The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood pressure in hemodialysis patients: a randomized controlled trial

Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population. Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population. Hypertension is the most common modifiable risk factor accompanying chronic kidney disease.1Sarafidis P.A. Li S. Chen S.C. et al.Hypertension awareness, treatment, and control in chronic kidney disease.Am J Med. 2008; 121: 332-340Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar Studies in American and European cohorts using ABPM showed that the prevalence of hypertension in patients undergoing hemodialysis is particularly high—between 80% and 85%.2Agarwal R. Nissenson A.R. Batlle D. et al.Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States.Am J Med. 2003; 115: 291-297Abstract Full Text Full Text PDF PubMed Scopus (381) Google Scholar, 3Sarafidis P.A. Mallamaci F. Loutradis C. et al.Prevalence and control of hypertension by 48-h ambulatory blood pressure monitoring in haemodialysis patients: a study by the European Cardiovascular and Renal Medicine (EURECA-m) working group of the ERA-EDTA.Nephrol Dial Transplant. 2018; 33: 1872Crossref PubMed Scopus (13) Google Scholar Furthermore, in contrast to previous data showing that pre- or posthemodialysis BP have no association with clinical outcomes,4Port F.K. Hulbert-Shearon T.E. Wolfe R.A. et al.Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients.Am J Kidney Dis. 1999; 33: 507-517Abstract Full Text Full Text PDF PubMed Google Scholar elegant studies using home or ambulatory BP showed that both are associated with increased mortality in patients undergoing hemodialysis.5Alborzi P. Patel N. Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings.Clin J Am Soc Nephrol. 2007; 2: 1228-1234Crossref PubMed Scopus (178) Google Scholar, 6Bansal N. McCulloch C.E. Lin F. et al.Blood Pressure and Risk of Cardiovascular Events in Patients on Chronic Hemodialysis: the CRIC Study (Chronic Renal Insufficiency Cohort).Hypertension. 2017; 70: 435-443Crossref PubMed Scopus (39) Google Scholar Outcome trials with common antihypertensive agents suggest that lowering BP in patients undergoing hemodialysis may result in a 30% lower risk of cardiovascular events and mortality7Heerspink H.J. Ninomiya T. Zoungas S. et al.Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials.Lancet. 2009; 373: 1009-1015Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar; however, adequate hypertension control is achieved in <30% of these patients.2Agarwal R. Nissenson A.R. Batlle D. et al.Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States.Am J Med. 2003; 115: 291-297Abstract Full Text Full Text PDF PubMed Scopus (381) Google Scholar, 3Sarafidis P.A. Mallamaci F. Loutradis C. et al.Prevalence and control of hypertension by 48-h ambulatory blood pressure monitoring in haemodialysis patients: a study by the European Cardiovascular and Renal Medicine (EURECA-m) working group of the ERA-EDTA.Nephrol Dial Transplant. 2018; 33: 1872Crossref PubMed Scopus (13) Google Scholar The inability of patients undergoing hemodialysis to maintain sodium and water homeostasis combined with the intermittent nature of hemodialysis treatment render sodium and water excess the major pathophysiologic mechanism underlying hypertension in these patients.8Sarafidis P.A. Persu A. Agarwal R. et al.Hypertension in dialysis patients: a consensus document by the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension (ESH).Nephrol Dial Transplant. 2017; 32: 620-640PubMed Google Scholar, 9Agarwal R. Flynn J. Pogue V. et al.Assessment and management of hypertension in patients on dialysis.J Am Soc Nephrol. 