Farahnak Assadi

Background: Hyponatremia remains a common and life‐threatening complication in children with traumatic brain injury, subarachnoid haemorrhage, brain tumours and post neurosurgical states, yet distinguishing its two primary neurogenic etiologies—syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral/renal salt wasting (C/RSW)—remains difficult. Misdiagnosis may result in inappropriate treatment strategies with a significant risk of morbidity. While adult studies suggest diagnostic roles for fractional excretion of uric acid (FEurate), fractional excretion of phosphate (PEphosphate) and NT‐proBNP level, no paediatric‐specific guidelines or reference thresholds currently exist. Objective: To evaluate the diagnostic accuracy of FEurate, FEphosphate and NT‐proBNP in distinguishing C/RSW from SIADH in hyponatremic children with neurologic conditions. Data Sources: A comprehensive literature search was performed across PubMed, Embase, Web of Science, Scopus and the Cochrane Library. Study Selection and Data Extraction: Eligible studies included RCTs, systematic reviews, meta‐analysis and prospective/retrospective studies involving paediatric patients diagnosed with SIADH or C/RSW using any of the three biomarkers. Systematic reviews were appraised using AMSTAR 2. Two reviewers independently assessed eligibility and extracted data. Results: Out of 69 identified studies, there were only two prospective paediatric cohort studies reported on the use of biomarkers in C/RSW versus SIADH syndromes. Limitation: Findings are limited by the absence of paediatric‐specific cut‐off values. Conclusions: Current evidence suggests that FEurate, FEphosphate and NT‐proBNP may provide diagnostic clues, but each biomarker has limitations related to assay variability, age‐dependent reference ranges, comorbidities and confounding medications. FEurate response to sodium correction appears most useful, though serial measurements are often required.

Background Probiotics have emerged as a promising therapeutic strategy for blood pressure control in hypertensive adult patients; however, the efficacy and safety of probiotics in childhood hypertension remain uncertain. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial in children with primary hypertension (HTN). Study endpoints included a reduction in absolute systolic or diastolic blood pressure of at least 3.0 mmHg and 2.0 mmHg, respectively, and the incidence of adverse events during the 4-month study period. Results Sixty-six patients were randomized to receive probiotics plus conventional drugs (study group, n = 33) or antihypertensive drugs alone (control group, n = 33) for 4 months. The study group (probiotics plus antihypertensive drugs, n = 33) and the control group (antihypertensive drugs alone, n = 33) had similar demographics, including age, sex, and body mass index. Most patients had stage-1 HTN (66%). The study group had a larger reduction in systolic and diastolic blood pressure (BP) compared to the control group. The mean change in systolic BP was -4.9 mmHg; 95% confidence interval [CI], − 6.96 to − 2.84 (study group) vs. -3.1 mmHg; 95% CI, − 4.12 to − 2.13 (control group), p = 0.02. For diastolic BP, it was -3.3 mmHg; 95% CI (-4.12 to -2.13) (study group) vs. -2.1 mmHg; 95% CI, -2.50 to -1.82, p = 0.04 (control group), p = 0.04. The reduction in BP was more significant in children with stage-1 HTN compared to those with stage-2 HTN. No serious adverse events (SAEs) were observed during the trial. Conclusions Probiotics combined with conventional antihypertensive drugs significantly reduced systolic and diastolic BP in children with primary HTN and have an acceptable safety profile. Trial Registration IRCT20200608047689N3, 07/14/2024, https://irct.behdasht.gov.ir. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

The spectrum of brain injury and the causative pathways in children with chronic kidney disease is largely unknown. We searched PubMed, Google Scholar, Embase, and Web of Science by combining synonyms of pediatric mild to moderate chronic kidney disease and brain lesions for the past 10 years. This resulted in 63 articles, of which 11 were finally included. The results from this study show that pediatric mild to moderate chronic kidney disease is associated with a variety of neurocognitive dysfunctions. Chronic kidney disease can experience a variety of neurologic disorders affecting the central nervous system and peripheral neuropathies. Clinical variables that can affect neurologic functioning include the severity and duration of chronic kidney disease, electrolytes, acid-base disequilibrium, hypertension, hypercoagulability, and underlying immunologic disturbances. Early diagnosis and proper management of these complications are essential for preventing long-term neurologic sequelae. Future studies are needed to understand the causative pathway better and establish whether preventive strategies and adequate management are beneficial.

