Diuretics are a cornerstone of supportive therapy in pediatric patients, widely used for the management of edema, fluid overload, hypertension, and various other kidney diseases. Their clinical utility, however, is stron...Diuretics are a cornerstone of supportive therapy in pediatric patients, widely used for the management of edema, fluid overload, hypertension, and various other kidney diseases. Their clinical utility, however, is strongly influenced by developmental differences in kidney physiology, age-related pharmacokinetics, underlying kidney disease, and the risk of adverse effects unique to children. This review presents an extensive, evidence-informed synthesis of diuretic therapy in pediatric kidney disorders, encompassing pharmacology, mechanisms of action, indications, drug interactions, and safety considerations. We review the role of diuretics across common conditions in pediatric nephrology, including nephrotic syndrome, chronic kidney disease, acute kidney injury, hypertension, hypercalcemia, hypercalciuria, and nephrogenic diabetes insipidus. Special populations, including neonates and adolescents, are discussed, highlighting developmental pharmacology, vulnerability to toxicity, and long-term growth and bone health concerns. The review also summarizes emerging data on newer diuretic therapies, including sodium-glucose cotransporter-2 inhibitors, vasopressin receptor antagonists, and non-steroidal mineralocorticoid receptor antagonists, while emphasizing the current limitations of pediatric evidence. Adverse effects, including electrolyte disturbances, nephrocalcinosis, ototoxicity, and metabolic complications, are systematically addressed with practical monitoring recommendations. Overall, this review underscores that diuretics in children should be used judiciously, individualized to age and kidney function, closely monitored for potential harm, and integrated with definitive disease-modifying therapies to optimize outcomes in pediatric kidney care.
BACKGROUND: To estimate the association of hypertensive disorders of pregnancy (HDP) with offspring kidney function in adolescence and young adulthood in individuals born preterm with very low birth weight. METHODS: Seco...BACKGROUND: To estimate the association of hypertensive disorders of pregnancy (HDP) with offspring kidney function in adolescence and young adulthood in individuals born preterm with very low birth weight. METHODS: Secondary analysis of data from a prospective cohort study of individuals born preterm with very low or extremely low birth weight (< 1500 g). The 213 participants were assessed at 14-15 and 19-23 years of age. Outcomes were estimated glomerular filtration rate (eGFR) and first-morning urine albumin-to-creatinine ratio (ACR). We estimated the relationships with multivariable generalized linear models informed by directed acyclic graphs. Causal mediation analysis was also performed to evaluate if adolescent kidney function indirectly mediated the effect of HDP on young adulthood kidney function. RESULTS: Thirty-seven percent (n = 79) were exposed to HDP. Kidney function in adolescence was associated with kidney function in young adulthood (eGFR adjusted β 0.48 mL/min/1.73 m, 95% CL 0.21-0.75; ACR adjusted β 0.19 mg/g, 95% CL 0.15-0.24). There was no significant association between HDP and kidney function in both adolescence and young adulthood. There was also no statistically significant causal mediation effect of HDP on young adulthood kidney function indirectly through adolescent kidney function. CONCLUSIONS: We found no significant association between HDP and offspring kidney function in adolescence and young adulthood and no evidence of mediation through adolescent kidney function. Next steps in this research may look to investigate the relationship of severity of prematurity on offspring kidney function, as HDPs are a factor in premature births and the degree of prematurity.
