The advent of high-throughput sequencing has fostered the identification of novel causative genes of kidney disorders, and has allowed the continuous discovery of genetic variants of unknown significance often raising the problem of the functional testing of their pathogenic role. However, emerging evidence implicates that influence of the genomic background of the patient, as well as epigenetic modifications are critical in determining the clinical phenotype. Renal progenitor cell (RPC) cultures obtained from the affected patient may represent an ideal alternative for personalized disease modeling. Since loss of renal cells in urine naturally occurs in patients, urine may represent a potential RPC source.
In this study, we selected and amplified RPC cultures from the urine of patients with renal disease, and we evaluated the possibility to use these cells for modeling of genetic kidney disorders. Urin-RPC were obtained from five children affected by Nephrotic Syndrome carrying mutations in genes encoding for podocyte cytoskeleton proteins, identified thought Next Generation Sequencing, as well as from children without genetic alterations (five). The first cells exhibited altered synthesis of mutated proteins, abnormal cytoskeleton structure and functional abnormalities; by contrast, the second ones showed normal phenotype, structure and function.
The development of functional assays with Urin-RPC could serve as a fundamental step for rapid testing of putative pathogenic mutations. In particular, this tool can provide an essential support for the clinical diagnosis of nephrotic syndrome in patients carrying variants of uncertain significance and provide information to optimize an affected individual’s personalized medical care
