Secondary Logo

Journal Logo

Prospective analysis of the association of ambulatory blood pressure characteristics with incident chronic kidney disease

McMullan, Ciaran J.a , b; Hickson, DeMarc A.c , d; Taylor, Herman A.c , d; Forman, John P.a , b

doi: 10.1097/HJH.0000000000000638

Objective: Ambulatory blood pressure measurement allows quantification of diurnal changes in blood pressure. While decreased nocturnal blood pressure dipping and elevated morning blood pressure surge are associated with an increased risk of cardiovascular events, the utility of ambulatory blood pressure measurements to predict renal events is unclear. African Americans, in addition to having an increased risk of chronic kidney disease (CKD), also have an increased prevalence of hypertension. Thus, we selected an African American population to study the association of ambulatory blood pressure parameters with incidence of CKD.

Methods: Prospective cohort study of 603 participants with normal renal function enrolled in the Jackson Heart Study who underwent baseline 24-h ambulatory blood pressure monitoring between 2000 and 2004, with median follow-up of 8.1 years. We analyzed the association of nocturnal dipping and morning surge with both incident CKD [estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2] and annual rate of eGFR decline. In additional analyses, we examined the relation of nocturnal, daytime, white-coat, and masked hypertension with CKD incidence.

Results: We found that 10% higher nocturnal dipping was significantly associated with a decreased risk of incident CKD [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.32–0.96] and a 0.4 ml/min per 1.73 m2 slower annual decline in eGFR. Morning surge was not associated with the incidence of CKD. Additional analyses revealed that isolated nocturnal hypertension and mean asleep SBP were associated with a nonsignificantly higher risk of CKD (OR 2.34, 95% CI 0.90–6.08) and (OR 1.31, 95% CI 0.99–1.72), respectively, in fully adjusted models.

Conclusions: Loss of nocturnal blood pressure dipping, but not morning blood pressure surge, may promote the decline in GFR and increase the risk for development of CKD in high-risk individuals.

aRenal Division, Department of Medicine, Brigham and Women's Hospital

bChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts

cJackson State University, Jackson Heart Study

dUniversity of Mississippi Medical Center, School of Medicine, Jackson, Mississippi, USA

Correspondence to Ciaran J. McMullan, MD, 41 Avenue Louis Pasteur, Suite 121, Boston, MA 02115, USA. Tel: +1 617 264 3070; fax: +1 617 264 5975; e-mail:

Abbreviations: ABPM, ambulatory blood pressure monitoring; ACR, albumin-to-creatinine ratio; ARIC, Atherosclerosis Risk in Communities; BP, blood pressure; CI, confidence interval; CKD, chronic kidney disease; CKD-, EPIChronic Kidney Disease Epidemiological Collaboration; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; JHS, Jackson Heart Study; KDIGO, Kidney Disease Improving Global Outcomes; OR, odds ratio

Received 22 January, 2015

Revised 21 April, 2015

Accepted 21 April, 2015

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Back to Top | Article Outline


Measuring blood pressure (BP) serially over a 24-h period reveals prognostically important BP patterns such as nocturnal BP, nocturnal BP dipping, and morning BP surge. Increased nocturnal BP as well as lack of nocturnal dipping (i.e. nondipping) predict higher rates of cardiovascular mortality [1] and stroke [2], and the prognostic value of these characteristics is superior to the standard, office-based BP measurement [3]. Morning surge in BP is a risk factor for cardiovascular disease in Japanese cohorts [4], but is protective against cardiovascular disease in several European cohorts [5,6].

In cross-sectional studies, patients with chronic kidney disease (CKD) are more likely to be nondippers than those with normal kidney function [7]. Nondippers with existing renal disease have an increased risk of progressive renal function decline [8]. Yet, the association of nondipping with the incidence of CKD among individuals with originally normal kidney function is less clear. In a small retrospective study of primarily white patients, nondipping was associated with a 9% faster annual decline in estimated glomerular filtration rate (eGFR) [9]. However, no prospective study has shown nondipping to be an independent risk factor for the development of CKD [10].

