Prevalence of Apparent Treatment-Resistant Hypertension in ESKD Patients Receiving Peritoneal Dialysis.

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is defined as failure to achieve adequate blood pressure (BP) control despite taking ≥3 antihypertensive medications from different categories or when taking ≥4 antihypertensives regardless of BP levels. METHODS: In this cross-sectional study, we estimated the prevalence of aTRH in 140 patients receiving long-term peritoneal dialysis (PD) in four centers of Northern Greece, using the "gold-standard" method of ambulatory BP monitoring for the assessment of BP control status. The presence of subclinical overhydration was evaluated with the method of bioimpedance spectroscopy (BIS). RESULTS: Incorporating the diagnostic threshold of 130/80 mmHg for 24-hour ambulatory BP, the prevalence of aTRH in the overall study population was 30%. Compared to patients without aTRH, those with aTRH tended to be older in age, had higher PD vintage, had higher dialysate-to-plasma creatinine ratio, had more commonly history of diabetes mellitus, and were more commonly current smokers. With respect to the volume status, the overhydration index in BIS was higher in those with versus without aTRH (2.0 ±â€…1.9 L vs. 1.1 ±â€…2.0 L, P < 0.05). The prevalence of volume overload, defined as an overhydration index in BIS > 2.5 L, was also higher in the subgroup of patients with aTRH (38.1% vs. 18.4, P = 0.01). CONCLUSION: The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population.The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population. CLINICAL TRIALS REGISTRATION: Trial Number NCT03607747.

Epidemiology of Hypertension among Patients on Peritoneal Dialysis Using Standardized Office and Ambulatory Blood Pressure Recordings.

INTRODUCTION: Prior studies conducted in peritoneal dialysis (PD) patients in the late 1990s provided considerably variable estimates of the prevalence and control of hypertension. The present study aimed to investigate the current state of hypertension management in this high-risk population. METHODS: In 140 stable PD patients, we performed standardized automated office blood pressure (BP) measurements and 24-h ambulatory BP monitoring (ABPM) using the Mobil-O-Graph device (IEM, Germany). Office and ambulatory hypertension was diagnosed in patients with office BP ≥140/90 mm Hg and 24-h BP ≥130/80 mm Hg, respectively. Patients treated with ≥1 BP-lowering medications were also classified as hypertensives. RESULTS: The prevalence of office and ambulatory hypertension was 92.9% and 95%, respectively. In all, 92.1% of patients were being treated with an average of 2.4 BP-lowering medications daily. Adequate BP control was achieved in 52.3% and 38.3% of hypertensives by office BP and ABPM, respectively. The agreement between these 2 techniques in the identification of patients with BP levels above the diagnostic thresholds of hypertension was moderate (k-statistic: 0.524). In all, 5% of patients were normotensives with both techniques, 31.4% had controlled hypertension, 5% had white-coat hypertension, 19.3% had masked hypertension, and 39.3% had sustained hypertension. Isolated nocturnal hypertension was detected in 23.6% of patients, whereas no patient had isolated daytime hypertension. CONCLUSION: Among PD patients, hypertension is highly prevalent and remains often inadequately controlled. The use of ABPM enables the better classification of severity of hypertension and identification of isolated nocturnal hypertension, which is a common BP phenotype in the PD population.

Physical examination for the detection of hypervolemia among patients on chronic dialysis: A diagnostic-test study.

INTRODUCTION: Assessment of dry-weight among patients on dialysis is challenging in the absence of reliable markers to define fluid overload (FO). This study aimed to explore the value of two simple clinical signs, pedal edema, and crackles at pulmonary auscultation, in diagnosing hypervolemia, using bioimpendence spectroscopy (BIS) as reference standard. METHODS: In a cohort of 107 asymptomatic dialysis patients, FO was assessed with physical examination and BIS shortly before the mid-week dialysis session. Patients were also asked to perform home blood pressure (BP) monitoring with a validated, automatic device (HEM-705, Omron, Healthcare) for 1 week in order to determine their BP outside of dialysis. FINDINGS: Patients within the high tertile of predialysis FO had longer dialysis vintage, lower serum albumin and higher home systolic BP, despite the more aggressive treatment with a higher average number of antihypertensives daily. In receiver-operating-characteristic (ROC) curve analysis, pedal edema (area under curve [AUC]: 0.534; 95% confidence interval [CI]: 0.416-0.651) and pulmonary crackles (AUC: 0.551; 95% CI: 0.432-0.671) had limited accuracy in detecting excess predialysis FO > 2.2 L. The agreement of pedal edema (k-coefficient: 0.065) and pulmonary crackles (k-coefficient: 0.122) with BIS-derived FO was poor. In multivariate linear regression analysis, longer dialysis vintage (ß: 0.306, p < 0.001) and higher home systolic BP (ß: 0.287, p < 0.01) were the two factors that were associated with predialysis FO. CONCLUSIONS: This study showed that among asymptomatic dialysis patients, pedal edema and pulmonary crackles in physical examination had limited discriminatory power in detection of FO, as assessed with the method of BIS.

Prevalence and control of hypertension among patients on haemodialysis.

BACKGROUND: Earlier studies provided considerably variable estimates on the prevalence and control rates of hypertension in haemodialysis because of their heterogeneity in definitions and blood pressure (BP) measurement techniques applied to detect hypertension. MATERIALS AND METHODS: In this cross-sectional study, 116 clinically stable haemodialysis patients from 3 dialysis centres of Northern Greece underwent home BP monitoring for 1 week with the validated automatic device HEM-705 (Omron, Healthcare). Routine BP recordings taken before and after dialysis over 6 consecutive sessions were also prospectively collected and averaged. Hypertension was defined as: (a) 1-week averaged home BP ≥ 135/85 mm Hg; (b) 2-week averaged predialysis BP ≥ 140/90 mm Hg; and (c) 2-week averaged postdialysis BP ≥ 130/80 mm Hg. Participants on treatment with ≥1 antihypertensives were also classified as hypertensives. RESULTS: The prevalence of hypertension was 88.8% by home, 86.2% by predialysis and 91.4% by postdialysis BP recordings. In all, 96 participants (82.7%) were being treated with an average of 2.0 ± 1.1 antihypertensive medications. Among drug-treated participants, 32.6% were controlled by home, 50.5% by predialysis and 45.3% by postdialysis BP recordings. In multivariate logistic regression analysis, greater use of antihypertensive medications and postdialysis overhydration, assessed with bioimpedance spectroscopy, were both independently associated with higher odds of inadequate home BP control. CONCLUSIONS: This study shows that the prevalence, but mainly the control rates of hypertension in patients on haemodialysis, differs between peridialytic and interdialytic BP recordings. Therefore, the wider use of home BP monitoring may improve the determination of BP control status in this high-risk population.

Calcification of coronary arteries and aortic valve and circulating a-klotho levels in patients with chronic kidney disease.

BACKGROUND: Evidence suggests that the anti-aging protein a-Klotho is a central modulator of mineral homeostasis. Circulating a-Klotho exerts endocrine activity and has been implicated in the process of vascular calcification, which is accelerated in patients with chronic kidney disease (CKD) and portends an unfavorable overall prognosis. However, the role of a-Klotho in this process remains unclear. The purpose of this study was to investigate the possible interaction between a-Klotho and the calcification of the aortic valve and coronary arteries in patients with CKD. METHODS: In this study we enrolled a total of 60 adult patients with CKD. Group 1 included 30 participants with CKD stage V and group 2 included 30 participants with CKD stage III. RESULTS: Participants in group 1 had lower levels of circulating a-Klotho compared to group 2 (390; 280-590 vs. 722; 501-897 pg/mL; P=0.001), were of younger age (55.5; 45-63 vs. 69; 62-74 years; P<0.001), had lower body mass index (25.6; 23.8-27.5 vs. 28.2; 25.7-31.1 kg/m2; P=0.036), higher serum phosphate (4.75; 4-5.6 vs. 3.35; 2.9-3.8 mg/dL; P<0.001), higher calcium-phosphate product (41; 35.1-49.2 vs. 31.5; 28.6-35 mg2/dL2; P<0.001), and higher parathyroid hormone (PTH) levels (28.4; 15-44.6 vs. 7.05; 4.3-10.2 pmol /L; P<0.001). CONCLUSIONS: No statistically significant difference was found between the two groups in terms of coronary arteries and aortic valve calcification. Calcitonin, PTH and phosphate were identified as predictors for circulating a-Klotho levels whereas, only hyperlipidemia was identified as predictor for coronary artery calcification. In conclusion, circulating a-Klotho is found to decrease with worsening CKD severity but no correlation was found between the levels of a-Klotho and severity of coronary arteries and aortic valve calcification.

Acute Interstitial Nephritis in a Patient with Non-Small Cell Lung Cancer under Immunotherapy with Nivolumab.

Immune-checkpoint-inhibitors (ICPIs) represent a novel class of immunotherapy against several malignancies. These agents are associated with several "immune-mediated" adverse effects, but the reported renal toxicity of ICPIs is less well defined. We present the case of a 60-year-old man with a history of non-small cell lung cancer, who developed acute kidney injury (AKI) approximately 3.5 months after initiation of immunotherapy with nivolumab. Urinalysis revealed sterile pyuria, without microscopic hematuria or proteinuria. Immunological examination was negative. A renal biopsy showed severe interstitial inflammatory infiltration of T-cells, monocytes, and eosinophils without interstitial granulomas and normal appearance of glomeruli, indicating acute interstitial nephritis (AIN) as the cause of AKI. After a short-term course of corticosteroids and permanent nivolumab discontinuation, partial recovery of renal function was noted. AIN is a rare adverse effect of ICPIs that mandates the close monitoring of renal function in patients under immunotherapy with these agents.

Arterial stiffness in end-stage renal disease-pathogenesis, clinical epidemiology, and therapeutic potentials.

