Randy Jenkins - Academia.edu (original) (raw)

Papers by Randy Jenkins

Research paper thumbnail of Phthalates cause a low-renin phenotype commonly found in premature infants with idiopathic neonatal hypertension

Research paper thumbnail of Transplantation von Spendernieren Erwachsener auf Kinder

Aktuelle Urologie, 1998

Die immunsuppressive Therapie richtete sich in sieben Fällen nach spenderspezifischen Transfusion... more Die immunsuppressive Therapie richtete sich in sieben Fällen nach spenderspezifischen Transfusionsprotokollen, bei elf Patienten erfolgte eine Cyclosporin-Induktionstherapie und eine Antilymphozytenantikörper-Induktionstherapie wurde in zwölf Fällen verwendet. Ergebnisse: Die 1-Jahres-und 5-Jahres-Transplantatüberlebensrate war 100%, respektive 50%, die 1-Jahres-und 5-Jahres-Patientenüberlebensrate war 100% und 94%. Eine chronische Abstoßung war für sieben der elf Transplantatverluste verantwortlich, bei vier Kindern waren Rezidive der prima n Nierenerkrankung ursächlich. Eine Todesfall war durch bronchopulmonale Dysplasie bedingt. Schlußfolgerungen: Spendernieren von Erwachsenen können mit guten Ergebnissen auf kleine Kinder transplantiert werden. Spezielle Probleme bei diesem Krankengut stellen sich wie folgt dar: Auf die geeignete Plazierung der verhältnismäßig großen Transplantate muß geachtet werden. Die hohe Kaliumkonzentration der Collins-Lösung ist vor der Gefäßanastomose durch Spülen des Transplantats zu verringern. Abdominale Katheter werden hinsichtlich der Desinfektion wie Haut behandelt. Der höheren Inzidenz von Harntraktanomalien ist Rechnung zu tragen. Der Gefäßbaum des Transplantats ist vor Fertigstellung der Gefäßanastomose zu füllen. Mit Wachstumsretardierung (kurze Statur) und krankhafter Übergewichtigkeit ist ebenso wie mit einem Rezidiv der fokal-segmentalen Glomerulosklerose und des hämolytisch-urämischen Syndroms zu rechnen. Es könnte eine sinnvolle Rolle für lebendspenderspezifische Transfusionsprotokolle geben, um die Kosten der Immunsuppression und Medikamentenspiegelüberwachung zu reduzieren. Transplantation of adult kidneys into small children: Materials and Methods: We transplanted thirty adult kidneys into children who weighed less than 20 kg between January 1 1983 and June 1, 1996. Twenty-six of the kidneys were from relatives and four were from cadaver donors. Immunosuppresion protocls were based on donor-specific transfusions in seven, cyclosporine induction in elven, and antilymphocyte antibody induction in twelve. Results: The one-and five-year kidney graft survival rates were 100% and 50%. The one-and five-year patient survival rates 100% and 94%. Chronic rejection was responsible for seven of the eleven kidney graft losses and four were due to recurrent primary renal disease. The one death was due to bronchopulmo

Research paper thumbnail of The changing spectrum of hypertension in premature infants

Journal of Perinatology, 2019

Objective The objective is to document changes in the etiologic spectrum of hypertension in prema... more Objective The objective is to document changes in the etiologic spectrum of hypertension in premature infants. Study design We reviewed all cases of systemic hypertension (HTN) in premature infants at two centers over 8 years. Infants were sorted into categorical groups as described in 2012 by Flynn. Analyses included frequency of diagnosis, timecourse of HTN, and diagnostics. Phthalate exposure via intravenous fluid and respiratory equipment was compared among groups and centers. Results One hundred and twenty-nine infants having 130 episodes of HTN met the inclusion criteria. Sixty-five percent of cases were classified as pulmonary and 16% as miscellaneous. Plasma renin activity (PRA) was undetectable or <11 ng/mL/h in almost all hypertensive infants. Cases categorized as Pulmonary, medications/intoxications, and miscellaneous presented near 40 weeks postmenstrual age, with low PRA and large phthalate exposures. Conclusions High PRA HTN has been replaced by low PRA in most cases, and may be due to phthalate exposure.