The African Americans have significantly higher rates of nondipping than the whites with similar clinic BP [11], and also have a four-fold higher incidence of end-stage renal disease (ESRD) [12]. The association of nocturnal BP dipping with incident CKD in African Americans is not known. In addition, the association between morning BP surge and incident CKD has not been studied in any population. Thus, we prospectively analyzed the independent association of ambulatory BP characteristics with the incidence of CKD in African Americans enrolled in the Jackson Heart Study (JHS).

Back to Top | Article Outline


Study population

The JHS is an ongoing population-based observational study to understand the cause of chronic diseases among African Americans. The JHS cohort includes a total of 5301 participants, partly recruited from the Jackson site of the Atherosclerosis Risk in Communities (ARIC) study, with additional randomly selected and volunteer residents of a tri-county area contained within Jackson MS, as well as their family members [13,14]. Participants underwent evaluation during a baseline clinic visit (exam 1) between years 2000 and 2004, and returned for two further clinic visits, exam 2 and exam 3, for a total median follow-up of 8.1 years (5–95 percentile range 7.0–9.9). All 5301 participants were invited to undergo 24-h ambulatory BP monitoring (ABPM) at the baseline visit, of whom 1150 (21.7%) completed this measurement.

The study protocol was approved by the institutional review boards of JHS Institutions (Jackson State University, Tougaloo College and the University Mississippi Medical Center), and written consent was obtained from all participants. The current study was approved by the institutional review board at Brigham and Women's Hospital.

Back to Top | Article Outline

Ambulatory and office blood pressure measurements

Twenty-four-hour ABPM was performed with the Spacelabs 90207 ABPM device (Medifacts, Rockville, Maryland, USA). The appropriate-sized BP cuff was placed on the nondominant arm of the participants and was programmed to take a measurement every 20 min throughout a 24-h cycle, for a total of 72 readings. The participants were asked to record the times that they went to sleep and woke up in a sleep diary to allow designation of awake and asleep BP measurements.

Nocturnal BP dipping was quantified as the difference between an individual's mean awake SBP and mean asleep SBP, and was expressed as the percentage of the mean awake SBP. Nocturnal BP dipping was used a continuous covariate in all analysis. Sleep-trough morning BP surge was defined as the difference between the mean SBP during the first 2 h after awakening and the mean of the three SBP measurements centered on the lowest night-time reading. Preawakening morning BP surge was defined as the difference in the mean SBP during the first 2 h after awakening and the mean of SBP measurements during the 2-h period immediately before awakening [4]. We used definitions for nocturnal and daytime hypertension put forward by the American Heart Association [15]. Nocturnal hypertension was defined as night-time SBP at least 125 mmHg or DBP at least 75 mmHg, and daytime hypertension was defined as daytime SBP at least 140 mmHg or daytime DBP at least 90 mmHg [15]. Participants with nocturnal hypertension, but normal awake BP, were categorized as having isolated nocturnal hypertension, whereas those with daytime hypertension, but normal nocturnal BP, were categorized as isolated daytime hypertension. Individuals with daytime and nocturnal hypertension were categorized as daytime–night-time hypertension, whereas individuals with normal daytime and night-time BPs were categorized as normotensive [15,16].

At exam 1, office BP was measured using a Hawskley random zero sphygmomanometer equipped with a range of four cuff sizes to achieve appropriate fit. BP was recorded as the average of the two seated measurements.

Back to Top | Article Outline

Outcomes and covariates

Serum creatinine was assessed from fasting blood samples collected during exams 1 and 3, and processed at the Central Laboratory (University of Minnesota). Among individuals who provided urine samples at these visits, the urine albumin and creatinine concentrations were assayed and were used to calculate the urine albumin-to-creatinine ratio (ACR).

Estimated GFR was calculated using the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) equation [17]. Our primary outcomes was incident CKD defined as an eGFR less than 60 ml/min per 1.73 m2 at exam 3. Our secondary endpoints were incident CKD defined as an eGFR less than 60 ml/min per 1.73 m2 at exam 3 in addition to decrease in eGFR above 10 ml/min per 1.73 m2 between exams 1 and 3, and incident CKD defined using the kidney Disease Improving Global Outcomes (KDIGO) definition at exam 3. The KDIGO definition of CKD is an eGFR below 60 ml/min per 1.73 m2 and/or urine ACR at least 30 mg/g, and therefore could only be applied in a substantially curtailed sample of individuals who had information on both serum creatinine and urine ACR available from exams 1 and 3 [18].

