Limitations of blood pressure target in non-dialysis chronic kidney disease: a question of method?

International guidelines recommend to reduce blood pressure (BP) levels below 130/80 mmHg in non-dialysis chronic kidney disease (CKD) patients. However, this BP target has not been validated by randomized controlled trials and is mainly driven by data obtained in observational and post-hoc analyses suggesting that it improves the renal and, to some extent, cardiovascular prognosis. The inconclusive results on the prognostic role of the BP target in patients with CKD might also relate to the limited ability of office BP readings to adequately stratify the global risk of this population. In fact, alterations of the pressure profile (such as white-coat hypertension) and nighttime hypertension are common in CKD patients. Recent studies have demonstrated that ambulatory blood pressure monitoring (ABPM) is superior to clinic BP measurements in predicting renal death and cardiovascular events. Therefore, while waiting for the results from the ongoing randomized Systolic Blood Pressure Intervention Trial (SPRINT) comparing the effect on cardiorenal prognosis of two BP target levels, the more widespread use of ABPM is desirable in CKD patients.     

Prevalence of Homocysteine‐Related Hypertension in Patients With Chronic Kidney Disease

Patients with both hypertension and hyperhomocysteinemia, termed H‐type hypertension, have a high risk for cardiocerebrovascular diseases. However, little is known about the prevalence of H‐type hypertension or its role in target organ damage in patients with chronic kidney disease (CKD). The authors recruited 1042 patients with CKD who were admitted to their hospital division. Multiple linear regression analyses were used to evaluate the association between H‐type hypertension and renal/cardiovascular parameters. A total of 460 (44.14%) CKD patients had H‐type hypertension. Multivariate logistic regression analysis showed that H‐type hypertension is associated with serum albumin, uric acid, estimated glomerular filtration rate (eGFR), and 24‐hour systolic blood pressure. Patients with H‐type hypertension had the worst renal function and left ventricular hypertrophy among all patients, while the levels of carotid intima‐media thickness (cIMT) in patients with H‐type hypertension were only slightly higher than in patients with normotension and normohomocysteinemia (P<.05). H‐type hypertension was associated with eGFR, left ventricular mass index, and cIMT according to multiple linear regression analyses. The prevalence of H‐type hypertension was high and H‐type hypertension was associated with target organ damage in patients with CKD.     

Treatment of hypertension in patients with nondiabetic chronic kidney disease

Hypertension is highly prevalent in patients with chronic kidney disease (CKD). As either the cause or the consequence of CKD, hypertension is an important independent factor determining the rate of loss of renal function. Hypertension is also a significant independent risk factor for cardiovascular events in patients with CKD, the leading cause of their morbidity and mortality. Based on evidence from observational cohort studies and randomized clinical trials, the Canadian Hypertension Education Program (CHEP) recommends a target blood pressure (BP) of lower than 130/80 mmHg in hypertensive patients with nondiabetic CKD. The CHEP also endorses the use of renin-angiotensin system blockers for the BP-lowering regimen in nondiabetic patients with CKD and significant proteinuria. It is recognized that the majority of nondiabetic patients with CKD will require two or more BP-lowering drugs to attain target BP. Furthermore, extracellular fluid volume expansion is a major contributor to hypertension in patients with CKD, and diuretics should be part of the BP-lowering regimen in the majority of patients. Patients with CKD are recognized to be at high risk for cardiovascular events, and studies testing new emerging treatments of hypertension to reduce the burden of CKD on renal and cardiovascular outcomes are underway. In this regard, the CHEP will continue to review and update all its recommendations annually.     

3～4期慢性肾脏病合并高血压265例用药控制情况及影响因素分析

目的了解慢性肾脏病(CKD)3～4期合并高血压患者血压控制情况、治疗现状,分析其影响因素。方法分析2010年4月至2011年4月265例在北京友谊医院CKD门诊规律随访3个月以上的CKD 3～4期合并高血压的患者的临床资料和治疗情况。结果高血压知晓率为97.7%,知道正确靶目标值的患者占83%,血压控制在130/80 mmHg以下的CKD高血压患者占39.2%。服用3种以上降压药物的患者占19.6%,利尿剂使用比例6.8%。结论应加强对CKD合并高血压患者的教育及自我管理的培训,临床医师应给予患者更加积极合理的降压治疗,提高血压控制率,改善预后。     

Hypertension management: Special considerations in chronic kidney disease patients

