Hypertensive Chronic Kidney Disease Research Articles

Extracellular Fluid Volume Is an Independent Determinant of Uncontrolled and Resistant Hypertension in Chronic Kidney Disease: A NephroTest Cohort Study.

BackgroundHypertension is highly prevalent during chronic kidney disease (CKD) and, in turn, worsens CKD prognosis. We aimed to describe the determinants of uncontrolled and resistant hypertension during CKD.Methods and ResultsWe analyzed baseline data from patients with CKD stage 1 to 5 (NephroTest cohort) who underwent thorough renal explorations, including measurements of glomerular filtration rate (clearance of 51Cr‐EDTA) and of extracellular water (volume of distribution of the tracer). Hypertension was defined as blood pressure (BP; average of 3 office measurements) ≥140/90 mm Hg or the use of antihypertensive drugs. In 2015 patients (mean age, 58.7±15.3 years; 67% men; mean glomerular filtration rate, 42±15 mL/min per 1.73 m2), prevalence of hypertension was 88%. Among hypertensive patients, 44% and 32% had uncontrolled (≥140/90 mm Hg) and resistant (uncontrolled BP despite 3 drugs, including a diuretic, or ≥4 drugs, including a diuretic, regardless of BP level) hypertension, respectively. In multivariable analysis, extracellular water, older age, higher albuminuria, diabetic nephropathy, and the absence of aldosterone blockers were independently associated with uncontrolled BP. Extracellular water, older age, lower glomerular filtration rate, higher albuminuria and body mass index, male sex, African origin, diabetes mellitus, and diabetic and glomerular nephropathies were associated with resistant hypertension.ConclusionsIn this large population of patients with CKD, a lower glomerular filtration rate, a higher body mass index, diabetic status, and African origin were associated with hypertension severity but not with BP control. Higher extracellular water, older age, and higher albuminuria were independent determinants of both resistant and uncontrolled hypertension during CKD. Our results advocate for the large use of diuretics in this population.

Albuminuria during treatment with angiotensin type II receptor blocker is a predictor for GFR decline among non-diabetic hypertensive CKD patients

BackgroundAlbuminuria is a predictor of disease progression in patients with chronic kidney disease (CKD). However, the ability of proteinuria parameters measured at various time periods to predict renal outcomes is unclear.MethodThis observational cohort study included 165 non-diabetic hypertensive CKD patients who took olmesartan medoxomil. We measured the albuminuria at five different time points (0, 2, 4, 26, and 38 months) and the mean levels. The mean albuminuria levels were calculated during 0–4 months, 0–26 months, and 0–38 months. The renal outcome was defined as a decline in eGFR ≥ 40% during the entire study period.ResultThe albuminuria at five different time points and the mean albuminuria levels were independent risk factors for a worse renal outcome after adjusting for age, sex, and estimated glomerular filtration rate (eGFR) at enrollment and were able to predict the renal outcome, although the performance of the estimation tended to be more effective using the mean albuminuria level at the 38-month follow-up time point. The risk of a decline in eGFR ≥ 40% was increased by 1.690-folds [95% CI 1.110–2.572, P = 0.014] per 500 mg/day increase in the mean albuminuria at 38 months. With a cut-off value of 897 mg/day for mean albuminuria at 38 months after treatment, a decline in eGFR ≥ 40% was predicted with a sensitivity of 88.9% and specificity of 81.3%. The ability of albuminuria to predict a renal event at different measurement points does not differ in CKD patients.ConclusionThe time-averaged albuminuria cut-off of 900 mg/day during the 3-year follow-up period showed high sensitivity and specificity for predicting a decline in eGFR ≥ 40% in CKD patients, although the albuminuria at different measurement points did not predict a worse renal outcome.

Bilateral Exudative Retinal Detachment Due to Hypertensive Retinopathy and Choroidopathy In Young Patient with Chronic Kidney Disease

Introduction: Severe systemic hypertension in chronic kidney disease can cause significant damage to the eye. Although hypertensive retinopathy is a well-known complication, hypertensive optic neuropathy and choroidopathy are much less common. The aim of this study is to report retinal manifestation in young patient with chronic kidney disease.
 Method: A 26-year-old man with underlying disease chronic kidney disease (CKD) gr-V underwent bilateral bullous exudative retinal detachments. Retinal arteriolar narrowing, vascular tortuosity, arteriovenous nicking, optic disc swelling, retinal haemorrhage, elschnig spot, siegrist streak were identified in both eyes. Blood pressure was 200/140mmHg with visual acuity 0,5/60 OU. The patient was diagnosed with bilateral hypertensive retinopathy and choroidopathy with bulous exudative retinal detachments.
 Results: After antihypertensive treatment, visual acuity improved, but the exudative retinal detachments and retinal hemorrhages reduced. A patient with those findings should be considered as having hypertensive retinopathy and choroidopathy and treated as soon as possible because of the poor prognostic.
 Conclusion: Hypertensive choroidopathy is a rare finding associated with acute increases in blood pressure. When the choroid is associated, the hypertensive event is often more acute and associated with increased morbidity. It is necessary to obtain fundus exam in any patient with elevated blood pressure and concomitant vision complaints. Therefore, screening hypertensive patients involves close collaboration between internist and ophthalmologist.

