Summary- paper 43:
Novel Mechanism for Tubular Injury in Nephropathic Cystinosis
Swastika Sur, Maggie Kerwin, Silvia Pineda, Poonam Sansanwal, Tara K. Sigdel, Marina Sirota, Minnie M. Sarwal1
Biorxiv, 2022
Questions/gaps addressed:
- Cystinosis is a rare autosomal recessive LSD, caused by mutations in the CTNS gene. The kidney is the first organ affected functionally despite lysosomal cystine loading in multiple tissues. The most severe form is nephropathic/infantile cystinosis, characterized by the development of renal Fanconi syndrome and glomerular dysfunction, resulting in end-stage renal disease (ESRD) by 10 years of age. Cystinosin or other key molecular perturbations impact renal tubular integrity and function besides cystine transport. What is the mechanism, what are these fubctions?
Major hypothesis:
- Defective lysosomal clearance may be a pivotal cause of the altered function of renal proximal tubular epithelial cells (RPTECs).
Key methods:
- whole-genome microarray transcriptional expression profiles in paired RPTECs (isolated from patient urine samples) and fibroblasts (isolated from the same patient skin biopsies) from patients with cystinosis and healthy age- and gender-matched controls.
Major takeaways: