Klotho in Chronic Kidney Disease-associated Pruritis (CKD-aP)

Uremic pruritus (UP), also known as Chronic Kidney Disease-associated pruritus (CKD-aP), is the most common cause of Generalized Pruritus (GP). UP is multifactorial; not due to a single cause but as a result of combined action of multiple factors. UP has a major clinical impact because it is strongly associated with poor quality of life, impaired sleep, depression, and increased mortality. UP patient always feels he is drained and distressed. Alpha Klotho is the protein product of the anti-aging klotho gene. This protein exists in two forms: soluble Klotho (s-Klotho) and membranous Klotho (m-Klotho). The kidney is the principal organ that produces, regulates, and metabolizes Klotho. Membranous Klotho acts as a co-receptor to enhance the binding of fibroblast growth factor 23 (FGF23) to FGF receptors (FGFRs) through the formation of Klotho/FGFR/FGF23 complex. Interestingly, soluble Klotho can also bind to FGF23/FGFR, but it prevents high FGF23-induced toxicity. In chronic kidney disease( CKD), soluble Klotho is still detectable although it is much lower than in healthy human beings, suggesting that it is produced from extrarenal organ(s) or tissue(s) not yet identified which may be the skin. FGF23 is a peptide released from bone tissue osteocytes and osteoblasts. It plays an important role in the bone-kidney axis and the regulation of calcium and phosphate homeostasis. In CKD, Klotho is linearly decreased prior to the rise of FGF23 so it is considered a biomarker for early detection of kidney damage. Klotho deficiency contributes to vascular and soft-tissue calcification in CKD patients. In CKD-aP patients, there is metastatic micro-calcification due to calcium deposition in skin and this is one of the etiological causes of UP. Whether Klotho has a role in this assumption is still unclear. Phototherapy is a proven method for the management of many pruritic disorders. Narrowband ultraviolet B (NB-UVB) can be considered as a feasible treatment option for CKD-aP. One of its possible mechanisms is the reduction of skin calcium-ion content. Whether this is via changing Klotho expression is still unknown. Therefore, our study aims at knowing whether Klotho and FGF23 have a role in UP and whether their expression change by NB-UVB with the improvement of pruritus.