Pediatric Nephrology最新文献

Background: Nephrotoxic medication (NTMx) exposure is a common cause of hospital-acquired acute kidney injury (AKI) in non-critically ill, hospitalized children. NINJA (Nephrotoxic Injury Negated by Just-In-Time Action), an AKI screening and quality improvement tool, has successfully decreased exposure to NTMx and associated AKI at various US children's hospitals. We explored NTMx exposure and AKI rates by admitting service to understand patient risk profiles further.

Methods: AKI screening was performed by daily serum creatinine when high NTMx exposure criteria were met (≥ 3 NTMx or ≥ 3 days of intravenous aminoglycosides or vancomycin). Centers separately reported data from children admitted to hematology-oncology (heme), bone marrow transplant (BMT), and pulmonary services over 5 years (n = 11, 2016-2021). Rates for NTMx exposure and AKI were expressed as events per 1000 patient days. AKI intensity (#AKI days/100 exposure days) was assessed. Adherence to recommended serum creatinine monitoring was a surrogate for AKI event reliability (observed/expected × 100).

Results: Mean exposure rates were highest in BMT (26.92), then pulmonary (22.73), and heme (13.01). AKI rates were highest in BMT (6.27), then pulmonary (4.24), and heme (1.82). Heme and BMT had the highest AKI intensity (12.93 and 12.25 AKI days per 100 high-NTMx exposure days, respectively) compared to pulmonary (7.50 AKI days/100 high-NTMx exposure days). Serum creatinine monitoring compliance varied between institutions (62.5-100%).

Conclusions: Nephrotoxic exposure and AKI rates vary by patient population, with BMT patients having the highest NTMx exposure, AKI rates, and AKI intensity. These findings suggest that sub-populations have different levels of exposure and may require different strategies to reduce the burden of nephrotoxic medications.

Chronic non-communicable diseases pose a significant global health challenge, with the human gut microbiota emerging as a key player in several (patho) physiological functions, including immunity, metabolic homeostasis, and inflammation. While dysbiosis, or imbalance in taxonomy and function of gut microbiota, has been implicated in chronic kidney disease (CKD), whether it is a cause or consequence of the disease remains controversial. Understanding the gut microbiota's role in CKD pathogenesis is essential for developing novel therapeutic interventions. CKD in children presents unique opportunities for studying disease-specific mechanisms due to the absence of comorbidities typically seen in adults, such as diabetes, obesity, and hypertension, although few studies exist. On the other hand, unlike the relatively stable gut microbiota of healthy adults, the infant's microbiome undergoes significant development and maturation during the early years of life. Integrating knowledge from both pediatric and adult populations may provide a comprehensive understanding of gut microbiota dysbiosis in CKD. This review aims to provide an overview of the gut microbiota's development in healthy individuals and CKD patients and discusses how these findings can inform personalized treatment approaches to CKD.

Background: Nephrolithiasis (NL) and nephrocalcinosis (NC) are common, recurrent conditions globally. While monogenic causes are increasingly recognized, data on their prevalence and spectrum remain limited in Saudi pediatric populations.

Methods: This retrospective cross-sectional study was conducted in our tertiary care center from January 2008 to April 2023. Pediatric patients (0-18 years) with radiologically confirmed NL/NC who underwent genetic testing were included. Clinical, biochemical, radiological, and genetic data were analyzed. Genetic variants were classified using ACMG criteria, and segregation analysis was performed when available.

Results: Of 186 pediatric patients diagnosed with NL/NC, 54 (29.03%) underwent genetic testing. Median age at diagnosis was 3 months [IQR: 3-60], with median follow-up 56 months [IQR: 24-108]. Genetic mutations related to NL/NC were identified in 35/54 patients (64.81%), most commonly in CLDN16 (28.57%), SLC2A2 (17.14%), AGXT (11.43%), and SLC12A1 (8.57%). Thirteen novel variants were identified, with eleven linked to NL/NC phenotypes. Eight patients (14.81%) developed kidney failure requiring kidney replacement therapy; CLDN16 was significantly associated with kidney failure and transplant (P = 0.003), and AGXT with liver transplant (P < 0.001). Notably, the MOCS1 gene was found in a patient with early-onset neurological symptoms, hypouricemia, and later confirmed NL/NC.