It has been estimated that approximately 11% of the US adult population has chronic kidney disease (CKD), and it has been demonstrated that the prevalence of hypertension rises significantly as renal function declines. Even mild CKD significantly increases mortality risk, and cardiovascular disease remains the main cause of death among these patients. Although CKD patients have generally been excluded from trials testing the effect of lowering blood pressure on cardiovascular outcomes, guidelines suggest lowering blood pressure in hopes of reducing cardiovascular mortality and slowing the progression of renal disease. The preferred antihypertensive agents among these patients are drugs that block the renin-angiotensin system. In most hypertensive CKD patients, however, multiple agents are necessary to reach blood pressure targets. In general, diuretics and calcium channel blockers are added subsequently as adjunctive therapy. Hopefully, with increased recognition of the unique aspects of treating hypertension in this population, end-stage renal disease and cardiovascular morbidity and mortality will be delayed or avoided in the millions of patients with CKD.     

Hypertension, dyslipidemia and cardiovascular risk in chronic renal disease]

Cardiovascular disease is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). The presence of CKD whether manifested by albuminuria or reduction in glomerular filtration rate is an independent risk factor for cardiovascular outcome. This is mainly due to both an overexpression of traditional cardiovascular risk factors, and the onset of new factors which are peculiar of CKD. In this revision the role of arterial hypertension and of dyslipidemia is analyzed in detail. Most interventional trials have demonstrated that a reduction of blood pressure and the normalization of lipid profile are associated with a significant reduction in the incidence of major cardiovascular events and mortality. According to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) recommendations, patients with CKD, regardless of the stage of disease, should be considered the highest risk group for cardiovascular events. For these patients the NKF-K/DOQI guidelines recommend strict blood pressure control, renin-angiotensin system blockade, and the use of statins with target LDL cholesterol levels < 100 mg/dl.     

Nocturnal Hypertension Correlates Better With Target Organ Damage in Patients With Chronic Kidney Disease than a Nondipping Pattern

Both nocturnal hypertension and nondipping pattern are associated with target organ damages (TODs); however, no data exist with respect to Chinese patients with chronic kidney disease (CKD). The authors recruited 1322 patients with CKD admitted to our hospital division and referred with data in this cross‐sectional study. Patients with nocturnal systolic hypertension had a lower estimated glomerular filtration rate (eGFR) and higher left ventricular mass index (LVMI) and carotid intima‐media thickness (cIMT) compared with patients with normal nocturnal systolic blood pressure (SPB; all, P<.001), while patients in the dipper and nondipper groups had similar levels of eGFR, LVMI, and cIMT when the patients had a similar nocturnal SBP. Factorial‐designed analysis of variance indicated that the main effect of nocturnal SBP was significant for all TOD differences (all, P<.001), but no significance existed with respect to the main effect of the dipper pattern and an interaction between the two factors (all, P>.05). Nocturnal systolic hypertension, rather than nondipping pattern, was an independent risk factor for TOD in CKD patients. Nocturnal hypertension, rather than a nondipping pattern, was better associated with TOD in CKD patients.     

Prevalence and predictors of chronic kidney disease among Ghanaian patients with hypertension and diabetes mellitus: A multicenter cross‐sectional study

The burden of chronic kidney disease (CKD) is rapidly rising in developing countries due to astronomical increases in key risk factors including hypertension and diabetes. We sought to assess the burden and predictors of CKD among Ghanaians with hypertension and/or diabetes mellitus in a multicenter hospital‐based study. We conducted a cross‐sectional study in the Ghana Access and Affordability Program (GAAP) involving adults with hypertension only (HPT), hypertension with diabetes mellitus (HPT + DM), and diabetes mellitus only (DM) in 5 health facilities in Ghana. A structured questionnaire was administered to collect data on demographic variables, medical history, and clinical examination. Serum creatinine and proteinuria were measured, and estimated glomerular filtration rate derived using the CKD‐EPI formula. A multivariable logistic regression model was used to identify factors associated with CKD. A total of 2781 (84.4%) of 3294 participants had serum creatinine and proteinuria data available for analysis. The prevalence of CKD was 242 (28.5%) among participants with both DM and HPT, 417 (26.3%) among participants with HPT, and 56 (16.1%) among those with DM alone. Predictors of CKD were increasing age aOR 1.26 (1.17‐1.36), low educational level aOR 1.7 (1.23‐2.35), duration of HPT OR, 1.02 (1.01‐1.04), and use of herbal medications aOR 1.39 (1.10‐1.75). Female gender was protective of CKD aOR 0.75 (0.62‐0.92). Among patients with DM, increasing age and systolic blood pressure were associated with CKD. There is high prevalence of CKD among DM and hypertension patients in Ghana. Optimizing blood pressure control and limiting the use of herbal preparations may mitigate CKD occurrence in high cardiovascular risk populations in developing countries.     

