Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum IgA levels. High polygenic score for IgAN was associated with earlier onset of kidney failure. In a comprehensive functional annotation analysis of candidate causal genes, we observed convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets.

CMV-associated collapsing focal segmental glomerulosclerosis after kidney transplant in a pediatric patient.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity among immunocompromised patients who have undergone kidney transplantation and is known to rarely induce collapsing focal segmental glomerulosclerosis (FSGS) among adults. METHODS: We present the first reported case of CMV-induced collapsing FSGS in a pediatric patient after kidney transplant. RESULTS: Our patient underwent a deceased donor kidney transplant due to end-stage renal disease secondary to lupus nephritis. Approximately 4 months after transplantation, he developed signs of worsening kidney function in the setting of CMV viremia and was found to have collapsing features of FSGS on kidney transplant biopsy. He was managed with a prompt escalation of antiviral therapy along with a reduction of immunosuppression and recovered without significant complication. At follow-up, he continued to have undetectable CMV titers, creatinine within normal limits, and no significant proteinuria. CONCLUSION: This report demonstrates CMV as a cause of collapsing FSGS and should be considered among pediatric transplant recipients who present with acute kidney injury, as should early assessment of APOL1 genetic status in both donor and recipient.

Pioglitazone enhances proteinuria reduction in complicated pediatric nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is a common pediatric kidney disease, yet current treatments for complicated NS are only partially effective and have significant toxicity. There is no Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved safe and effective treatment for NS. Thiazolidinediones (TZDs) have been shown to reduce proteinuria in both diabetic and non-diabetic kidney disease and in preclinical studies to directly protect podocytes from injury and reduce proteinuria. Here, we report on the potential utility of the addition of the TZD pioglitazone (PIO) to enhance proteinuria reduction in 8 children and young adults with steroid dependent NS and steroid resistant NS. METHODS: Clinical data were analyzed in comparable time periods before and after the addition of PIO to their medical regimens. Eight NS patients with minimal change NS (n = 2), focal segmental glomerulosclerosis (FSGS) (n = 4), or collapsing FSGS (n = 2) were evaluated. RESULTS: Prior to PIO initiation, all children and young adults had already received multiple immunosuppressive medications (mean = 3.75). Five of eight patients (63%; "Responders") had notable proteinuria reduction within 1 month of PIO initiation (62% reduction; P = 0.04) and normalization within 6 months (97% reduction; P = 0.04). PIO-related benefits among the responders included notable increases in serum albumin (2.5 to 3.7 g/dl; P = 0.08), dramatic reductions in hospitalizations for IV albumin infusions and diuresis (11 to 0; P < 0.01), and considerable reduction in total immunosuppression (43% reduction; P > 0.1). Importantly, no patients experienced any adverse events attributable to PIO during a total of 136 patient-months of treatment. CONCLUSIONS: While confirmatory safety and efficacy studies are needed, these findings suggest pioglitazone (a non-immunosuppressive drug) may be useful to enhance proteinuria reduction in some children and young adults with complicated NS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Utility of the 2018 revised ISN/RPS thresholds for glomerular crescents in childhood-onset lupus nephritis: a Pediatric Nephrology Research Consortium study.

