NON-DIPPING STATUS IN CHRONIC KIDNEY DISEASE AND RISK OF MORTALITY, CARDIOVASCULAR EVENTS AND PROGRESSION OF KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

In the normal population, blood pressure (BP) exhibits a circadian rhythm, as measured by a 24-hour ambulatory blood pressure monitor (ABPM).  At night-time, there is a normal reduction in BP by 10-20%. Absence of a normal night-time dipping pattern is called non-dipping. Non-dipping has clinical implications, with an association found between non-dippers, left ventricular hypertrophy, and increased risk of stroke, cardiovascular events, and developing chronic kidney disease (CKD). CKD is a common disease with an increasing prevalence. A meta-analysis we conducted showed that the prevalence of non-dipping status in CKD patients can be as high as 56%. However, the implications of a non-dipping status in CKD patients is poorly understood.

We therefore undertook a meta-analysis to compare the risk of adverse events between CKD patients with a non-dipping status and CKD patients with a normal dipping status. Adverse events included 1) mortality, 2) cardiovascular events, and 3) CKD progression 

MEDLINE, EMBASE, and CENTRAL databases were searched for cohort or randomised trials examining BP status in CKD patients who underwent a 24-hour ABPM. The search covered until Dec 2023. Studies were included if they contained a CKD cohort with an ABPM measurement to document non-dipping prevalence, normal dipping prevalence, and adverse events between the two groups. Adverse events were defined as mortality, cardiovascular events, and CKD progression (decline in eGFR by more than 50%, progression to kidney failure, or a composite endpoint of both). Data were screened, extracted independently, with risk of bias assessment done by 2 authors. Risk of bias was assessed through the Newcastle-Ottawa Scale (NOS), with a score <5 assigned as a low-quality study. Random effects in meta-analysis were used to determine the risk of adverse events between CKD patients with a non-dipping status and normal dippers

We identified 2,541 articles and 9 were eligible for inclusion. Risk of bias was low in five studies and moderate in four, with no studies having a low risk of bias.

For mortality, five studies (1,122 dippers and 1,943 non-dippers) showed a significant reduction in dippers compared to non-dippers (RR 0.59, 95%CI 0.50- 0.70, P<0.001). Heterogeneity was low among studies (I2= 0%, P=0.70). For cardiovascular events, five studies were included (1,649 dippers and 2,623 non-dippers) with a lower risk of cardiovascular events in dippers compared to non-dippers (RR 0.63, 95%CI 0.47- 0.84, P<0.001) with a moderate heterogeneity (I2= 73%, P=0005). For CKD progression, six studies were included (2,089 dippers and 3,425 non-dippers). For the composite endpoint of eGFR decline by >50% and progression to kidney failure, dippers had a lower risk compared to non-dippers (RR 0.64, 95%CI 0.55- 0.875, P<0.001) with a low heterogeneity (I2=44%, P=0.09). Subgroup analysis among the 3 individual endpoints of CKD progression only, kidney failure only and both CKD progression and kidney failure, showed no subgroup differences (P=0.9)

The prevalence of non-dipping in CKD is high, and our current analysis shows that non-dipping status in CKD patients confers an increased risk of adverse events compared to having a normal dipping pattern. Randomised trials should be considered to determine if medical therapy to manage non-dipping status results in a lower risk of adverse events.