The incidence and prevalence of genetic diseases associated with chronic kidney disease (CKD) have been increasing over the last decades. To identify the monogenic causes of kidney stone disorders linked to CKD, a comprehensive literature review was conducted to identify monogenic genes causing nephrolithiasis and CKD. Among 41 identifiable monogenic causes of nephrolithiasis the following diseases primary hyperoxaluria familial hypomagnesemia with hypercalciuria and nephrocalcinosis, cystinuria; Dent disease, adenine phosphoribosyltransferase deficiency, Lesch–Nyhan syndrome, and idiopathic Infantile hypercalciuria have been linked to CKD and may progress to end‐stage kidney disease (ESKD). Autosomal dominant hypocalcemia and Bartter syndrome (BS) are also hereditary kidney diseases that can cause urolithiasis but are rarely associated with CKD. A few BS type III can be complicated with CKD. A substantial number of kidney stone patients with genetic disorders progress to CKD. Genetic diagnosis should be initiated in all children presenting with kidney stones.

OBJECTIVE: Hyperuricemia is associated with the progression of chronic kidney disease (CKD). Whether urate-lowering treatment with allopurinol can delay disease progression remains controversial. METHODS: Relevant databases were searched. Randomized clinical trials comparing the efficacy and ­safety of allopurinol in patients with CKD were selected. The primary outcomes were changes in serum uric acid concentration and estimated glomerular filtration rate (eGFR). Random-effects modeling was used to ­calculate the standard mean difference (SMD) with 95% CIs. RESULTS: Four trials enrolling 698 participants were included. All were 2-arm parallel trials with a mean duration follow-up of 22.5 months. Congenital anomalies of the kidney and urinary tract were the most common cause of CKD in children, whereas diabetes was the leading cause of CKD in adults. Allopurinol significantly increased the eGFR compared with control groups (SMD, 2.04; 95% CI, 0.60–3.49; p = 0.005; I2 = 98.23%). Allopurinol led to a significant decrease in serum uric acid concentration compared with the control group (SMD, −5.16; 95% CI, −8.31 to −2.01; p = 0.001; I2 = 98.80%). No significant difference in adverse effects was identified between treatment and control groups. CONCLUSIONS: Allopurinol treatment in patients with CKD and hyperuricemia slows the decline in eGFR as compared with placebo, without risk of increased adverse effects.

Effective optimal pharmacotherapy requires a comprehensive understanding of the drug’s pharmacokinetic properties. Chronic kidney disease (CKD) influences medication pharmacokinetics. However, whether sex differences exist in the pharmacokinetics of drugs for children with CKD is unknown. The primary aim of this article was to evaluate the effect of sex on pharmacokinetics of drugs commonly used for CKD treatment in children. Secondary outcome was to address the impact of sex in CKD disease progression. Electronic databases, PubMed, EMBASE, Google Scholar, and Web of Science were searched from inception, using Mesh terms in English for sex differences in the pharmacokinetics of drugs in children with CKD. No studies have documented sex-related differences in the pharmacokinetics of drugs for the treatment of CKD in children. As a consequence, it is difficult to predict the effect of sex on pharmacokinetics by extrapolating data from adult studies to children. Evidence to date suggests that girls generally have a higher prevalence and disease progression of CKD when compared to boys regardless of age. Understanding the pharmacokinetics and pharmacodynamics of drugs provides practical consideration for dosing optimal medication regimens. Future kinetic studies are needed evaluating the effect of sex on the pharmacokinetics and pharmacodynamics of drugs in children with CKD.

Validity of the Adrogué-Madias formula for the management of acute dysnatremias in critically ill children: a prospective multicenter analysis. Objective: Current conventional formulas do not predict the expected changes in serum sodium after administration of various fluids to correct serum sodium abnormalities. The Adrogué-Madias formula is currently the preferred and widely used fluid prescription for adult patients with dysnatremias, but its therapeutic efficacy has not been validated in pediatric patients. Methods: In this prospective study, we used the Adrogué-Madias formula for calculating the appropriate rate of various fluids administration to correct serum sodium abnormalities in 7 critically ill children with acute dysnatremias. Results: After administration of various intravenous fluids using the Adrogué-Madias formula, the anticipated as well as the achieved sodium concentrations were almost similar. Conclusions: This study demonstrates that the use of the Adrogué-Madias quantitative formula allows to calculate the appropriate rate of administration of various fluids. The calculated fluid administration resulted in the subsequent actual laboratory values and clinical changes.