ABSTRACT:In contrast to acute dehydration, which is usually recognized through identifiable risk factors, clinical signs, and laboratory abnormalities, chronic dehydration develops insidiously and frequently goes unrecognized. This is particularly true in older adults, among whom many of its nonspecific manifestations-such as weakness, constipation, headache, dizziness, gait instability, and confusion-are often mistakenly attributed to normal aging. This population is especially vulnerable to chronic dehydration because of age-related normal physiological changes, compounded by physical, cognitive, psychological, climate and other environmental influences. Inadequate hydration is associated with impairments in physical, cognitive, and emotional functioning, reduced alertness, and diminishes exercise tolerance. It may also alter drug pharmacokinetics and pharmacodynamics, increasing the risk of medication-related adverse events. Emerging evidence suggests that chronic dehydration contributes to neurocognitive decline and the progression of some chronic diseases, while increasing susceptibility to acute fluid deficits associated with substantial morbidity and mortality. Because its presentation is often subtle and nonspecific, recognizing chronic dehydration in older adults, including those who are otherwise healthy, requires a high index of suspicion. Greater awareness is essential for prevention, early detection, and management of chronic dehydration in this vulnerable population.

BACKGROUND:About 90% of cases with idiopathic nephrotic syndrome (NS) respond to corticosteroids. The remaining 10%, classified as steroid-resistant nephrotic syndrome (SRNS), typically undergo a kidney biopsy before receiving additional immunosuppression. This study examined the extent to which kidney biopsy findings influenced management in children and young adults with newly diagnosed idiopathic SRNS. METHODS:We conducted a retrospective chart review of patients aged 1-21 years and diagnosed with SRNS at the Detroit Medical Center from January 2000 to December 2024. Exclusion criteria were patients with syndromic diagnoses and presentation with gross hematuria, hypertension, or identifiable systemic disease. RESULTS:The study included 55 patients, 46 underwent kidney biopsy after the diagnosis of SRNS (mean age 10.9 ± 4.6 years), and 9 had elective biopsies based on age before being diagnosed with SRNS (mean age 16 ± 1.7 years). Biopsy diagnoses included focal segmental glomerulosclerosis (72%), minimal change disease (24%), and membranous nephropathy (4%). Sixty-five percent of cases had mild to moderate interstitial fibrosis/tubular atrophy. Most patients (84%) were admitted overnight, 71% had flank or back pain, and 15% had a hematoma. Post-biopsy, 96% of patients received calcineurin inhibitors (CNIs): cyclosporine (n = 38) or tacrolimus (n = 15). At one year, 96% remained on CNIs. CONCLUSIONS:Kidney biopsy did not significantly alter immunosuppressive management in newly diagnosed patients with SRNS at our center. Larger multicenter studies are needed to confirm these findings and evaluate whether more selective biopsy criteria could spare patients from a potentially avoidable invasive procedure, improve clinical management, and reduce healthcare costs.

Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) are disorders of podocytes in the slit diaphragm. CNS manifests during the first three months of life, and INS between 3–12 months, with severe proteinuria due to mutations in the NPHS1 and NPHS2 genes. This study aimed to establish specific genotype-phenotype characteristics of CNS and INS in the North American population. Eleven Pediatric Nephrology Research Consortium (PNRC) sites retrospectively reviewed charts of 36 patients born between 1998–2019 who had CNS or INS and underwent genetic testing. The genetic database confirmed the variant’s pathogenicity. NPHS1 mutations were more frequently seen in CNS patients, while variant mutations in the WT1 and NPHS2 genes were more common in the INS group. Like c.2335-1 G > A splice mutation, the frequent compound heterozygous mutations of the NPHS1 gene were associated with more severe proteinuria (112.4 ± 135.6 vs. 53.9 ± 57.3). Additionally, NPHS1/WT1 and NPHS1/NPHS2 digenic inheritance featuring biallelic or tri-allelic hits were associated with patient transplantation, regardless of the disease onset. Identification of compound heterozygous mutations in the NPHS1 gene as an indicator of an aggressive course of CNS in infants. This finding could lead to earlier and targeted interventions of patients, through a precision therapeutic approach

