Pediatric Nephrology最新文献

Iron is an essential cofactor in metabolic and developmental processes. Iron deficiency (ID) is the most common micronutrient deficiency in pregnancy, especially impacting medically underserved populations worldwide. Iron deficiency (ID) in pregnancy predisposes neonates to poor iron status, i.e., congenital ID and associated adverse effects. The role of congenital ID on human kidney development is unstudied, but impaired fetal kidney development is possible. Both vascular and global nutrient restriction rat models report impaired fetal kidney development, as well as induce hypertension, supporting the developmental origins of health and disease (DOHaD) hypothesis. This review compiles findings from 17 published studies in rats examining congenital or early postnatal ID, showing the same. The review compares histological and physiological findings in both congenital and postnatal ID, placing these in the context of recent knowledge describing molecular mechanistic pathways regulating nephrogenesis. Findings in rat early-life ID include lower kidney iron levels, lower glomerular generations and estimated glomerular numbers, larger maculae densa size, interstitial fibrosis, and prolonging active glomerulogenesis past normal temporal cessation. Additionally, several physiological studies in rat congenital ID promote altered renin-angiotensin signaling and hypertension with maturation, especially in males. Key findings of morphological kidney maldevelopment, altered renin-angiotensin signaling, and hypertension in early-life ID underscore the urgent need for future mechanistic data in animals such as rats. The long-term goal would be to leverage understanding from these data into either preventative or early therapeutic strategies in children.

Background: Patients with chronic kidney disease (CKD) stage 5D receiving peritoneal dialysis (PD) are at risk for thiamin deficiency (TD). This study compared the proportion of TD in pediatric CKD patients undergoing PD with that in healthy controls and evaluated the associations of various factors with TD in CKD patients.

Methods: Thirty-two patients with CKD stage 5D and 34 healthy children were recruited. The participants reported their consumption of foods containing antithiamin factors and completed a 3-day food record to assess their intake of thiamin, energy, and macronutrients. The medical records of the CKD group were reviewed. Thiamin status was assessed via an erythrocyte transketolase activity assay, where the thiamin pyrophosphate effect was determined.

Results: Thirteen percent of participants in the CKD group had TD, whereas 29% of the healthy controls did (p = 0.093). The CKD group had significantly greater total thiamin intake per 1,000 kcal of energy due to thiamin supplementation (2.14 [1.83, 2.99] vs. 0.87 [0.59, 1.14] mg/1,000 kcal; p < 0.001), despite inadequate dietary thiamin intake. A longer PD duration (in months) and a high-transport peritoneal membrane status were significantly associated with poorer thiamin status (β = + 0.59, p < 0.001, and β = + 0.38, p = 0.013, respectively). In contrast, greater total thiamin intake was correlated with improved thiamin status (β = -0.35, p = 0.022).

Conclusions: Thiamin deficiency was observed in 13% of pediatric CKD patients on PD and 29% of healthy controls. In CKD patients, TD was associated with longer PD duration (in months), high-transport peritoneal membrane status, and low total thiamin intake.

Given the complex relationship between the gut microbiome and chronic kidney disease (CKD), exploring the potential role and scope of microbiota-targeted therapies in pediatric CKD is highly relevant. We aim to provide an overview of gut-targeted therapeutic strategies, including nutritional interventions (fiber, phytochemicals, fermented foods, and traditional Chinese medicines), probiotics, synbiotics, oral absorbents, and fecal microbial transplantation. Enhancing physical activity and preventing constipation are additional strategies that may promote gut microbiome health. In a uremic environment, gut microbiota-targeted therapies could potentially rebalance the gut microbiota, improve gut barrier function, decrease uremic toxin concentrations, enhance the production of short-chain fatty acids (SCFA), and reduce inflammation. While research in adult CKD patients has provided insights into these approaches, there are limited data in children with CKD. This review aims to summarize potential targeted therapies for restoring a balanced gut microbiota, emphasizing the need for studies that evaluate their effects on clinical outcomes in pediatric CKD.

Background: Aquaporins (AQPs) are a class of proteins that transport water molecules across membranes, which can promote water transport in cells. We aimed to explore the correlation between different polymorphisms of AQP1 and peritoneal function in children on peritoneal dialysis (PD).

Methods: Children who underwent PD at the Children's Hospital of Fudan University from January 1, 2014, to December 31, 2023, were included. The AQP1 genotypes of the four polymorphisms were rs2075574 (TT, CT, CC), rs1049305 (GG, CG, CC), rs10253374 (TT, CT, CC) and rs17159702 (TT, CT, CC).

