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Renal agenesis and hypodysplasia (RAH) are major congenital anomalies of the kidney and urinary tract that often cause chronic kidney disease in children. Genetic factors are closely related to the pathogenesis of RAH. As whole genome sequencing techniques advance, gene mutations have been increasingly reported to be associated with RAH, among which the association of GREB1L gene mutation with renal dysplasia has been confirmed. We reported a cases of unilateral renal atrophy due to GREB1L gene c.4688A>G heterozygous mutation, and reviewed related literature. The gene mutation of the child originated from his mother, which is a rare variation and has incomplete explicit characteristics, and is assessed to be a harmful mutation by a variety of protein hazard prediction softwares. The new mutation site of GREB1L gene found by us, may expand the gene mutation spectrum and clinical spectrum related to RAH.

Background MicroRNAs (miRNAs, miRs) are involved in most physiological, developmental, and pathological processes. miR-192 and miR-205 are expressed preferentially in the renal cortex and closely relevant to the renal cell biology. In the present study, we aim to measure the serum levels of miR-192 and miR-205 and their correlation with clinicopathological data in patients with primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Methods Fifty-six patients (35 male, 21 female) with idiopathic nephrotic syndrome (FSGS 30, MCD 26) and 20 healthy controls were enrolled in the study. We quantified the serum levels of miR-192 and miR-205 in patients with FSGS and MCD by RT-qPCR. Results Patients with FSGS had higher serum levels of miR192 and miR-205 than those with MCD (324.49±42.74 fmol/l versus 90.19[+ or -]27.14 fmol/l, p Conclusions miR-192 and miR-205 have the potential as markers to differentiate FSGS from MCD. Keywords Focal segmental glomerulosclerosis * Minimal change disease * Nephrotic syndrome * miRNAs, Introduction Primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), lumped together as podocytopathy, are both characterized by heavy proteinuria and the nephrotic syndrome (NS) as well as extensive [...]

Abstract: Background: The complexes of β2-glycoprotein I (β2-GPI) with lipoprotein(a) [β2-GPI-Lp(a)] exist in human circulation and are increased in serum from patients with some autoimmune diseases. This study aims to investigate the concentration of β2-GPI-Lp(a) in serum of children with idiopathic nephrotic syndrome (NS) and its relationship with serum lipids, oxidized lipoprotein and renal function parameters to explore the potential of the complexes as an additional marker for evaluating pediatric NS. Methods: Serum concentrations of β2-GPI-Lp(a) complexes and oxidized Lp(a) [ox-Lp(a)] were measured by “Sandwich” ELISAs in 80 NS children and 82 age/sex-matched healthy controls. The levels of serum lipids and kidney parameters were also determined. Multivariate logistic regression analysis was performed to identify correlate of β2-GPI-Lp(a) and NS. Results: The serum concentrations of β2-GPI-Lp(a) complexes in children with NS were significantly higher than those in controls (median 0.95U/ml vs 0.28U/ml, P <0.0001). Ox-Lp(a) levels were also markedly elevated (median 14.55mg/l vs 2.60mg/l, P <0.0001] in NS children. The concentrations of β2-GPI-Lp(a) were positively correlated with ox-Lp(a) (r =0.246, P =0.028), but not with Lp(a) level, and the concentrations of ox-Lp(a) were positively related with Lp(a) (r =0.301, P =0.007) in NS children. Multivariate logistic regression analysis identified a positive association between NS and β2-GPI-Lp(a) (OR=13.694, 95% CI 6.400–29.299, P <0.0001), after adjusting for kidney function parameters, serum lipids and ox-Lp(a). Conclusions: Elevated β2-GPI-Lp(a) level was an independent and significant risk factor for pediatric NS and, enhanced Lp(a) oxidation partly contributes to the formation of β2-GPI-Lp(a) complexes. [Copyright &y& Elsevier]

Podocyte injury plays a vital role in focal segmental glomerulosclerosis (FSGS), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is highly expressed in podocytes and mutations mediate podocyte injury. We found TRPC6 gene mutation (N110S) was a new mutation and pathogenic in the preliminary clinical work. The purpose of this study was to investigate the potential mechanism of mutation in TRPC6 (TRPC6-N110S) in the knock-in gene mouse model and in immortalized mouse podocytes (MPC5). Transmission electron microscopy was used to evaluate renal injury morphology. We measured 24-hour urinary albumin-to-creatinine ratios and major biochemical parameters such as serum albumin, urea nitrogen, and total cholesterol. The results of CCK-8 assay and apoptosis experiments showed that the TRPC6-N110S overexpression group had slower proliferative activity and increased apoptosis than the control group. FluO-3 assay revealed increased calcium influx in the TRPC6-N110S overexpression group. Podocin level was decreased in TRPC6-N110S group, while TRPC6 and desmin levels were increased in TRPC6-N110S group. The 24 h uACR at 6 weeks was significantly higher in the pure-zygotes group than in the WT and heterozygotes groups, and this difference was found at 8 and 10 weeks.TRPC6 levels showed no significant difference between homozygote and WT mice. Compared to homozygote group, expression of podocin and nephrin were increased in WT, but levels of desmin was decreased in WT. Our results suggest that this new mutation causes podocyte injury probably by enhancing calcium influx and podocyte apoptosis, accompanied by increased proteinuria and decreased expression of nephrin and podocin.