OBJECTIVE: To systematically evaluate the efficacy and safety of first-line therapies and first-line-based combination therapies for treating monosymptomatic nocturnal enuresis (MNE) in children using a network meta-anal...OBJECTIVE: To systematically evaluate the efficacy and safety of first-line therapies and first-line-based combination therapies for treating monosymptomatic nocturnal enuresis (MNE) in children using a network meta-analysis. METHODS: PubMed, Embase, the Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov were comprehensively searched to identify randomized controlled trials (RCTs) comparing either different first-line therapies or combination regimens involving first-line treatments versus monotherapy for MNE. Two researchers independently screened studies, extracted data according to predefined criteria, and assessed the methodological quality of the included trials. Data were analyzed using R software, with relative risk (RR) used as the effect size for dichotomous outcomes. The certainty of evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) approach. RESULTS: A total of 23 RCTs involving 2424 children and eight interventions were included. The network meta-analysis showed that desmopressin combined with oxybutynin, propiverine, solifenacin, or tolterodine was significantly more effective in achieving complete response (CR) than desmopressin monotherapy. Additionally, combinations of desmopressin with oxybutynin or tolterodine were superior to alarm monotherapy. No statistically significant differences were found among interventions regarding partial response (PR). For relapse rate, alarm monotherapy, desmopressin plus alarm, and desmopressin plus solifenacin were significantly better than desmopressin monotherapy. No significant differences in adverse events (AEs) were found across the interventions. In terms of CR, the top three interventions were desmopressin plus oxybutynin, desmopressin plus tolterodine, and desmopressin plus solifenacin. For PR, the leading treatments were desmopressin plus oxybutynin, desmopressin monotherapy, and alarm therapy. Regarding relapse rate, desmopressin plus solifenacin, alarm therapy, and desmopressin plus tolterodine ranked highest. For AEs, alarm therapy, desmopressin plus propiverine, and desmopressin monotherapy had the lowest incidence. The certainty of evidence for the primary outcome ranged from moderate to low according to the CINeMA assessment. CONCLUSION: Desmopressin combined with anticholinergic agents significantly improved CR versus desmopressin monotherapy and demonstrated partial significant superiority over alarm therapy alone. Among these, desmopressin plus oxybutynin demonstrated the best overall efficacy. Alarm therapy and desmopressin alone showed similar therapeutic effectiveness. Desmopressin monotherapy was associated with a higher relapse rate. Importantly, combination therapy did not significantly increase the risk of AEs compared to monotherapies. According to the CINeMA framework, the certainty of evidence was mostly low to moderate, highlighting the need for cautious interpretation and further high-quality trials.
BACKGROUND: Target weight assessment remains challenging, particularly in children, where ongoing growth adds complexity. Lung ultrasound (LUS) has emerged as a promising tool for assessing hydration, although pediatric...BACKGROUND: Target weight assessment remains challenging, particularly in children, where ongoing growth adds complexity. Lung ultrasound (LUS) has emerged as a promising tool for assessing hydration, although pediatric data are limited. METHODS: We conducted a retrospective, single-center study between January and September 2024. Target weight was assessed using clinical examination, pre-dialysis NT-proBNP level, relative overhydration by bioimpedance analysis (BIA), inferior vena cava (IVC) diameter, and LUS score (12-zone protocol). The primary outcome was the association between LUS and other assessment methods. Secondary outcomes included the reliability of LUS with dialysis-related weight loss and its contribution to multimodal evaluation. Mixed-effects regression models were used. RESULTS: Sixty-eight dialysis sessions of 10 children on hemodialysis were analyzed. The median pre-dialysis LUS score was 7 (IQR 5-9), which decreased to 4 (IQR 3-6) post-dialysis. LUS correlated significantly with NT-proBNP level (p = 0.006) but not with BIA or IVC. A trend was observed for clinical signs (p = 0.072). Changes in the LUS score correlated with dialysis-related weight loss (p < 0.001). CONCLUSIONS: LUS is a sensitive, dynamic complementary tool for assessing target weight in pediatric hemodialysis patients. It provides additional information on extravascular fluid status and should be considered within multimodal target weight strategies, especially in cases of discordance.
BACKGROUND: Pediatric renal abscess is an uncommon but serious complication of urinary tract infection, often characterized by nonspecific symptoms and delayed diagnosis. METHODS: We retrospectively analyzed 69 children...BACKGROUND: Pediatric renal abscess is an uncommon but serious complication of urinary tract infection, often characterized by nonspecific symptoms and delayed diagnosis. METHODS: We retrospectively analyzed 69 children with radiologically confirmed renal abscesses treated between November 2012 and February 2024. Clinical characteristics, laboratory findings, imaging results, management, and outcomes were evaluated across different age groups. RESULTS: The median patient age was 24.0 months (IQR 7.3-66.8). There was a marked male predominance in infants (1-24 months) versus a female predominance in children over 60 months, with fever present in 98.6% of cases. Diagnosis was confirmed in all patients by contrast-enhanced CT or MRI, which revealed a mean attenuation difference of 28.8 ± 8.0 HU between the abscess and renal parenchyma; ultrasound sensitivity was 79.7%. Urine cultures were positive in 33.3% of cases, predominantly for Escherichia coli. Notably, vesicoureteral reflux was detected in 52.6% of evaluated patients. While surgical intervention was required in only 7.2% (5/69), these patients had a significantly higher rate of acute kidney injury compared to the conservative group (60% vs. 3.1%; P = 0.0018). The median hospital stay was 12.0 days (IQR 9.0-15.0) and was significantly prolonged in patients with left-sided or bilateral involvement (adjusted P = 0.032 and 0.033, respectively). CONCLUSION: Most pediatric renal abscesses can be successfully managed conservatively. Vesicoureteral reflux is common, and acute kidney injury is markedly more frequent among children who require surgical treatment.
Prescribing an adequate intraperitoneal dialysate volume is essential in peritoneal dialysis (PD) to balance optimal solute and fluid removal against the risk of increased intraperitoneal pressure (IPP) and to prevent in...Prescribing an adequate intraperitoneal dialysate volume is essential in peritoneal dialysis (PD) to balance optimal solute and fluid removal against the risk of increased intraperitoneal pressure (IPP) and to prevent increased reabsorption and mechanical complications. Since the description of manual hydrostatic IPP measurement (IPPM) in children in 1996, a few small observational studies in children and adults have provided limited evidence on the acceptable upper limit of IPP and associated complications. We conducted a practice survey across European pediatric dialysis centers, which showed that of the responding 47 centers, 68% routinely perform IPPM, but the frequency, mode of measurement, accepted upper limit of IPP, and interpretation of IPPM results vary considerably. In this narrative review, we present the current knowledge on IPP and the rationale for a standardized three-point IPPM, a prerequisite to obtain valid scientific data on the relation of IPP with patient outcome, e.g., by means of registries and adequately powered prospective studies. To date, the role of IPPM in improving outcomes for children on PD is uncertain. Advanced, continuous IPPM technologies providing precise, large-scale IPP data together with PD efficiency and tolerability data will improve our understanding of the impact of IPP on patient outcomes.
Özcan EB, Vardar Yagli N, Bakkaloglu SA
… +8 more, Büyükkaragöz B, Kavaz Tufan A, Özdemir Atikel Y, Leventoglu E, Pektas Leblebicier S, Hüseynli B, Basol Göksülük M, Saglam M
BACKGROUND: Hypertension in adolescents is associated with early cardiovascular risk, yet functional and vascular differences between primary and secondary hypertension remain poorly characterized. This study aims to com...BACKGROUND: Hypertension in adolescents is associated with early cardiovascular risk, yet functional and vascular differences between primary and secondary hypertension remain poorly characterized. This study aims to compare body composition, muscle strength, arterial stiffness, physical activity, and sedentary behavior among adolescents with primary and secondary hypertension compared with normotensive peers. METHODS: Adolescents with primary hypertension (n = 35), secondary hypertension (n = 17), and normotensive controls (n = 21) were assessed for anthropometric characteristics, handgrip strength (HGS), hemodynamic and arterial stiffness parameters, physical activity levels, sedentary behavior, and perceived barriers to physical activity. Subgroup analyses were performed in adolescents with primary hypertension according to obesity status. RESULTS: Adolescents with primary hypertension exhibited significantly higher body mass index and fat-free mass compared with other groups (p < 0.001). Pulse wave velocity was significantly higher in the primary hypertension group (p = 0.041), indicating increased arterial stiffness. Non-dominant HGS percentage was lowest in adolescents with secondary hypertension (p < 0.005). Physical activity levels were similarly low across groups, while weekend sedentary time was higher in the primary hypertension group (p = 0.021). Within the primary hypertension group, obesity status was not associated with differences in HGS, sedentary behavior, or arterial stiffness after adjustment for age, sex, height, and fat-free mass. CONCLUSIONS: Adolescents with primary and secondary hypertension demonstrate distinct functional and vascular profiles early in the disease course. Arterial stiffness and reduced muscular strength highlight early cardiovascular risk, while low physical activity and high sedentary behavior are common across all groups. These findings support the need for early, individualized assessment and lifestyle-based interventions in adolescent hypertension.
