Epidemiology of Hypertension in CKD Bruce Horowitz, Dana Miskulin, and Philip Zager Both hypertension (HTN) and CKD are serious interrelated global public health problems. Nearly 30% and 15% of US adults have HTN and CKD, respectively. Because HTN may cause or result from CKD, HTN prevalence is higher and control more difficult with worse kidney function. Etiology of CKD, presence and degree of albuminuria, and genetic factors all influence HTN severity and prevalence. In addition, socioeconomic and lifestyle factors influence HTN prevalence and control. There are racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of HTN in patients with CKD. Control of blood pressure (BP) in Hispanic and African Americans with CKD is worse than it is whites. There are disparities in the patterns of treatment and rates of progression of CKD in patients with HTN. The presence and severity of CKD increase treatment resistance. HTN is also extremely prevalent in patients receiving hemodialysis, and optimal targets for BP control are being elucidated. Although the awareness, treatment, and control of HTN in CKD patients is improving, control of BP in patients at all stages of CKD remains suboptimal. Q 2015 by the National Kidney Foundation, Inc. All rights reserved. Key Words: Hypertension, Chronic kidney disease, Health disparities, Epidemiology

Introduction Hypertension (HTN) and CKD are inter-related and represent global public health challenges. In this review, we examine trends in the prevalence and awareness of HTN among CKD patients, the adequacy of HTN control and the variability in these measures across demographic and clinical factors.

Definitions of HTN and CKD The American Heart Association defines HTN as a blood pressure (BP) of 140/90 mm Hg or more, measured as shown in Table 1. The Eighth Joint National Committee (JNC 8) guidelines define thresholds for pharmacologic treatment rather than focusing on definitions of HTN and prehypertension. It recommends beginning antihypertensive therapy (AHT) to lower diastolic blood pressure (DBP) to less than 90 mm Hg in patients aged 30 to 59 years and to less than 150/90 mm Hg in hypertensive patients of 60 years or older.1 Criteria for CKD include an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 for more than 3 months or a urine albumin-to-creatinine ratio (ACR) more than 30 mg of albumin per gram of creatinine (30 mg/g). Stages of CKD are defined by eGFR (Table 2). GFR is commonly assessed using estimating equations derived from the Modification of Diet and Renal Disease (MDRD) Study.2 More recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed to obtain more precise estimates of GFR. The CKD-EPI equation outperforms the MDRD forFrom University of New Mexico, Albuquerque, NM; Tufts University, Boston, MA; and Dialysis Clinic, Inc, Nashville, TN. Financial Disclosure: B.H. has nothing relevant to disclose; D.M. receives salary support from DCI; P.Z. has received honoraria for participation on the Keryx Medical Advisory Board. He also is an employee of both University of New Mexico and Dialysis Clinic, Inc. Address correspondence to Philip Zager, MD, University of New Mexico, 1500 Indian School Road, NE Suite 200, Albuquerque, NM 87102. E-mail: [email protected] Ó 2015 by the National Kidney Foundation, Inc. All rights reserved. 1548-5595/$36.00 http://dx.doi.org/10.1053/j.ackd.2014.09.004

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mula, especially when the measured GFR is more than 60 mL/min/1.73 m2.3

Epidemiology of HTN and CKD Primary HTN and CKD are highly prevalent and increasing dramatically worldwide, especially among those older than 65 years. In the National Health and Nutrition Examination Survey (NHANES) 2009 to 2010, a nationally representative sample of noninstitutionalized adults aged 20 years or older, the age-adjusted prevalence estimate for HTN was 28.6%.4 The prevalence estimates of HTN, stratified by age, race and sex, are shown in Table 3. Coresh and colleagues5 conducted a cross-sectional analysis of NHANES 1988 to 1994 and NHANES 1999 to 2004 data. CKD prevalence was determined by persistent albuminuria and decreased eGFR by the MDRD estimating equation. From 1988 to 1994 to 1999 to 2004, the prevalence of CKD stages 1 to 4 increased from 10.0% (95% confidence interval [CI], 9.2%-10.9%) in 1988 to 1994 to 13.1% (95% CI, 12.0%-14.1%) in 1999 to 2004.5 However, the prevalence estimates of CKD may differ slightly depending on the estimating equation used. The difference between measured and eGFR is smaller with the CKD-EPI vs the MDRD estimating equation. Use of the CKD-EPI equation for participants with an eGFR of 30 to 59 mL/min/1.73 m2 reduced bias from 4.9 to 2.1 mL/min/1.73 m2. For eGFR of 60 to 89 mL/min/1.73 m2, bias was decreased from 11.9 to 4.2 mL/min/1.73 m2.6 The relationship between HTN and CKD is complex. HTN is a commonly reported cause of CKD. In contrast, HTN may complicate CKD among previously normotensive patients. Overall, the prevalence of HTN is high among CKD patients and increases by stage.7,8 However, some cases of CKD previously attributed to HTN may reflect genetic polymorphisms.9 Apolipoprotein CIII (Apo CIII) gene has been identified as a candidate region for HTN, hyperlipidemia, and atherosclerosis.10 The etiology of primary HTN is multifactorial. Although there are rare cases of monogenic HTN, most frequently HTN results from multiple genes acting in concert.