2014; 25: 1630-1646Crossref PubMed Scopus (113) Google Scholar Indeed, sodium and fluid accumulation during the interdialytic interval results in both brachial and aortic BP increase, which are proportionate to weight gain, a phenomenon superimposed on circadian BP variation.10Agarwal R. Epidemiology of interdialytic ambulatory hypertension and the role of volume excess.Am J Nephrol. 2011; 34: 381-390Crossref PubMed Scopus (65) Google Scholar, 11Karpetas A. Sarafidis P.A. Georgianos P.I. et al.Ambulatory recording of wave reflections and arterial stiffness during intra- and interdialytic periods in patients treated with dialysis.Clin J Am Soc Nephrol. 2015; 10: 630-638Crossref PubMed Scopus (55) Google Scholar, 12Kelley K. Light R.P. Agarwal R. Trended cosinor change model for analyzing hemodynamic rhythm patterns in hemodialysis patients.Hypertension. 2007; 50: 143-150Crossref PubMed Scopus (42) Google Scholar Thus the role of ultrafiltration during dialysis to reduce water and sodium overload to achieve dry weight is fundamental for hypertension control.8Sarafidis P.A. Persu A. Agarwal R. et al.Hypertension in dialysis patients: a consensus document by the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension (ESH).Nephrol Dial Transplant. 2017; 32: 620-640PubMed Google Scholar, 13Loutradis C.N. Tsioufis C. Sarafidis P.A. The clinical problems of hypertension treatment in hemodialysis patients.Curr Vasc Pharmacol. 2017; 16: 54-60Crossref PubMed Scopus (11) Google Scholar In the seminal Dry Weight Reduction in Hypertensive Hemodialysis Patients (DRIP) study,14Agarwal R. Alborzi P. Satyan S. et al.Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial.Hypertension. 2009; 53: 500-507Crossref PubMed Scopus (268) Google Scholar careful dry-weight reduction (probing) in hypertensive patients undergoing hemodialysis without volume overload (averaging 0.9 kg weight reduction in the active arm over 4 weeks) resulted in 7.6/3.4 mm Hg reduction in 44-hour BP favoring the active arm. However, observations in an uncontrolled study guided by clinical criteria suggested that ultrafiltration intensification may increase arteriovenous fistula problems and the risk of cardiovascular events.15Curatola G. Bolignano D. Rastelli S. et al.Ultrafiltration intensification in hemodialysis patients improves hypertension but increases AV fistula complications and cardiovascular events.J Nephrol. 2011; 24: 465-473Crossref PubMed Scopus (32) Google Scholar Assessment of volume balance in patients undergoing hemodialysis with clinical criteria (e.g., peripheral edema or signs of lung congestion) is a method with limited reliability.8Sarafidis P.A. Persu A. Agarwal R. et al.Hypertension in dialysis patients: a consensus document by the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension (ESH).Nephrol Dial Transplant. 2017; 32: 620-640PubMed Google Scholar, 9Agarwal R. Flynn J. Pogue V. et al.Assessment and management of hypertension in patients on dialysis.J Am Soc Nephrol. 2014; 25: 1630-1646Crossref PubMed Scopus (113) Google Scholar, 16Chou J.A. Kalantar-Zadeh K. Volume balance and intradialytic ultrafiltration rate in the hemodialysis patient.Curr Heart Fail Rep. 2017; 14: 421-427Crossref PubMed Scopus (25) Google Scholar Identifying objective methods to estimate volume excess and dry weight is an unmet clinical need. Previous efforts using biomarkers (e.g., renin, aldosterone, natriuretic peptides, and others) or ultrasonographic measurement of inferior vena cava diameter were largely inaccurate or impractical.17Agarwal R. Andersen M.J. Pratt J.H. On the importance of pedal edema in hemodialysis patients.Clin J Am Soc Nephrol. 