Research paper thumbnail of Pathology findings in pediatric patients with COVID-19 and kidney dysfunction

Research paper thumbnail of The extra-corporeal circuit: physical principles and monitoring

Critical Care Nephrology

The human kidney and continuous hemofiltration have some remarkable similarities in physical oper... more The human kidney and continuous hemofiltration have some remarkable similarities in physical operation. Both contain a conduit system leading blood to capillary membrane ultrafilters which produce plasma water. A parallel configuration of capillary membranes is found in both. The depurative ability of both is largely through ultrafiltration of large quantities of blood. This bulk removal of water and solute is convective in nature. Hemofiltration, unlike the kidney, has no resorptive (or secretory) ability, making replacement of certain substances necessary.

Research paper thumbnail of Elimination of Intravenous Di-2-Ethylhexyl Phthalate Exposure Abrogates Most Neonatal Hypertension in Premature Infants with Bronchopulmonary Dysplasia

Toxics

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Postoperative inappropriate secretion of antidiuretic hormone in children

International pediatrics, 1989

Research paper thumbnail of Reducing Toxic Phthalate Exposures in Premature Infants

Neonatal Intensive Care Unit [Working Title]

Phthalates are a ubiquitous group of industrial compounds used as industrial solvents and as addi... more Phthalates are a ubiquitous group of industrial compounds used as industrial solvents and as additives to plastics to make products softer avnd more flexible. Phthalates are found in a variety of products including medical devices, personal care products, flooring, and food packaging. Infants in the neonatal intensive care unit are exposed to phthalates both in the building materials, but more importantly in the medical supplies and devices. Toxicity from phthalates has been of concern to researchers for many decades. Toxicity concerns to neonates includes male reproductive toxicity, hepatotoxicity, cardiotoxicity (including hypertension), neurotoxicity, and neurodevelopmental abnormalities. Limited recommendations have been given for reducing phthalate exposures to premature infants. These include avoiding infusing lipids or blood products through intravenous tubing containing phthalates. Storage of blood in containers made with phthalates has been a strong recommendation and has l...

Research paper thumbnail of Phthalate Exposures in the Neonatal Intensive Care Unit

Toxics

Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may ... more Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may cause toxic effects in premature infants. In this study, the objective is to quantify DEHP exposures from various intravenous and respiratory therapy devices, and to use these values to predict typical exposure for an infant in a neonatal unit. Methods: Common IV products used on infants are directed through various types of IV tubing (IVT) and analyzed for DEHP content. DEHP exposure for infants receiving respiratory therapy was determined indirectly through analysis of urine DEHP metabolites. By deriving these values for DEHP we calculated the daily exposure to DEHP from common IV fluids (IVF) and respiratory devices during hospitalization in a neonatal unit. Results: IVF labeled DEHP-positive showed very high concentrations of DEHP, but when passed through IVT, substantial amounts were adsorbed. DEHP was undetectable with all DEHP-negative IVF tests, except when passed through DEHP-po...

Research paper thumbnail of BK Virus Infection With Alemtuzumab Induction in Pediatric Kidney Transplant Recipients. A Single Center Experience

Research paper thumbnail of Novel Use of Dried Blood Spots for Home Monitoring in Children After Kidney Transplanation

Research paper thumbnail of Severe Henoch-Shonlein Purpura Nephritis in Children: A Single Center Twelve Year Review

Biomedical Journal of Scientific & Technical Research

Research paper thumbnail of Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study

