Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined inborn error of immunity mainly caused by PIK3CD mutations. We herein describe a 4-year-old Chinese boy who was admitted for recurrent pneumonia and persistent hematuria and exhibited multisystem involvement and anti-neutrophil cytoplasmic antibody (ANCA) positivity. He was initially diagnosed with ANCA-associated vasculitis. However, genetic testing revealed a c.1574A>G PIK3CD mutation, resulting in a diagnosis of APDS1.

The renoprotective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in both diabetic and nondiabetic nephropathy are widely recognized due to results from randomized controlled trials notably the DAPA-CKD and EMPA-KIDNEY trials. Research exploring the mechanisms of renoprotection indicates that SGLT2 inhibitors exert protective effects on podocytes by enhancing autophagy and stabilizing the structure of podocytes and basement membranes. Furthermore, reductions in lipotoxicity, oxidative stress, and inflammation have been confirmed with SGLT2 inhibitor treatment. Recent clinical studies have also begun to explore the effects of SGLT2 inhibitors on nondiabetic podocytopathies, such as focal segmental glomerulosclerosis. In this review, we summarize clinical and laboratory studies that focus on the podocyte-protective effects of SGLT2 inhibitors, exploring the potential for broader applications of this novel therapeutic agent in kidney disease.

Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality among kidney transplant recipients (KTRs). The administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is the only reliable strategy to prevent COVID-19 and alleviate the severity of COVID-19 in this particular population. The aim of this article was to evaluate the clinical protection by vaccines (breakthrough infections, deaths, and hospitalizations) in KTRs. There were 135 KTRs with COVID-19 breakthrough infections for whom patient-level data were available in PubMed and Web of Science. There was a male predominance (61.4%), 97 were given the standard vaccination regimen, and 38 received three or four doses of the vaccine. The median age was 59.0 (IQR: 49.0–69.0) years. A total of 67 patients were hospitalized, and 10 patients died. In 72.6% of cases, triple-maintenance immunosuppression was employed. The deceased patients were older than the survivors (p < 0.05); an age over 60 years was a risk factor for death (p < 0.05). The KTRs with booster vaccines had a longer time interval from the last vaccine to COVID-19 infection and lower hospitalization rates than the individuals who received the standard vaccination regimen (33.3% vs. 54.8%, p < 0.05). The hospitalized patients were older than the outpatients (p < 0.05). Among 16,820 fully vaccinated or boosted KTRs from 14 centers, there were 633 breakthrough infections (3.58%) and 73 associated deaths (0.41%). The center-level breakthrough infection rates varied from 0.21% to 9.29%. These findings highlight the need for booster doses for KTRs. However, more research is needed to define the long-term effectiveness and immunogenicity of booster doses and to identify methods to boost the protective response to vaccination in these immunocompromised patients.

Fanconi syndrome is one of the primary renal manifestations of mitochondrial cytopathies caused by mitochondrial DNA (mtDNA) mutation. The common 4977-bp mtDNA deletion has been reported to be associated with aging and diseases involving multiple extrarenal organs. Cases of Fanconi syndrome caused by the 4977-bp deletion were rarely reported previously. Here, we report a 6-year-old girl with growth retardation in the course of Fanconi syndrome. She had mild ptosis and pigmented retinopathy. Abnormal biochemical findings included low-molecular-weight proteinuria, normoglycemic glycosuria, increased urine phosphorus excretion, metabolic acidosis, and hypophosphatemia. Growth records showed that her body weight and height were normal in the first year and failed to thrive after the age of three. Using a highly sensitive mtDNA analysis methodology, she was identified to possess the common 4977-bp mtDNA deletion. The mutation rate was 84.7% in the urine exfoliated cells, 78.67% in the oral mucosal cells, and 23.99% in the blood sample. After three months of oral coenzyme Q10 and levocarnitine treatment in combination with standard electrolyte supplement, her condition was improved. This is a report of growth retardation as the initial major clinical presentation of Fanconi syndrome caused by the deletion of the 4977-bp fragment. Renal tubular abnormality without any other extrarenal dysfunction may be an initial clinical sign of mitochondrial disorders. Moreover, considering the heterogeneity of the phenotypes associated with mtDNA mutations, the risk of developing Kearns–Sayre syndrome (KSS) with age in this patient should be noted because she had ptosis, retinal involvement, and changes in the brain and skeletal muscle.

Background and Objectives: PAX2 serves as a critical transcription factor integral to the process of embryogenesis. Variations in the PAX2 gene could result in the aberrant development of numerous organs. Despite the identification of numerous mutations within the PAX2 gene, the correlation between specific genotypes has yet to be fully clarified. The objective of this study was to examine the clinical phenotypes and genotypes associated with PAX2 mutation-induced disorders in pediatric patients of Chinese descent. The aim of our study was to forecast the pathogenic potential of these genetic mutations and to ascertain possible correlations between genotypic variations and the clinical manifestations of disorders linked to PAX2 mutations. Materials and Methods: We recruited 14 pediatric subjects with PAX2 mutations, meticulously examining the clinical characteristics and genetic alterations present in these individuals. Computational techniques were utilized to evaluate the pathogenicity, stability, and biophysical characteristics. A range of computational tools were employed for this assessment, including PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf, and SNP effect. Results: The age at onset ranged from prenatal to 12 years. Five patients progressed to end-stage renal disease. Proteinuria and bilateral renal hypoplasia were observed in 92% of cases. Ocular and auditory abnormalities were also noted. We identified eleven different PAX2 mutations, including five novel variants not previously reported in the literature. We predicted that all mutations, with the exception of p.F27-L33 del and N188S, exhibited high pathogenicity scores. In particular, R117P and R140W are strongly associated with disease pathogenicity and are likely to cause more significant damage than other gene mutants. Conclusions: This study expands the mutational and phenotypic spectrum of PAX2-related disorders in the pediatric population. The identification of five novel variants enhances our understanding of the genetic basis of these conditions. Despite recurrent mutations, marked phenotypic heterogeneity persists, underscoring the need for further research.

To investigate the clinicopathological features and outcomes of primary IgA nephropathy with nephrotic-range proteinuria in Chinese children. Patients with biopsy-proven IgA nephropathy and nephrotic-range proteinuria between January 2011 and December 2017 were included, and their proteinuria and renal function were followed up. A total of 90 patients were enrolled, and 21.1% (19/90) of them had decreased renal function at diagnosis. Complete remission, partial remission, and no response of proteinuria occurred in 88.6% (70/79), 10.1% (8/79), and 1.3% (1/79), respectively, of the 79 patients who were followed up for 6 to 104 months. 73.7% (14/19) of the patients with decreased renal function at diagnosis recovered to normal level while 26.3% (5/19) of them did not recover or progressed to end-stage renal disease. Two patients with normal renal function at diagnosis progressed to renal insufficiency during follow-up period. By multivariate analysis, the risk for renal function deterioration was significantly higher in the partial remission and no response groups than in the complete remission group. Remission of proteinuria was important for improving renal prognosis in children with IgA nephropathy and nephrotic-range proteinuria. The outcomes for pediatric patients appeared to be better than that reported in adults.