BACKGROUND: The revised 2018 ISN/RPS Classification System for lupus nephritis (LN) includes calculations for both activity index (A.I.) and chronicity index (C.I.). Unchanged were the thresholds of < 25%, 25-50%, and > 50% crescents to distinguish between mild, moderate, and severe activity/chronicity. We aimed to evaluate these thresholds for percent crescents in childhood-onset LN. METHODS: Eighty-six subjects < 21 years of age were enrolled from the Pediatric Glomerulonephritis with Crescents Registry, a retrospective multi-center cohort sponsored by the Pediatric Nephrology Research Consortium. Thresholds of 10%, 25%, and 50% for both cellular/fibrocellular and fibrous crescents were interrogated for primary outcomes of kidney failure, eGFR, and eGFR slope. RESULTS: Median age at time of initial biopsy was 14 years (range 1-21). Median follow-up time was 3 years (range 1-11). Cumulative incidence of kidney failure was 6% at 1 year and 10% at latest follow-up. Median eGFR slope was - 18 mL/1.73 m2/min (IQR - 51 to + 8) at 1 year and - 3 mL/min/1.73 m2/year (IQR - 19 to + 6) at latest follow-up. We found no difference in kidney failure at the proposed < 25% and 25-50% cellular crescents thresholds, and thus added a new provisional threshold of 10% that better predicted outcomes in children. Moreover, use of 10% and 25% thresholds for fibrous crescents showed a fourfold and sevenfold increase in risk of kidney failure. CONCLUSIONS: In children with crescentic LN, use of 10% and 25% thresholds for cellular crescents better reflects disease activity, while these thresholds for fibrous crescents better discriminates kidney disease outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Relationship Between Neighborhood Disadvantage and Kidney Disease Progression in the Chronic Kidney Disease in Children (CKiD) Cohort.

RATIONALE & OBJECTIVE: To examine the relationship between neighborhood poverty and deprivation, chronic kidney disease (CKD) comorbidities, and disease progression in children with CKD. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Children with mild to moderate CKD enrolled in the CKiD (Chronic Kidney Disease in Children) study with available US Census data. EXPOSURE: Neighborhood poverty and neighborhood disadvantage. OUTCOME: Binary outcomes of short stature, obesity, hypertension, and health care utilization for cross-sectional analysis; a CKD progression end point (incident kidney replacement therapy [KRT] or 50% loss in estimated glomerular filtration rate), and mode of first KRT for time-to-event analysis. ANALYTICAL APPROACH: Cross-sectional analysis of health characteristics at time of first Census data collection using logistic regression to estimate odds ratios. Risk for CKD progression was analyzed using a Cox proportional hazard model. Multivariable models were adjusted for race, ethnicity, sex, and family income. RESULTS: There was strong agreement between family and neighborhood socioeconomic characteristics. Risk for short stature, hospitalization, and emergency department (ED) use were significantly associated with lower neighborhood income. After controlling for race, ethnicity, sex, and family income, the odds of hospitalization (OR, 1.71 [95% CI, 1.08-2.71]) and ED use (OR, 1.56 [95% CI, 1.02-2.40]) remained higher for those with lower neighborhood income. The hazard ratio of reaching the CKD progression outcome for participants living in lower income neighborhoods was significantly increased in the unadjusted model only (1.38 [95% CI, 1.02-1.87]). Likelihood of undergoing a preemptive transplant was decreased with lower neighborhood income (OR, 0.47 [95% CI, 0.24-0.96]) and higher neighborhood deprivation (OR, 0.31 [95% CI, 0.10-0.97]), but these associations did not persist after controlling for participant characteristics. LIMITATIONS: Limited generalizability, as only those with consistent longitudinal nephrology care were studied. CONCLUSIONS: Neighborhood-level socioeconomic status (SES) was associated with poorer health characteristics and CKD progression in univariable analysis. However, the relationships were attenuated after accounting for participant-level factors including race. A persistent association of neighborhood poverty with hospitalizations and ED suggests an independent effect of SES on health care utilization, the causes for which deserve additional study.

IgA-dominant infection-associated glomerulonephritis in the pediatric population.

BACKGROUND: IgA-dominant infection-associated glomerulonephritis is well-documented in adults but has not been studied in depth in children. We assessed the incidence of pediatric IgA-dominant infection-associated glomerulonephritis and clinical and kidney biopsy findings. METHODS: Pediatric native kidney biopsies over a 10-year period with IgA dominance, strong C3, and findings indicative of infection-associated etiology were identified. RESULTS: We identified 9 cases of IgA-dominant infection-associated glomerulonephritis, 0.8% of pediatric native kidney biopsies. Seven patients presented with elevated creatinine. All had hematuria and proteinuria. Eight patients had clinical evidence of infection: one each with central port infection by methicillin-sensitive Staphylococcus aureus, recurrent streptococcal pharyngitis and recent otitis media, streptococcal pharyngitis demonstrated 8 months after biopsy, suspected streptococcal scalded skin syndrome, and viral gastroenteritis, and three with serologic evidence of Streptococcal infection but no identified site of infection. All but one patient experienced short-term normalization of creatinine and resolution of proteinuria, though two eventually progressed to kidney failure: one 3 years later due to progressive disease and one 11 years later due to focal segmental glomerulosclerosis without concurrent immune deposits. CONCLUSIONS: Pediatric IgA-dominant infection-associated glomerulonephritis is rare, and generally has a favorable prognosis, contrasting that seen in adults with severe comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary.

