 5 month, +/- 4.4 yr). 1 patient experienced seizures, felt to be related to malignant hypertension. No other episode of severe neurotoxicity was documented. Most patients (12/14) reported at least one mild neurologic symptom, and half stated their symptoms were present at least 'most of the time'. The most frequent complaints were myalgias (7/14, 50%) and tremors (7/14, 50%) followed by fatigue (5/14, 38%). Severe neurotoxicity may be relatively infrequent in pediatric renal transplant patients treated with tacrolimus. Milder neurologic complaints may be commonly seen in this population, but in general are not severe enough to cause discontinuation of tacrolimus.