Alicia M. Neu

Growth failure, risk of hospitalization and death for children with end-stage renal disease

Abstractu2002Growth failure remains a significant problem for children with chronic renal insufficiency and end-stage renal disease (ESRD). We examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. We studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990: severe (<–3 SDS), moderate growth failure (>–3 and <–2 SDS), and normal growth (>–2 SDS). Among 1,112 prevalent pediatric dialysis and transplant patients (<17 years, Tanner I–IV), those with severe and moderate growth failure had higher hospitalization rates {relative risk (RR) 1.14 [95% confidence interval (CI) 1.1, 1.2] and 1.24 [95% CI 1.2, 1.3]} respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality (dialysis or transplant) in 1990. Kaplan-Meier survival analysis showed 5-year survival of 85% and 90% for patients with severe and moderate growth failure, respectively, compared with 96% for patients with normal growth (P<0.001, log-rank). Cox proportional hazards analysis revealed that those with severe (RR 2.9, 95% CI 1.6, 5.3) and moderate growth failure (RR 2.01, 95% CI 1.1, 3.6) had an increased risk of death compared with youths with normal growth, after adjustment. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22% and 18.7%, respectively) than in the normal growth group (15.6%). We conclude that growth failure is associated with a more-complicated clinical course and increased risk of death for children with kidney failure.

Design of the nephrotic syndrome study network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multi-center collaborative consortium established to develop a translational research infrastructure for Nephrotic Syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary studies program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy for detailed clinical, histopathologic, and molecular phenotyping at the time of clinically-indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and bi-annually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histologic data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for Nephrotic Syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.

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

Abstract:u2002 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.

Tacrolimus vs. cyclosporine A as primary immunosuppression in pediatric renal transplantation: a NAPRTCS study.

Abstract:u2002 Using the North American Renal Transplant Cooperative Study (NAPRTCS) database, we performed a retrospective cohort study of 986 pediatric renal transplant recipients (index transplant 1997–2000) who were treated either with Cyclosporine A (CSA), Mycophenolate Mofetil (MMF) and steroids (nu2003=u2003766) or tacrolimus (TAC), MMF and steroids (nu2003=u2003220) to examine potential difference in clinical outcomes between these two groups. In the first year post‐transplant, time to first rejection (29.1% vs. 29%, pu2003=u20030.840), risk for rejection [Adjusted Relative Risk (aRR) 1.01, 95% Confidence Interval (CI) 0.77, 1.323], graft survival (96.8% vs. 97.9%, pu2003=u20030.607) and risk for graft failure (aRR 0.988, 95% CI 0.64, 1.928) were not significantly different in TAC and CSA‐treated patients. At 2u2003yr post‐transplant, there was also no difference in risk for rejection (aRR 0.918, 95% CI 0.669, 1.259), graft survival (91.4% vs. 95.1%, pu2003=u20030.152) and risk for graft failure (aRR 0.702, 95% CI 0.461, 1.762) in the subset of 391 CSA‐treated patients and 77 TAC‐treated patients on whom 2u2003yr follow data were available in the database. TAC‐treated patients were significantly less likely to require antihypertensive medication at 1u2003yr [aRR 0.74 (95% CI 0.454, 0.637)] and 2u2003yr post‐transplant [aRR 0.67 (95% CI 0.56, 0.793)]. At 1u2003yr post‐transplant, TAC‐treated patients enjoyed a higher mean GFR as estimated by the Schwartz formula [89.1u2003mL/min/1.73u2003m2 (SE 2.64) vs. 78.6u2003mL/min/1.73u2003m2 (SE 1.07), pu2003=u20030.0003]. In addition, in the subset of patients with 2u2003yr of follow‐up, TAC patients had a higher mean GFR at both 1u2003yr [98.6u2003mL/min/1.73u2003m2 (SE 3.83) vs. 78.0u2003mL/min/1.73u2003m2 (SE 1.44), pu2003=u20030.0003] and 2u2003yr post‐transplant [96.7u2003mL/min/1.73u2003m2 (SE 3.33) vs. 73.2u2003mL/min/1.73u2003m2 (SE 1.48), pu2003<u20030.0001]. In summary, TAC and CSA, in combination with MMF and steroids, produce similar rejection rates and graft survival in pediatric renal transplant recipients. However, TAC is associated with improved graft function at 1 and 2u2003yr post‐transplant. Further analysis as more patient data are obtained will be necessary to determine if this difference in graft function persists and translates into improved graft survival.