Arterial stiffness is an important risk factor for cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD). Arterial stiffness aggravates cardiovascular risk via multiple pathways, such as augmentation of aortic systolic pressure, subendocardial hypoperfusion, and excess pulsatile energy transmission from macro- to microcirculation. Pathogenesis of the arteriosclerotic process in ESRD is complex and not yet fully understood. Several factors unique to ESRD, such as mineral metabolism disturbances, vascular calcifications, formation of advanced glycation end-products, and acute and chronic volume overload, are proposed to play a particular role in the progression of arteriosclerosis in ESRD. As these and other mechanistic pathways of arterial stiffening in ESRD are elucidated, there is hope that this knowledge will be translated into novel therapeutic interventions targeting arterial stiffness. In the meantime, blood pressure (BP) lowering via strict volume control and appropriate use of antihypertensive drugs is a fundamental step in reversing accelerated arterial stiffening and modifying the cardiovascular risk profile of ESRD patients. In this article, we review the pathogenesis, clinical epidemiology, and therapies targeting arterial stiffness in ESRD, discussing recent advances and high-priority goals of future research in these important areas.

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease.

Evaluation of the tolerability and efficacy of sodium polystyrene sulfonate for long-term management of hyperkalemia in patients with chronic kidney disease.

PURPOSE: Sodium polystyrene sulfonate (SPS) is a cation-exchanging resin that has been widely used for several decades as first-line therapy of mild chronic hyperkalemia in patients with chronic kidney disease (CKD). However, evidence to prove the long-term tolerability and efficacy of SPS for the treatment of this condition is still missing. METHODS: In this retrospective, observational study, we enrolled 26 outpatients with stages 3-4 CKD who received oral therapy with low-dose SPS for mild chronic hyperkalemia in the Outpatient Nephrology clinic of our Department during 2010-2016. We obtained medical records on side effects potentially attributable to SPS use, and we analyzed the changes in serum electrolytes before and after the initiation of SPS therapy. RESULTS: Serum potassium levels fell from 5.9 ± 0.4 to 4.8 ± 0.5 mmol/l (P < 0.001) over a median follow-up of 15.4 months (range 3-27 months). SPS use was associated with a slight, but significant elevation in serum sodium levels (139.5 ± 2.9 vs 141.2 ± 2.4, P = 0.006), whereas serum calcium and phosphate remained unchanged before and after the initiation of SPS. We recorded ten episodes of recurrent serum potassium elevation ≥ 5.5 mmol/l, none of which required hospitalization or acute dialysis. No episode of colonic necrosis or any other serious drug-related adverse event was observed. SPS therapy was well-tolerated, since only 1 out of 26 patients discontinued SPS at 3 months due to gastrointestinal intolerance. CONCLUSION: This study suggests that low-dose SPS is well-tolerated and can effectively normalize elevated serum potassium over several weeks in CKD outpatients with mild chronic hyperkalemia.

Hemodialysis patients with intradialytic rise in blood pressure display higher baseline aortic stiffness and negligible drop in augmentation index with dialysis.

BACKGROUND: In hemodialysis patients, the intradialytic rise in blood pressure (BP) is associated with increased mortality risk. However, the mechanisms of this adverse effect are not yet elucidated. This study examined whether intradialytic rise in BP is associated with increased arterial stiffness and wave reflections, which are powerful cardiovascular risk predictors in hemodialysis. METHODS: The pattern of intradialytic hemodynamic response was evaluated in 70 prevalent hemodialysis patients, by measuring seated brachial BP before and after the mid-week dialysis session. All patients had pre- and post-dialysis determination of aortic pulse wave velocity (PWV) and heart rate-adjusted augmentation index [AIx(75)], as measures of arterial stiffness and wave reflections, with the Sphygmocor device. RESULTS: Intradialytic rise in brachial systolic BP (SBP) was evident in 17 patients, whereas intradialytic change in SBP (ΔSBP) of -10 to 0 mmHg was observed in 23 and ΔSBP greater than -10 mmHg in 30 patients. Participants with intradialytic SBP rise had significantly higher pre-dialysis aortic PWV (10.4 ± 1.6 vs 8.3 ± 1.9 vs 9.4 ± 2.4 m/s, P < 0.01) and AIx(75) (28.1 ± 7.3 vs 21.7 ± 8.6 vs 25.8 ± 8.2%, P < 0.05) than those experiencing intradialytic ΔSBP of -10 to 0 and greater than -10 mmHg, respectively. Patients with rise in SBP during dialysis exhibited also lower intradialytic reduction in AIx(75) (-1.5 ± 4.9 vs -5.4 ± 5.9 vs -6.7 ± 5.3%, P < 0.001). CONCLUSIONS: This study shows that aortic stiffness and wave reflections are higher and not affected by dialysis procedure in patients with intradialytic SBP rise, suggesting that accelerated arteriosclerosis may be one possible explanation for the heightened cardiovascular risk associated with intradialytic hypertension.