BACKGROUND: Urinary tract and kidney infections are potential complications in pediatric chronic kidney disease (CKD), especially among patients with congenital anomalies of the kidney and urinary tract (CAKUT). We chara...BACKGROUND: Urinary tract and kidney infections are potential complications in pediatric chronic kidney disease (CKD), especially among patients with congenital anomalies of the kidney and urinary tract (CAKUT). We characterized the prevalence of self-reported infections from childhood through young adulthood; evaluated risk factors; and quantified the association with CKD progression. METHODS: Infections in the past year were self-reported at annual Chronic Kidney Disease in Children (CKiD) study visits. Age-specific infection prevalences were stratified by sex and CKD diagnoses (glomerular, non-glomerular non-CAKUT, CAKUT low-risk for infections, and three CAKUT high-risk categories: reflux nephropathy, obstructive uropathy, and other high-risk). Repeated measures logistic regression quantified associations between infections and clinical variables. Estimated glomerular filtration rate (eGFR) change in the year after infection was assessed using linear regression, adjusted for age, sex, diagnoses, previous year eGFR, medications, and bladder catheterization. RESULTS: 943 participants contributed 4707 person-visits. Among 175 with obstructive uropathy, approximately one-third of boys and two-thirds of girls reported a previous year infection; infection prevalence for other CAKUT diagnoses ranged from about 20% to 50%. Bladder catheterization and history of infections were significantly associated with recent infections. Adjusted eGFR decline in the year after reporting infection was -1.7% faster compared to those free of infection (95%CI: -3.2%, -0.1%, p < 0.05), but this was attenuated when adjusted for catheterization (p = 0.082). CONCLUSIONS: CAKUT diagnoses were associated with higher infection risk, especially among those with obstructive uropathy, and girls reported more infections than boys. Self-reported infection was significantly associated with accelerated eGFR decline in the following year.
BACKGROUND: Children with nephrotic syndrome (NS) are frequently exposed to chronic inflammation, hypertension, and multiple metabolic abnormalities, such as hyperlipidemia, that may contribute to early development of at...BACKGROUND: Children with nephrotic syndrome (NS) are frequently exposed to chronic inflammation, hypertension, and multiple metabolic abnormalities, such as hyperlipidemia, that may contribute to early development of atherosclerosis and cardiovascular disease. However, the extent of subclinical cardiovascular involvement remains unclear. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the presence of subclinical atherosclerosis and cardiovascular disease in pediatric patients with NS, using carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (c-f PWV), and left ventricular mass (LVM) index as surrogate markers. DATA SOURCES: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, and Cochrane Library databases from their inception until December 20, 2024. STUDY ELIGIBILITY CRITERIA: Eligible studies included observational studies that evaluated early markers of atherosclerosis and cardiovascular disease in children with NS. PARTICIPANTS AND INTERVENTIONS: Children and adolescents with NS under the age of 18 years were compared to healthy controls. Surrogate markers included cIMT, PWV, and LVI index. Blood pressure was evaluated as a cardiovascular risk factor. STUDY APPRAISAL AND SYNTHESIS METHODS: The Newcastle-Ottawa Scale was used to assess study quality. The mean difference with 95% confidence intervals was used for continuous outcomes. Statistical significance was set at p < 0.05. Sensitivity and subgroup analyses and meta-regression were conducted for further exploration of the outcomes. Statistical analyses were performed using R software (Version 4.3.2). RESULTS: Sixteen studies with a total of 1461 participants (668 patients with NS and 793 healthy controls) met inclusion criteria. Children with NS had significantly increased cIMT compared to controls (MD = 0.06 mm; 95% CI: 0.05-0.07; p < 0.001), with substantial heterogeneity across studies. No statistically significant differences were observed for c-f PWV and LVM index. Moderate correlations were found between cIMT and disease duration (r = 0.47) and number of relapses (r = 0.45). A small positive correlation was observed between cIMT and triglycerides, but not with total or LDL cholesterol. LIMITATIONS: This meta-analysis is limited by the observational and predominantly cross-sectional nature of the included studies, substantial heterogeneity across studies, and the highly diverse study population. Furthermore, in many studies, the phenotypes of NS were poorly characterized, or grouped together, and insufficient data were provided for treatment regimens, limiting interpretation of the results. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Children with NS exhibit increased cIMT, which may be associated with increased future cardiovascular risk. However, prospective longitudinal studies are needed to determine whether these surrogate markers can predict such an association.