Prevalence and Awareness of HTN in CKD The prevalence of HTN increases with declining eGFR. The prevalence of HTN among patients with an eGFR

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less than 60 mL/min/1.73 m2 (84%) or an ACR more than CKD patients. In CRIC, the prevalence of HTN was lower 30 mg/g (69%) did not change between 1988 to 1994 and among patients with at least a high school education, higher 2005 to 2010.11 In the Chronic Renal Insufficiency Cohort income levels, lower body mass index, and in current or (CRIC) Study, a longitudinal study of 3939 diverse adults former smokers.12 For additional information on HTN in minorities, please see the article by Dr Ferdinand entitled Hyaged 21 to 74 years, the prevalence of HTN was inversely pertension in Minority Populations in this issue of related to eGFR (Table 4).12 The National Kidney Foundation’s Kidney Early EvaluaAdvances in Chronic Kidney Disease.25 Several studies have suggested that the increased risk of tion Program (KEEP), a community-based health CKD and ESRD attributed to HTN has a genetic composcreening of over 115,000 adults with risk factors for nent.26 In the African American Study of Kidney Disease CKD, including personal or family history of diabetes or and Hypertension (AASK) trial, progression of CKD was HTN, yielded prevalence estimates similar to those more rapid in individuals with certain variants of the nonobserved in CRIC.13-15 The higher prevalence estimates in CRIC and KEEP vs NHANES likely reflect the muscle myosin 2a (MYH9), suggesting a possible role for selection of high-risk individuals. In China,16 India,17 this protein in the pathogenesis and progression of focal and Mexico,18 the prevalence estimates for HTN among segmental glomerulosclerosis.27 In addition, an associaCKD patients were similar to those in CRIC. Although tion was identified between nondiabetic kidney diseases the prevalence of HTN among CKD patients increases as in non-Hispanic blacks with the MYH9 gene on chromoeGFR declines, HTN may be more closely related to albusome 22 using mapping by admixture linkage disequilibminuria than to eGFR.19 rium.28-30 HTN-related CKD is more strongly associated The prevalence of HTN among CKD patients varies by with variants in an adjacent gene, apolipoprotein the etiology of CKD. In an academic outpatient nephrology L1 (APOL1), which localizes to human glomeruli31 and confers resistance to African trypanosomiasis.32 Two alleles clinic in Spain, HTN was more common among patients of the APOL1 gene are associated with lower age of onset of with polycystic kidney disease (74%), diabetic nephropaESRD in non-Hispanic thy (87%), and kidney artery blacks and Hispanics stenosis (93%), compared with nondiabetic CKD.33 with chronic pyelonephritis CLINICAL SUMMARY Therefore, genetic factors (63%), glomerulonephritis may predispose to CKD, (54%), hereditary congenital  Hypertension and CKD are inter-related and present global which in turn may lead to disease (19%), and tubulopublic health challenges. HTN.34 pathies (5%).20 Diabetes is  Hypertension may cause or complicate CKD. In the MDRD study, consistently associated with  The prevalence of hypertension increases and control body mass index was a a high prevalence of HTN, becomes more difficult with progression of CKD. strong predictor of HTN independent of eGFR.12 Pooled data from NHAamong patients with a  There are racial, ethnic, and sex disparities in the NES III and NHANES 1999 GFR 25 to 55 mL/min/ awareness, prevalence, and treatment of hypertension in to 2006 demonstrated that 1.73 m2.7 Surprisingly, diepatients with CKD. tary sodium intake, asalbuminuria was an indepensessed by 24-hour urine dent risk factor for HTN.21,22 The prevalence ratios of sodium excretion, was not HTN increased progressively through an ACR of 100 mg/g. associated with HTN.7 In a follow-up study of MDRD participants, weight loss was associated with a significant However, the association with HTN was attenuated after decrease in BP, whereas dietary sodium restriction had adjustment for age, consistent with colinearity.21 In NHANES IV, albuminuria was independently associated with inadeonly a modest effect.35 quate HTN control in patients with CKD (adjusted odds ratio Resistant HTN in CKD [OR] of 2.4 [95% CI, 1.4-4.1]).22 The relationship between Resistant HTN, defined as BP that remains above goal albuminuria and HTN may stem from the relationship of despite treatment with 3 different classes of AHT both albuminuria and HTN to inflammation, kidney sodium agents,36,37 is common in CKD. An eGFR less than handling, and endothelial dysfunction. 60 mL/min/1.73 m2 was more common in participants There are significant disparities in the prevalence of HTN with uncontrolled (33.7%) vs controlled HTN (16.5%). among CKD patients. The prevalence of HTN is higher An Italian study confirmed that mean eGFR was lower among non-Hispanic blacks than non-Hispanic whites.7,12,15 among those with resistant HTN (35 mL/min/1.73 m2) vs In CRIC, HTN was present in 80% of whites and 93% of controlled HTN (45 mL/min/1.73 m2).38 Resistance to African Americans with a GFR less than 60 mL/min/ 2 HTN therapy at low eGFR levels results, in part, from 1.73 m . In the general population, the prevalence of HTN impaired sodium excretion and fluid retention. is similar among Hispanics and non-Hispanic whites,4 but Hispanics have a greater risk for CKD. Among CRIC participants, the prevalence of ESRD among Hispanics was 1.5Awareness and Adequacy of HTN Control Increased awareness and treatment of HTN among CKD fold higher than in non-Hispanics.23,24 Self-reported HTN was present in 89% of Hispanics vs 79% of non-Hispanic patients has improved HTN control. JNC 8 recommends whites and 93% of non-Hispanic blacks. Socioeconomic stathat initial or add on therapy of HTN in CKD patients tus and lifestyle behaviors influence the risk for HTN among should be a renin-angiotensin-aldosterone system