Pediatric Nephrology

Background Phthalates are associated with increased blood pressure in children. Large exposures t... more Background Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern. Methods We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11β-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index. Results Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures (p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants (p < 0.05). SBP index was related to DEHP exposure from IV fluid (p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index (p < 0.05). Sodium transporter/channel expression was also related to SBP index (p < 0.05). Conclusions Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11β-HSD2. Keywords Hypertension. Neonatal. Phthalates. Blood pressure Abbreviations DEHP Di-(2-ethylhexyl) phthalate PVC Polyvinyl chloride IV Intravenous NICU Newborn intensive care unit MR Mineralocorticoid receptor 11β-HSD2 11β-Hydroxysteroid dehydrogenase 2 AME Apparent mineralocorticoid excess MEHP Mono-(2-ethylhexyl) phthalate SBP Systolic blood pressure PMA Postmenstrual age PRA Plasma renin activity MEHHP Mono-(2-ethyl-5-hydroxyhexyl) phthalate MEOHP Mono-(2-ethyl-5-oxohexyl) phthalate ENaC Epithelial Na+ channel pNCC Phosphorylated (activated) Na+-Cl − cotransporter Electronic supplementary material The online version of this article (

Research paper thumbnail of Characteristics of hypertension in premature infants with and without chronic lung disease: a long-term multi-center study

Pediatric Nephrology

BackgroundMany causes for neonatal hypertension in premature infants have been described; however... more BackgroundMany causes for neonatal hypertension in premature infants have been described; however in some cases no etiology can be attributed. Our objectives are to describe such cases of unexplained hypertension and to compare hypertensive infants with and without chronic lung disease (CLD).MethodsWe reviewed all cases of hypertension in premature infants referred from 18 hospitals over 16 years. Inclusion criteria were hypertension occurring at <6 months of age and birth at <37 weeks gestation; the main exclusion criterion was known secondary hypertension. Continuous variables were compared using analysis of variance. Nominal variables were compared using chi-square tests.ResultsA total of 97 infants met the inclusion criteria, of whom 37 had CLD. Among these infants, hypertension presented at a mean of 11.3 ± 3.2 chronological weeks of age and a postmenstrual age of 39.6 ± 3.6 weeks. Diagnostic testing was notable for plasma renin activity (PRA) being <11 ng/mL/h in 98% of hypertensive infants. Spironolactone was effective monotherapy in 51 of 56 cases of hypertension. Hypertension resolved in all infants, with an average treatment duration of 25 weeks. Significant differences between the two groups of infants were a 0.4 kg lower birthweight and a 2.5 weeks younger gestational age at birth in those with CLD (p < 0.01, p < 0.01, respectively). Hypertension presented in those with CLD 1.8 weeks later, but at the same postmenstrual age as those without CLD (p < 0.01, p = 0.45, respectively).ConclusionPremature infants with unexplained hypertension, with and without CLD, presented at a postmenstrual age of 40 weeks with low PRA, transient time course, and a favorable response to spironolactone treatment.

Research paper thumbnail of Estimating Time to ESRD in Children With CKD

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2018

The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) ... more The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. Observational cohort study. Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m. eGFR was estimated using the CKiD-derived "bedside" equation. Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to a...

Research paper thumbnail of Causes of a Decreased Ultrafiltration Rate in CAVH

Seminars in Dialysis

ABSTRACT

Research paper thumbnail of Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease

Pediatric Nephrology

Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosp... more Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosphorus intake, dialysis, and treatment with oral phosphate binders, none of which were approved by the Federal Food and Drug Administration in pediatric patients at the time of this study. This was a phase 2, multicenter study (NCT01574326) with a 2-week, randomized, placebo-controlled, fixed-dose period (FDP) followed by a 6-month, single-arm, open-label, dose-titration period (DTP), with the aim to evaluate the safety and efficacy of sevelamer carbonate (SC) in hyperphosphatemic pediatric patients with CKD. Following a 2-4 week screening phase, pediatric patients with a serum phosphorus level higher than age-appropriate levels were randomized to receive either SC or placebo as powder/tablets in 0.4-1.6 g doses, based on body surface area. The primary efficacy outcome was the change in serum phosphorus from baseline to end of the FDP in the SC versus placebo arms (analysis of covariance). The secondary outcome was mean change in serum phosphorus from baseline to end of DTP by treatment group and overall. Treatment-emergent/serious adverse events (AEs) were recorded. Of 101 enrolled patients (29 centers), 66 completed the study. The majority of patients were adolescents (74%; mean age 14.1 years) and on dialysis (77%). Renal transplant was the main reason for discontinuation. SC significantly reduced serum phosphorus from baseline levels (7.16 mg/dL) during the FDP compared to placebo (least square mean difference - 0.90 mg/dL, p = 0.001) and during the DTP (- 1.18 mg/dL, p &amp;amp;amp;amp;amp;amp;lt; 0.0001). The safety and tolerability of SC and placebo were similar during the FDP, with patients in both groups reporting mild/moderate gastrointestinal AEs during the DTP. Sevelamer carbonate significantly lowered serum phosphorus levels in hyperphosphatemic children with CKD, with no serious safety concerns identified.

