Sarah J. Swartz

Cost-effectiveness of ambulatory blood pressure monitoring in the initial evaluation of hypertension in children.

OBJECTIVE. The goal was to determine the cost-effectiveness of ambulatory blood pressure monitoring in the initial evaluation of stage 1 hypertension. METHODS. Retrospective chart review of data for children referred to Texas Childrens Hospital hypertension clinic between January 2005 and August 2006 was performed. We compared the costs of standard evaluations versus the initial use of ambulatory blood pressure monitoring for children with clinic blood pressure measurements suggesting stage 1 hypertension. Charges for clinic visits, laboratory tests, and imaging were obtained from the Texas Childrens Hospital billing department. RESULTS. A total of 267 children were referred. One hundred thirty-nine children did not receive ambulatory blood pressure monitoring; 54 met clinical indications for ambulatory blood pressure monitoring but did not receive it because it was not a covered expense (44 children) or the family refused the study (10 children). One hundred twenty-six children received clinically indicated ambulatory blood pressure monitoring, paid for either through insurance or by the family. Fifty-eight children (46%) had confirmed white-coat hypertension, 62 (49%) stage 1 hypertension, and 6 (5%) stage 2 hypertension. With the observed prevalence of white-coat hypertension, initial ambulatory blood pressure monitoring use yielded net savings after evaluation of 3 patients, with projected savings of

Minimal change disease with IgM+ immunofluorescence: a subtype of nephrotic syndrome

2.4 million per 1000 patients. CONCLUSIONS. Ambulatory blood pressure monitoring in the initial evaluation of suspected childhood hypertension is highly cost-effective. Awareness of cost saving potential may increase the availability of ambulatory blood pressure monitoring for evaluation of new-onset hypertension.

Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene

Immunoglobulin (Ig) M nephropathy is defined by electron-dense mesangial deposits and mesangial IgM visible by immunofluorescence (IF) without other histopathologic and immunofluorescent microscopic abnormalities. Certain patients have only immuno-positive (IgM+) IF. Children presenting with steroid-dependent or steroid-resistant nephrotic syndrome have a high prevalence of IgM+ IF with or without electron-dense deposits. We reviewed the clinical course of children with steroid-dependent or steroid-resistant nephrotic syndrome who underwent renal biopsy at Texas Children‘s Hospital from 1989 to 2006 to further characterize IgM+ IF in children with nephrotic syndrome. Of the 55 children with steroid-resistant or -dependent minimal change disease (MCD), 23 had IgM+ IF. Of these 23 children, 61% had microscopic hematuria at presentation, 48% (11/23) were steroid-dependent, and 48% (11/23) steroid-resistant (one underwent biopsy prior to steroid therapy). We compared the efficacy of adjuvant treatment with cyclophosphamide and cyclosporine: 18% initially treated with cyclophosphamide obtained remission, while 55% had no response; 83% obtained subsequent remission with cyclosporine. Of those initially treated with cyclosporine, 88% obtained complete or partial remission. IgM+ IF may be surrogate marker for the severity of MCD. Based on our results, children with MCD and IgM+ IF have a better response to cyclosporine than cyclophosphamide.

Outcomes after peritoneal dialysis catheter placement

Purpose:To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis for patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT).Methods:WES was performed in 62 families with CAKUT. WES data were analyzed for single-nucleotide variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs).Results:In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. The clinical database of the Baylor Miraca Genetics laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these eight individuals with FOXP1 SNVs have syndromic urinary tract defects, implicating this gene in urinary tract development.Conclusion:We conclude that WES can be used to identify molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.Genet Med 19 4, 412–420.

Dialysis in Children and Adolescents: The Pediatric Nephrology Perspective

BACKGROUND The purpose of this study was to review surgical outcomes after elective placement of peritoneal dialysis (PD) catheters in children with end-stage renal disease. METHODS Children with PD catheters placed between February 2002 and July 2014 were retrospectively reviewed. Outcomes were catheter life, late (>30days post-op) complications (catheter malfunction, catheter malposition, infection), and re-operation rates. Comparison groups included laparoscopic versus open placement, age<2, and weight<10kg. Univariate and multivariate analysis were performed. RESULTS One hundred sixteen patients had 173 catheters placed (122 open, 51 laparoscopic) with an average patient age of 9.7±6.3years. Mean catheter life was similar in the laparoscopic and open groups (581±539days versus 574±487days, p=0.938). The late complication rate was higher for open procedures (57% versus 37%, p=0.013). Children age<2 or weight<10kg had higher re-operation rates (64% versus 42%, p=0.014 and 73% versus 40%, p=0.001, respectively). Adjusted for age and weight, open technique remained a risk factor for late complications (OR 2.44, 95% CI 1.20-4.95) but not re-operation. DISCUSSION Laparoscopic placement appears to reduce the rate of late complications in children who require PD dialysis catheters. Children <2years age or <10kg remain at risk for complications regardless of technique.