Control of hypertension in adults with chronic kidney disease in the United States

Although improved control of hypertension is known to attenuate progression of chronic kidney disease (CKD), little is known about the adequacy of hypertension treatment in adults with CKD in the United States. Using data from the Fourth National Health and Nutrition Survey, we assessed adherence to national hypertension guideline targets for patients with CKD (blood pressure <130/80 mm Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure, and we evaluated determinants of adequate blood pressure control. Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m2 or presence of albuminuria (albumin:creatinine ratio >30 microg/mg). Multivariable logistic regression with appropriate weights was used to determine predictors of inadequate hypertension control and related outcomes. Among 3213 participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control, 59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic < or =80 mm Hg, whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with systolic blood pressure < or =130 mm Hg. Non-Hispanic black race (odds ratio [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with inadequate blood pressure control. We conclude that control of hypertension is poor in participants with CKD and that lack of control is primarily attributable to systolic hypertension. Future guidelines and antihypertensive therapies for patients with CKD should target isolated systolic hypertension.     

Nocturnal pulse rate correlated with ambulatory blood pressure and target organ damage in patients with chronic kidney disease

The relationship between resting pulse rate (PR) and the occurrence of hypertension and cardiovascular (CV) mortality has been described in the general population. Few studies have examined the relationship between ambulatory PR, ambulatory blood pressure (BP), and target organ damage (TOD) in patients with chronic kidney disease (CKD). A total of 1509 patients with CKD were recruited in our hospital. Ambulatory blood pressure monitoring (ABPM) over a 24‐hours period was performed and referenced with clinical data in this cross‐sectional study. TOD was measured by estimated glomerular filtration rate (eGFR), left ventricular hypertrophy (LVH), and carotid intima‐media thickness (cIMT). Univariate and multivariate analyses were used to evaluate the relationship between PR, BP, and TOD. The percentage of male patients was 58.3% with a mean age of 44.6 ± 16.2 years. Nocturnal PR rather than 24‐hours PR or daytime PR was an independent risk factor for clinical hypertension, 24‐hours hypertension, BP dipper state, poor renal function, and LVH. In addition, the authors found that nighttime PR >74 beats/min (bpm) group was independently associated with clinical hypertension, 24‐hours hypertension, day and night hypertension, nondipping BP, lower eGFR, and LVH when compared with nighttime PR <64 bpm group. Furthermore, 1:1 propensity score matching between PR ≤74 bpm group and PR >74 bpm group was performed. Multivariate analyses indicated nighttime PR >74 bpm remained independently associated with clinical hypertension, daytime and nighttime hypertension, and LVH. An increased nocturnal PR is associated with TOD, higher BP, and nondipping BP in patients with CKD.     

Diabetes and Hypertension: A Comparative Review of Current Guidelines

Cardiovascular disease plays a major role in the morbidity and mortality of patients with diabetes mellitus. In turn, hypertension is a major risk factor for cardiovascular disease, and its prevalence is increased in diabetes mellitus. Therefore, the detection and management of elevated blood pressure (BP) is a critical component of the comprehensive clinical management of diabetics. Despite significant advances in our understanding of the pathogenesis and treatment of hypertension, there continues to be debate regarding the pharmacologic treatment of hypertension, especially in high‐risk groups such as in patients with diabetes mellitus with and without chronic kidney disease (CKD). This debate largely involves at what BP (ie, treatment threshold BP) to initiate pharmacologic antihypertensive therapy and subsequently what treatment target BP should be achieved (ie, goal BP). Presently, there are several guidelines that address hypertension in diabetes mellitus, including the recently released guideline from the Eighth Report of the Joint National Committee (JNC 8). Therefore, this review will compare and contrast these current guidelines, as they relate to the management and treatment of hypertension in diabetes mellitus. Since diabetes mellitus and CKD are significantly inter‐related, the presence of CKD as it relates to patients with diabetes mellitus will also be addressed.     

The African American Study of Kidney Disease: Do these results indicate that 140/90 mm Hg is good enough?