Conclusion: Monogenic causes were identified in 35 of 54 (64.81%) Saudi pediatric patients with NL/NC who underwent genetic testing, a prevalence higher than reported internationally, likely due to the high consanguinity rate. Our findings underscore the importance of genetic testing in early-onset NL/NC. We recommend adding MOCS1 to the list of genes associated with monogenic NL/NC.

Autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD) is a chronic and progressive kidney disease that typically presents with elevated serum creatinine and gout between the second and fourth decades of life. Our patient presented at age 6 years with persistent headaches and nosebleeds that began the year prior to presentation with nephrology. Stage 2 hypertension prompted her nephrology referral from the pediatrician. Laboratory evaluation was not initially remarkable for significant elevation in creatinine as would be expected; however, her creatinine level did eventually rise to a concerning level after months of antihypertensive therapy. Kidney biopsy was remarkable for findings consistent with UMOD-associated ADTKD. This case demonstrates an unusual presentation of ADTKD-UMOD with Stage 2 hypertension at an early age in the absence of significant kidney injury and highlights a further emerging role for genetic testing in suspected secondary hypertension.

Alport syndrome (AS) is a hereditary glomerulopathy caused by mutations in the COL4A3, COL4A4, or COL4A5 genes, leading to progressive kidney decline and extrarenal manifestations. Advances in genetic testing have enabled the reclassification of AS into X-linked, autosomal recessive, and autosomal dominant forms, facilitating more accurate diagnosis and risk stratification. While renin-angiotensin-aldosterone system (RAAS) blockade remains the foundation of treatment to delay kidney failure, it does not directly target the underlying molecular pathology. Adjunctive commercially available metabolic modulators, including SGLT2i, mineralocorticoid receptor antagonists, ezetimibe and GLP-1 receptor agonists, may offer additional kidney protection. Ameliorating therapies being tested in Phase II trials include endothelin receptor antagonists (e.g., atrasentan), dual endothelin receptor antagonist and angiotensin II receptor inhibition (e.g., sparsentan) FXR agonists (e.g., vonafexor), inducers of cholesterol efflux (e.g., VAR200 and R3R01), and NOX1/4 inhibitors (e.g., setanaxib), several of which are currently being evaluated in clinical trials. Novel strategies such as exon skipping, gene editing, and nonsense mutation readthrough (e.g., ELX-02) are advancing toward precision medicine approaches as disease modifying agents targeting the genetic cause of AS. Moreover, therapies targeting mitochondrial function, such as mitophagy enhancers, have demonstrated preclinical promise. Stem cell-based approaches are also being explored for their regenerative and anti-fibrotic effects. This review summarizes the current landscape of AS classification and treatment, highlighting both standard interventions and experimental therapies. Emphasis is placed on the molecular mechanisms underlying podocyte injury and fibrosis, recent preclinical findings, and ongoing clinical trials that may shift future therapeutic paradigms.

Background: Acute kidney disease (AKD) is defined as kidney dysfunction lasting 7-90 days after the onset of acute kidney injury (AKI). Although widely recognized in adults and children, its significance in neonates is unclear. We aimed to investigate the risk factors and outcomes of neonatal AKD in a cohort of neonates with AKI.

Methods: We performed a retrospective cohort study at a tertiary NICU in Japan. Among 345 neonates with AKI between 2014 and 2024, 280 were included after excluding cases with congenital kidney disease, early death (< 7 days), or missing data. AKD was defined by KDIGO/ADQI criteria. We compared clinical features and outcomes between neonates with and without AKD and used multivariable logistic regression to identify predictors.

Results: Of 280 neonates with AKI, 85 (30%) developed AKD. Compared to non-AKD neonates, those with AKD had higher 90-day mortality (8% vs. 2%, P = 0.005) and MAKE90 (17% vs. 7%, P = 0.014). Chronic lung disease (78% vs. 50%, P < 0.001) and intraventricular hemorrhage (38% vs. 16%, P = 0.002) were also more common in the AKD group. In multivariable analysis, aminoglycoside exposure (OR = 2.04; 95% CI, 1.07-4.04; P = 0.031) and lower birth weight (per 100 g) (OR = 2.73; 95% CI, 1.11-1.22; P = 0.002) were independently associated with AKD.