At exam 1, information regarding participants’ past medical history, marital status, and health insurance was obtained through standard, technician-administered questionnaires. Participants were considered current smokers if they had ever smoked, used chewing tobacco or nicotine gum, or were wearing a nicotine patch at the time of interview. Daily alcohol consumption was assessed by a validated food frequency questionnaire. Physical activity was assessed using the JHS Physical Activity Cohort survey [19]. BMI was calculated as the weight (in kilograms) divided by the height (in meters) squared.

Back to Top | Article Outline

Statistical analysis

Out of 1150 (21.7%) individuals who completed 24-h ABPM at the baseline visit, we excluded 173 individuals with incomplete sleep diary recording. Of the remaining 977 individuals, 830 had adequate 24-h ABPM recordings (successful recording of more than 75% of the 72 programmed measurements), and 644 of those participants had serum creatinine measured at exams 1 and 3. To calculate preawake and sleep through morning surge, we required more than three readings in the 2 h before and after awakening. For the purposes of our primary endpoint of incident CKD, we included only 603 participants with normal renal function at the baseline visit, defined as an eGFR above 60 ml/min per 1.73 m2, (Fig. 1). For the secondary incident CKD endpoint using the KDIGO definition, we analyzed the 440 individuals with information on both serum creatinine and urine albumin excretion at exams 1 and 3 who were without CKD at baseline (eGFR >60 ml/min per 1.73 m2 and urine ACR <30 mg/g at exam 1) to determine the association of 24-h ABPM characteristics with incident CKD using the KDIGO definition [20]. In secondary analyses, we analyzed the association of 24-h ABPM characteristics with the rate of eGFR decline in all 644 participants with exams 1 and 3 serum creatinine values. We calculated the distribution of baseline variables in the entire population and also among those with and without incident CKD. Differences in baseline covariates between participants with and without incident CKD were assessed using a t test for continuous variables and a chi-square test for categorical variables.



The association of nocturnal BP dipping at baseline with the incidence of CKD was analyzed by multivariable logistic regression analysis. Nocturnal BP dipping was used as a continuous variable in all analysis and all odds ratios (ORs) were expressed per 10% change in nocturnal BP dipping. We performed a similar analysis of the associations of both sleep-trough and preawakening morning BP surge with incidence of CKD. We generated multivariable models controlling for the following baseline covariates: sociodemographic factors including age, sex, marital status, and health insurance status; lifestyle factors including smoking status, BMI, alcohol consumption, and physical activity; clinical factors including fasting glucose, clinic SBP, eGFR, urine ACR, and history of cardiovascular disease. These variables were chosen because of their known association with BP and/or CKD. We also performed similar analyses examining other phenotypes based upon 24-h ABPM (i.e. isolated nocturnal hypertension, isolated daytime hypertension, daytime–night-time hypertension, white-coat hypertension and masked hypertension) in relation to the incidence of CKD using logistic regression analysis, and we implemented the same modeling strategy as presented above. In a sensitivity analysis, the association of nocturnal dipping and morning BP surge with incident CKD and annualized rate of eGFR decline was repeated with adjustment for mean 24-h SBP, replacing clinic BP in the multivariate model.

The association of nocturnal BP dipping at baseline and the subsequent rate of decrease in eGFR from exam 1 to exam 3 were assessed by multivariable linear regression analysis. We controlled for the same covariates as in the analysis of nocturnal dipping with incident CKD. In another secondary analysis, we assessed the associations of mean awake and asleep diastolic pressures and nocturnal dipping (calculated from mean awake and asleep DBPs) with incident CKD. Lastly, we repeated our analyses in a curtailed study population (n = 440) after redefining incident CKD based upon the KDIGO definition, using either eGFR less than 60 ml/min per 1.73 m2 or urine ACR at least 30 mg/g at visit 3 [20]. All statistical analyses were performed with SAS, version 9.3 (SAS Institute, Inc., Cary, North Carolina, USA).