Current national guidelines recommend aggressive lowering of blood pressure (< 130/80 mm Hg) in patients with chronic kidney disease (CKD). In this paper, we summarize recent clinical trial data evaluating the effect of lower blood pressure goals on renal outcomes. The epidemiologic data relating blood pressure to progression of kidney disease, the Modification of Diet in Renal Disease (MDRD) study (in patients with > 1 g proteinuria/d), and meta-analyses of angiotensin-converting enzyme (ACE) inhibitor clinical trials all support lower blood pressure goals in CKD patients, particularly those with proteinuria. The African American Study of Kidney Disease and Hypertension (AASK) supports lower blood pressure goals in terms of reduction of proteinuria, but demonstrates no additional benefit for clinical renal outcomes. Similarly, the second Ramipril Efficacy in Nephropathy study (REIN-2) shows that in patients with proteinuric nondiabetic renal disease who are receiving ACE inhibitors, a lower than usual blood pressure goal does not improve renal outcomes. However, there are limited clinical trial data evaluating the effects of low blood pressure on the increased cardiovascular risk seen in patients with CKD. Pending further clinical studies, current recommendations to target tight blood pressure control (< 130/80 mm Hg) in patients with CKD appear reasonable.     

Antihypertensive therapy prescribing patterns and correlates of blood pressure control among hypertensive patients with chronic kidney disease

We used electronic health records (EHRs) data from 5658 ambulatory chronic kidney disease (CKD) patients with hypertension and prescribed antihypertensive therapy to examine antihypertensive drug prescribing patterns, blood pressure (BP) control, and risk factors for resistant hypertension (RHTN) in a real‐world setting. Two‐thirds of CKD patients and three‐fourths of those with proteinuria were prescribed guideline‐recommended renoprotective agents including an angiotensin‐converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB); however, one‐third were not prescribed an ACEI or ARB. CKD patients, particularly those with stages 1‐2 CKD, who were prescribed regimens including beta‐blocker (BB) + diuretic or ACEI/ARB + BB + diuretic were more likely to have controlled BP (<140/90 mm Hg) compared to those prescribed other combinations. Risk factors for RHTN included African American race and major comorbidities. Clinicians may use these findings to tailor antihypertensive therapy to the needs of each patient, including providing CKD stage‐specific treatment, and better identify CKD patients at risk of RHTN.     

Endothelin Antagonism and Its Role in the Treatment of Hypertension

Hypertension contributes greatly to global disease burden and in many patients current treatments do not adequately control blood pressure (BP). Endothelin-1 (ET-1) is a potent vasoconstrictor that is implicated in the pathogenesis of hypertension, including the hypertension that is often associated with chronic kidney disease (CKD) and the metabolic syndrome. ET receptor antagonists, currently licensed for the treatment of pulmonary arterial hypertension and scleroderma-related digital ulcers, are being investigated for the treatment of hypertension. Clinical trials have addressed the use of ET receptor antagonists as monotherapy in primary hypertension, as an add-on therapy in resistant hypertension and in CKD. This review will evaluate the current evidence regarding the therapeutic potential of ET receptor antagonists in hypertension, as well as highlighting important issues that still need to be addressed.     

Insufficient control of morning home blood pressure in Japanese patients with hypertension associated with diabetes mellitus

Aims/Introduction: The combination of hypertension with diabetes mellitus (DM) has been recognized as a critical risk factor for cardiovascular disease (CVD). We investigated the blood pressure levels in hypertensive patients with DM (HDM patients) compared with those without DM (HnDM patients). Furthermore, we examined the effect of risk factors, including chronic kidney disease (CKD) and stroke, on the management of both office blood pressure (OBP) and morning home blood pressure (MHBP). Materials and Methods: OBP and MHBP were evaluated in 1230 essential hypertensive patients in 30 institutions. Among them, 366 (30%) were complicated with DM. Results: The ratio of masked hypertensives whose systolic OBP was <140 mmHg and systolic MHBP was more than 135 mmHg in HDM patients was significantly higher than that in HnDM patients (P < 0.02). HDM patients had significantly lower systolic and diastolic OBP and diastolic MHBP than HnDM patients (P < 0.05, respectively). However, systolic MHBP in HDM patients tended to be higher compared with HnDM patients (P = 0.0623). A stratified analysis showed that HDM patients with CKD or stroke had significantly higher systolic MHBP than others (P < 0.05, respectively). The adjusted odds ratio for morning hypertension defined by a systolic MHBP more than 135 mmHg was significantly higher in the HDM patients with CKD (1.98) compared with HnDM patients without CKD (reference). Conclusions: Diabetes, CKD and stroke are risk factors for MHBP. More intensive treatment is needed to achieve the thera‐peutic goal for systolic MHBP in HDM patients, especially those who are complicated with CKD or stroke. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00056.x, 2010) .     