2008; 3: 153-158Crossref PubMed Scopus (105) Google Scholar Applying intradialytic blood volume monitoring with the relative-volume-plasma method in the Crit Line Intradialytic Monitoring Benefit (CLIMB) study was associated with increased access-related hospitalizations and mortality.18Reddan D.N. Szczech L.A. Hasselblad V. et al.Intradialytic blood volume monitoring in ambulatory hemodialysis patients: a randomized trial.J Am Soc Nephrol. 2005; 16: 2162-2169Crossref PubMed Scopus (165) Google Scholar The usefulness of bioelectrical impedance analysis was explored in a pilot study19Onofriescu M. Hogas S. Voroneanu L. et al.Bioimpedance-guided fluid management in maintenance hemodialysis: a pilot randomized controlled trial.Am J Kidney Dis. 2014; 64: 111-118Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar and, although promising, the validity of this method still needs to be tested in larger studies. Lung ultrasound (US) is a novel, easily applied technique that objectively quantifies fluid excess in this critical organ.20Zoccali C. Lung ultrasound in the management of fluid volume in dialysis patients: potential usefulness.Semin Dial. 2017; 30: 6-9Crossref PubMed Scopus (24) Google Scholar The technique is well validated in patients undergoing hemodialysis,21Mallamaci F. Benedetto F.A. Tripepi R. et al.Detection of pulmonary congestion by chest ultrasound in dialysis patients.JACC Cardiovasc Imaging. 2010; 3: 586-594Crossref PubMed Scopus (195) Google Scholar and at least 2 studies demonstrated that the number of US-B lines, a parameter that quantifies lung water content,22Picano E. Gargani L. Ultrasound lung comets: the shape of lung water.Eur J Heart Fail. 2012; 14: 1194-1196Crossref PubMed Scopus (28) Google Scholar shows strong correlations with left ventricular mass and function21Mallamaci F. Benedetto F.A. Tripepi R. et al.Detection of pulmonary congestion by chest ultrasound in dialysis patients.JACC Cardiovasc Imaging. 2010; 3: 586-594Crossref PubMed Scopus (195) Google Scholar and predicts mortality and cardiovascular events.23Zoccali C. Torino C. Tripepi R. et al.Pulmonary congestion predicts cardiac events and mortality in ESRD.J Am Soc Nephrol. 2013; 24: 639-646Crossref PubMed Scopus (188) Google Scholar Lung Water by Ultrasound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk End-Stage Renal Disease Patients with Cardiomyopathy (LUST) is an ongoing trial testing the effects of a lung-ultrasound–guided treatment strategy on major outcomes in high-risk patients undergoing hemodialysis.24Lung Water by Ultrasound Guided Treatment in Hemodialysis Patients (The Lust Study). (LUST).https://clinicaltrials.gov/ct2/show/NCT02310061?titles=LUST&id=NCT02310061&rank=1Google Scholar Since reduction of extracellular volume is central for hypertension control, within the frame of the LUST study we designed a substudy to evaluate the effect of dry weight reduction with a standardized lung-ultrasound–guided strategy on ambulatory BP in hypertensive patients undergoing hemodialysis independent of background comorbidities and risk factors; that is, this study included patients with hypertension who either had established cardiovascular disease (and thus were also eligible for the main LUST study) or did not have established cardiovascular disease. To this scope, we extended the study to include hypertensive patients who did not qualify for the main study. The trial flow chart of this study is presented in Figure 1. Table 1 presents demographic, clinical, and laboratory characteristics of the 2 study groups. A total of 71 hypertensive patients undergoing hemodialysis were included in this study; 35 (23 male and 12 female patients) were randomized to the active group and 36 (24 male and 12 female patients) were randomized to the control group. The first subject was recruited in September 2016, and the last was recruited in February 2018. All