BACKGROUND: Hypertension (HTN) is a well-known complication among patients on pediatric kidney replacement therapy (KRT). We aimed to evaluate demographics, longitudinal changes and outcomes of high blood pressure (BP) a...BACKGROUND: Hypertension (HTN) is a well-known complication among patients on pediatric kidney replacement therapy (KRT). We aimed to evaluate demographics, longitudinal changes and outcomes of high blood pressure (BP) among children and adolescents on KRT. METHODS: Data on BP and antihypertensive (AH) medications reported to the ESPN/ERA Registry on 6071 patients from 28 European countries starting KRT < 20 years of age between 2007 and 2021, were included. RESULTS: Hypertension (HTN), AH medication use, and uncontrolled HTN were reported in 60.7%, 45.0%, and 32.0% of patients, respectively. Prevalence of uncontrolled HTN was 49.7% in HD, 42.3% in PD, and 27.3% in transplanted patients. Younger age, dialysis, and shorter KRT vintage were risk factors for uncontrolled HTN. AH medication use was lower among young patients, females and those on dialysis, and higher with a shorter KRT vintage and non-CAKUT kidney disease. Among AH medication users, 27.9% of transplantation, 48.1% of PD and 58.9% of HD patients showed a systolic BP > 95th percentile. Uncontrolled HTN significantly decreased over time in HD patients (52.3% at dialysis start vs. 42.5% after 5 years; annual percentage change [APC] - 3.5%; 95%CI: - 6.2; -0.7), despite similar AH medication use. After 5 years, transplanted patients showed a significant reduction in both prevalence of uncontrolled HTN (APC - 3.6%; 95%CI: - 5.7; - 1.5) and AH medication use (APC - 1.6%; 95%CI: - 2.6; - 0.6%). No trends were found for PD patients. Uncontrolled HTN was not associated with mortality (aHR 1.02; 95%CI: 0.79-1.33). CONCLUSIONS: HTN is highly prevalent in children and adolescents on KRT. Younger children and HD patients should be carefully evaluated for BP status after entering dialysis or shortly after transplantation.