Back to Top | Article Outline


Of the 603 individuals (mean age 57.8 ± 10.4 years, 68% women) with sufficient 24-h ABPM data and with no CKD at baseline, 74 (12%) went on to develop CKD by the time of their third visit (median follow-up 8.1 years). Individuals with incident CKD were older, had lower baseline eGFR, higher SBP (clinic, awake, and asleep), higher fasting glucose, higher urine ACR, and a greater prevalence of pre-existing cardiovascular disease than individuals who did not develop CKD (Table 1). The mean eGFR decline was 27.4 ± 18.6 ml/min per 1.73 m2 for the individuals who developed CKD compared with 4.3 ± 14.5 ml/min per 1.73 m2 among those who remained free of CKD. Those who developed CKD by exam 3 had less nocturnal dipping at baseline (P < 0.001).



Increased nocturnal BP dipping was independently associated with a decreased incidence of CKD (Table 2); the fully adjusted OR was 0.55 for every 10% greater dipping [95% confidence intervals (CIs) 0.32–0.96]. Mean awake and mean asleep SBP were associated with an increased risk for incident CKD (Table 2) in unadjusted analyses with ORs for every 10 mmHg higher SBP of 1.42 (95% CI 1.18–1.71) and 1.52 (95% CI, 1.30–1.79), respectively. After adjustment for potential confounders, the association of mean awake SBP with incident CKD lost significance (OR 1.07, 95% CI 0.79–1.45). However, the association of mean asleep SBP with incident CKD remained nearly significant after adjustment (OR 1.31 for every 10 mmHg increase in higher SBP, 95% CI 0.99–1.72). Similarly, in unadjusted analyses, isolated nocturnal hypertension was associated with a greater odds of developing CKD (OR 2.25, 95% CI 1.19–4.26), as was daytime–night-time hypertension (OR 2.62, 95% CI 1.46–4.29). These relationships remained significant after controlling for clinical risk factors [fasting glucose level, history of cardiovascular disease (myocardial infarction, stroke), eGFR, ACR], but only daytime–night-time hypertension remained significant in the full model (OR 2.33, 95% CI 1.02–5.32; Fig. 2). In contrast, neither sleep-trough nor preawakening morning BP surge was associated with the incidence of CKD (Table 2). Only those individuals with sustained hypertension were found to be at increased risk of developing incident CKD (OR 2.77, 95% CI 1.15–6.67) relative to normotensive individuals, whereas individuals with either white-coat hypertension or masked hypertension demonstrated a nonsignificant trend for increased risk of incident CKD (OR 3.38, 95% CI 0.90–12.62; and OR 2.32, 95% CI 0.97–5.61; Supplemental Fig. 1). Nocturnal dipping calculated from DBP measurements was also associated with an increased OR of incident CKD in unadjusted analysis (OR 0.66 for every 10% greater dipping, 95% CI 0.50–0.87), but failed to remain significant after adjustment for risk factors (Supplemental Table 1).





Consistent with our finding that greater nocturnal dipping was associated with a lower odds of incident CKD, greater dipping was also related to a lower rate of decline in eGFR between exam 1 and exam 3. This persisted in a fully adjusted model which included baseline eGFR and albuminuria, and every 10% greater dipping was associated with a 0.4 ml/min per 1.73 m2 slower annual decline in eGFR (P = 0.005) (Table 3).



When CKD was defined using the KDIGO guidelines, 94 out of the 440 individuals in this analysis developed CKD by their third visit. The association of greater nocturnal dipping with a reduced incidence of CKD persisted in the unadjusted analysis (OR 0.56 for every 10% greater dipping, 95% CI 0.40–0.78), but was not significant in the fully adjusted analysis (OR 0.74 for every 10% greater dipping, 95% CI 0.47–1.17; Supplemental Table 2).