Research paper thumbnail of Effects of Access Catheter Dimensions on Bloodflow in Continuous Arteriovenous Hemofiltration1

Contributions to Nephrology, 1991

Research paper thumbnail of Continuous Renal Replacement in Infants and Toddlers

Contributions to Nephrology, 1991

Research paper thumbnail of Benefit of bicarbonate dialysis during CAVHD

ASAIO transactions / American Society for Artificial Internal Organs

The effect of bicarbonate dialysate (BD) on acid-base status in six pediatric CAVHD patients was ... more The effect of bicarbonate dialysate (BD) on acid-base status in six pediatric CAVHD patients was examined during seven episodes of metabolic acidosis. When metabolic acidosis was not corrected with CAVHD, a sterile BD was substituted for either acetate- or lactate-based dialysate. Pre- and post-BD substitution levels of lactate, HCO3, PCO2, anion gap, and pH were recorded, as well as dose of intravenous (i.v.) bicarbonate. Improvements in pH and serum HCO3 were seen in all seven cases. Anion gap decreased in all but one of the patients who were switched from lactate to bicarbonate dialysate, with improvement most marked in those patients with marked elevation of the anion gap. No adverse effect on PCO2 was noted. Lactate dialysate may be less effective when serum lactate levels are high, and may contribute to further elevation of lactate levels and anion gap. These data suggest that bicarbonate dialysate may be preferable to lactate or acetate dialysate in CAVHD patients with persis...

Research paper thumbnail of Phthalates cause a low-renin phenotype commonly found in premature infants with idiopathic neonatal hypertension

Research paper thumbnail of Transplantation von Spendernieren Erwachsener auf Kinder

Aktuelle Urologie, 1998

Die immunsuppressive Therapie richtete sich in sieben Fällen nach spenderspezifischen Transfusion... more Die immunsuppressive Therapie richtete sich in sieben Fällen nach spenderspezifischen Transfusionsprotokollen, bei elf Patienten erfolgte eine Cyclosporin-Induktionstherapie und eine Antilymphozytenantikörper-Induktionstherapie wurde in zwölf Fällen verwendet. Ergebnisse: Die 1-Jahres-und 5-Jahres-Transplantatüberlebensrate war 100%, respektive 50%, die 1-Jahres-und 5-Jahres-Patientenüberlebensrate war 100% und 94%. Eine chronische Abstoßung war für sieben der elf Transplantatverluste verantwortlich, bei vier Kindern waren Rezidive der prima n Nierenerkrankung ursächlich. Eine Todesfall war durch bronchopulmonale Dysplasie bedingt. Schlußfolgerungen: Spendernieren von Erwachsenen können mit guten Ergebnissen auf kleine Kinder transplantiert werden. Spezielle Probleme bei diesem Krankengut stellen sich wie folgt dar: Auf die geeignete Plazierung der verhältnismäßig großen Transplantate muß geachtet werden. Die hohe Kaliumkonzentration der Collins-Lösung ist vor der Gefäßanastomose durch Spülen des Transplantats zu verringern. Abdominale Katheter werden hinsichtlich der Desinfektion wie Haut behandelt. Der höheren Inzidenz von Harntraktanomalien ist Rechnung zu tragen. Der Gefäßbaum des Transplantats ist vor Fertigstellung der Gefäßanastomose zu füllen. Mit Wachstumsretardierung (kurze Statur) und krankhafter Übergewichtigkeit ist ebenso wie mit einem Rezidiv der fokal-segmentalen Glomerulosklerose und des hämolytisch-urämischen Syndroms zu rechnen. Es könnte eine sinnvolle Rolle für lebendspenderspezifische Transfusionsprotokolle geben, um die Kosten der Immunsuppression und Medikamentenspiegelüberwachung zu reduzieren. Transplantation of adult kidneys into small children: Materials and Methods: We transplanted thirty adult kidneys into children who weighed less than 20 kg between January 1 1983 and June 1, 1996. Twenty-six of the kidneys were from relatives and four were from cadaver donors. Immunosuppresion protocls were based on donor-specific transfusions in seven, cyclosporine induction in elven, and antilymphocyte antibody induction in twelve. Results: The one-and five-year kidney graft survival rates were 100% and 50%. The one-and five-year patient survival rates 100% and 94%. Chronic rejection was responsible for seven of the eleven kidney graft losses and four were due to recurrent primary renal disease. The one death was due to bronchopulmo

