[Retrospective study on the diagnosis, treatment, and follow-up of 85 cases of hypophosphatemic rickets in children]. / 85ä¾‹ä½Žè¡€ç£·æ€§ä½å»ç— æ‚£å„¿è¯Šæ–­ã€æ²»ç–—ä¸Žéšè®¿çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients. METHODS: A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022. RESULTS: Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs (P<0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease (P<0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis (OR=1.740, P<0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42). CONCLUSIONS: For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682.

[Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children]. / è¡€æ¸ æˆçº¤ç»´ç»†èƒžç”Ÿé•¿å› å­23å¯¹å„¿ç«¥ä½Žè¡€ç£·æ€§ä½å»ç— çš„è¯Šæ–­ä»·å€¼ç ”ç©¶.

OBJECTIVES: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. METHODS: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. RESULTS: The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). CONCLUSIONS: Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Role of Aldosterone in Renal Fibrosis.

Aldosterone is a mineralocorticoid hormone, as its main renal effect has been considered as electrolyte and water homeostasis in the distal tubule, thus maintaining blood pressure and extracellular fluid homeostasis through the activation of mineralocorticoid receptor (MR) in epithelial cells. However, over the past decade, numerous studies have documented the significant role of aldosterone in the progression of chronic kidney disease (CKD) which has become a subject of interest. It is being studied that aldosterone can affect cardiovascular and renal system, thereby contributing to tissue inflammation, injury, glomerulosclerosis, and interstitial fibrosis. Aldosterone acts on renal vessels, renal cells (glomerular mesangial cells, podocytes, vascular smooth muscle cells, tubular epithelial cells, and interstitial fibroblasts), and infiltrating inflammatory cells, inducing reactive oxygen species (ROS) production, upregulated epithelial growth factor receptor (EGFR), and type 1 angiotensin (AT1) receptor expressions, and activating nuclear factor kappa B (NF-κB), activator protein-1 (AP-1), and EGFR to further promote cell proliferation, apoptosis, and proliferation. Phenotypic transformation of epithelial cells stimulates the expression of transforming growth factor-ß (TGF-ß), connective tissue growth factor (CTGF), osteopontin (OPN), and plasminogen activator inhibitor-1 (PAI-1), eventually leading to renal fibrosis. MR antagonisms are related to inhibition of aldosterone-mediated pro-inflammatory and pro-fibrotic effect. In this review, we will summarize the important role of aldosterone in the pathogenesis of renal injury and fibrosis, emphasizing on its multiple underlying mechanisms and advances in aldosterone research along with the potential therapeutics for targeting MR in a renal fibrosis.

Mitochondria and Renal Fibrosis.

Mitochondria are important organelles in eukaryotic cells and perform a variety of biosynthetic and metabolic functions. Many human diseases are closely related to mitochondrial dysfunction. Kidney is an organ with high-energy requirements, which is distributed with a large number of mitochondria. Mitochondrial dysfunction plays a crucial role in the pathogenesis of kidney disease, and studies have shown that mitochondrial dysfunction is involved in the physiological process of renal fibrosis. This review introduced the biogenesis and pathophysiology of mitochondria, illustrated the involvement of mitochondrial dysfunction in renal fibrosis based on various kinds of cells, and finally summarized the latest mitochondria-targeted therapies.

Heat shock protein 70-2 and tumor necrosis factor-α gene polymorphisms in Chinese children with Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) or IgA-associated vasculitis is related to immune disturbances. Polymorphisms of the heat shock protein 70-2 gene (HSP70-2) and the tumor necrosis factor-a gene (TNF-α) are known to be associated with immune diseases. The purpose of this study was to investigate the likely association of HSP70-2 (+1267A/G) and TNF-α (+308A/G) gene polymorphisms with HSP in children. METHODS: The polymerase chain reaction restriction fragment length polymorphism method was used to detect the HSP70-2 and TNF-α polymorphisms in 205 cases of children with HSP and 53 controls; and the association of these polymorphisms with HSP and HSP nephritis (HSPN) was analyzed. RESULTS: The G/G genotypic frequencies at the +1267A/G position of HSP70-2 in the HSP group (22.9%) were significantly higher than those in the healthy control group (9.4%) (χ(2)=4.764, P<0.05). The frequencies of the A/A, A/G and G/G genotypes of HSP70-2 in patients in the nephritis-free group and the HSPN group showed no statistically significant difference. The A/A genotype frequency at the +308G/A position of TNF-α in the HSP group was 8.3%, which was higher than that in the control group (χ(2)=6.447, P<0.05). The A allele frequency of TNF-α in the HSP group was higher than that in the control group, with a statistically significant difference (χ(2)=7.241, P<0.05). CONCLUSIONS: The HSP70-2 (+1267A/G) and TNF-α (+308G/A) gene polymorphisms were associated with HSP in children. The G/G homozygosity of HSP70-2 and the A/A homozygosity of TNF-α may be genetic predisposing factors for HSP.

Use of off-label nephrology-related drugs in hospitalized pediatric patients: a retrospective study.

BACKGROUND: The information about the use of off-label drugs in pediatric nephrology is still lacking, which leads to increased adverse reactions and medical disputes. We retrospectively analyzed the use of off-label drugs in the in-patient ward of the nephrology department of Nanjing Children's Hospital, China in order to provide more complete information about the use of drugs for children. METHODS: Proportional stratified random sampling was applied to select patients with renal diseases aged 1 month to 18 years, who were admitted to the hospital from October 1, 2012 to September 30, 2013. All nephrology-related drugs prescribed in the hospitalization period and take-home drugs prescribed on discharge were recorded and evaluated as off-label drugs or not from three different perspectives: person-time, prescription, and drug category. RESULTS: From 385 person-times of patients with 1424 prescriptions, according to the ratio between off-label drugs and person-times, drug prescriptions, and drug products, the rates of off-label drugs were 40.78%, 16.64%, and 31.43%, respectively. Low-molecular-weight heparin, alfacalcidol and diltiazem were the most commonly used off-label drugs. Infants and younger children were the high-risk population of off-label drug use. The high rate off-label nephrology-related drug use in children was mainly related to lacking clinical research into drugs in children and the pace of drug label's revision, which cannot follow the development of medical science. CONCLUSION: Approximaely half of pediatric patients with renal diseases are usually prescribed with off-label nephrology-related drugs. Analyzing the off-label conditions from different perspectives may lead to various results. More clinical research into drugs for infants and younger children is needed so as to update drug descriptions.