Finally, in a sensitivity analysis examining the association of nocturnal dipping with incident CKD and annualized eGFR decline, replacing clinic SBP with mean 24-h SBP in the fully adjusted model had a marginal impact on the results for incident CKD (OR 0.59 for every 10% greater dipping, 95% CI 0.34–1.01) and for annualized eGFR decline (0.33 ml/min per 1.73 m2/year slower annual decline for every 10% greater dipping; P value = 0.02; Supplemental Tables 3–4).

Back to Top | Article Outline


In this prospective study in African Americans with normal kidney function at baseline, we found that greater nocturnal SBP dipping was independently associated with a lower incidence of subsequently developing CKD. Furthermore, individuals whose SBP dipped more had slower rates of eGFR decline over the follow-up period. Other 24-h BP characteristics determined from ABPM, including morning surge, isolated night-time hypertension, and isolated daytime hypertension, did not predict the incidence of CKD in multivariable models. To our knowledge, this is the first prospective study to document the association of nocturnal BP dipping with incident CKD in African American individuals, as well as the first to study the association of morning surge with incident CKD in any population. Characteristics of the 24-h BP profile shown to predict cardiovascular outcomes include nocturnal dipping [21], morning surge [4], and isolated nocturnal hypertension [22]. Although the association of 24-h ABPM characteristics with renal disease has been studied in patients with pre-existing CKD [8,23–25], studies among those with normal renal function are small and retrospective [9,26,27], and none have examined African Americans – a population at increased risk of having both abnormalities in the diurnal BP pattern and renal disease [11,28,29]. In a retrospective study of 102 hypertensive Korean patients clinically referred for ABPM, nondippers had a substantially higher risk of developing CKD (hazard ratio 30.8, 95% CI 1.8–542.1) over roughly 4 years of follow-up [26]. However, only 11 individuals in that study developed CKD, which accounts for the unstable association. A larger retrospective study of 322 mostly white hypertensive patients, referred for ABPM, found that nondipping was associated with a 9% faster decline in eGFR, and a six-fold higher risk of developing CKD [9]. In both these studies, the study populations included patients with clinical indications for ABPM, introducing the risk for selection bias, and outcomes were ascertained retrospectively from clinical records, introducing the risk of follow-up bias. Additionally, neither of these studies adjusted for baseline albuminuria – an important confounder – given the association of albuminuria with ESRD and mortality [30,31]. The JHS is a prospective population-based study, and therefore minimizes patient selection bias and measurement bias, which is prevalent in retrospective studies of ABPM and CKD detection. Due to the JHS collecting baseline blood and urine samples, we are able to better define the baseline population, and in longitudinal analysis adjust for important risk factors for renal disease, including baseline eGFR, albuminuria, smoking status, and BMI.

In addition to the association of dipping with incident CKD, we also found that nocturnal dipping independently predicted a slower decrease in eGFR decline over time – a finding which is consistent with results from a smaller case-control study of hypertensive patients with CKD [25]. In the secondary analysis, we found that the association of nocturnal dipping with incident CKD, defined using the KDIGO definition, did not remain significant in the fully adjusted analysis (OR 0.74 for every 10% greater dipping, 95% CI 0.47–1.17). This may be due to loss of power in the analysis due to exclusion of individuals who did not provide urine samples to allow measurement of albuminuria. Alternatively, with the KDIGO definition of CKD, some incident cases are due to an increase in urine ACR to at least 30 mg/g, with no or little decrement in eGFR. Since nocturnal dipping was not associated with an accelerated increase in ACR (data not shown), these incident cases would bias the association of nocturnal dipping and incident CKD towards the null.

We failed to find an association between morning surge in BP and incident CKD. An increase in the magnitude of the morning BP surge is a risk factor for cerebrovascular events in Japanese individuals [4] and, in cross-sectional analyses, is associated with markers of kidney damage such as proteinuria [32]. However, morning surge has not previously been examined as a risk factor for renal disease. In our analysis, neither sleep-trough nor preawakening BP surge was related to incident CKD. This might indicate that the cerebral vascular bed is more sensitive than the renal vascular bed to surges in BP, or that the risks of morning surge may be population-specific. Evidence for the latter possibility comes from studies among Italian individuals, suggesting that a decrease (not increase) in the magnitude of the morning BP surge is associated with increased cardiovascular events [5].