Efficacy of Sphincter Control Training and medical device in the treatment of premature ejaculation: A multicenter randomized controlled clinical trial.

A new line of treatment for premature ejaculation (PE) based on the use of masturbation aid device in combination with behavioral techniques has emerged in recent years. We report a multicenter randomized clinical trial with a parallel group design to determine the effectiveness of an electronic device called Myhixel I© in the treatment of PE. Forty patients who met the criteria for the diagnosis of lifelong PE, were assigned to two treatment groups completed the Sphincter control training (SCT) program in eight weeks. The only difference between groups was the use of the device. The main measure was the "fold increase" (FI) of the intravaginal ejaculatory latency time (IELT). The geometric means of IELT show, at the end of the treatment at week 8, a superiority of the device group. The mean FI 4.27 (SD 2.59) at the end of treatment for the device group was clearly higher than obtained in the previous clinical trial, in which a specific medical device was not used. No side effects were observed and it required little therapeutic input and no partner involvement. The SCT program in combination with the Myhixel I© is an effective treatment for PE.

Renal Survival in Children with Glomerulonephritis with Crescents: A Pediatric Nephrology Research Consortium Cohort Study.

There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortium's Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome. Median age at biopsy was 11 years (range 1-21). The percentage of crescents was 3-100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis (19%) and ANCA-associated GN (13%), post-infectious GN (5%), and anti-glomerular basement membrane disease (3%). The prevalence of ESKD was 12% at one year and 16% at last follow-up (median = 3 years, range 1-11). Median time to ESKD was 100 days. Risk factors for ESKD included %crescents, presence of fibrous crescents, estimated GFR, and hypertension at biopsy. For each 1% increase in %crescents, there was a 3% decrease in log odds of 1-year renal survival (p = 0.003) and a 2% decrease in log odds of renal survival at last follow-up (p < 0.001). These findings provide an evidence base for enrollment criteria for crescentic glomerulonephritis in future clinical trials.

A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis.

BACKGROUND: This randomized phase 3 study evaluated the efficacy and safety of cinacalcet in children with secondary hyperparathyroidism (SHPT) receiving dialysis. METHODS: This study had double-blind and open-label phases. Eligible patients aged 6-< 18 years were randomized to cinacalcet (starting dose ≤ 0.20 mg/kg) or placebo. The primary endpoint was ≥ 30% reduction from baseline in mean intact parathyroid hormone (iPTH). Secondary endpoints included mean iPTH ≤ 300 pg/mL; percentage change from baseline in corrected total serum calcium, phosphorus, and calcium phosphorus product (Ca × P); and safety. RESULTS: The double-blind phase comprised 43 patients (cinacalcet, n = 22; placebo, n = 21). Nineteen months into the study, regulatory authorities were notified of a fatality; the study was subsequently terminated after a 14-month clinical hold. Before the hold, 12 patients (55%) on cinacalcet and four (19%) on placebo achieved the primary endpoint (p = 0.017), and 27% and 24%, respectively, achieved iPTH ≤ 300 pg/mL. The between-group differences (95% CI) in percentage changes for total serum calcium, phosphorus, and Ca × P were - 4% (- 9 to 1%), - 6% (- 21 to 8%), and - 10% (- 23 to 3%). The mean maximum actual weight-adjusted daily cinacalcet dosage administered was 0.99 mg/kg/day. Overall, 82% of patients on cinacalcet and 86% on placebo had ≥ 1 treatment-emergent adverse event; the most common were vomiting (32%, 24%, respectively), hypocalcemia (23%, 19%), nausea (18%, 14%), and hypertension (14%, 24%). CONCLUSIONS: Despite early termination, efficacy and safety outcomes observed with cinacalcet in children with SHPT on dialysis were consistent with adult observations, suggesting cinacalcet may meet an unmet medical need for this population.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial.