Research paper thumbnail of The changing spectrum of hypertension in premature infants

Journal of Perinatology, 2019

Objective The objective is to document changes in the etiologic spectrum of hypertension in prema... more Objective The objective is to document changes in the etiologic spectrum of hypertension in premature infants. Study design We reviewed all cases of systemic hypertension (HTN) in premature infants at two centers over 8 years. Infants were sorted into categorical groups as described in 2012 by Flynn. Analyses included frequency of diagnosis, timecourse of HTN, and diagnostics. Phthalate exposure via intravenous fluid and respiratory equipment was compared among groups and centers. Results One hundred and twenty-nine infants having 130 episodes of HTN met the inclusion criteria. Sixty-five percent of cases were classified as pulmonary and 16% as miscellaneous. Plasma renin activity (PRA) was undetectable or <11 ng/mL/h in almost all hypertensive infants. Cases categorized as Pulmonary, medications/intoxications, and miscellaneous presented near 40 weeks postmenstrual age, with low PRA and large phthalate exposures. Conclusions High PRA HTN has been replaced by low PRA in most cases, and may be due to phthalate exposure.

Research paper thumbnail of Pathology findings in pediatric patients with COVID-19 and kidney dysfunction

Research paper thumbnail of The extra-corporeal circuit: physical principles and monitoring

Critical Care Nephrology

The human kidney and continuous hemofiltration have some remarkable similarities in physical oper... more The human kidney and continuous hemofiltration have some remarkable similarities in physical operation. Both contain a conduit system leading blood to capillary membrane ultrafilters which produce plasma water. A parallel configuration of capillary membranes is found in both. The depurative ability of both is largely through ultrafiltration of large quantities of blood. This bulk removal of water and solute is convective in nature. Hemofiltration, unlike the kidney, has no resorptive (or secretory) ability, making replacement of certain substances necessary.

Research paper thumbnail of Elimination of Intravenous Di-2-Ethylhexyl Phthalate Exposure Abrogates Most Neonatal Hypertension in Premature Infants with Bronchopulmonary Dysplasia

Toxics

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Postoperative inappropriate secretion of antidiuretic hormone in children

International pediatrics, 1989

Research paper thumbnail of Reducing Toxic Phthalate Exposures in Premature Infants

Neonatal Intensive Care Unit [Working Title]

Phthalates are a ubiquitous group of industrial compounds used as industrial solvents and as addi... more Phthalates are a ubiquitous group of industrial compounds used as industrial solvents and as additives to plastics to make products softer avnd more flexible. Phthalates are found in a variety of products including medical devices, personal care products, flooring, and food packaging. Infants in the neonatal intensive care unit are exposed to phthalates both in the building materials, but more importantly in the medical supplies and devices. Toxicity from phthalates has been of concern to researchers for many decades. Toxicity concerns to neonates includes male reproductive toxicity, hepatotoxicity, cardiotoxicity (including hypertension), neurotoxicity, and neurodevelopmental abnormalities. Limited recommendations have been given for reducing phthalate exposures to premature infants. These include avoiding infusing lipids or blood products through intravenous tubing containing phthalates. Storage of blood in containers made with phthalates has been a strong recommendation and has l...