We found associations for increased mean asleep SBP and isolated nocturnal hypertension with incident CKD in unadjusted analyses, but these findings were nonsignificant after multivariable adjustment, likely due to diminished statistical power (sample size for analysis decreased from 603 without covariates in the model to 408 with covariates). This potential relationship of nocturnal BP and isolated nocturnal hypertension with risk of CKD has been described in the Ohasama cohort [10]. The Ohasama cohort study is a large longitudinal study (N = 843 without CKD at baseline) that has information about baseline ABPM and a high incidence of CKD (26%) during 8 years of follow-up [10]. In this well characterized cohort of lean, older, mostly female Japanese individuals, mean 24-h and asleep SBP, but not awake SBP, was associated with an increased incidence of CKD. This suggests asleep SBP may be a more significant predictor of decline in renal function than awake SBP. However, although nocturnal dipping was a robust predictor of incident CKD and decline in eGFR in our population of African Americans, it was not associated with incident CKD in the Ohasama cohort. This may be due to racial differences in the renal risks associated with diurnal BP patterns, similar to the difference in cardiovascular risk associated with diurnal BP patterns between the African American and the Japanese [33].

Our study has several limitations. Ambulatory BP was measured only once in the JHS and therefore prone to inaccuracies, since the diurnal pattern of BP can change over time within an individual. As an example, the intraclass correlation coefficient among individuals without CKD was 0.60 [34], suggesting that relying upon a single 24-h measurement may result in misclassification of some participants. However, this type of misclassification is likely to be random and therefore bias our estimates toward the null; as a result, the OR we found may actually be an underestimate of the true strength of the association. Second, only 21.7% of the participants in the JHS underwent ABPM, and of the 1150 that underwent monitoring, 173 were excluded from the analysis due to inadequate recording of sleep diaries and 147 were excluded due to less than 75% of the 72 programmed measurements being recorded (147). However, mean values of age, BMI, fasting glucose, as well as clinic BP (systolic and diastolic) of the sample used for our study are representative of the mean values for the larger cohort [35]. Third, incident CKD was defined based on a single measurement of eGFR or urine ACR, whereas KDIGO requires two measurements of eGFR 3 months apart, and so misclassification is possible. Again, this misclassification is likely to be random, as there is no evidence that nocturnal dipping is associated with acute kidney injury. As before, this type of misclassification would have caused us to underestimate the true association. Furthermore, our finding that dipping was also associated with slower eGFR decline supports the notion that nocturnal dipping is associated with a better renal prognosis. Fourth, we had limited information on cardiovascular measurements such as arterial stiffness or left ventricular dysfunction and sleep patterns such as obstructive sleep apnea, and therefore could not analyze potential mechanisms for the associations that we found. Fifth, the population was predominantly female (68%), which could limit the generalizability to men. Sixth, this was an observational study, and causality cannot be inferred from the results; it is possible that incipient kidney disease was responsible for the reduction in dipping. Even if this was the case, the independent association of dipping with CKD provides useful clinical information. Seventh, full data on antihypertensive medication prescribed at baseline or initiated during follow-up were not available. The short-term and long-term effects on eGFR of antihypertensive medications, as shown in the African American Study of Kidney Disease and Hypertension, (AASK) trial, can be difficult to predict as are their effects on nocturnal dipping [36]. Therefore, the effect of antihypertensive medications on the association reported is unclear. Lastly, the difference in mean nocturnal dipping between the group that developed incident CKD and the group that did not was small (7.7 vs. 4.6%), and this difference may not seem clinically relevant. However, the association was independent of multiple potential confounders, suggesting that small changes in dipping may correspond to important change in renal function.

We found a prospective association between decreased nocturnal BP dipping and increased incidence of CKD in a community-based sample of African Americans. This represents an important clinical finding to support the use of ABPM in high-risk populations such as this, in which case BP measured in the clinic may be an inadequate measurement of hypertension and an inadequate risk factor for CKD. Furthermore, it highlights the importance of future research into the mechanisms of nocturnal BP dipping and how modification of these may lead to effective therapies to reduce the incidence of CKD.

