P0686THE CIRCADIAN RHYTHM IN CKD PATIENTS
Authors: Yang Jie , Xiao Gong , Xiao Xiangcheng 
Published: June 2020

Background and Aims

It is common to see that patients with chronic kidney disease CKD are complaint with sleep disorders. The data reveal that lymphocytes are under the regulation of circadian rhythm in the peripheral blood of humans. CKD patients have shown to stay up in a low-grade inflammatory status. And these patients are associated with systemic inflammation and acquired immune deficiency. In this condition, there are disorders of expression of chemokine receptors and function of lymphocytes in patients with CKD. Since the disorders of circadian rhythm have been reported, it is supposed that some proteins regulating circadian rhythm of lymphocytes may involve in sleep disorders. It is reported that circadian clock gene edcoded proteins, nuclear PER and CRY ptochrome (CRY), play an important role in the regulation of circadian rhythm. Therefore, we designed a questionnaire to patients with CKD stages 1-5 and investigated the levels of CRY mRNA and protein in PB lymphocytes.

Method

This research enrolled 101 patients (52 male and 49 female) with CKD stages 1-5, who were admitted to Xiangya Hospital, Changsha, China from August 2017 to August 2018. CKD was defined as the reduced level of eGFR when they received the Pittsburgh Sleep Quality-Index (PSOI) questionnaire. Patients were screened by strict exclusion criteria. The clinical files included general information of patients and blood biochemical test data. Subjective sleep quality was assessed in all patients using the Pittsburgh Sleep Quality-Index (PSQI). The expression of circadian clock genes PER1 and CRY1 in peripheral blood leukocytes using quantitative RT-PCR and Western blotting.

Results

Sleep questionnaires were obtained from the 101 patients from CKD stage 1 to 5. There were significant differences between the group of PSQI ≤ 5 and PSQI &gt; 5 in aging, Hb, HCT, Alb, ALT and CRP (Table1). The six valuables were chosen with Scr, eGFR, Ca, P, Hb and Anxiety/Depression score with logistic anlaysis. It was found that the values of Aging and Scr were significantly increased in high PSQI (Table 2). It also found that the PSQI score was negative correlated with the stage of CKD (Table 3). The higher level of PER1 and CRY1 in PBMC of CKD stage 1 patients was confirmed by Western blot and qRT-PCR. It was also found that the expression of PER1 and CRY1 significantly down regulated in the PBMC of CKD stage 5 patients. However, the expression of PER1 and CRY1 was no obviously differences of in the patients with CKD stage 2 to CKD stage 4 (Figure 1 and Figure 2).

Conclusion

It was found that the progress of CKD was associated with the degree of sleep disorders in our research. The score of PSQI was negativly correlated with the lower eGFR. It indicated that there is association between sleep quality and eGFR. It also found that Hb, HCT, Alb and ALT were significantly better in the group whose PSQI score was lower than 5. CRP is a hallmark of inflammations a close relation with sleep disorders. There is correlation between decreased sleep quality and elevated CRP level. It also found that the more aging and CRP, the higher PSQI score with logistical analysis in our research. It suggested that there is a chronic inflammation are associated with the sleep of the patients with CKD. PBMCs are invloved in status of inflammation. It indicated that the PBMCs of patients with CKD may be affected by the sleep disorders. The circadian rhythm can be also shown in human’s PBMCs. The proteins of Per and CRY were two of period circadian clock proteins. In our research, we test that the expression of PER1 and CRY1 in PBMCs of patients with CKD. It found that PER1 and CRY1 were higher expressed in patients with CKD stage 1 and lowest in patients with CKD stage 5. It suggested that the circadian rhythm of PBMCs was associated with the stage of CKD. It was said that the function of PBMCs also are affected in CKD, such as the regulation of cellular calcium homeostasis, which can influence the circadian rhythm.