Results: A total of 187 children on chronic PD were included in the study. We found that the TT group with rs2075574 exhibited a lower baseline peritoneal equilibration test (PET) ultrafiltration level than the CC group (302 ± 129 vs. 408 ± 168 ml/m², P = 0.015). For rs1049305, the CC group had a higher pKT/V than both the GG (2.71 ± 1.25 vs. 2.27 ± 0.79, P = 0.04) and CG groups (2.71 ± 1.25 vs. 2.24 ± 0.88, P = 0.03). Additionally, at 12-month follow-up, the CC (410 ± 160 ml/m², P = 0.04) and CG (393 ± 174 ml/m², P = 0.04) groups of rs1049305 showed higher PET ultrafiltration than the GG group (239 ± 288 ml/m²). No significant correlation was observed between the four genotypes and adverse events.

Conclusions: AQP1 rs2075574 and rs1049305 polymorphisms might be associated with ultrafiltration and urea transport in children with PD.

Background: Serum creatinine (Scr) centile values were recently described in a cohort of 1136 (near)-term neonates that underwent therapeutic hypothermia (TH) because of moderate to severe hypoxic-ischemic encephalopathy. Recent methodological progress enables conversion of these Scr centiles to estimated glomerular filtration rate (eGFR) values.

Methods: Scr centiles in the TH dataset during the first 10 days of life were converted to eGFR values, using the Schwartz formula, with the Smeets k-value (0.31) and fixed body length (50 cm) to generate postnatal reference eGFR values, centiles, and an equation for median eGFRs. These findings were compared to published eGFR data in term controls.

Results: A polynomial function was estimated: $\mathrm{eGFR}\left(\frac{\mathrm{mL}}{\min },\bullet ,1.73,m^2\right)=9.1667+7.1173-0.3439x^2,(x=\mathrm{days})$ for eGFR in TH neonates. The median eGFR increases 2- to threefold over the first week (day 1: 16.1; day 2: 19.4; day 7: 41.2 mL/min∙1.73 m²), while the polynomial function does not fully reflect the interindividual variability in eGFR values (intra-day variability is also 2- to threefold). Patterns in acute kidney injury (AKI) TH cases differ significantly from non-AKI TH cases. Based on pooling of published eGFR data, this was compared to a function in healthy term neonates: $\mathrm{eGFR}\left(\frac{\mathrm{mL}}{\min },\bullet ,1.73,m^2\right)=14.2167+6.7644-0.3901x^2(x=\mathrm{days})$ (day 1: 20; day 2: 26; day 7: 42 mL/min/1.73 m²).

Conclusions: Based on a pooled dataset in TH cases, we converted Scr centiles to eGFR centiles. Based on median values, this resulted in a polynomial function in TH cases, compared to healthy term neonates. This eGFR function enables precision pharmacotherapy for GFR-cleared drugs in this vulnerable population.

The reversed cortico‑medullary differentiation in fetal kidneys on ultrasound has been described in the literature, but there have been no descriptions of such a finding on fetal magnetic resonance imaging (MRI) so far. The authors present three unrelated fetuses with hyperechoic kidneys on ultrasound (US) and reversed signal intensity of their cortex and pyramids on SSFSE/T2WI and FIESTA images on magnetic resonance imaging (MRI). All of them shared the same deletion of the long arm of chromosome 17 in the 17q12 region, responsible for the expression of clinical features of renal cysts and diabetes (RCAD) syndrome. All of them had multiple tiny kidney cysts on US after birth. This specific finding on fetal MRI may point at this specific genetic condition.

The increasing prevalence of non-communicable diseases like chronic kidney disease signals the need for a deeper understanding of the impact of the intra-uterine milieu on developmental programming and its impact on health outcomes through the lifespan of an individual. Maternal health in the pre-gestational and gestational phases, including nutrition, exposure to drugs, environmental toxins, infectious and non-infectious diseases, and socio-economic conditions influence the overall development of the fetus as well as the fetal kidney. The small, vulnerable newborn, born from an adverse developmental environment, is predisposed to low nephron number and is at risk for acute kidney injury in the neonatal period. Developmental programming has far-reaching consequences, including a higher risk for cardio-kidney-metabolic diseases, including hypertension and chronic kidney disease, and pregnancy complications, which perpetuates an intergenerational cycle of non-communicable disease risk. This risk can be mitigated by optimizing the care of individuals in the reproductive age group, identifying high-risk pregnancies early, and providing optimal treatment and monitoring. Care of the small vulnerable neonate includes prevention of acute kidney injury and life-long surveillance and modulation of cardio-kidney-metabolic risk. The review focuses on highlighting the influence of maternal health in the pre-gestational and gestational phases on kidney health from the neonatal period to adulthood.