Increased risk of death in pediatric and adult patients with ESRD secondary to lupus

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can cause significant kidney disease. Our goal was to assess the relative mortality risk associated with SLE in pediatric and adult populations with end-stage renal disease (ESRD) maintained on hemodialysis (HD). We performed Kaplan–Meier survival analysis from data collected by the United States Renal Data System (USRDS) in strata of pediatric and adult patients. This file includes data on all Medicare-reimbursed renal replacement patients. Cox proportional hazard models were used to assess mortality after adjusting for race and gender. Subjects were censored at transplantation or at end of follow-up. Pediatric patients with ESRD secondary to SLE had a 2-fold increased risk of death compared with other pediatric patients with ESRD (hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.5–3.7). Adult patients with ESRD secondary to SLE were also at increased risk of death compared with other adult patients (HR: 1.7, 95% CI: 1.2–2.7). The most common causes of death in both pediatric and adult patients with SLE were cardiovascular disease and cardiac arrest. Our study demonstrates that there is a significant increase in mortality secondary to cardiovascular disease in pediatric and adult patients with ESRD secondary to SLE. Patients with ESRD secondary to SLE may need aggressive monitoring for traditional risk factors for atherosclerosis and the diagnosis of SLE alone may be an independent risk factor for death in patients with ESRD.

Drug dosing during intermittent hemodialysis and continuous renal replacement therapy: special considerations in pediatric patients

Chronic renal failure is, fortunately, an unusual occurrence in children; however, many children with various underlying illnesses develop acute renal failure, and transiently require renal replacement therapy — peritoneal dialysis, intermittent hemodialysis (IHD), or continuous renal replacement therapy (CRRT). As children with acute and chronic renal failure often have multiple comorbid conditions requiring drug therapy, generalists, intensivists, nephrologists, and pharmacists need to be aware of the issues surrounding the management of drug therapy in pediatric patients undergoing renal replacement therapy. This article summarizes the pharmacokinetics and dosing of many drugs commonly prescribed for pediatric patients, and focuses on the management of drug therapy in pediatric patients undergoing IHD and CRRT in the intensive care unit setting. Peritoneal dialysis is not considered in this review. Finally, a summary table with recommended initial dosages for drugs commonly encountered in pediatric patients requiring IHD or CRRT is presented.

Risk for anemia in pediatric chronic kidney disease patients: a report of NAPRTCS.

Previous studies in children with chronic kidney disease (CKD) have identified low hemoglobin as a risk factor for poor outcomes. A retrospective review of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) CKD registry was performed to identify the prevalence of and risk factors for anemia among children with stage 3 CKD, including both patients with low hemoglobin and those whose hemoglobin normalized with an erythropoiesis-stimulating agent (ESA). At enrollment, 2,792 patients had stage 3 CKD. Mean age was 9.5 (±0.11) years, 62.1% were male, 61.3% were white, and 43.7% had structural/urologic disease. Among 1,640 of those patients with 12xa0month follow-up data available for multivariate analysis, 73% met the criteria for anemia. Multivariate logistic regression analysis identifying risk factors for anemia at the 12-month follow-up revealed that, after controlling for estimated glomerular filtration rate, age >2xa0years, male sex, earlier era of study entry, and prescription of anti-hypertensive medications are associated with an increased risk for anemia at 12xa0months. In addition, multivariate Cox proportional hazards regression analysis revealed that when patients with ESA-corrected hemoglobin are included in the definition, anemia is not associated with increased risk of progression to end stage renal disease (dialysis initiation or transplantation).

Immunization practices in children with renal disease: a report of the North American Pediatric Renal Transplant Cooperative Study.

