151. Increased Expression of Orexin-A in Patients Affected by Polycystic Kidney Disease.
- Author
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Nigro E, D'Arco D, Moscatelli F, Pisani A, Amicone M, Riccio E, Capuano I, Argentino F, Monda M, Messina G, Daniele A, and Polito R
- Subjects
- Humans, Male, Female, Middle Aged, Adult, TRPP Cation Channels genetics, TRPP Cation Channels metabolism, Polycystic Kidney, Autosomal Dominant metabolism, Polycystic Kidney, Autosomal Dominant genetics, Polycystic Kidney, Autosomal Dominant blood, Case-Control Studies, Aged, Blood Pressure, Polycystic Kidney Diseases genetics, Polycystic Kidney Diseases metabolism, Polycystic Kidney Diseases blood, Orexins metabolism, Orexins genetics, Polymorphism, Single Nucleotide, Orexin Receptors metabolism, Orexin Receptors genetics
- Abstract
Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group ( p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure ( p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.
- Published
- 2024
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