Background: Nephrotic syndrome, a prevalent childhood glomerular disorder, manifests with proteinuria, hypoalbuminemia, edema, and hypercholesteremia. Hypercalcemia, though rare, occasionally complicates these cases. Familial hypocalciuric hypercalcemia, an autosomal dominant disorder, is characterized by lifelong hypercalcemia, hypocalciuria, and normal or elevated parathyroid hormone levels due to loss-of-function mutations., Case Presentation: We detail a 2-year-old girl with nephrotic syndrome whose proteinuria responded effectively to steroid therapy without side effects. Hypercalcemia emerged after one month, prompting a familial history investigation, revealing a predisposition to hypercalcemia. Genetic analysis identified a heterozygous mutation c.1394G>A (p.R465Q) in the calcium-sensing receptor gene, shared among the patient, her grandmother, her father, and one sister. Notably, hypercalcemia required no intervention., Conclusions: This case report is the first documenting familial hypocalciuric hypercalcemia in a child with primary nephrotic syndrome and delineates the familial pedigree. While familial hypocalciuric hypercalcemia is infrequent, our findings affirm its generally benign nature. A critical aspect of patient care involves monitoring for potential complications, including acute pancreatitis or chondrocalcinosis. The indispensability of genetic studies in both diagnosis and the differentiation of related conditions is underscored, emphasizing their pivotal role in enhancing our understanding of this rare yet clinically significant disease. Continued research is imperative for advancing knowledge and improving clinical management.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are closely associated with neutrophil recruitment and activation, but the impact of the neutrophil apoptosis process in autoimmune disease has been rarely explained. Here, by integrating and analyzing single-cell transcriptome datasets, we found that the caspase-8-associated pathway in neutrophils was highly activated in the kidney rather than in the blood. To verify the function of caspase-8 in neutrophils on AAVs progression, we constructed neutrophil-specific caspase-8 knockout mice combined with an AAVs model induced by human ANCA from AAVs patients, a rapid and powerful model developed in this study. Our results show that caspase-8 activation of neutrophils up-regulates the expression of several inflammatory and immunoregulatory factors, especially IL23A, regulating the activation and differentiation of tissue-resident CD4 + effector memory T cells. This study reveals that the activation of caspase-8 in neutrophils can worsen glomerulonephritis of AAVs by regulating inflammation and immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Huang, Yu, Zhang, Xia and Gao.)

Background: In mainland China, dialysis for children with end-stage renal disease (ESRD) was not introduced until the 1980s. To describe the development of pediatric dialysis in different regions of China, a national pediatric dialysis network, namely, International Pediatric Dialysis Network-China (IPDN-China) ( www.pedpd.org.cn ), was launched in 2012., Methods: Original and updated information from the renal centers registered with the IPDN-China was collected between 2012 and 2016 from two sources, namely, the registry and the survey, and demographic features were analyzed., Results: Due to promotion by the IPDN-China, the number of registered renal centers increased from 12 to 39 between 2012 and 2016, with a significant increase in the coverage of the Chinese administrative divisions (from 26.5 to 67.6%) (p < 0.01); and the coverage of the pediatric (0~14 years old) population increased to nearly 90% in 2016. The distribution of renal centers indicated that East China had the highest average number of registered centers per million population (pmp) 0~14-year-old age group. Seventeen relatively large dialysis centers were distributed across 14 divisions. Various modalities of renal replacement therapy (RRT) were available in most centers. The IPDN-China has promoted collaborations between dieticians, psychologists, and social workers on dialysis teams to provide better service to children with ESRD and their families. The proportion of centers with all three types of paramedic support (i.e., dieticians, psychologists, and social workers) as well as the proportion of centers with a partial paramedic team significantly increased between 2012 (25.0%) and 2016 (69.2%) (p < 0.05). In terms of the point prevalent cases of patients (aged < 18 years), data from the survey of 39 registered centers revealed that the number of children with ESRD who were on RRT was 578 (49% received a kidney transplant) at the end of 2016, which was more than that reported in previous surveys. Data from the registry showed that 349 dialysis patients had been enrolled as of the end of 2016. The median age at RRT start was 9.5 years, and the leading cause of ESRD was congenital abnormalities of the kidney and urinary tract (CAKUT)., Conclusions: The IPDN-China has helped to promote the development of pediatric dialysis for ESRD in China by improving the organization of care for dialysis patients and increasing the availability and the quality of RRT for patients who need it. To improve knowledge about the epidemiology and outcomes of pediatric RRT around the country, a sustained effort needs to be made by the IPDN-China to increase the enrollment of dialysis patients and increase the number of registered centers in the future.

The protective effect of aspirin-triggered lipoxin (ATL) on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its possible mechanisms were explored. To induce acute renal injury, mice were treated with LPS. Concentration of serum creatinine (SCr) and blood urea nitrogen (BUN) was detected, and inflammatory cytokines and AKI biomarkers were determined by ELISA. The relative protein expression levels of TLR4/myeloid differentiation factor 88 (MyD88)/NF-κB signal pathway was assessed by Western blot. Mice subjected to LPS (4 mg/kg) treatment exhibited AKI demonstrated by markedly increased SCr and BUN levels compared with controls (P <0.01). Treatment with ATL decreased SCr and BUN levels after LPS injection (P <0.01). AKI biomarkers, such as urine NGAL, KIM-1, netrin-1, and L-FABP levels, increased by LPS and were inhibited by ATL (P <0.01). ATL also reduced LPS-induced secretion of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, and IL-8 (P <0.01). Furthermore, mice pretreated with ATL before exposure to LPS showed a reduction in TLR, MyD88, and p65 phosphorylation (P <0.01), which are the key factors of the TLR/MyD88/NF-κB signaling pathway. These results indicated that ATL had protective effects on renal function and showed amelioration of LPS-induced kidney injury. The mechanisms underlying the protective effects of ATL can be considered are related to attenuation of the TLR4/MyD88/NF-κB signaling pathway.