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Table 1. Blood Pressure Measurement Techniques Method

Notes

In office Ambulatory BP monitoring Patient self-check

Two readings, 5 min apart, sitting in chair. Confirmed elevated reading in contralateral arm. Indicated for evaluation of “white coat hypertension.” Absence of 10%-20% BP decrease during sleep may indicate increased CVD risk. Provide information on response to therapy. May help improve adherence to therapy and is useful for evaluating “white coat hypertension.”

Abbreviations: BP, blood pressure; CVD, cardiovascular disease. Source: US Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program.

(RAAS) inhibitor, regardless of race or diabetes status.1 Egan and others,39 relying on NHANES data, reported that between 1988 to 1994 and 1999 to 2008, HTN control increased from 27.3% to 50.1%. This was accompanied by increases in awareness (69.1% vs 80.7%) and treatment (54.0% vs 72.5%) of HTN. KEEP participants had even higher rates of awareness (80.2%) and treatment (70.0%), although HTN was controlled in only 13.2%.40 In NHANES 1988 to 1994, only 11% of those with an elevated serum creatinine (.1.6 mg/dL for men and .1.4 mg/dL for women) had their BP in the JNC 6 target range of less than 130/85 mm Hg.41 Comparing the 2010 and 1988 to 2004 NHANES participants (Fig 1), HTN awareness among individuals with GFR less than 60 mL/min/1.73 m2 increased (82% vs 73%), HTN control increased (32% vs 10%), and the percentage of patients who were aware but not treated decreased (12% vs 3%). Despite the increased awareness and treatment, uncontrolled HTN was present in approximately 50% of patients with HTN and CKD in NHANES 2010. This is in concert with CRIC, in which 67.1% and 46.1% of participants had BP less than 140/90 and less than 130/80 mm Hg, respectively.12 There are significant racial and ethnic disparities in HTN control among CKD patients. HTN control was poorer among non-Hispanic blacks and Hispanics vs nonHispanic whites at all stages of CKD. Data from CRIC and the Hispanic-Chronic Renal Insufficiency Cohort (HCRIC) studies demonstrated that a BP more than 130/ 80 mm Hg was more common among Hispanics (62%) and non-Hispanic blacks (57%) vs non-Hispanic whites