Conclusion: Neonatal AKD was common and associated with increased mortality and major adverse kidney events. Our findings support AKD as a useful concept for identifying high-risk neonates and highlight the need for long-term kidney monitoring in this vulnerable population.

Renal tubular dysgenesis (RTD) is a rare disorder characterized by impaired development of the proximal tubules and kidney dysfunction due to decreased fetal renal plasma flow and renin-angiotensin system (RAS) inhibition. Fetal anuria causes severe oligohydramnios and Potter sequence, and most patients die within days after birth due to refractory hypotension, anuria, and respiratory distress. While vasopressin and fludrocortisone therapy have been reported, the long-term efficacy remains unclear due to the rarity of survivors. We report a 10-year-old girl with autosomal recessive renal tubular dysgenesis (ARRTD), a genetic form of RTD caused by mutations in RAS-related genes. She initially experienced recurrent dehydration, electrolyte abnormalities, and kidney dysfunction due to polyuria but showed long-term improvement following fludrocortisone therapy.

Background: Automated peritoneal dialysis (APD) consists of dwells with the same dwell volume and time. New cyclers allow modification of time and volume to prescribe adapted APD (AAPD), i.e., a series of short, small dwells followed by long, large dwells. Safety, efficacy, and underlying mechanisms of AAPD in children are uncertain.

Methods: Two double mini-PET were performed in randomized sequence. The standard test consisted of two identical cycles (fill volume 1000 ml/m², 75 min) and the adapted test of a short, small cycle (600 ml/m² BSA, 30 min) followed by a long, large cycle (1400 ml/m², 120 min). Solute and water fluxes were quantified together with intraperitoneal pressure (IPP). Nine pediatric PD patients (5-21 years) were treated per protocol.

Results: Residual dialysate volume was 422 ± 190 ml/m² BSA. There were no differences in ultrafiltration rates, glucose uptake, and creatinine, urea, and electrolyte clearances with the adapted and standard double mini-PET, despite identical cumulative dialysate volume and time. IPP varied by 1.7 ± 3.4 (range -2 to 9) cm H₂O with a drained volume of 1123 ± 386 and 1159 ± 210 ml/m² BSA for each standard dwell. IPP decreased from 1.9 with small volume to 1.0 cm H₂O /m²/100 ml with large volume dwells (p < 0.001) and was above 14 cm H₂O in 21 out of 63 measurements.

Conclusion: Within the limitation of small patient numbers, this proof-of-concept study suggests similar ultrafiltration and clearance rates with a single adapted versus standard double mini-PET. High residual dialysate volumes and high IPPs highlight the challenges of AAPD prescription in children.

Background: Peritoneal dialysis (PD) sustains children with chronic kidney disease stage 5 (CKD5) but promotes peritoneal membrane remodeling. Neutrophil extracellular traps (NETs) orchestrate antimicrobial defense and sterile inflammation; their involvement in PD-induced transformation is unknown.

Methods: Forty-five children were enrolled in the International Pediatric Peritoneal Biobank. Peritoneal biopsies taken at PD initiation and after ≥ 12 months of low-glucose-degradation-product PD were compared with surgical biopsies from non-uremic peers. Histomorphometry quantified microvessel density, submesothelial thickness, leukocyte infiltration, collagen I/III, and NET markers (citrullinated histone H3, neutrophil elastase, myeloperoxidase). Dialysate and plasma collected every 2 months for 18 months were assayed for cell-free DNA, NET proteins, DNase1, and DNase1L3.

Results: After chronic PD, the peritoneum displayed doubled microvessel density, tripled submesothelial thickness, and marked immune-cell infiltration (all p < 0.01). NET structures were prominent in tissue, while dialysate and plasma concentrations of cell-free DNA, citrullinated histone H3, neutrophil elastase, and myeloperoxidase increased two- to fourfold versus baseline (p < 0.05). DNase1 levels correlated with membrane thickness (r = 0.46, p = 0.003) and DNase1L3 with vascular density (r = 0.51, p = 0.001), suggesting limited compensatory NET clearance.

Conclusions: Chronic PD elicits NET-driven sterile inflammation that parallels structural remodeling of the pediatric peritoneum. Supplementing PD fluids with exogenous NET-degrading enzymes may preserve membrane integrity and prolong PD suitability in children.