| [Background and Objective]The abnormal circadian rhythm of blood pressure(BP) is presented at the early stage of Chronic Kidney Disease (CKD) by emerging evidences. The damages of abnormal BP circadian rhythm to target organs were independent of blood pressure loads.The abnormal BP circadian rhythm was associated with the accelerated renal injury and it is the independent risk of CKD progression also.The possible risk factors of disturbance of circadian BP rhythm are sodium sensitivity and proteinuria. The studies of BP rhythm in the past were focused on middle age or the elder patients at advanced CKD stage. The mechanism of disturbed BP rhythm in patients with CKD is not clear. Adriamycin Nephropathy rats developed significant proteinuria and have been shown to represent a useful rat model to study nephrotic syndrome. There is no report about the BP circadian rhythm and sodium sensitivity in the ADR nephropathy rats by now. In the present study we determined the BP levels, their circadian variability, and their regulation by changes in salt intake.The objective of the present research is to explore the circadian BP rhythm of the youth and middle age patients at CKD stage 1-3 and establish the CKD animal model with abnormal BP rhythm.[Methods]Consecutive hospitalized patients at CKD stage 1-3 who were youth or middle age were recruited. The patients underwent 24-hour ambulatory BP monitoring and were asked to collect the urines divided into daytime and nighttime synchronously. The urines were analyzed for the concentration of sodium,potassium,chloride,creatinine and albumin. ADR nephropathy rats BP were monitored by DSI radiotelemetry and collected urines in Dark and Light period synchronously.[Results]Clinic Study Part1.62 youth or middle age patients at CKD stage 1-3 were enrolled. Classified by Dipper status,76.6% patients presented as Nondipper BP pattern; Classified by Phase status, 59.7% presented as Phase-less or Out-of-phase BP pattern. Compared with the Dipper group, night SBP[(107.35±10.80) mmHg v.s (116.44±12.67)mmHg, P=0.015], night DBP[(65.42±6.64)mmHg v.s(73.03±9.24) mmHg, P=0.005] and night MAP[(80.01±7.05) mmHg v.s (87.36±9.36)mmHg, P=0.007] in the Nondipper group were higher significantly.2. Both the 24hUP [(3.64±3.00) g/d v.s(1.67±1.73)g/d, P=0.014] and the night Rate of Urinary Sodium Excretion (RUNa) [(6.84±3.81) mmol/h v.s (4.91±4.18) mmol/h, P=0.011] in the Nondipper group were significantly higher than those in the Dipper group.3. Night SBP, night DBP and night MAP increased significantly with the increase of night RUNa and 24hUP from the first to the third tertile (P<0.050) adjusted by age, drugs and eGFR.4. In the Nondipper group, the circadian rhythm of RUNa was reversed. Night RUNa was higher than day RUNa [(6.84±3.81) mmol/h v.s (6.26±3.55) mmol/h]. The circadian rhythm of RUNa was normal in the Dipper group. In the linear regression equations, with the night/day ratio value of RUNa increasing by one, the night SBP, DBP and MAP increased by 2.51 mmHg,2.54 mmHg and 2.44 mmHg respecitively.5. FENa increased significantly from 0.38±0.21 in the first tertile to 1.22±0.57 in the third tertile of night RUNa(P<0.001), which demonstrated that the increase of night RUNa was correlated with the decreased reabsorption of urine sodium.6. By the binary logistic analysis, the night RUNa and 24hUP were the risk factors of Nondipper BP pattern, the OR values were 2.37(95%CI,1.00-5.60,P=0.050)and 1.42 (95%CI,1.03-1.95,P=0.031) respectively.Animal Experiment Part1,The 24 hour average BP had no significant difference between the ADR nephropathy rats and SD control rats. In the control group, the SBP and MAP in Dark period(active status) was both 3.2mmHg higher than those in Light period(rest status), significantly (P=0.005). In the ADR nephropathy rats, the SBP and MAP in Dark period was 2.6mmHg and 2.9mmHg higher than those in Light period respectively, neither of the differences was significant(P>0.050). So the circadian BP rhythm vanished in the ADR nephropathy rats.2,In the ADR nephropathy rats, the circadian rhythm of the urine sodium excretion was disturbed. The RUNa in Dark period was significantly lower than that in the Light period of the same group[(14.69±3.65)umol/h v.s (27.66±5.84)umol/h, P=0.00\] and also significantly lower than that in the Dark period of the control group[(14.69±3.65)umol/h v.s (39.49±22.44)mol/h,P=0.023].3,In the ADR nephropathy rats, The FENa in Dark period was significantly lower than that in the Light period of the same group(0.15±0.06 v.s 0.29±0.06,P=0.008) and also significantly lower than that in Dark period of the control group(0.15±0.06 v.s 0.31±0.19,=0.050).4,Under high salt diet, in the ADR nephropathy rats, the SBP and MAP in Dark period increased significantly by 19.8mmHg and 18.5mmHg respectively than those before high salt diet(P<0.001); In the control group, the SBP and MAP in Dark period increased significantly by 8.4mmHg and 6.2mmHg respectively than those before high salt diet (P<0.001). In the ADR nephropathy rats, the SBP and MAP in Light period increased significantly by 20.1mmHg and 17.7mmHg respectively than those before high salt diet(P<0.001); In the control group, the SBP and MAP in Light period increased by 7.2mmHg and 3.0mmHg respectively than those before high salt diet, but both differences were not significant. After the high salt diet,control rats maintained the normal BP rhythm and ADR nephropathy rats still presented disturbed BP rhythm.[Conclusion]The abnormal circadian BP rhythm in the youth and middle age patients at CKD stage 1-3 was common. The clinical research and animal experiment both demonstrated that both of proteinuria and disturbed circadian rhythms of the RUNa were correlated with the abnormal circadian BP rhythm. The animal experiment study demonstrated abnormal circadian BP rhythm in the ADR nephropathy rats was existed and the BP of ADR nephropathy rats had sodium sensitivity. The ADR nephropathy rat was an suitable CKD animal model with disturbed circadian BP rhythm and sodium sensitivity. |
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