(35%).42 In NHANES 1999 to 2002, non-Hispanic blacks (OR 2.4) and age greater than 75 (OR 4.7) were independently associated with inadequate HTN control among CKD patients.22 Among KEEP participants with advanced CKD, non-Hispanic blacks were 20% less likely to meet BP targets than non-Hispanic whites (OR 0.79, P , .01).43 In the Multiethnic Study of Atherosclerosis, a populationbased study of 6814 adults without CKD, HTN control was less common among non-Hispanic blacks vs nonHispanic whites.44 In the MDRD study, non-Hispanic blacks randomized to a target BP less than 140/90 mm Hg required a mean of 2.7 concurrent AHT medications vs 1.8 in non-Hispanic whites.45 There were important differences in control and management of HTN among Hispanics, non-Hispanic blacks, and non-Hispanic whites in CRIC/H-CRIC.42 HTN was more common among Hispanics (67%) vs non-Hispanic blacks (57%). Overall, there were no differences in using RAAS-blocking agents among the 3 groups. However, among high-risk participants, including those with diabetes, proteinuria, and a BP more than 130/80 mm Hg, Hispanics were less likely than non-Hispanic blacks and non-Hispanic whites to receive a RAAS inhibitor (P , .05). Only 60% of Hispanics with eGFR less than 30 mL/min/ 1.73 m2 were prescribed RAAS-inhibiting drugs, compared with 75% of non-Hispanic whites and 67% of non-Hispanic blacks. Hispanics with an eGFR less than 30 mL/min/1.73 m2 were less likely to have a BP less than 130/80 mm Hg.39,42

Table 3. Age-Specific and Age-Adjusted Prevalence of Hypertension in Adults Aged $18 Years: United States, 2009-2010 Table 2. Stages of CKD Stage 1 2 3 4 5

Characteristics 2

Description

GFR (mL/min/1.73 m )

Kidney damage with normal or [GFR Kidney damage with mild YGFR Moderate YGFR Severe YGFR Kidney failure

$90 60-89 30-59 15-29 ,15 (or dialysis)

Abbreviation: GFR, glomerular filtration rate. CKD is defined as either kidney damage or GFR ,60 mL/min/1.73 m2 for $3 months. Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. Reprinted with permission from National Kidney Foundation, Inc.

Overall Age (y) 18-39 40-59 $60 Sex Men Women Race and Hispanic origin Hispanic Non-Hispanic white Non-Hispanic black

Prevalence Percent (SE) 28.6 (0.9) 6.8 (0.7) 30.4 (2.0) 66.7 (1.8) 29.4 (1.3) 27.5 (0.9) 26.1 (0.9) 27.4 (1.2) 40.4 (1.7)

Source: CDC/NCHS, National Health and Nutrition Examination Survey 2009-2010.

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Table 4. Prevalence of Hypertension by Estimated GFR eGFR (ml/min/1.73 m2)

Prevalence (%)

.60 50-59 40-49 30-39 ,30

67 82 88 91 92

Abbreviation: eGFR, estimated glomerular filtration rate. Reprinted with permission from the American Journal of Kidney Disease.