Primary vesicoureteral reflux (VUR) is one of the most common urological abnormalities in infants and children. The association of VUR, urinary tract infection (UTI) and renal parenchymal damage is well established. The most serious complications of VUR-associated reflux nephropathy are hypertension and proteinuria with chronic kidney disease. Over the past two decades, our understanding of the natural history of VUR has improved, which has helped to identify patients at increased risk of both VUR and VUR-associated renal injury. The main goals in the treatment of paediatric patients with VUR are the prevention of recurrent UTIs and minimizing the risk of renal scarring and long-term renal impairment. Currently, there are four options for managing primary VUR in infants and children: surveillance or intermittent treatment of UTIs with management of bladder and bowel dysfunction; continuous antibiotic prophylaxis; endoscopic subureteral injection of tissue-augmenting substances; and ureteral reimplantation via open, laparoscopic or robotic-assisted surgery. Current debates regarding key aspects of management include when to perform diagnostic imaging and how to best identify the paediatric patients that will benefit from continuous antibiotic prophylaxis or surgical intervention, including endoscopic injection therapy and minimally invasive ureteral reimplantation. Evolving technologies, such as artificial intelligence, have the potential to assist clinicians in the decision-making process and in the individualization of diagnostic imaging and treatment of infants and children with VUR in the future.

A prompt diagnosis of urinary tract infection (UTI) is necessary to minimize its symptoms and limit sequelae. The current UTI screening by urine test strip analysis and microscopic examination has suboptimal diagnostic accuracy. A definitive diagnosis of UTI by urine culture takes two to three days for the results. These limitations necessitate a need for better biomarkers for the diagnosis and subsequent management of UTI in children. Here, we review the value of currently available UTI biomarkers and highlight the potential of emerging biomarkers that can facilitate a more rapid and accurate UTI diagnosis. Of the newer UTI biomarkers, the most promising are blood procalcitonin (PCT) and urinary neutrophil gelatinase-associated lipocalin (NGAL). PCT can provide diagnostic benefits and should be considered in patients who have a blood test for other reasons. NGAL, which is on the threshold of clinical care, needs more research to address its scope and utilization, including point-of-care application. Employment of these and other biomarkers may ultimately improve UTI diagnosis, guide UTI therapy, reduce antibiotic use, and mitigate UTI complications.

BACKGROUND:The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS:In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS:A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS:In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).

The use of continuous antibiotic prophylaxis in the prevention of urinary tract infection (UTI), particularly in children with vesicoureteral reflux, has been studied extensively during the past 15 years. Double-blind, placebo-controlled trials such as the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial and the Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) trial showed that continuous antibiotic prophylaxis significantly reduced the risk of UTI among children with vesicoureteral reflux.(1,2) However, other randomized trials showed either no beneficial effect(3-7) or a beneficial effect that was limited to female patients.(8) These variations . . .