Research paper thumbnail of Phthalate Exposures in the Neonatal Intensive Care Unit

Toxics

Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may ... more Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may cause toxic effects in premature infants. In this study, the objective is to quantify DEHP exposures from various intravenous and respiratory therapy devices, and to use these values to predict typical exposure for an infant in a neonatal unit. Methods: Common IV products used on infants are directed through various types of IV tubing (IVT) and analyzed for DEHP content. DEHP exposure for infants receiving respiratory therapy was determined indirectly through analysis of urine DEHP metabolites. By deriving these values for DEHP we calculated the daily exposure to DEHP from common IV fluids (IVF) and respiratory devices during hospitalization in a neonatal unit. Results: IVF labeled DEHP-positive showed very high concentrations of DEHP, but when passed through IVT, substantial amounts were adsorbed. DEHP was undetectable with all DEHP-negative IVF tests, except when passed through DEHP-po...

Research paper thumbnail of BK Virus Infection With Alemtuzumab Induction in Pediatric Kidney Transplant Recipients. A Single Center Experience

Research paper thumbnail of Novel Use of Dried Blood Spots for Home Monitoring in Children After Kidney Transplanation

Research paper thumbnail of Severe Henoch-Shonlein Purpura Nephritis in Children: A Single Center Twelve Year Review

Biomedical Journal of Scientific & Technical Research

Research paper thumbnail of Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study

Pediatric Nephrology

Background Phthalates are associated with increased blood pressure in children. Large exposures t... more Background Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern. Methods We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11β-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index. Results Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures (p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants (p < 0.05). SBP index was related to DEHP exposure from IV fluid (p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index (p < 0.05). Sodium transporter/channel expression was also related to SBP index (p < 0.05). Conclusions Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11β-HSD2. Keywords Hypertension. Neonatal. Phthalates. Blood pressure Abbreviations DEHP Di-(2-ethylhexyl) phthalate PVC Polyvinyl chloride IV Intravenous NICU Newborn intensive care unit MR Mineralocorticoid receptor 11β-HSD2 11β-Hydroxysteroid dehydrogenase 2 AME Apparent mineralocorticoid excess MEHP Mono-(2-ethylhexyl) phthalate SBP Systolic blood pressure PMA Postmenstrual age PRA Plasma renin activity MEHHP Mono-(2-ethyl-5-hydroxyhexyl) phthalate MEOHP Mono-(2-ethyl-5-oxohexyl) phthalate ENaC Epithelial Na+ channel pNCC Phosphorylated (activated) Na+-Cl − cotransporter Electronic supplementary material The online version of this article (

Research paper thumbnail of Characteristics of hypertension in premature infants with and without chronic lung disease: a long-term multi-center study

Pediatric Nephrology

BackgroundMany causes for neonatal hypertension in premature infants have been described; however... more BackgroundMany causes for neonatal hypertension in premature infants have been described; however in some cases no etiology can be attributed. Our objectives are to describe such cases of unexplained hypertension and to compare hypertensive infants with and without chronic lung disease (CLD).MethodsWe reviewed all cases of hypertension in premature infants referred from 18 hospitals over 16 years. Inclusion criteria were hypertension occurring at <6 months of age and birth at <37 weeks gestation; the main exclusion criterion was known secondary hypertension. Continuous variables were compared using analysis of variance. Nominal variables were compared using chi-square tests.ResultsA total of 97 infants met the inclusion criteria, of whom 37 had CLD. Among these infants, hypertension presented at a mean of 11.3 ± 3.2 chronological weeks of age and a postmenstrual age of 39.6 ± 3.6 weeks. Diagnostic testing was notable for plasma renin activity (PRA) being <11 ng/mL/h in 98% of hypertensive infants. Spironolactone was effective monotherapy in 51 of 56 cases of hypertension. Hypertension resolved in all infants, with an average treatment duration of 25 weeks. Significant differences between the two groups of infants were a 0.4 kg lower birthweight and a 2.5 weeks younger gestational age at birth in those with CLD (p < 0.01, p < 0.01, respectively). Hypertension presented in those with CLD 1.8 weeks later, but at the same postmenstrual age as those without CLD (p < 0.01, p = 0.45, respectively).ConclusionPremature infants with unexplained hypertension, with and without CLD, presented at a postmenstrual age of 40 weeks with low PRA, transient time course, and a favorable response to spironolactone treatment.