Abstract.u2003To determine the current immunization recommendations of practicing pediatric nephrologists, a questionnaire was sent to the members of the North American Pediatric Renal Transplant Cooperative Society. Sixty-two percent of the centers responded. The results of the survey suggest that although consensus for approaching immunization does exist, recommendations do vary from center to center. Virtually all centers recommend standard vaccines [DTP, oral poliovirus (OPV), hepatitis B (Hep B), and Haemophilus influenzae B (Hib)] for their renal insufficiency and dialysis patients. Despite the fact that they are not infectious, standard killed vaccines (DTP, Hep B, Hib) are recommended less frequently for transplanted patients (86%) than their renal insufficiency (98%) and dialysis (near 100%) counterparts. Additionally, OPV and measles/mumps/rubella (MMR), both live viral vaccines, are rarely recommended post transplant. Almost 90% of centers recommend the use of influenza vaccine, while only 60% of centers recommend pneumococcal vaccine for children with renal disease. Over 70% of centers recommend the newly licenced varicella vaccine for patients on dialysis and those with renal insufficiency. Between 5% and 12% of centers recommend live viral vaccines, including OPV, MMR, and varicella vaccine, for immunosuppressed patients post renal transplant.

MEDICAL COMORBIDITIES ASSOCIATED WITH PEDIATRIC KIDNEY STONE DISEASE

OBJECTIVESnTo characterize the relationship between pediatric kidney stone disease and the presence of hypertension (HTN), diabetes mellitus (DM), and obesity. In adults, kidney stone disease has been associated with medical comorbidities such as HTN, DM, and obesity. Similar analyses have never been performed for the pediatric population.nnnMETHODSnThe 2003 and 2006 Kids Inpatient Databases were queried to identify subjects treated for kidney stone disease (International Classification of Diseases codes 9592.0 and 592.1). The comorbidities of HTN, DM, and obesity were identified using the provided comorbidity software. The risk of kidney stone disease associated with age, sex, and comorbidity status was evaluated using multivariate logistic regression.nnnRESULTSnA total of 6,115,443 subjects were evaluated. Of these, 14,245 (0.2%) had a diagnosis of upper tract calculus (4092 boys and 10,045 girls, sex unavailable for 108). Age was the strongest independent predictor of stone risk (P < .0001). HTN was associated with a significantly increased risk of stone diagnosis in children ≤10 years old and DM for children ≤5 years old. Stone risk was not affected by obesity in any age group.nnnCONCLUSIONSnThe results of our study have shown that kidney stone disease is significantly associated with age among all children and both HTN and DM for young children. Although exploratory, these findings are novel and suggest that kidney stone disease among young children might be associated with nonrenal, systemic disease states.

Growth in adolescent hemodialysis patients: Data from the Centers for Medicare & Medicaid Services ESRD Clinical Performance Measures Project

The Centers for Medicare & Medicaid Services’ (CMS) end-stage renal disease (ESRD) Clinical Performance Measures (CPM) Project has collected data on all adolescent hemodialysis patients since 2000. Thus, by 2002 data were available on all adolescents on hemodialysis in the USA for 3 consecutive years. Possible associations between clinical parameters and linear growth in this cohort were evaluated. Ninety-four adolescents were on hemodialysis for the 3 study years. The mean height standard deviation score (ht SDS) fell from −1.97 to −2.36 over the 3 study years. Compared with patients with ht SDS ≥−1.88, patients with ht SDS <−1.88 in the 2002 study year (n =53) were more likely to be male (66% vs 44%, p <0.05), on dialysis longer (6.9±4.5xa0years vs 4.1±2.3xa0years, p <0.001), and had lower height SDS in the 2000 study year (−2.90±1.31 vs −0.772±1.10, p <0.001). Patients with a ht SDS <−1.88 had a lower mean hemoglobin (11.4±1.6xa0g/dl vs 12.0±1.1xa0g/dl, p <0.05), but there were no differences in other clinical parameters. Among patients with ht SDS <−1.88, 38.8% (n =20) were prescribed recombinant human growth hormone (rhGH) in the 2002 study year. There were no differences in demographic or clinical parameters between rhGH treated and untreated patients. Many adolescents who remain on hemodialysis have poor linear growth. Further evaluation is needed to delineate contributory factors and the possible underutilization of rhGH.