Diastolic blood pressure variability in 24 hour-ABPM and outcomes of chronic kidney disease .

Blood pressure variability (BPV) has been associated with increased morbidity and mortality. There are a few studies that reported worse outcomes of chronic kidney disease (CKD) with greater visit-to-visit BPV (VVV), but data with ambulatory blood pressure monitoring (ABPM) is scarce. Ambulatory hypertensive CKD (stage 2 - 4) patients (>18 years old) with complete 24hours of ABPM study (SpaceLabs), who were followed up between January 2012 and December 2016, were retrospectively analyzed for the baseline characteristics and outcomes of CKD. Coefficient of variation (CV) in diastolic blood pressure (DBP) was used as an index of BPV. Data of 191 patients (mean age 59.7±12.4 years, 54.9% males, 42.1% diabetic, mean eGFR-EPI (Chronic Kidney Disease Epidemiology Collaboration) 51.7±22.0 mL/min/1.73m2, mean follow-up 26.2±10.4 months) were available for the analysis. On multivariate linear regression analysis, greater DBP-CV was associated with slower decline in eGFR-EPI per year (B -0.648, p=0.000). Likewise, the hazard ratio (HR) for dialysis inception (occurred in 9.4%) was found significantly lower with increasing DBP-CV in unadjusted and fully adjusted Cox models (HR 0.730, 95% CI 0.618-0.861, p=0.000, and HR 0.678, 95% CI 0.526-0.874, p=0.003, respectively). These findings suggest that DBP variability in 24-hour ABPM may be a good prognostic factor for the outcomes of CKD. Further studies are needed to determine the impact of 24-hour ABPM BPV on CKD progression and its differences from VVV. .

Treatment of Hypertension in Chronic Kidney Disease.

Chronic kidney disease (CKD) is recognized as a worldwide epidemic. Hypertension commonly coexists with CKD and its prevalence is progressively increasing as kidney function declines. For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal < 130/80mmHg. Blood pressure level above 130/80mmHg in CKD patients requires lifestyle modifications and multiple antihypertensive medications. According to recent guidelines, angiotensin-converting enzyme (ACE) inhibitors should be the drugs of first choice. Angiotensin II receptor blockers (ARBs) should be used if the ACE inhibitor is not tolerated. Non-dihydropyridine CCBs consistently reduce albuminuria and slow the decline in kidney function. Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. Diuretics are commonly used and represent the cornerstone in the management of CKD patients. All the other agents are used when treatment with the other primary agents have failed. In patients with CKD, an intensive BP goal < 130/80mmHg has been recommended. We review current treatment options.

Effects of fenoldopam on renal blood flow in hypertensive chronic kidney disease.

The synthetic drug fenoldopam mesylate (FM) may have a renoprotective role, and a "renal dose" of 0.1µg/kg/min intravenous (IV) infusion of FM has been reported as able to increase renal blood flow without affecting systemic blood pressure. But conclusive data are still lacking. We aimed to investigate by color-Doppler ultrasonography the effects of IV administration of FM at this dosage in hypertensive chronic kidney disease (CKD) patients, and verify whether it may induce any systemic hemodynamic alteration. In 60 hypertensive CKD patients, we measured by duplex Doppler ultrasonography, at baseline and during infusion of 0.1µg/kg/min of FM, the systolic and diastolic flow velocity (sampled at the renal hilum, intermediate section and origin of both renal arteries) and the intra-parenchymal renal resistive index (RRI) sampled on interlobular arteries of both kidneys. Patients were divided into four subgroups (I-IV) according to classification of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-DOQI). Infusion of 0.1µg/kg/min FM significantly decreased the RRI (0.73 ± 0.05 vs. 0.65 ± 0.06; p < 0.0001) and increased the systolic and diastolic flow velocities in all renal artery tracts examined. No single episode of systemic hypotension was observed. Very low-dose FM may significantly increase renal blood flow and exert a renal protective effect in hypertensive CKD patients. Infusion of FM at such low dosage appears also to be quite safe, even in CKD and hypertensive patients.

