The role of sleep and sildenafil in the progression of chronic kidney disease: A new therapeutic approach

Abstract

Introduction The prevalence of chronic kidney disease (CKD) is increasing rapidly throughout the world. Also, CKD is associated with comorbidities such as sexual dysfunction and sleep disorders which may impact the patients’ quality of life. Although sleep loss is inherent to the lifestyle of people suffering from CKD, its effects on the disease progression are unknown. Moreover, there are few studies evaluating potential alternative treatments that could attenuate some CKD comorbidities. Thus, the aim of this study was to evaluate the outcomes of a chronic treatment with sildenafil in an animal model of CKD subjected to sleep restriction (SR). Materials and methods The study was performed using 140 male adult Wistar rats distributed into 4 groups: sham treated with vehicle (SHAM + V), sham treated with sildenafil (SHAM + S), CKD treated with vehicle (CKD + V) and CKD treated with sildenafil (CKD + S). After 46 days, all groups were sub distributed in sleep control (SC) and SR. Blood pressure and heart rate was assessed once a week. In the end, we performed the evaluation of the sexual behavior followed by euthanasia and collection of blood. Results Sildenafil was able to prevent the disease progression, demonstrated by higher levels of serum creatinine in CKD + V + SC compared to SHAM + V + SC and CKD + S + SC groups. Nevertheless, creatinine levels of CKD + S + SR was significantly higher than SHAM + S + SR group. Moreover, sildenafil prevented the development of systemic hypertension, although this was not sustained after SR. Heart rate was only affected by disease and SR, both contributing to tachycardia. Sildenafil treatment also reduced the excessive body weight loss, the iron deficit, the dyslipidemia, the decrease of serum testosterone and LH and the increase of proinflammatory cytokines IL-1 α , TNF α e IL-17. However, many of these effects were attenuated or abolished by SR. Regarding the sexual behavior, CKD + V + SC group had lower sexual activity index than SHAM + V + SC and CKD + S + SC. Overall, SR had a stimulant-like effect on sexual behavior by increasing the sexual motivation and performance in the animals. This effect was also followed by increased corticosterone, progesterone and FSH levels. Conclusion The early chronic treatment with sildenafil in CKD plays a role as possible adjuvant in the therapy for CKD and its comorbidities. Importantly, its effectiveness demands the maintenance of the sleep quality. Acknowledgements This work was supported by grants from AFIP , FAPESP , CAPES and CNPq .