Research paper thumbnail of Estimating Time to ESRD in Children With CKD

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2018

The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) ... more The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. Observational cohort study. Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m. eGFR was estimated using the CKiD-derived "bedside" equation. Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to a...

Research paper thumbnail of Causes of a Decreased Ultrafiltration Rate in CAVH

Seminars in Dialysis

ABSTRACT

Research paper thumbnail of Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease

Pediatric Nephrology

Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosp... more Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosphorus intake, dialysis, and treatment with oral phosphate binders, none of which were approved by the Federal Food and Drug Administration in pediatric patients at the time of this study. This was a phase 2, multicenter study (NCT01574326) with a 2-week, randomized, placebo-controlled, fixed-dose period (FDP) followed by a 6-month, single-arm, open-label, dose-titration period (DTP), with the aim to evaluate the safety and efficacy of sevelamer carbonate (SC) in hyperphosphatemic pediatric patients with CKD. Following a 2-4 week screening phase, pediatric patients with a serum phosphorus level higher than age-appropriate levels were randomized to receive either SC or placebo as powder/tablets in 0.4-1.6 g doses, based on body surface area. The primary efficacy outcome was the change in serum phosphorus from baseline to end of the FDP in the SC versus placebo arms (analysis of covariance). The secondary outcome was mean change in serum phosphorus from baseline to end of DTP by treatment group and overall. Treatment-emergent/serious adverse events (AEs) were recorded. Of 101 enrolled patients (29 centers), 66 completed the study. The majority of patients were adolescents (74%; mean age 14.1 years) and on dialysis (77%). Renal transplant was the main reason for discontinuation. SC significantly reduced serum phosphorus from baseline levels (7.16 mg/dL) during the FDP compared to placebo (least square mean difference - 0.90 mg/dL, p = 0.001) and during the DTP (- 1.18 mg/dL, p &amp;amp;amp;amp;amp;amp;lt; 0.0001). The safety and tolerability of SC and placebo were similar during the FDP, with patients in both groups reporting mild/moderate gastrointestinal AEs during the DTP. Sevelamer carbonate significantly lowered serum phosphorus levels in hyperphosphatemic children with CKD, with no serious safety concerns identified.

Research paper thumbnail of Effects of Access Catheter Dimensions on Bloodflow in Continuous Arteriovenous Hemofiltration1

Contributions to Nephrology, 1991

Research paper thumbnail of Continuous Renal Replacement in Infants and Toddlers

Contributions to Nephrology, 1991

Research paper thumbnail of Benefit of bicarbonate dialysis during CAVHD

ASAIO transactions / American Society for Artificial Internal Organs

The effect of bicarbonate dialysate (BD) on acid-base status in six pediatric CAVHD patients was ... more The effect of bicarbonate dialysate (BD) on acid-base status in six pediatric CAVHD patients was examined during seven episodes of metabolic acidosis. When metabolic acidosis was not corrected with CAVHD, a sterile BD was substituted for either acetate- or lactate-based dialysate. Pre- and post-BD substitution levels of lactate, HCO3, PCO2, anion gap, and pH were recorded, as well as dose of intravenous (i.v.) bicarbonate. Improvements in pH and serum HCO3 were seen in all seven cases. Anion gap decreased in all but one of the patients who were switched from lactate to bicarbonate dialysate, with improvement most marked in those patients with marked elevation of the anion gap. No adverse effect on PCO2 was noted. Lactate dialysate may be less effective when serum lactate levels are high, and may contribute to further elevation of lactate levels and anion gap. These data suggest that bicarbonate dialysate may be preferable to lactate or acetate dialysate in CAVHD patients with persis...