Weight loss has an additive effect on the proteinuria reduction of angiotensin II receptor blockers in hypertensive patients with chronic kidney disease.

BackgroundWeight reduction is a lifestyle intervention that has been introduced for prevention and management of chronic kidney disease (CKD). We investigate the additive anti-proteinuric effect of weight reduction on the usage of angiotensin II receptor blockers (ARBs) and its potential mechanisms in hypertensive CKD patients.MethodsThis study is a subanalysis of data from an open-label, randomized, controlled clinical trial. Among the 235 participants, 227 were assigned to subgroups according to changes in body weight.ResultsFifty-eight participants (25.6%) were assigned to group 1 (≥1.5% decrease in body weight after 16 weeks), 32 participants (14.1%) were assigned to group 2 (1.5–0.1% decrease in body weight), and 136 participants (59.9%) were assigned to group 3 (≥ 0.0% increase in body weight). Characteristics at enrollment were not different among the three groups, but mean differences in weight and percent changes in urinary sodium excretion over the period were statistically different (P < 0.001 and P = 0.017). Over the study period, unintentional weight loss independently increased the probability of reduced albuminuria (group 1, relative risk 6.234, 95% confidence interval 1.913–20.315, P = 0.002). Among urinary cytokines, only podocalyxin level decreased significantly in participants who lost weight (P = 0.013).ConclusionWe observed that weight loss had an additive effect on the anti-proteinuric effects of ARBs in nondiabetic hypertensive CKD patients, although it was minimal. An additive effect was shown in both obese and non-obese participants, and its possible mechanism is related to reduction of podocyte damage.

AT1 Receptor Antagonism Improves Structural, Functional, and Biomechanical Properties in Resistance Arteries in a Rodent Chronic Kidney Disease Model.

The renin-angiotensin system, in particular Angiotensin II (AngII), plays a significant role in the pathogenesis of hypertension in chronic kidney disease (CKD). Effects of chronic AT1 receptor antagonism were investigated in a genetic hypertensive rat model of CKD, the Lewis polycystic kidney (LPK) rat. Mixed-sex LPK and Lewis control rats (total n = 31) were split between treated (valsartan 60 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Animals were assessed for systolic blood pressure and urine biochemistry, and after euthanasia, blood collected for urea and creatinine analysis, confirming the hypertensive and renal phenotype. Mesenteric resistance vasculature was assessed using pressure myography and histology. Valsartan treatment improved vascular structure in LPK rats, increasing internal and external diameter values and reducing wall thickness (untreated vs. treated LPK: 53.19 ± 3.29 vs. 33.93 ± 2.17 μm) and wall-lumen ratios (untreated vs. treated LPK: 0.52 ± 0.09 vs. 0.16 ± 0.01, all P < 0.0001). Endothelium dysfunction, as measured by maximal response to acetylcholine (Rmax), was normalized with treatment (untreated vs. treated LPK: 69.56 ± 4.34 vs. 103.05 ± 4.13, P < 0.05), increasing the relative contributions of nitric oxide and endothelium-derived hyperpolarization to vasorelaxation while downregulating the prostanoid contribution. Biomechanical properties also improved with treatment, as indicated by an increase in compliance, decrease in intrinsic stiffness and alterations in the artery wall composition, which included decreases in collagen density and collagen/elastin ratio. Our results highlight the importance of AngII as a driver of resistance vessel structural, functional, and biomechanical dysfunction and provide insight as to how AT1 receptor blockade exerts therapeutic efficacy in CKD.

Hypertension Control in Adults With CKD in China: Baseline Results From the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

Hypertension contributes to increased morbidity and mortality in the chronic kidney disease (CKD) population. Studies on blood pressure control in CKD patients in China are limited. In this study, we aimed to describe the status of blood pressure control in Chinese CKD patients based on the first national prospective CKD cohort data. A subgroup of Chinese Cohort Study of Chronic Kidney Disease participants with hypertension at baseline was included in the present study. Uncontrolled blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg. Defined daily doses (DDDs) are used as a standard measurement of drug utilization in this population. Factors associated with uncontrolled blood pressure were analyzed using multivariable logistic regression. There were 2,251 hypertensive CKD subjects among 2,873 predialysis CKD participants. The awareness, treatment, and control rates of hypertension were 80.7%, 95.6%, and 57.1%, respectively. Factors independently associated with uncontrolled blood pressure were overweight, obesity, albuminuria, decreased estimated glomerular filtration rate (eGFR), and diabetes. Over 50% of study subjects were prescribed 2 or more antihypertensive medications and only 7% were prescribed diuretics. Uncontrolled hypertensive patients were prescribed less antihypertensive medication than controlled hypertensives (DDD 1.3 [1.0-2.3] vs. 2.0 [1.0-3.1], P < 0.001). Hypertension control was suboptimal among hypertensive CKD patients in China, especially among those overweight or with obesity, albuminuria, lower eGFR, and diabetes. Patients with uncontrolled hypertension should undergo treatment regimen evaluation to select the appropriate dosage and type of antihypertensive medications.