BACKGROUND: Chronic kidney disease (CKD), characterized by chronic inflammation and uremic toxicity, represents a state of premature immune aging. However, data on T-cell receptor (TCR) repertoire alterations in pediatri...BACKGROUND: Chronic kidney disease (CKD), characterized by chronic inflammation and uremic toxicity, represents a state of premature immune aging. However, data on T-cell receptor (TCR) repertoire alterations in pediatric CKD are limited. The TCR variable beta (Vβ) region defines distinct T-cell subfamilies generated by V(D)J recombination and reflects T-cell repertoire diversity and clonal composition. Alterations in TCR Vβ distribution indicate repertoire remodeling associated with chronic antigenic stimulation and immune aging beyond quantitative lymphocyte changes. This study aimed to characterize TCR Vβ family repertoire in children with advanced CKD and explore their associations with clinical and biochemical parameters. METHODS: In this single-center, cross-sectional study, 35 children with CKD stages 3b-5 (21 non-dialysis, 14 dialysis) and 15 age- and sex-matched healthy controls were enrolled. Peripheral blood lymphocyte subsets and TCR Vβ1-Vβ23 distributions were assessed by flow cytometry and compared with clinical and laboratory measures. Group comparisons were performed using the Mann-Whitney U test, and associations were assessed using Spearman correlation analysis. RESULTS: Children with CKD exhibited a skewed TCR Vβ repertoire, with reduced expression of Vβ9 and Vβ11 and increased Vβ17 (p = 0.041, 0.001, 0.014, respectively) with corresponding moderate-to-large effect sizes (r = 0.37, r = 0.61, and r = 0.44). Dialysis patients showed lower Vβ11 and higher Vβ12 expression compared with non-dialysis patients (p = 0.034 and p = 0.048), with large effect sizes (r = 0.68 and r = 0.66). Reduced Vβ9 correlated with low BMI and higher proteinuria, and reduced Vβ11 correlated with hypoalbuminemia, whereas elevated Vβ12 was associated with higher CRP and creatinine levels. Total lymphocyte counts were preserved, although dialysis patients demonstrated a higher CD4/CD8 ratio. CONCLUSIONS: Pediatric CKD is associated with selective and non-uniform remodeling of the T-cell repertoire, reflecting premature immune senescence. The associations between TCR Vβ alterations, inflammation, and nutritional markers suggest synergistic effects of uremic toxicity and protein-energy imbalance on immune aging, warranting larger mechanistic studies.
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by the classical triad of acute hemolytic anemia, thrombocytopenia, and kidney impairment. We report a 10-year-old boy with acute pancreatitis...Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by the classical triad of acute hemolytic anemia, thrombocytopenia, and kidney impairment. We report a 10-year-old boy with acute pancreatitis presenting simultaneously with atypical HUS (aHUS) with two such episodes occurring 1 year apart. The child presented with abdominal pain, vomiting, oliguria, epigastric tenderness, and had a right undescended testis. During the initial episode, anti-factor H antibodies were mildly elevated while they were normal in the subsequent episode with normal complement components. Whole exome sequencing identified a heterozygous pathogenic CFTR variant, predisposing to recurrent pancreatitis and cryptorchidism, as well as a probable heterozygous CFHR1/CFHR3 deletion, the gene responsible for recurrent aHUS. Treatment of pancreatitis, hemodialysis, and plasma infusions led to complete recovery of acute kidney injury (AKI) and HUS on both occasions.
BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a severe pediatric condition often requiring red blood cell transfusion, yet its transfusion risk factors remain unclear. This study investigated the incidenc...BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a severe pediatric condition often requiring red blood cell transfusion, yet its transfusion risk factors remain unclear. This study investigated the incidence, temporal trends, and determinants of transfusion in children with SA-AKI. METHODS: Using the U.S. Nationwide Inpatient Sample (2010-2019), pediatric patients (< 18 years) with SA-AKI were identified by ICD-9/10 codes. Demographic, hospital, comorbidity, and complication data were compared and then analyzed using multivariate logistic regression to identify independent risk factors for transfusion. RESULTS: Among 7,521 children with SA-AKI, 30.17% received transfusions. The annual transfusion rate declined from 45.6% (2010) to 21.6% (2019). Independent risk factors included younger age, Black/Hispanic/Asian race, higher comorbidity burden, teaching hospital admission, elective admission, and Northeast hospital location. Specific comorbidities (coagulopathy, disseminated intravascular coagulation, lymphoma, fluid/electrolyte disorders, neurological disorders, and solid tumor without metastasis) and complications (continuous trauma ventilation, acute respiratory failure, gastrointestinal bleeding, thrombocytopenia, septic shock, hepatic insufficiency) significantly increased transfusion likelihood. Protective factors included chronic pulmonary disease, uncomplicated diabetes, paralysis, and urinary tract infection. CONCLUSION: Pediatric SA-AKI transfusion rates have markedly decreased over the past decade. Risk factors reflect disease severity and acute complications, while certain chronic conditions appear protective. These findings highlight the complexity of transfusion decision-making in SA-AKI and may inform strategies to optimize transfusion practices.