There are conflicting data on the relationship of the stage of CKD to HTN control. A population-based study from Turkey found an inverse relationship of CKD stage to HTN control. Overall, HTN control was present in 13.4% with the lowest rate in CKD Stage 1 (12.3%) and the highest in CKD Stage 4 (40%).46 This is in concert with data from KEEP in which HTN control among participants with CKD Stage 3 was 2.2-fold more common than those with CK Stage 1.40 In contrast, among CRIC participants, there was no difference in HTN control by CKD stage, although overall HTN control was better than in previous studies.12 A recent survey of nearly 9000 inpatients with nondialysis CKD conducted in China found that the percentage of patients with uncontrolled HTN was highest among those with advanced CKD.16

Changing Patterns of HTN Treatment NHANES data provide evidence that significant changes have occurred in HTN management. Overall, the percentage of hypertensive participants who were prescribed AHT medications increased from 63.5% in 2001 to 2002 to 77.3% in 2009 to 2010 and the percentage of patients taking multiple AHT increased from 36.8% to 47.7%.48 During the same period, the percentage of hypertensive NHANES participants with CKD who were prescribed AHT medications increased from 79.0% to 83.9% in 2009 to 2010. The mean number of AHT medications was also higher in CRIC vs MDRD. Among MDRD participants in the low BP arm (,140/90 mm Hg), the mean number of AHT drugs used was 2.1, whereas in the more recent CRIC study in

Figure 1. Awareness, treatment, and control of BP in US Population with estimated glomerular filtration rate less than 60 mL/min/1.72 m2, NHANES 1998 to 2004 vs 2010. Awareness had increased and very few patients (3%) are not treated, but the proportion of patients with BP in control (,140/90 mm Hg) remains low at 32%.47 Abbreviations: BP, blood pressure; NHANES, National Health and Nutrition Examination Survey.

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which the target BP was less than 130/80 mm Hg, 58% of hypertensive participants required 3 or more AHT medications.12 The higher mean number of AHT medications in CRIC vs MDRD likely reflects the lower BP target in the former study. The most commonly prescribed AHT drugs in the MDRD were diuretics and calcium channel blockers.49 In contrast, in the more recent CRIC study, the most commonly prescribed AHT drugs were agents inhibiting the RAAS system.12

HTN and CKD: A 2-Way Street HTN is a risk factor for the onset and progression of CKD.41,50,51 Among participants in NHANES 1988 to 1994, an elevated serum creatinine was 8-fold higher among those with HTN (9.1%) vs those with a normal BP.41 The US Renal Data System Annual Data Report 2013 attributed up to 25% of cases of CKD to HTN.11 Kidney biopsies in 39 AASK trial participants demonstrated hypertensive nephrosclerosis.52 Although there is compelling evidence from large observational studies that uncontrolled HTN causes kidney failure, there is uncertainty about the degree and duration required to produce CKD. In the Multiple Risk Factor Intervention Trial,53 systolic blood pressure (SBP) and DBP were strong independent risk factors for progression to ESRD.54 The risk for ESRD was over 20-fold greater among those with BP more than 210/120 mm Hg vs less than 120/80 mm Hg. Data from NHANES 1988 to 1994 demonstrated an association between HTN and reduced kidney function.41 Even mild HTN increases the risk of kidney disease, including ESRD, particularly in non-Hispanic blacks.55,56 However, definitive evidence that aggressive BP lowering in established CKD slows progression is lacking.57 A metaanalysis of trials of HTN treatment in nondiabetic CKD found that the lowest risk for CKD progression occurred in patients with SBP of 110 to 130 mm Hg.58 Similarly among type 2 diabetic patients, lowering BP with irbesartan decreased the risk for CKD progression.59 In the MDRD trial, HTN control failed to slow the progression of CKD. Overall, in the AASK trial, lowering BP to less than 120/80 mm Hg vs less than 140/90 mm Hg was not associated with slowing CKD progression.60 However, a post hoc analysis demonstrated that lowering BP blood slowed progression of CKD among those with significant proteinuria. Among CKD patients, race may influence the risk for ESRD. Among MDRD participants with similar eGFR values, non-Hispanic blacks were nearly 5-fold more likely than non-Hispanic whites to progress to ESRD.51 However, mean SBP and DBP were higher among African Americans (147/82 mm Hg) vs whites (137/77 mm Hg).61 Current BP targets do not differ according to race or ethnicity. The BP targets in patients with CKD are discussed in detail in this issue of Advances in Chronic Kidney Disease.