Background: Various methods, including bioelectrical impedance analysis (BIA), are used for total body water (TBW) estimation. The objective of our study by BIA was to develop a new predication model based on corrected TBW for normal adult BMI, a concept similar to the standardization of glomerular filtration rate by relating it to the average adult body surface area. Method: We measured TBW by BIA in 335 children 3-21 years old with normal or excessive body weight. Based on our data, we derived a new prediction model for TBW (L) for females {[(72.784 + 0.4093 x weight)*Corrected TBW]/100} and males {[(57.944 + 0.6551 x weight)*Corrected TBW]/100}. For validation, we compared our prediction model with three other models on TBW by BIA and dilution methods. Results: Our model's error size to predict TBW showed lower cross-validated root mean square error (CV-RMSE) as compared to three other models versus our dataset by BIA and two other datasets by dilution methods. Our model also showed a smaller error (2.059) in CV-RMSE as compared to other models by dilution methods (2.126, 2.873, and 4.384) for normal and excessive weight combined. This implies that our model is more robust when excessive weight individuals are included in the data.. Conclusion: Our prediction model for TBW estimation by BIA performs better as compared to some other models based on BIA and dilution method datasets. Furthermore, our prediction model is the only one that is devised to be applicable to children and young adults with both normal as well as excessive weight. (c) 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Background Total body water (TBW) increases with growth, but the body water percentage (TBW%) decreases with aging. The objective of our study was to delineate TBW% in males and females by bioelectrical impedance analysis (BIA) from early childhood to old age. Methods We enrolled 545 participants aged 3 to 98 years (258 male, 287 female). Among the participants, 256 had a normal weight and 289 were overweight. The TBW was measured by BIA, and TBW% was derived by dividing the TBW (L) value by body weight (kg). For analysis, we divided participants into the four age groups of 3–10, 11–20, 21–60, and ≥61 years. Results In normal-weight subjects, the TBW% was similar at 62% between males and females in the 3–10-year group. It remained unchanged in males until and through adult life, then decreased to 57% in the ≥61-year group. In normal-weight female subjects, the TBW% decreased to 55% in the 11–20-year group, remained relatively unaltered in the 21–60-year group, then decreased to 50% in the ≥61-year group. In overweight subjects, the TBW% values in males, as well as females, were significantly lower as compared to those with normal weight. Conclusion Our study showed that the TBW% in normal-weight males changes very little from early childhood to adult life compared to that of females, who showed a decrease in TBW% during the pubertal years. In normal-weight subjects of both sexes, the TBW% decreased after the age of 60 years. Overweight subjects had significantly lower TBW% as compared to those with normal weight.

Congenital anomalies of kidney and the urinary tract constitute the commonest cause of chronic kidney disease (CKD) in children. The incidence and prevalence of CKD in children is underreported because of lack of symptoms in initial stages of the disease, though increased use of antenatal ultrasonography is helping diagnose more patients before they become symptomatic. Growth failure in pre-pubertal children with CKD is a common complication. Nutritional management is, therefore, critically important and this often involves gavage feeding in younger children. Those with persistent growth failure also need recombinant growth hormone administration. Long-term renal replacement therapy for end-stage kidney disease (ESKD) is possible even in babies and infants. Kidney transplantation significantly improves the life expectancy of ESKD patents. A multidisciplinary team that includes psychosocial support is essential for the management of children with advanced CKD.

The aim of this study was to evaluate the physico-chemical stability of compounded total parenteral nutrition admixtures through peroxidation assay and ultraviolet-visible spectroscopy, high-performance liquid chromatography analysis, nuclear magnetic resonance spectrometry, pH meter, and dynamic light scattering.The present study considered parenteral nutrition (PN) admixtures for pediatric and adult patients. The admixtures were characterized by a high content of vitamins and trace elements. They were prepared in one- or two-chamber bags in the hospital pharmacy using an automatic compounding system in a sterile room with laminar airflow at different temperature conditions and light exposure. The experiment setup comprised fat emulsions, lipid-free PN solutions, and single-chamber bags before and after adding vitamins and trace elements. The stability at room temperature (+25°C) and cold temperature (+2–8°C) was assessed by various means.Two-compartment admixtures, single-chamber bags, and all-in-one PN supplemented with vitamins and trace elements are stable up until 35, 9, and 7 d, respectively, when protected from light and stored at +2 to 8°C. Also, the supplemented single-chamber PN was found to be stable up to 48 h when stored at +25°C with light exposure.The results obtained will help improve PN management at the compounding center and in hospital wards, because they allow for the extension of the validity time frame provided so far by the different formulations and, therefore, therapy scheduling over several days.