BACKGROUND AND OBJECTIVES: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS: The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS: ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

Glomerular Filtration Rate Estimation by Serum Creatinine or Serum Cystatin C in Preterm (<31 Weeks) Neonates.

Glomerular filtration rate (GFR) was estimated by serum creatinine (Schwartz's equation) and serum cystatin C (Filler's equation) in preterm neonates (24-31 weeks of gestation) in a prospective cohort study. Serum creatinine and cystatin C was obtained at birth and then every two weeks during the first month. We found a poor fit between two methods, and a steadier GFR assessment by cystatin C.

Síndrome de transfusión feto-fetal: experiencia de 69 casos / Twin-to-twin transfusion syndrome: experience with 69 cases

La fetoscopia por síndrome de transfusión feto fetal es la cirugía fetal más realizada en el mundo. Los resultados deben ser reportados, para que las pacientes puedan elegir su opción de atención. Objetivo: Determinar los resultados de cirugía fetal en el síndrome de transfusión feto-fetal. Diseño: Estudio retrospectivo. Lugar: Clínica Alemana, Santiago, Chile. Participantes: Gestantes con gemelares. Intervenciones: La cirugía fetal se realizó con anestesia local, endoscopios Storz de 3,3 mm, específicos para fetoscopia. Principales medidas de resultados: Sobrevida fetal. Resultados: La serie de casos se inició en el año 2005, y hasta la fecha se han realizado 71 cirugías, con 69 que han resuelto su embarazo. Treinta y tres mujeres tuvieron ambos hijos vivos (48%), 25 solo un hijo vivo (36%) y 11 concluyeron sin hijos vivos (16%). Conclusiones: La tasa de embarazos con uno o ambos niños vivos fue 84%, superando 90% en los últimos 30 casos. Hubo 6 pacientes de Perú, de las cuales cuatro tuvieron ambos hijos vivos.

Fetoscopy for fetal-fetal transfusion syndrome is the most frequent fetal surgery performed in the world. The results should be reported, so that the patients can choose their choice of care. Objective: To determine the results of fetal surgery on twin-to-twin transfusion syndrome. Design: Retrospective study. Setting: Clínica Alemana, Santiago, Chile. Participants: Pregnant women with twins. Interventions: Fetal surgery was performed under local anesthesia, with 3.3mm fetoscopy-specific Storz endoscopes. Main outcome measures: Fetal survival. Results: The series of cases began in the year 2005, and to date 71 surgeries were carried out, with 69 that resolved their pregnancy. Thirty-three women had both living children (48%), 25 only one living child (36%) and 11 concluded without living children (16%). Conclusions: The rate of pregnancies with one or both children born alive was 84%, exceeding 90% in the last 30 cases. There were 6 patients from Peru, of which four had two living children.

Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report.

OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age.