Back to Top | Article Outline


The Jackson Heart Study is supported by 352 contracts, N01-HC-95170, N01-HC-95171, N01-HC-95172 from the National Heart, Lung, and Blood Institute and the National Institute of Minority Health and Health Disparities, with additional support from the National Institute on Biomedical Imaging and Bioengineering.

Contributions: Research idea and study design: C.M., J.F., D.H.; data acquisition: D.H., H.T.; data analysis/interpretation: C.M., J.F.; statistical analysis: C.M.; supervision or mentorship: J.F.

C.M. takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Back to Top | Article Outline

Conflicts of interest

C.M. was funded by the ASN Research Fellowship – 2012D000333.

None of the other authors report financial disclosures or conflicts of interest.

Back to Top | Article Outline

Reviewers’ Summary Evaluations Referee 1

Strengths: Large number; adequate follow-up; novel observations; adequate statistical analysis; well written and referenced manuscript.

Weakness: You can always try for a larger and longer study with more events!

Back to Top | Article Outline


1. Ohkubo T, Imai Y, Tsuji I, Nagai K, Watanabe N, Minami N, et al. Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study. Am J Hypertens 1997; 10:1201–1207.
2. Kario K, Pickering TG, Matsuo T, Hoshide S, Schwartz JE, Shimada K. Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives. Hypertension 2001; 38:852–857.
3. Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension 2005; 46:156–161.
4. Kario K, Pickering TG, Umeda Y, Hoshide S, Hoshide Y, Morinari M, et al. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation 2003; 107:1401–1406.
5. Verdecchia P, Angeli F, Mazzotta G, Garofoli M, Ramundo E, Gentile G, et al. Day-night dip and early-morning surge in blood pressure in hypertension: prognostic implications. Hypertension 2012; 60:34–42.
6. Israel S, Israel A, Ben-Dov IZ, Bursztyn M. The morning blood pressure surge and all-cause mortality in patients referred for ambulatory blood pressure monitoring. Am J Hypertens 2011; 24:796–801.
7. Mojon A, Ayala DE, Pineiro L, Otero A, Crespo JJ, Moya A, et al. Comparison of ambulatory blood pressure parameters of hypertensive patients with and without chronic kidney disease. Chronobiol Int 2013; 30:145–158.
8. Timio M, Venanzi S, Lolli S, Lippi G, Verdura C, Monarca C, Guerrini E. Nondipper’ hypertensive patients and progressive renal insufficiency: a 3-year longitudinal study. Clin Nephrol 1995; 43:382–387.
9. Davidson MB, Hix JK, Vidt DG, Brotman DJ. Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate. Arch Intern Med 2006; 166:846–852.
10. Kanno A, Kikuya M, Asayama K, Satoh M, Inoue R, Hosaka M, et al. Night-time blood pressure is associated with the development of chronic kidney disease in a general population: the Ohasama Study. J Hypertens 2013; 31:2410–2417.
11. Jehn ML, Brotman DJ, Appel LJ. Racial differences in diurnal blood pressure and heart rate patterns: results from the Dietary Approaches to Stop Hypertension (DASH) trial. Arch Intern Med 2008; 168:996–1002.
12. Flessner MF, Wyatt SB, Akylbekova EL, Coady S, Fulop T, Lee F, et al. Prevalence and awareness of CKD among African Americans: the Jackson Heart Study. Am J Kidney Dis 2009; 53:238–247.
13. Taylor HA Jr. The Jackson Heart Study: an overview. Ethn Dis 2005; 15 (4 Suppl 6): S6-1-3.
14. Quan SF, Howard BV, Iber C, Kiley JP, Nieto FJ, O’Connor GT, et al. The Sleep Heart Health Study: design, rationale, and methods. Sleep 1997; 20:1077–1085.
15. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension 2005; 45:142–161.
16. Ogedegbe G, Spruill TM, Sarpong DF, Agyemang C, Chaplin W, Pastva A, et al. Correlates of isolated nocturnal hypertension and target organ damage in a population-based cohort of African Americans: the Jackson Heart Study. Am J Hypertens 2013; 26:1011–1016.
17. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150:604–612.
18. Foundation NK. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39 (2 Suppl 1):S1–S266.
19. Smitherman TA, Dubbert PM, Grothe KB, Sung JH, Kendzor DE, Reis JP, et al. Validation of the Jackson Heart Study Physical Activity Survey in African Americans. J Phys Activity Health 2009; 6 (Suppl 1):S124–S132.
20. Leproult R, Deliens G, Gilson M, Peigneux P. Beneficial impact of sleep extension on fasting insulin sensitivity in adults with habitual sleep restriction. Sleep 2014; Oct 28, [Epub ahead of print].
21. Zweiker R, Eber B, Schumacher M, Toplak H, Klein W. Nondipping’ related to cardiovascular events in essential hypertensive patients. Acta Med Austriaca 1994; 21:86–89.
22. Li Y, Staessen JA, Lu L, Li LH, Wang GL, Wang JG. Is isolated nocturnal hypertension a novel clinical entity? Findings from a Chinese population study. Hypertension 2007; 50:333–339.
23. Agarwal R, Andersen MJ. Prognostic importance of ambulatory blood pressure recordings in patients with chronic kidney disease. Kidney Int 2006; 69:1175–1180.
24. Agarwal R, Kariyanna SS, Light RP. Prognostic value of circadian blood pressure variation in chronic kidney disease. Am J Nephrol 2009; 30:547–553.
25. Agarwal R, Light RP. GFR, proteinuria and circadian blood pressure. Nephrol Dial Transplant 2009; 24:2400–2406.
26. An HR, Park S, Yoo TH, Kang SW, Ryu JH, Lee YK, et al. Nondipper status and left ventricular hypertrophy as predictors of incident chronic kidney disease. J Korean Med Sci 2011; 26:1185–1190.
27. Hackshaw A. Small studies: strengths and limitations. Eur Respir J 2008; 32:1141–1143.
28. Pogue V, Rahman M, Lipkowitz M, Toto R, Miller E, Faulkner M, et al. Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease. Hypertension 2009; 53:20–27.
29. Dirks JH, de Zeeuw D, Agarwal SK, Atkins RC, Correa-Rotter R, D’Amico G, et al. Prevention of chronic kidney and vascular disease: toward global health equity: the Bellagio 2004 Declaration. Kidney Int Suppl 2005; S1–S6.
30. Peralta CA, Shlipak MG, Judd S, Cushman M, McClellan W, Zakai NA, et al. Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality. JAMA 2011; 305:1545–1552.
31. Tonelli M, Muntner P, Lloyd A, Manns BJ, James MT, Klarenbach S, et al. Using proteinuria and estimated glomerular filtration rate to classify risk in patients with chronic kidney disease: a cohort study. Ann Intern Med 2011; 154:12–21.
32. Polonia J, Amado P, Barbosa L, Nazare J, Silva JA, Bertoquini S, et al. Morning rise, morning surge and daytime variability of blood pressure and cardiovascular target organ damage. A cross-sectional study in 743 subjects. Portuguese J Cardiol 2005; 24:65–78.
33. Ciaran J, McMullan YY, Bakris George L, Kazuomi Kario, Phillips Robert A, Forman John P. Racial impact of diurnal variations in blood pressure on cardiovascular events in chronic kidney disease. J Am Soc Hypertens 2015; 9:299–306.
34. McGowan NJ, Gough K, Padfield PL. Nocturnal dipping is reproducible in the long term. Blood Press Monit 2009; 14:185–189.
35. Fox CS, Yang Q, Cupples LA, Guo CY, Larson MG, Leip EP, et al. Genomewide linkage analysis to serum creatinine, GFR, and creatinine clearance in a community-based population: the Framingham Heart Study. J Am Soc Nephrol 2004; 15:2457–2461.
36. Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP, et al. Effect of ramipril vs. amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001; 285:2719–2728.

African Americans; incident chronic kidney disease; nocturnal blood pressure dipping

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.