Handling of Drugs in Children with Abnormal Renal Function

Filler, Guido; Kirpalani, Amrit; Urquhart, Bradley L.

doi:10.1007/978-3-662-43596-0_83

Cited by 3 publications

(15 citation statements)

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“…We use creatininebased methods to estimate the glomerular filtration rate (GFR) for predicting drug clearance. However, drug dissipation occurs primarily through active secretion of acids and bases (mainly in the proximal tubule), and to a much lesser extent through glomerular filtration [2]. Cationic drugs are secreted into the urine through two main transporter molecules, human organic cation transporters and multidrug and toxin extrusion proteins [4].…”

Section: Introductionmentioning

confidence: 99%

“…Organic anion transporters (OATs) have been described, and they are remarkable for their broad substrate specificity and their ability to exchange extracellular against intracellular organic anions [5]. Several classes of drugs interact with human OAT1, OAT2, and OAT3, including (1) Changes in the integumentary development (2) Changes in the volume of distribution (newborns have the highest total body water volume) (3) Changes in gastrointestinal function, hydrochloric acid production, and bile acid excretion (4) Changes in the metabolic capacity of key enzymes (5) Acquisition of renal function.…”

Section: Introductionmentioning

confidence: 99%

“…Exposure to a variety of drugs that have not been studied carefully in this population and developmental changes of renal function are among the most important reasons. Sixty-one percent of drugs are excreted through the urine [2], therefore, the accurate assessment of renal function is critical. This is the age period where the developmental changes of kidney function are substantial, with renal function changing daily after delivery [3].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Assessment of glomerular filtration rate in the neonate

Filler

Guerrero-Kanan

Álvarez-Elías

2016

Current Opinion in Pediatrics

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Assessment of glomerular filtration rate in the neonate

Filler

Guerrero-Kanan

Álvarez-Elías

2016

Current Opinion in Pediatrics

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“…The main site for the renal handling of drugs is in the proximal tubules 1 . Many small molecule drugs are eliminated here, including antibiotics, antivirals, diuretics, nonsteroidal anti‐inflammatory drugs and important metabolites 1 . Cationic drugs are secreted into the urine through two main transporter molecules: human organic cation transporters and multidrug and toxin extrusion proteins 1,67 .…”

Section: Are Drugs Actually Cleared By Gfr?mentioning

confidence: 99%

“…Assessment of renal function is of critical importance since more than 60% of drugs are cleared by the kidneys 1 . In the first 18 months of life, renal function undergoes substantial changes.…”

Section: Introductionmentioning

confidence: 99%

How should we assess renal function in neonates and infants?

et al. 2020

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Aim Review of current knowledge on assessing renal function in term and preterm neonates. Methods Literature review and analysis of own data. Results Prematurity, genetic, environmental and maternal factors may alter peak nephron endowment and life‐long renal function. Nephrogenesis continues until 34‐36 weeks of gestation, but it is altered with premature delivery. Variability of nephron endowment has a substantial impact on the clearance of renally excreted drugs. Postnatally, glomerular function rate (GFR) increases daily, doubles by two weeks, and slowly reaches full maturity at 18 months of age. Ideally, renal function biomarkers should be expressed as age‐independent z‐scores, and evidence suggests indexing these values to post‐conceptual age rather than chronological age. Newborn and maternal serum creatinine correlate tightly for more than 72 hours after delivery, rendering this biomarker unsuitable for the assessment of neonatal renal function. Cystatin C does not cross the placenta and may be the preferred biomarker in the neonate. Here, we provide preliminary data on the natural evolution of the cystatin C eGFR in infancy. Conclusion Cystatin C may be superior for GFR estimation in neonates, but the best approach to drug dosing of renally excreted drugs remains to be established.

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Markers of Kidney Function in Early Childhood and Association With Maternal Comorbidity

et al. 2022

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ImportanceKidney functional capacity is low at birth but doubles during the first 2 weeks of life and reaches near-adult levels at age 1 to 2 years. Existing reference intervals for markers of kidney function in newborns are mostly based on preterm newborns, newborns with illness, or small cohorts of term newborns, and the consequences of maternal comorbidities for newborn kidney function are sparsely described.ObjectiveTo establish robust reference intervals for creatinine and urea in healthy children in early childhood and to assess whether maternal comorbidity is associated with newborn creatinine and urea concentrations.Design, Setting, and ParticipantsThis multicenter, prospective, population-based cohort study assessed data and umbilical cord blood samples from participants in the Copenhagen Baby Heart Study (CBHS) who were born between April 1, 2016, and October 31, 2018, and venous blood samples from a subsample of CBHS participants who were enrolled in the COMPARE study between May 3, 2017, and November 4, 2018. Cord blood samples of 13 354 newborns from the CBHS and corresponding venous blood samples of 444 of those newborns from the COMPARE study were included. Blood samples were collected at birth, age 2 months, and age 14 to 16 months, with follow-up completed on February 12, 2020. Healthy nonadmitted term newborns from maternity wards at 3 hospitals in the Capital Region of Denmark were included.ExposuresMaternal comorbidity.Main Outcomes and MeasuresCreatinine and urea concentrations.ResultsAmong 13 354 newborns in the CBHS cohort, characteristics of 12 938 children were stratified by sex and gestational age (GA). Of those, 6567 children (50.8%) were male; 5259 children (40.6%) were born at 37 to 39 weeks’ GA, and 7679 children (59.4%) were born at 40 to 42 weeks’ GA. Compared with children born at 40 to 42 weeks’ GA, those born at 37 to 39 weeks’ GA had lower birth weight, Apgar scores at 5 minutes, placental weight, and placental-fetal weight ratio. Children born at 37 to 39 weeks’ GA vs those born at 40 to 42 weeks’ GA were more frequently small for GA at birth and more likely to have placental insufficiency and exposure to maternal preeclampsia, maternal diabetes, maternal kidney disease, and maternal hypertension. Among children born at 37 to 39 weeks’ GA, reference intervals were 0.54 to 1.08 mg/dL for creatinine and 5.32 to 14.67 mg/dL for urea; among children born at 40 to 42 weeks’ GA, reference intervals were 0.57 to 1.19 mg/dL for creatinine and 5.60 to 14.85 mg/dL for urea. At birth, multifactorially adjusted odds ratios among children exposed to preeclampsia were 9.40 (95% CI, 1.68-52.54) for a venous creatinine concentration higher than the upper reference limit, 4.29 (95% CI, 1.32-13.93) for a venous creatinine concentration higher than the 90th percentile, and 3.10 (95% CI, 1.14-8.46) for a venous creatinine concentration higher than the 80th percentile.Conclusions and RelevanceIn this study, improved reference intervals for creatinine and urea concentrations were generated. Preeclampsia was associated with an increased risk of high newborn creatinine concentrations, suggesting that newborns of mothers with preeclampsia need closer observation of their kidney function.

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Handling of Drugs in Children with Abnormal Renal Function

Cited by 3 publications

References 87 publications

Assessment of glomerular filtration rate in the neonate

Assessment of glomerular filtration rate in the neonate

How should we assess renal function in neonates and infants?

Markers of Kidney Function in Early Childhood and Association With Maternal Comorbidity

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