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BACKGROUND: Alport syndrome (AS) is a multisystem hereditary disorder characterized by persistent hematuria, progressive renal insufficiency, sensorineural hearing loss, and ocular abnormalities. Its pathogenesis is mainly due to mutations in COL4A3, COL4A4, or COL4A5 genes encoding type IV collagen α chains, leading to glomerular dysfunction and end-stage renal disease. A systematic evaluation of its global research landscape is lacking, and bibliometric analysis can fill this gap. METHODS: A comprehensive bibliometric analysis was conducted using Biblioshiny, VOSviewer, and CiteSpace. Data were extracted from the Web of Science Core Collection (2000-2025), with 1205 valid publications included. Multiple dimensions including annual output, citations, co-authorship, and keywords were analyzed. RESULTS: Bibliometric analysis showed that AS-related annual publications had a consistent upward trend from 2000 to 2025. The 1205 included publications accumulated 34,314 citations, with the most cited being R. C. Wiggins' 2007 original study (622 citations). Co-authorship analysis identified Judy Savige as the most prolific author and the United States as the leading contributing country. Co-citation analysis mapped the field's intellectual structure, and keywords included "natural history," "IV collagen," and "identification" besides core terms "Alport syndrome" and "mutations". CONCLUSION: Global interest in AS research has increased significantly. With academic exchanges and international cooperation, its pathogenesis mechanisms are gradually clarified. This bibliometric analysis identifies research hotspots and guides future directions, providing references for related research and clinical practice.

BACKGROUND: Coenzyme Q10 (CoQ10) nephropathy is a rare mitochondrial kidney disease caused by defects in CoQ10 biosynthesis and represents a unique form of steroid-resistant nephrotic syndrome with a disease-specific therapy. However, data on treatment outcomes of this disease in Japanese patients remain limited. METHODS: We conducted a retrospective observational study of Japanese patients. Patients with a genetically confirmed diagnosis of CoQ10 nephropathy who received CoQ10 supplementation and had available longitudinal clinical data were included. Changes in the urinary protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate before and after treatment were evaluated, and adverse events were assessed. RESULTS: Twelve patients were included in the analysis. The median age at treatment initiation was 9.0 years, and COQ8B was the predominant causative gene (n = 11). One patient harbored a COQ6 variant. CoQ10 supplementation was initiated at a median dose of 10.0 mg/kg/day. The median UPCR decreased from 1.66 g/gCr at baseline to 0.19 g/gCr at 12 months, and 6/7 (86%) patients with available 12-month data achieved a ≥ 50% reduction in proteinuria. Kidney function remained stable, and no patients progressed to end-stage kidney disease during a median follow-up of 28.8 months. Adverse events were mild and did not lead to treatment discontinuation. CONCLUSIONS: In Japanese patients with CoQ10 nephropathy, CoQ10 supplementation was associated with a substantial reduction in proteinuria and stabilization of kidney function. These findings indicate the importance of early genetic diagnosis and prompt initiation of targeted therapy for this treatable hereditary kidney disease.

INTRODUCTION: Hematuria is an understudied condition associated with kidney disease and related outcomes. Sex and gender influence many aspects of human health, including kidney traits. However, sex-differential genetic effects, which can be attributed to hormones, gene regulation, and other factors, have not been comprehensively explored. METHODS: To identify genetic effects that differ by sex for hematuria, we performed sex-specific genome-wide association analyses in the UK Biobank (UKB), with replication results in 2 independent cohorts: the Million Veteran Program (MVP) and Geisinger MyCode. Sex-differential genetic effects were evaluated using locus-specific sex-by-genotype interaction analysis. We further performed observational analyses between hematuria and sex hormones (estradiol and testosterone) in the UKB. RESULTS: We identified significant sex-differential effects in the UKB (Bonferroni-corrected P < 0.006), corresponding to larger effect sizes in females than in males, but in the same direction of effect, at genetic variants within 2 autosomal type IV collagen genes that encode key structural components of the glomerular basement membrane: COL4A3 and COL4A2. CONCLUSION: Although males are known to experience more severe kidney disease than females in X-linked Alport syndrome, our findings highlight important sex differential effects in hematuria, where the presence of COL4A3 variation in females results in stronger association effect sizes than in males, which replicated in an independent cohort. In addition, we identify that COL4A2 is associated with hematuria, also with greater effect size in females than in males, only in the UKB.

BACKGROUND: Chronic kidney disease significantly impacts health and lifespan, but its progression remains difficult to predict. Therefore, there is a need for biomarkers to identify patients at risk of a rapid decline in kidney function. Alport syndrome (AS) exemplifies this challenge, as some patients experience rapid progression, while others exhibit a more gradual decline in kidney function. We hypothesized that urinary proteins, such as albumin, immunoglobulin G (IgG), or alpha-1-microglobulin, could serve as predictors of kidney function decline. METHODS: This observational, non-interventional, retrospective study investigated 127 patients with AS from two centres. Yearly estimated glomerular filtration rate (eGFR) loss was modelled in a linear regression model. RESULTS: Over a 42 ± 26-month follow-up, 24% of the patients had rapid eGFR decline (defined as a loss of >6 ml/min/1.73 m2 per year). Urinary albumin-to-creatinine ratio (UACR) showed the highest negative correlation with the change in eGFR (ρ = -0.435, P < 0.001; n = 109). After adjusting for age, gender, renin-angiotensin system inhibition, mode of inheritance, and eGFR, UACR was independently associated with the yearly eGFR loss (P < 0.001). Urinary IgG had the highest sensitivity in identifying patients with kidney function decline. CONCLUSION: In this study, the amount of albuminuria was independently associated with the yearly loss of kidney function in patients with AS. Combined measurement of albuminuria and urinary IgG may identify patients with the highest risk of rapid decline in kidney function. Following external validation in a larger, prospective cohort, this approach could be used to identify patients who could potentially benefit from closer monitoring and earlier intervention.

Alport syndrome (AS) is a genetically heterogeneous disorder caused by mutations in type IV collagen genes, clinically characterized by progressive renal function deterioration. Despite advances in genetic screening technologies, cases resulting from non-canonical splice site variants remain diagnostically challenging, frequently leading to missed diagnoses or delayed therapeutic intervention. Here, we report a pediatric patient with AS and his mother, both harboring a novel splicing variant in the COL4A5 gene. The proband presented with microscopic hematuria and was found to carry a hemizygous COL4A5 variant (NM_033380.3: c.3374-3T > G) through whole-exome sequencing. To determine the pathogenicity of this variant, in vitro functional validation was performed using a minigene splicing assay, which confirmed aberrant mRNA splicing leading to exon 38 skipping. These findings established this variant as the genetic etiology of AS in this family. Through the integration of whole-exome sequencing and minigene splicing analysis, this study identifies c.3374-3T > G as a novel pathogenic non-canonical splice site mutation in the COL4A5 gene. Our findings not only expand the mutational spectrum of Alport syndrome and provide critical insights for early diagnosis and clinical management of similar cases, but also underscore the necessity of functional validation for non-canonical splice site variants.