Thiazide diuretics in advanced chronic kidney disease

Chronic kidney disease (CKD) is prevalent in 3%–4% of the adult population in the United States, and the vast majority of these people are hypertensive. Compared with those with essential hypertension, hypertension in CKD remains poorly controlled despite the use of multiple antihypertensive drugs. Hypervolemia is thought to be a major cause of hypertension, and diuretics are useful to improve blood pressure control in CKD. Non-osmotic storage of sodium in the skin and muscle may be a novel mechanism by which sodium may modulate hypertension; further work is need to study this novel phenomenon with diuretics. Among people with stage 4 CKD, loop diuretics are recommended over thiazides. Thiazide diuretics are deemed ineffective in people with stage 4 CKD. Review of the literature suggests that thiazides may be useful even among people with advanced CKD. They cause a negative sodium balance, increasing sodium excretion by 10%–15% and weight loss by 1–2 kg in observational studies. Observational data show improvement in seated clinic blood pressure of about 10–15 mm Hg systolic and 5–10 mm Hg diastolic, whereas randomized trials show about 15 mm Hg improvement in mean arterial pressure. Volume depletion, hyponatremia, hypokalemia, hypercalcemia, and acute kidney injury are adverse effects that should be closely monitored. Our review suggests that adequately powered randomized trials are needed before the use of thiazide diuretics can be firmly recommended in those with advanced CKD.     

Hypertension in patients with chronic kidney disease

Hypertension is very common in patients with chronic kidney disease (CKD); it causes early loss of kidney function and accelerated cardiovascular morbidity and mortality. African American patients with hypertension and genetic disposition are at an even higher risk for renal disease and ultimately renal failure. Hypertensive patients with CKD should aim for stringent blood pressure (BP) control (target < 130/80 mm Hg) requiring more than one drug with renin-angiotensin-aldosterone system blockade as a component of therapy targeting both hyper tension and proteinuria. Management of hypertension in the dialysis population should focus on ambulatory measurements of BP and the use of longer-acting antihypertensive drugs, with their dosage and timing adjusted according to their dialytic clearances. Hypertension is also common among kidney transplant recipients and contributes to graft loss and premature death. The target BP in transplant recipients is the same as in the CKD population, with no preference for one drug group over another. Unless contraindicated, angiotensin-converting enzyme inhibitors remain the drugs of choice for hypertension in patients with autosomal-dominant polycystic kidney disease, in whom diastolic cardiac dysfunction is a prominent feature.     

Hypertension in the Aging Patient: New Imperatives, New Options

Over half of all people over the age of 65 in the U.S. have hypertension. In most cases this is diagnosed because of increased systolic blood pressure. It is now recognized that systolic blood pressure is more predictive of cardiovascular events than diastolic blood pressure; since these events are the major cause of death and disability in this population, current hypertension guidelines now emphasize more aggressive blood pressure criteria for both diagnosing and treating systolic hypertension. This process has been stimulated by evidence from large clinical trials that reducing systolic blood pressure improves survival and prevents strokes, heart failure, and other cardiovascular outcomes. The guidelines of both the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and the World Health Organization-International Society of Hypertension (WHO-ISH) recommend that, regardless of age, hypertension can be diagnosed when the systolic blood pressure is >140 mm Hg. The treatment target is <140 mm Hg, though in the presence of concomitant conditions like diabetes mellitus or cardiac or renal impairment, which are common findings in the elderly, even lower target levels may be justified. For patients with systolic blood pressures in the range 140 mm Hg–159 mm Hg but who are without other cardiovascular risk factors, it is not yet certain that aggressive treatment is warranted. New clinical trials are now addressing this question. So far, most experience with treating systolic hypertension in older persons has been with diuretics and calcium channel blockers. But growing evidence indicates that most antihypertensive drug classes are effective and that agents should be selected to best match the needs of individual patients.     

Resistant Hypertension and Chronic Kidney Disease: a Dangerous Liaison

Treatment-resistant hypertension is an increasingly recognised problem and is markedly over-represented in patients with chronic kidney disease (CKD). Recent evidence has clarified the heightened risk for both adverse renal and cardiovascular outcomes associated with resistant hypertension, even when blood pressure control is attained. The diagnosis of resistant hypertension in CKD is reliant on accurate blood pressure measurement, and out of office measurements are important due to the high prevalence of masked hypertension in these patients. Treatment strategies include careful dietary measures to restrict sodium intake, and a focus on improving adherence to antihypertensive medications. Medication choices should focus on a sensible foundation and then diuretic titration to combat the salt and volume retention inherent in CKD. In this review, we discuss the epidemiology, pathogenesis and consequences of resistant hypertension in CKD, and then review the optimal diagnostic and management strategies.