Nocturnal Hypertension and Attenuated Nocturnal Blood Pressure Dipping is Common in Pediatric Lupus

The care of children with end-stage renal disease (ESRD) is highly specialized and often poorly understood by nonpediatric providers and facility/institution administrators. As such, this position paper has been created to offer provider, facility, and institutional guidance regarding the components of care necessary for children receiving dialysis. Key differences between adult and pediatric dialysis units are highlighted. Responsibilities and expectations of the members of the interdisciplinary dialysis team are outlined as they pertain specifically to the care of pediatric dialysis patients. Physical and staffing requirements of the dialysis facility are reviewed, again focusing on unique needs and challenges faced by the pediatric dialysis care team. Among these, vascular access options and proper planning of ESRD care are underscored. Pediatric quality-of-life metrics differ significantly from adult quality variables, and proper tools for assessment must be used. Endorsed by the Council of the American Society of Pediatric Nephrology (ASPN), this position paper serves as a reference tool for the provision of care to pediatric patients with ESRD.

Cefazolin in 4 Children on Chronic Hemodialysis: A Proposed Dosing Regimen.

Hypertension is an important manifestation of systemic lupus erythematosus (SLE) but reports of prevalence vary between 20-70% in published reports of adult and pediatric patients. For both children and adults with SLE, the clinical diagnosis and management of hypertension has traditionally been based on guidelines developed for the general population. In clinical trials, the criteria used for defining participants with hypertension are mostly undefined. As a first step towards formally assessing the blood pressure (BP) patterns of children diagnosed with SLE, 24-hr ambulatory BP monitoring data was analyzed on clinic patients who presented with prehypertension or stage I hypertension. In this pediatric SLE cohort (n=10), 20% met daytime criteria for a diagnosis of hypertension. Patterns of BP elevation varied widely with white coat, masked, isolated systolic, and diastolic nocturnal hypertension all identified. Nocturnal hypertension was detected in 60% and attenuated nocturnal BP dipping in 90% of both hypertensive and normotensive SLE patients. In SLE patients, the median nighttime systolic and diastolic loads were 25% and 15.5% compared with median daily loads of 12.5% and 11.5%. Daytime and nighttime systolic and diastolic BP load and nocturnal dipping was compared to a control population consisting of 85 non-SLE patients under 21 years old with prehypertension or stage 1 hypertension presenting to hypertension clinic. Median systolic BP dipped 5.3 mmHg in SLE patients compared to 11.9 mmHg in non-lupus ( p-value = 0.001). Median diastolic BP dipped 12.9 mmHg versus 18.5 mmHg in non-lupus ( p-value = 0.003). Patterns of BP dysregulation in pediatric SLE merit further exploration. Children with or without SLE displaying prehypertensive or stage 1 casual BP measurements had similar rates of hypertension by ambulatory BP monitoring. However, regardless of BP diagnosis, and independent of kidney involvement, there was an increased proportion with attenuated nocturnal dipping and nocturnal hypertension in SLE patients.

Milky appearance of peritoneal fluid in a neonate on peritoneal dialysis due to end-stage renal disease: Questions