HTN Control and Cardiovascular Outcomes in CKD HTN is an important risk factor for left ventricular hypertrophy,62 cardiovascular events,63 and stroke64 in the general population. Unfortunately, large randomized clinical

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trials assessing the impact of HTN control or AHT drug class on prespecified cardiovascular outcomes in CKD patients have not been conducted. Despite limited evidence, JNC 765 recommended a target BP of less than 130/80 mm Hg for patients with CKD. More recent recommendations in JNC 81 acknowledge the limitations of available evidence. Two recent retrospective cohort studies highlight the need for evidence-based guidelines.66,67 In the first, Kovesdy and colleagues66 assessed all-cause mortality in veterans with an eGFR less than 60 mL/min/1.73 m2 and initially uncontrolled HTN. Surprisingly, mortality was higher among patients treated to an SBP less than 120 mm Hg vs 120 to 139 mm Hg (adjusted hazard ratio 1.7, [95% CI, 1.63 to 1.78]). In the second study, Sim and others67 performed in a hypertensive population, a quarter of whom had CKD, there was a U-shaped curve for the prespecified composite outcome of all-cause mortality or ESRD. The lowest risk for the combined end point was in the SBP range of 130 to 139 mm Hg. Similarly, the adjusted hazard ratio for mortality was lowest in those whom BP was treated to 130 to 139 mm Hg. Hazard ratio for mortality were 4.26 for SPB less than 110 mm Hg and 3.72 for SBP more than 169 mm Hg. Evidence generated from randomized clinical trials is necessary to write meaningful guidelines.

HTN in Hemodialysis Patients HTN is present in more than 80% of hemodialysis (HD) patients, most of whom have isolated systolic or combined systolic and diastolic HTN.68,69 Predialysis BP varies substantially within individuals70 and higher BP variability has been associated with cardiovascular events and mortality.71 The mean number of antihypertensive drug classes prescribed 6 months after starting HD is 2.5. Beta-adrenergic blocking agents are most commonly prescribed antihypertensive class, followed by RAASblocking agents and dihydropyridine calcium channel blockers.72 No large randomized clinical trials have been conducted in HD patients that have demonstrated benefit of a particular AHT class or BP level. However, results from 2 meta-analyses of small, randomized clinical trials have suggested that treatment with AHT may decrease cardiovascular events, even though the reduction in BP was modest.68,73 Kidney Disease Outcome Quality Initiative guidelines recommend pre- and postdialysis BP of 140/90 mm Hg and less than 130/80 mm Hg, respectively. However, these recommendations are based on data extrapolated from the general population. Moreover, observational data indicate that patients who achieve these targets may experience more frequent episodes of symptomatic hypotension and increased mortality.74-77 The inclusion of untreated patients with low BP reflecting underlying cardiac disease may have contributed to these surprising results. Extracellular fluid overload is a major contributor to HTN in HD patients.78-88 The Dry-Weight Reduction in Hypertensive Hemodialysis Patients Study demonstrated that reducing the estimated dry weight by a mean of 1 kg over 8 weeks was associated with reductions in SBP (6.6 mm Hg [95% CI, 1.0-12.2]) and DBP (3.3 mm Hg [95% CI, 0.2-6.4]).49,87,89-93 However, this was

accompanied by an increase in vascular access thrombosis. The Blood Pressure in Dialysis Study is an ongoing pilot study that is assessing the feasibility of conducting a large-scale randomized clinical trial comparing usual to intensive treatment of HTN in HD patients.94 Among HD patients, home BP measurements and ambulatory BP monitoring are stronger than routine dialysis unit BP measurements in predicting clinical outcomes.95 Extending treatment time and increasing the frequency of HD may improve HTN control, decrease the number of AHT used, and lower risk for an increase in left ventricular mass.96-102 This may reflect a reduction in estimated dry weight, reduced neurostimulation,103 and/or greater removal of vasoactive hormones.82,84 The Time to Reduce Mortality in End-Stage Renal Disease Trial is a pragmatic trial designed to explore the hypothesis that increasing treatment time for 3.5 to 4.25 hours will decrease mortality (http://clinicaltrials.gov/show/ NCT02019225). Both HTN and CKD HTN are interwoven and present a global health challenge. As CKD progresses, HTN becomes more common and more difficult to control. There are socioeconomic and racial/ethnic disparities in the prevalence, treatment, risks, and outcomes of HTN among CKD patients. Although awareness, treatment, and control of HTN in CKD patients are improving, there is much yet to be done.

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