Gaining the Patient Reported Outcomes Measurement Information System (PROMIS) perspective in chronic kidney disease: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND AND OBJECTIVES: Chronic kidney disease is a persistent chronic health condition commonly seen in pediatric nephrology programs. Our study aims to evaluate the sensitivity of the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric instrument to indicators of disease severity and activity in pediatric chronic kidney disease. METHODS: This cross sectional study included 233 children 8-17 years old, with chronic kidney disease from 16 participating institutions in North America. Disease activity indicators, including hospitalization in the previous 6 months, edema, and number of medications consumed daily, as well as disease severity indicators of kidney function and coexisting medical conditions were captured. PROMIS domains, including depression, anxiety, social-peer relationships, pain interference, fatigue, mobility, and upper extremity function, were administered via web-based questionnaires. Absolute effect sizes (AES) were generated to demonstrate the impact of disease on domain scores. Four children were excluded because of missing glomerular filtration rate (GFR) estimations. RESULTS: Of the 229 children included in the final analysis, 221 completed the entire PROMIS questionnaire. Unadjusted PROMIS domains were responsive to chronic kidney disease activity indicators and number of coexisting conditions. PROMIS domain scores were worse in the presence of recent hospitalizations (depression AES 0.33, anxiety AES 0.42, pain interference AES 0.46, fatigue AES 0.50, mobility AES 0.49), edema (depression AES 0.50, anxiety AES 0.60, pain interference AES 0.77, mobility AES 0.54) and coexisting medical conditions (social peer-relationships AES 0.66, fatigue AES 0.83, mobility AES 0.60, upper extremity function AES 0.48). CONCLUSIONS: The PROMIS pediatric domains of depression, anxiety, social-peer relationships, pain interference, and mobility were sensitive to the clinical status of children with chronic kidney disease in this multi-center cross sectional study. We demonstrated that a number of important clinical characteristics including recent history of hospitalization and edema, affected patient perceptions of depression, anxiety, pain interference, fatigue and mobility. The PROMIS instruments provide a potentially valuable tool to study the impact of chronic kidney disease. Additional studies will be required to assess responsiveness in PROMIS score with changes in disease status over time.

Association of income level with kidney disease severity and progression among children and adolescents with CKD: a report from the Chronic Kidney Disease in Children (CKiD) Study.

BACKGROUND: Among adults, lower socioeconomic status (SES) is a risk factor for chronic kidney disease (CKD), progression to end-stage renal disease, and poor health outcomes; but its impact on young people with CKD is not established. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: 572 children and adolescents aged 1-16 years with mild to moderate CKD residing in the United States and Canada who were enrolled in the Chronic Kidney Disease in Children (CKiD) Study. PREDICTOR: Self-reported annual household income category as a proxy measure for SES: ≥$75,000 (high income), $30,000 to <$75,000 (middle income) and <$30,000 (low income). OUTCOMES & MEASUREMENTS: Clinical characteristics and CKD severity at baseline (glomerular filtration rate [GFR] and comorbid conditions related to disease severity and management) and longitudinally (GFR decline and changes in blood pressure z scores and height z scores per year). RESULTS: At baseline, low and middle household incomes, compared to high income, were associated with minority race (39% and 20% vs. 7%), lower maternal education (28% and 5% vs. 1%), abnormal birth history (34% and 32% vs. 21%), and having at least one clinical comorbid condition (66% and 64% vs. 55%). Baseline median GFRs were similar across income categories (43-45 mL/min/1.73 m2). After adjusting for baseline differences, average GFR declines per year for the low-, middle-, and high-income categories were -2.3%, -2.7%, and -1.9%, respectively, and were not statistically significantly different among groups. Blood pressure control tended to improve in all groups (z score, -0.10 to -0.04) but higher income was associated with a faster improvement. Each group showed similar deficits in height at baseline. Height deficits diminished over time for participants from high-income families, but not among those from low-income families (z scores for height per year, 0.05 and -0.004, respectively; P = 0.03 for comparison of high and low income). LIMITATIONS: Income is an imperfect measure for SES; CKiD participants are not representative of children and adolescents with CKD who are uninsured or not receiving care; statistical power to detect associations by income level is limited. CONCLUSIONS: GFR decline was similar across income groups but better improvement in BP was observed among those with high income. Children and adolescents with CKD from lower income households are at higher risk of impaired growth.

Gaining the PROMIS perspective from children with nephrotic syndrome: a Midwest pediatric nephrology consortium study.

