In children with Henoch-Schonlein purpura nephritis (HSPN), the degree of proteinuria has been proven to be not only a sign of kidney damage, but also an accelerator of kidney disease progression. Nephrotic proteinuria at disease onset has been proposed as a predictor of a poor renal outcome. This study aims to assess the clinical and pathological features of HSPN with nephrotic proteinuria in a single center. One hundred thirty-seven patients with HSPN who visited Shanghai Children’s Hospital from January 2009 to December 2013 were retrospectively reviewed. The patients were divided into 2 groups based on the 24-h urinary protein levels: nephrotic proteinuria group (NP group: 24-h urinary protein ≥50 mg/kg) and non-nephrotic proteinuria group (NNP group: 24-h urinary protein <50 mg/kg). In addition, data regarding their sex, age, clinical features, renal pathology, and prognosis were collected. (1) There were 34 boys and 20 girls in the NP group with a mean age of 8.39 ± 2.85 years. The peak age of incidence was 6 to 11 years (72.22%). (2) There were 8 cases (14.81%) with joint symptoms and 9 cases (16.67%) with gastrointestinal symptoms in the NP group. According to the analysis of the laboratory test results, the serum albumin and IgG levels of the NP group were significantly lower than that of the NNP group (35.04 ± 8.45 in the NP group vs. 41.55 ± 4.46 in the NNP group, P < 0.0001; 7.68 ± 3.12 in the NP group vs. 9.53 ± 2.74 in the NNP group, P < 0.001, respectively); their blood urea nitrogen and cystatin C levels increased significantly (P < 0.05). (3) The majority of the pathological changes in the NP group were above the International Study of Kidney Disease in Children (ISKDC) grade III (62.97%). The NP group patients with tubulointerstitial injurie with grade 2 and above (50%) were prioritized. Immune complex deposition in the NP group was dominated by IgA. (4) The prognosis of the NP group was in complete remission (A), and their cases did not develop into end-stage renal disease; their prognosis was also associated with clinical classification (P < 0.01) but was not related to pathologic grading and tubulointerstitial injury (P > 0.05). The serum albumin and IgG levels of the NP group were significantly lower; however, their blood urea nitrogen and cystatin C levels were higher. The ISKDC grades were mainly above grade III. The prognosis of the NP group was associated with clinical classification and improved after a timely and early treatment.

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H₂S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H₂S nearby under stress conditions. We found that H₂S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H₂S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H₂S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSE^D187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H₂S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSE^D187A) may be a potential target for drug therapy.

Chylopericardium effusion is characterized by the accumulation of milky effusion in the pericardium. It is often idiopathic but it can be secondary to trauma, chest radiation, tuberculosis and malignancy. If cardiac tamponade ensues, it becomes life-threatening. Herein we describe chylopericardium tamponade in a child with IgA nephropathy. To the best of our knowledge, this is the first reported case of chylopericardium tamponade in IgA nephropathy. A 6 years old boy with IgA nephropathy presented with dyspnea, orthopnea, pretibial pitting edema, ascites and fever. Muffled heart sounds and hepatomegaly were also noted. Echocardiography and thoracic CT revealed that there was a large volume of hydropericardium. Moreover, the pericardial milky fluid by pericardiocentesis was analyzed and chylopericardium effusion was eventually confirmed. Pericardial drainage was continued and his diet was modified to low fat, rich MCT and high protein. Complete remission was achieved after 3 weeks of this combined treatment. Chylopericardial tamponade could be a rare and life-threatening complication of IgA nephropathy. Etiological analysis is critical for determining the therapeutic approach in patients with pericardial effusion.

Background/Objectives: Fibronectin glomerulopathy (FNG) is a rare autosomal dominant inherited kidney disease. Approximately 40% of genetically confirmed FNG cases are associated with likely pathogenic variants in FN1. Patients with FNG have similar clinical features as those with chronic nephritis. Due to nonspecific clinical manifestations mimicking common childhood glomerular diseases, FNG poses significant diagnostic challenges in children, frequently resulting in delayed diagnosis. Case Description: A 9-year-old Chinese girl presented with manifestations suggestive of acute poststreptococcal glomerulonephritis (APSGN), including edema, hypertension, hypocomplementemia, nephrotic-range proteinuria (3.34 g/24 h), and microscopic hematuria (45–55 cells/HP). Despite resolution of edema and normalized complement C3 after initial therapy, proteinuria and hematuria persisted. Renal biopsy revealed prominent mesangial deposits extending to glomerular capillary walls, with strong fibronectin (FN) immunoreactivity and fibrillary electrondense deposits on electron microscopy. Genetic testing identified a heterozygous FN1 missense variant c.3051G>C (p.Trp1017Cys) in the proband and her asymptomatic father, classified as likely pathogenic per ACMG guidelines (supporting evidence: PS1, PM2, PP3, PP4). mRNA and cDNA sequencing confirmed the transcription of the mutant allele in the family members. Notably, these transcriptional analyses cannot provide direct evidence for the functional pathogenicity of the variant. The patient received combined angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy, and renal function remained stable during 3 years of follow-up. Conclusions: The FN1 c.3051G>C represents a novel nucleotide variant, while the corresponding amino acid alteration p.Trp1017Cys has been reported in the previous literature. This case expands the variant spectrum of FN1 and emphasizes the critical value of renal biopsy and genetic testing for diagnosing FNG in pediatric patients with persistent renal manifestations after suspected APSGN. Family screening is essential for identifying asymptomatic carriers. Our findings also highlight the phenotypic heterogeneity of FNG.

Mutations in the MMACHC (metabolism of cobalamin associated C) gene are associated with cobalamin C disorder and have been reported in infants with renal thrombotic microangiopaopathy (TMA). The pathophysiology underlying these mutations and their role in causing endothelial damage remains elusive. We generated a transgenic pluripotent stem cell (iPSC) line expressing MMACHC protein harbouring the renal 2 thrombotic microangiopapathy-causing mutation (p.Q27R). The iPSC exhibits a typical stem cell morphology, expresses pluripotency markers, and displays a normal karyotype. The iPSC line provides a valuable platform for exploring the pathogenesis of endothelial injury induced by metabolism-mediated TMA and for screening drugs to reduce endothelial damage.