Introduction and Background:
The introduction provides a comprehensive overview of the significance of proteinuria, its causes, and the role of cubilin in protein reabsorption by the proximal tubules. It effectively summarizes the existing knowledge on the link between CUBN mutations and Imerslund-Gräsbeck syndrome (IGS) and proteinuria.
Study Design and Methods
The authors have utilized three different cohorts of patients with suspected hereditary renal disease and chronic proteinuria, which provides a robust sample size for their analysis.
Results
The identification of 39 patients with biallelic pathogenic CUBN variants associated with chronic isolated proteinuria and normal renal function is a significant finding.
The authors have provided detailed clinical and biological data for these patients, including age of onset, proteinuria range, urinary albumin-to-protein ratio, renal biopsy findings, and treatment responses.
The genotype-phenotype correlation observed, with C-terminal CUBN variants causing proteinuria without vitamin B12 malabsorption, is an important observation and sheds light on the functional domains of cubilin.
The meta-analysis of population-based cohorts and the association of four CUBN variants with albuminuria and higher eGFR further strengthen the study’s findings.
Discussion
The authors provide a comprehensive discussion of their findings in the context of existing knowledge and hypotheses regarding the role of cubilin in renal protein reabsorption.
Conclusion
In summary, this article presents a significant contribution to the understanding of the role of cubilin in renal protein reabsorption and the clinical implications of CUBN mutations. The study design, methods, and data analysis appear rigorous, and the authors have provided a comprehensive discussion of their findings in the context of existing knowledge.
Reviewed Paper citation: Bedin M, Boyer O, Servais A, Li Y, Villoing-Gaudé L, Tête MJ, Cambier A, Hogan J, Baudouin V, Krid S, Bensman A. Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function. The Journal of clinical investigation. 2022 Jun 1;130(1).