BACKGROUND AND OBJECTIVES: Nephrotic syndrome (NS) represents a common disease in pediatric nephrology typified by a relapsing and remitting course and characterized by the presence of edema that can significantly affect the health-related quality of life in children and adolescents. The PROMIS pediatric measures were constructed to be publically available, efficient, precise, and valid across a variety of diseases to assess patient reports of symptoms and quality of life. This study was designed to evaluate the ability of children and adolescents with NS to complete the PROMIS assessment via computer and to initiate validity assessments of the short forms and full item banks in pediatric NS. Successful measurement of patient reported outcomes will contribute to our understanding of the impact of NS on children and adolescents. DESIGN: This cross-sectional study included 151 children and adolescents 8-17 years old with NS from 16 participating institutions in North America. The children completed the PROMIS pediatric depression, anxiety, social-peer relationships, pain interference, fatigue, mobility and upper extremity functioning measures using a web-based interface. Responses were compared between patients experiencing active NS (n = 53) defined by the presence of edema and patients with inactive NS (n = 96) defined by the absence of edema. RESULTS: All 151 children and adolescents were successfully able to complete the PROMIS assessment via computer. As hypothesized, the children and adolescents with active NS were significantly different on 4 self-reported measures (anxiety, pain interference, fatigue, and mobility). Depression, peer relationships, and upper extremity functioning were not different between children with active vs. inactive NS. Multivariate analysis showed that the PROMIS instruments remained sensitive to NS disease activity after adjusting for demographic characteristics. CONCLUSIONS: Children and adolescents with NS were able to successfully complete the PROMIS instrument using a web-based interface. The computer based pediatric PROMIS measurement effectively discriminated between children and adolescents with active and inactive NS. The domain scores found in this study are consistent with previous reports investigating the health-related quality of life in children and adolescents with NS. This study establishes known-group validity and feasibility for PROMIS pediatric measures in children and adolescents with NS.

Metabolic syndrome in pediatric renal transplant recipients: comparing early discontinuation of steroids vs. steroid group.

Steroids have played a valuable role in transplantation as a treatment option. The purpose of this study is to assess the prevalence of MS in pediatric RT patients receiving SG or early SWG; SG discontinued five days after transplantation. We retrospectively reviewed 58 pediatric RT patients between 2000 and 2007. MS criterion was defined as the presence of any three of five criteria: (i) BMI >97th percentile, (ii) hypertension (SBP/DBP > 95th percentile or on medications); (iii) triglycerides > 95thpercentile, (iv) HDL cholesterol < 5th percentile, (v) fasting glucose > 100 mg/dL. Twenty-five patients (43%) received SG and 33 patients (57%) received SWG. The prevalence of MS in SG was 68% compared to 15% in SWG. At six months and one yr after transplantation, mean serum glucose, total cholesterol, and triglycerides were significantly lower in the SWG. The prevalence of hypertension was significantly lower in the SWG, and patients in the SWG received significantly less lipid-lowering and anti-hypertensive medications than SG. Mean BMI percentile was significantly higher in SG one yr after transplantation but not after six months, although always significantly higher in patients with MS (p < 0.05). From this study, we conclude that for pediatric RT patients, cardiovascular risk factors are significantly lower in SG withdrawal groups.

Obstacles to the prescribing of growth hormone in children with chronic kidney disease.

Despite its effectiveness, recombinant human growth hormone (rhGH) is under-utilized in short children with chronic kidney disease (CKD). We conducted a multicenter study to explore the obstacles preventing children with CKD from receiving rhGH. We investigated the use of rhGH in 307 children with CKD from seven pediatric nephrology centers. Among the 110 patients who fell below the 5th percentile, 56 (51%) had not received rhGH. The most common reasons given for these children not receiving rhGH were family refusal, secondary hyperparathyroidism, and non-compliance. However, no explanation was apparent for 25% of the short children with CKD. Boys were more likely than girls to receive rhGH (65% vs 31%; P = 0.002). Use of rhGH was similar in African Americans and non-Hispanic Whites. Children who had received rhGH achieved a 0.5 increase in height z-score in the first year after the initiation of rhGH therapy. Children who had not received rhGH achieved a 0.03 increase in height z-score during the first year after falling below the 5th percentile (P = 0.005 vs the children who had received rhGH). Waiting for insurance company approval led to a significant delay in the initiation of rhGH treatment in 18% of patients. The fact that more than 50% of short children with CKD did not receive rhGH is secondary to multiple factors, many of which may be amenable to intervention efforts.