BackgroundThe duration of initial corticosteroid therapy in newly diagnosed Idiopathic nephrotic syndrome (INS) is about 3 months. Our study was designed to test the feasibility of a shorter duration of corticosteroid therapy in newly diagnosed INS who show a quicker response.MethodsPatients who responded within 10 days (Group A) received 8 weeks of corticosteroid therapy as compared to 12–14 weeks of standard therapy in those who responded between >10 days to 28 days (Group B), and follow up for 52 weeks. The primary endpoint is time to first relapse after treatment completion. (NCT03878914, March 18, 2019)ResultsA total of 33 children with INS were enrolled and the follow-up data were analyzed. The clinical and laboratory characteristics of patients in both groups were similar. No significant difference was found in time to first relapse [65(14.5, 159) days for Group A vs. 28(17, 61.5) days for Group B, P = 0.371], the incidence of frequently relapsing nephrotic syndrome [6/18 (33.3%) vs. 5/10(50%), P = 0.644] or requirement for alternative immunosuppressant [4/18 (22.2%) vs. 1/10 (10%), P = 0.769]. Group A received similar corticosteroid dose compare with Group B (3511 ± 2421 mg/m2 vs. 4117 ± 2556 mg/m2, P = 0.524). Frequency and severity of corticosteroid-related complications was similar in both groups.ConclusionsThe time to first relapse and the number of relapses per patient were comparable between the two groups. However, more patients in Group A relapsed and the mean total dose of prednisolone for the study period was very similar between the two groups.

A state-of-the art review of current literature on UTI in children, with a particular focus on its diagnosis and management by general pediatricians. Urinary tract infection (UTI) is common in children, and girls are at a significantly higher risk, as compared to boys, except in early infancy. Most cases are caused by Escherichia coli. Collection of an uncontaminated urine specimen is essential for accurate diagnosis. Oral antibiotic therapy for 7 to 10 days is adequate for uncomplicated cases that respond well to the treatment. A renal ultrasound examination is advised in all young children with first febrile UTI and in older children with recurrent UTI. Most children with first febrile UTI do not need a voiding cystourethrogram; it may be considered after the first UTI in children with abnormal renal and bladder ultrasound examination or a UTI caused by atypical pathogen, complex clinical course, or known renal scarring. Long-term antibiotic prophylaxis is used selectively in high-risk patients. Few patients diagnosed with vesicoureteral reflux after a UTI need surgical correction. The most consequential long-term complication of acute pyelonephritis is renal scarring, which may increase the risk of hypertension or chronic kidney disease later in life. Treatment of acute pyelonephritis with an appropriate antibiotic within 48 hours of fever onset and prevention of recurrent UTI lowers the risk of renal scarring. Pathogens causing UTI are increasingly becoming resistant to commonly used antibiotics, and their indiscriminate use in doubtful cases of UTI must be discouraged.

Primary hypertension in children is not as common as in adults; recent studies suggest a prevalence of 3–4 % in the pediatric population. However, more recent reports have highlighted an increasing prevalence of HTN and prehypertension, likely due to childhood obesity. Given the global burden of hypertension, identification and management of primary HTN is beneficial to the individual child and has important implications for society as well, particularly since tracking studies have established that adult primary HTN has its antecedents during childhood. Studies are limited on the pathophysiology of primary HTN in children; however, evidence suggests that the proposed multifactorial and complex genetic, environmental, and biological interactions involved in the development of hypertension in adults provide a basis to understand HTN in children as well. Primary HTN in young children is a diagnosis of exclusion, and selective workup is needed to rule out any underlying secondary causes; however, in adolescents, primary hypertension is much more common than secondary hypertension. Early identification and management of elevated BP in the pediatric population is important to decrease the risks for end-organ injury in both the pediatric and adult population.

Nephrotic syndrome in children is mostly idiopathic in origin. About 90% of patients respond to corticosteroids; 80-90% have at least one relapse and 3-10% become corticosteroid resistant after the initial response. A kidney biopsy is seldom indicated for diagnosis except in patients with atypical presentation or corticosteroid resistance. For those in remission, the risk of relapse is reduced by the administration of daily low dose corticosteroids for 5-7 days at the onset of an upper respiratory infection. Some patients may continue having relapses through adult life. Many country-specific practice guidelines have been published, which are very similar with clinically insignificant differences.