Management of hypertension in chronic kidney disease

Management of hypertension in chronic kidney disease

Pathophysiology of Hypertension in Chronic Kidney Disease

Pathophysiology of Hypertension in Chronic Kidney Disease

Prevalence and Clinical Correlates of White Coat Effect in Patients with Chronic Kidney Disease and the Role of Automated Blood Pressure Device in its Assessment.

Context:Hypertension in chronic kidney disease (CKD) is an important modifiable cardiovascular risk factor. Patients with CKD can have clinically significant white coat effect (WCE), making routine clinic blood pressure (BP) measurements an unreliable indicator of actual BP control. Automated BP monitoring is useful in identifying WCE. The utility of automated BP monitoring has seldom been part of clinical practice in developing countries.Aim:The goal of this study was to estimate the prevalence and determinants of WCE in adult patients with CKD in an outpatient setting using an automated BP device.Materials and Method:In this prospective observational study, patients with CKD attending the nephrology clinic over a period of 6 months (January 2016 to July 2016), who were suspected to have WCE by the treating physician, were assigned to measurement of BP by both the standardized manual BP recording by a single nephrologist and with automated machine as per a defined protocol. Clinical, demographic characters that would influence outcomes were also studied.Results:Among 118 patients with CKD with suspected WCE, 57.6% showed WCE. The mean systolic and diastolic BPs were significantly lower with automated machine when compared with manual BP recordings in patients with WCE (p = 0.04). WCE was seen in all stages of CKD. Occurrence of WCE in CKD was not dependent on factors such as old age, sex, diabetes mellitus, or smoking status in our study.Conclusion:WCE is a highly prevalent and underdiagnosed entity in patients with CKD. Automated machine is a useful and time-saving tool in detection of WCE in patients with CKD attending the outpatient clinic and guide management.

Effect of alogliptin on hypertensive chronic kidney disease patients with type 2 diabetes mellitus

Effect of alogliptin on hypertensive chronic kidney disease patients with type 2 diabetes mellitus

Impact of Body Mass Index on Outcomes after Mesenteric Revascularization for Chronic Mesenteric Ischemia

Historically, patients with chronic mesenteric ischemia (CMI) are underweight with a low body mass index (BMI). However, with the recent obesity epidemic many of these patients now are overweight with a high BMI. We evaluated the impact of BMI on outcomes after mesenteric revascularization for CMI. A retrospective chart review of patients undergoing open or endovascular mesenteric revascularization for CMI between January 2000 and June 2015 was performed. Demographics, comorbidities, BMI, Society for Vascular Surgery-combined comorbidity score, treatment modality, postoperative complications, reintervention, and all-cause mortality were analyzed. The primary end point for the study was all-cause mortality at 5years. Patients were stratified using the World Health Organization BMI criteria. Univariate, Kaplan-Meier survival, and multivariate analyses were performed. In the study period, 104 unique patients underwent mesenteric revascularization for CMI, for 77 of whom BMI information was available. Of these 77, 30 patients were treated by endovascular revascularization, and 47 patients were treated by open revascularization. Overall, 27 (35.1%) were overweight or obese with a BMI ≥25. Median follow-up time was 41months. High BMI patients were less likely to have weight loss at the time of surgery (P=0.004). Stratified by BMI <25 versus BMI ≥25, 5-year survival for patients treated by open revascularization was 90% versus 50% (P=0.02); survival for patients treated by endovascular revascularization was 27% vs. 53% (P=0.37). Multivariate survival analysis identified active smoking, hypertensive chronic kidney disease, open repair with the use of venous conduit instead of prosthetic conduit (P<0.001), and history of peripheral arterial disease (PAD) (P=0.002), as independent predictors of increased all-cause mortality. BMI needs to be considered in assessing and counseling patients on outcomes of mesenteric revascularization for CMI, as a BMI over 25 is associated with poorer long-term survival after open revascularization. Smoking, hypertensive chronic kidney disease, PAD, and open repair with the use of venous conduit are independent predictors of long-term mortality after mesenteric revascularization independent of BMI.

FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC): study protocol for randomized controlled trial

BackgroundFimasartan is the ninth angiotensin receptor blocker to be developed. However, it has not yet been evaluated for reno-protective effects in hypertensive diabetic chronic kidney disease (CKD). The target blood pressure (BP) for hypertensive diabetic CKD is also a controversial topic. This trial was designed to assess the reno-protective effects of fimasartan compared to those of losartan as a primary outcome. This study also compares the two drugs with regard to cardiovascular and renal outcomes in accordance with target systolic BP (SBP) (as secondary outcomes).MethodsThis study is a prospective, phase III, randomized, double-blind, active-controlled, non-inferiority, four-parallel group, dose-titration, multicenter trial. We recruit patients with hypertensive diabetic CKD with overt proteinuria. Participants will be randomized into four groups (1:1:1:1): fimasartan standard SBP control (SBP < 140 mmHg); fimasartan strict SBP control (SBP < 130 mmHg); losartan standard SBP control; and losartan strict SBP control. After 24 weeks, all individuals are treated with fimasartan for an additional 120 weeks in an open-label design, maintaining their assigned SBP control groups as randomized. The primary endpoint is the rate of change in proteinuria, which is assessed using the spot urine albumin–creatinine ratio at 24 weeks. The secondary endpoints are the cardiovascular and renal outcomes at 144 weeks compared between the strict SBP and standard SBP control groups.DiscussionThe FANTASTIC is a clinical study to provide: (1) the reno-protective effect of fimasartan; and (2) the target BP to reduce adverse outcomes in hypertensive diabetic CKD with overt proteinuria.Trial registrationClinicaltrials.gov, NCT02620306. Registered on 1 December 2015.

Spleno-renal artery transposition in a solitary functioning kidney for treatment-resistant hypertension and acute kidney injury

Renal Artery Stenosis (RAS) is an important cause of treatment-resistant hypertension. Uncontrolled hypertension with RAS can cause progressive chronic kidney disease (CKD) leading to end-stage kidney disease. Therapeutic revascularisation can...

Poor sleep quality is responsible for the nondipper pattern in hypertensive but not in normotensive chronic kidney disease patients.

This study was designed to evaluate the relationship between sleep quality and hypertension and to determine if there was an association between nondipper blood pressure (BP) and sleep quality in chronic kidney disease (CKD) patients. A total of 775 pre-dialysis CKD patients (314 normal BP patients, 461 hypertension patients) defined as dippers or nondippers by ambulatory BP monitoring were recruited for this study. Demographics and clinical correlates were collected, including body mass index, estimated glomerular filtration rate (eGFR) and other measures. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). A total of 185 (58.9%) patients with normal BP and 341 (74.0%) hypertensive patients had a nondipper BP pattern. The hypertension group had a higher prevalence of the nondipper BP pattern, smoking, alcohol intake and diabetes mellitus (DM) and lower eGFR levels and poorer sleep quality than the normal BP group. Patients with the nondipper BP pattern had lower haemoglobin, worse renal function and poorer sleep quality when compared with hypertensive CKD patients with the dipping BP pattern. PSQI scores were significantly associated with the rate of nocturnal BP decline (P < 0.05) in the hypertension group but not in the normal BP group. Poor sleep quality was an independent factor affecting BP pattern in hypertensive CKD patients using multivariate linear and logistic regression analyses. There was no association between sleep quality and hypertension in CKD patients after multivariate logistic regression analyses. Poor sleep quality, which is commonly observed in pre-dialysis CKD patients, is an independent associated factor of the nondipper BP pattern in hypertensive CKD patients. No association was found between poor sleep and nondipper BP in normotensive patients.

Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis.

Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of the normal 24-h BP dipping pattern in chronic kidney disease (CKD) patients is not known. To investigate the effect of an evening dosing regimen of antihypertensive drugs on BP patterns of CKD patients with hypertension. A systematic review was conducted by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models. Five randomised controlled trials and one comparative study, including 3732 patients, met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio (RR), 95% CI, (0.43, 0.84)). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD -3.17 mmHg, 95% CI (-5.41, -0.94)), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD -1.37 mmHg, 95% CI (-2.05, -0.69)) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI (0.10, 2.19)) in patients assigned to the evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality. This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients.

Prevalence and Risk of Pulmonary Hypertension in Chronic Kidney Disease

Prevalence and Risk of Pulmonary Hypertension in Chronic Kidney Disease

Pulmonary hypertension in chronic kidney disease: a hemodynamic characterization.

Pulmonary hypertension in chronic kidney disease: a hemodynamic characterization.