Cefazolin, a first-generation cephalosporin, is recommended for treatment of infections caused by Gram-positive and Gram-negative organisms. The pharmacokinetics of cefazolin have been studied with defined dosing regimens after hemodialysis (HD) in adult patients, but no such data exist in pediatric patients. Currently, expert opinion recommends a dosing interval of 24 hours, which makes cefazolin an impractical treatment option in an outpatient dialysis unit. We describe our experience dosing cefazolin after HD in pediatric patients with susceptible Gram-positive organisms at 1 large academic hospital over a 3-month time period. This report was approved by the institutional review board of Baylor College of Medicine. Patients underwent dialysis 3 or 4 days a week using Polysulfone (Fresenius F3) or Polyflux (Revaclear) dialyzers under standard settings (blood flow rate: 4.3-8.9 mL/kg/min; dialysate flow rate: 500-800 mL/min; duration: 3-4 hours). Cefazolin 35 mg/kg was given intravenously over 30 minutes after each HD session. After at least 2 doses, serum cefazolin concentrations were checked before the next HD session from the venous port (3 mL). Samples were checked after at least 2 doses to ensure concentrations were closer to steady state. Doses and monitoring plans were adjusted as needed, thereafter, to target a preHD concentration greater than 8 μg/mL. Assays were processed by Atlantic Diagnostic Laboratories using liquid chromatography–tandem mass spectrometry (Bensalem, PA). Four patients received cefazolin therapy dosed after HD (Table 1). All patients had normal liver function. All cefazolin concentrations remained above the minimum inhibitory concentration (MIC) of 8 μg/ mL. All patients exhibited signs and symptoms of infection resolution. A dose adjustment was made for 1 patient as a result of a pre-HD cefazolin concentration of 183.0 μg/mL, which greatly exceeded the MIC; a repeat with the next dialysis session was 93.9 μg/mL. The dose was reduced to 15-mg/ kg for 1 dose and then changed to 25-mg/kg thereafter. A sample drawn after 2 reduced doses (one 15-mg/kg and one 25-mg/kg dose) was 54.8 μg/mL. This 17-year old’s concentrations ultimately proved most stable on a dose of 25-mg/kg, closer to the recommended dose for adults. Of note, he was the only one of our patients with residual urine output. Although toxic concentrations are not well established, reports of cefazolin neurotoxicity have been reported at levels greater than 500 μg/mL. No adverse events were observed in our patients. Alternative antibiotics, such as vancomycin, have serious side effects and are inferior in efficacy. A study of 123 adult patients on HD with methicillin-sensitive Staphylococcus aureus bacteremia found treatment failure more commonly among patients receiving vancomycin compared with cefazolin dosed thrice weekly, 2 or 3 g after HD (31.2% vs 13%; P = 0.02). Our dose was chosen based on this study; 2 or 3 g post-HD translated into approximately 30 or 40 mg/kg post-HD for the average 70-kg patient. 667381 AOPXXX10.1177/1060028016667381Annals of PharmacotherapyLee et al letter2016

Thrombocytopenia-associated multi-organ failure secondary to hyperglycemic, hyperosmolar non-ketotic syndrome: A case report

A 5-week-old Caucasian male infant was born at 37 weeks and 3 days of gestation, with a birth weight of 3.375 kg and a pre-natal diagnosis of lower urinary tract obstruction with normal amniotic fluid. The post-natal ultrasound [day of life (DOL) 1] was consistent with a diagnosis of bilateral cystic renal dysplasia. The initial serum creatinine (Cr) level was 1.34 mg/dL at birth. A voiding cystourethrogram on DOL 3 identified dilated posterior urethra and right vesicoureteral reflux. On DOL 6, the infant underwent diagnostic cystoscopy which showed a congenital bulbar urethra stricture without valves and dilation of the stricture; a peritoneal dialysis (PD) catheter (39 cm single cuff curled) was put in place at this time. Due to the non-oliguric nature of the infant’s renal failure, the PD catheter was allowed to heal prior to use. Continuous manual PD (Gesco AG, Wuppertal, Germany) was started on DOL 12 when the Cr level peaked at 6.69 mg/dL, with hourly cycles and a fill volume of 10 mL/kg (30 ml) using 1.5% Dianeal solution; average ultrafiltration ranged from 90 to 170 mL/day. His neonatal course was further complicated by the development of Escherichia coli urosepsis on DOL 18 with bacteremia and cerebrospinal fluid pleocytosis which was treated with intravenously administered ceftriaxone for a total of 21 days. He received expressed breast milk (380 mL) + Similac PM 60/40 10 kcal/oz. + Duocal 3 kcal/oz. + 1.2 g Beneprotein/100 mL (Diet 1) to limit electrolyte content due to end-stage renal disease while providing adequate nutrition for growth at 100 kcal/kg/day and volume 100 mL/kg/day. He tolerated feeds well while on the Gesco PD system and showed good interval weight gain. The fill volume was adjusted by 5 mL/kg every 1–2 weeks to achieve the eventual target of 40 mL/kg fill volume. On DOL 34, at which time the infant had been receiving PD on the Gesco PD system for approximately 3 weeks, and 48 h after the fill volume had been increased to 60 mL (15 mL/kg), his peritoneal fluid turned milky in appearance (Fig. 1).

Difficult Vascular Access

Thrombocytopenia associated multi‐organ failure (TAMOF) is a clinical syndrome with features of new onset thrombocytopenia, increased lactate dehydrogenase, and multi‐organ failure in critically ill patients. TAMOF can be the initial presentation of an underlying disease process or can develop during the course of illness either during the hospital stay. TAMOF has a high mortality rate if not treated; therefore, early detection is critical. TAMOF has been rarely reported in diabetic ketoacidosis. We are describing the first case of a patient diagnosed with hyperglycemic, hyperosmolar non‐ketotic syndrome who developed TAMOF on the third day of his hospital course. In addition to supportive care in the intensive care unit the patient received serial therapeutic plasma exchanges and improved quickly after treatment. Early diagnosis and treatment of TAMOF decreases morbidity and mortality.