patients were white. From the total population of this study, 28 patients (39%) also were eligible for the main LUST trial, whereas 43 patients (61%) were not eligible. The 2 groups had similar age (63.11 ± 13.52 vs. 61.67 ± 13.67 years, P = 0.655), body mass index (27.53 ± 4.92 vs. 26.97 ± 5.36 kg/m2, P = 0.646), and hemodialysis vintage. The prevalence of cardiovascular risk factors, such as dyslipidemia and smoking, was similar between the groups, but diabetes was more common in the active group (42.9% vs. 11.1%, P = 0.003); heart failure and cardiovascular disease rates were also similar in the 2 groups. No differences were observed for common laboratory parameters, vascular access type, or antihypertensive drug use (Table 1). Patient evaluation at baseline and at the end of the study was performed during the first interdialytic interval of the week in 9 patients and during the second interval in 62 patients.Table 1Baseline characteristics of the study participantsaContinuous variables are presented with mean ± SDs or median (interquartile range) according to normality and categorical variables as absolute and relevant frequencies (n, %). Statistically significant P values are in bold type.CharacteristicActive groupControl groupP valueN3536–Age, yr63.11 ± 13.5261.67 ± 13.670.655Male, n (%)23 (65.7)24 (66.7)0.932Dry weight, kg76.19 ± 14.6476.17 ± 16.540.994Height, cm166.37 ± 9.00168.03 ± 10.130.469BMI, kg/m227.53 ± 4.9226.97 ± 5.360.646Dialysis vintage, mo (median IQR)26.12 (59.96)40.94 (84.96)0.340Diabetes mellitus, n (%)15 (42.9)4 (11.1)0.003Dyslipidemia, n (%)23 (65.7)16 (44.4)0.072Heart Failure, n (%)9 (25.7)8 (22.2)0.730History of smoking, n (%)10 (28.6)11 (30.6)0.855Atherosclerotic cardiovascular disease (coronary heart disease, stroke and/or peripheral vascular disease), n (%)17 (48.6)10 (27.8)0.071Chronic obstructive pulmonary disease, n (%)6 (17.1)4 (11.1)0.514Vascular access0.937 Arteriovenous fistula, n (%)25 (71.4)27 (75.0) Arteriovenous graft, n (%)2 (5.7)2 (5.6) Central venous catheter, n (%)8 (22.9)7 (19.4)Predialysis weight, kg77.95 ± 15.1178.31 ± 16.920.924Postdialysis weight, kg76.19 ± 14.6976.14 ± 16.520.990Residual renal output, ml/24 h429 ± 435459 ± 6670.825Ultrafiltration rate, ml/kg/h6.69 ± 3.247.91 ± 3.180.194Interdialytic weight gain, kg1.81 ± 0.952.13 ± 0.910.156Hemoglobin, g/dl11.43 ± 1.5111.57 ± 1.580.708Serum urea, mg/dl137.65 ± 31.10145.33 ± 28.800.283Urea reduction rate, %73.95 ± 7.9170.99 ± 7.800.118Serum sodium, mEq/l137.96 ± 2.80137.96 ± 2.200.990Serum potassium, mEq/l4.88 ± 0.564.94 ± 0.590.665Serum calcium, mg/dl8.87 ± 0.799.00 ± 0.730.458Serum phosphate, mg/dl4.60 ± 1.644.59 ± 1.190.991Parathormone, ng/l (median IQR)218.0 (244.0)294.0 (162.6)0.036Albumin, g/dl3.94 ± 0.324.01 ± 0.310.367Receiving ≥1 antihypertensive drugs, n (%)29 (82.9)30 (83.3)0.957RAAS blockers, n (%)12 (34.3)11 (30.6)0.737CCBs, n (%)9 (25.7)11 (30.6)0.650β blockers, n (%)22 (62.9)22 (61.1)0.880Loop diuretics, n (%)9 (25.7)5 (13.9)0.211Centrally active drugs, n (%)3 (8.6)2 (5.6)0.674Statins, n (%)20 (57.1)14 (38.9)0.124Erythropoietin, n (%)17 (48.6)19 (52.8)0.723BMI, Body mass index; CCBs, calcium channel blockers; IQR, interquartile range; RAAS, renin-angiotensin-aldosterone system.a Continuous variables are presented with mean ± SDs or median (interquartile range) according to normality and categorical variables as absolute and relevant frequencies (n, %). Statistically significant P values are in bold type. Open table in a new tab BMI, Body mass index; CCBs, calcium channel blockers; IQR, interquartile range; RAAS, renin-angiotensin-aldosterone system. Figure 2 presents net changes (Δ) in US-B lines score (a), dry weight (b), and 48-hour systolic blood pressure (SBP; c) and diastolic blood pressure (DBP; d) during the study in the intention-to-treat analysis. The number of US-B lines reduced in the active group while it slightly increased in the control group (–5.31 ± 12.53 vs. 2.17 ± 7.62, P <0.001). This went along with a modest reduction in dry weight in the active group versus a slight increase in the control group (–0.71 ± 1.39 vs. 0.51 ± 0.98 kg, P <0.001 or, for percentage changes in dry weight, –0.95 ± 1.89% vs. 0.68 ± 1.36%, P <0.001). With regard to the primary outcome, changes in 48-hour SBP (–6.61 ± 9.57 vs. –0.67 ± 13.07, P =0.033) were significantly greater in the active group; this was the case for DBP (–3.85 ± 6.34 vs. –0.55 ± 8.28, P =0.031; Figure 2). Comparisons in patients who completed the 8-week evaluation (n = 32 vs. n = 35 patients), that is, per-protocol analysis, showed similar results (Supplementary Table S1). As shown in Table 2, in the active group, US-B lines score (9.20 ± 14.55 vs. 3.89 ± 4.57, P = 0.017) and dry weight (76.19 ± 14.64 vs. 75.49 ± 14.75 kg, P = 0.005) were significantly reduced from baseline to the end of the study. In the control group, the US-B lines score did not change, but dry weight was 0.4 kg higher at study’s end (P =0.003) compared with baseline. Pre- and posthemodialysis BP levels were reduced in the active group in the 8-week evaluation; however, the changes did not reach statistical significance. In contrast, intradialytic BP (136.94 ± 14.93/83.77 ± 9.13 vs. 129.26 ± 15.48/80.13 ± 11.25 mm Hg, P = 0.007 and P = 0.014 for SBP/DBP), as well as 44-hour (136.11 ± 15.21/80.31 ± 10.19 vs. 129.61 ± 14.57/76.44 ± 9.25, P < 0.001 and P = 0.001 for SBP/DBP) and 48-hour ambulatory BP were significantly reduced from baseline to study’s end in the active group. In contrast, none of the aforementioned BP parameters was different between baseline and study’s end in the control group. Per-protocol analysis again yielded similar results.Table 2US-B lines score, dry weight, and peridialytic and ambulatory BP levels at baseline and study’s end for patients in the active and control study groups (intention-to-treat analysis)ParameterActive groupP valueControl groupP valueBaseline8-wk evaluationBaseline8-wk evaluationUS-B lines scores (lines)9.20 ± 14.553.89 ± 4.570.0176.36 ± 10.418.53 ± 12.220.097Dry weight, kg76.19 ± 14.6475.49 ± 14.750.00576.17 ± 16.5476.68 ± 16.660.003Prehemodialysis SBP, mm Hg148.06 ± 18.73141.80 ± 25.030.142149.36 ± 21.83148.22 ± 15.190.738Posthemodialysis SBP, mm Hg131.34 ± 19.94127.20 ± 20.200.285136.53 ± 25.97136.14 ± 23.780.915Intradialytic SBP, mm Hg136.94 ± 14.93129.26 ± 15.480.007136.37 ± 18.30134.72 ± 17.610.52444-hour SBP, mm Hg136.11 ± 15.21129.61 ± 14.57<0.001134.14 ± 16.04133.53 ± 16.370.78348-hour SBP, mm Hg136.19 ± 14.78129.58 ± 14.13<0.001134.34 ± 15.88133.67 ± 16.040.760Prehemodialysis DBP, mm Hg88.97 ± 13.1086.63 ± 13.940.22491.81 ± 15.1091.61 ± 11.760.922Posthemodialysis DBP, mm Hg80.26 ± 14.4377.71 ± 10.650.24082.22 ± 14.9284.47 ± 12.600.307Intradialytic DBP, mm Hg83.77 ± 9.1380.13 ± 11.250.01483.67 ± 13.7683.67 ± 12.240.99744-hour DBP, mm Hg80.31 ± 10.1976.44 ± 9.250.00181.17 ± 13.3980.50 ± 12.840.64548-hour DBP, mm Hg80.72 ± 9.8376.87 ± 9.200.00181.41 ± 13.2480.86 ± 12.530.692BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure; US, ultrasound. Statistically significant P values are in bold type. Open table in a new tab BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure; US, ultrasound. Statistically significant P values are in bold type. Similarly, patients in the active group had significant reductions in BP levels from baseline to study’s end for the various periods of daytime and nighttime of day 1 and day 2 of the 48-hour period, when these were studied separately (Supplementary Table S2). Patients in the control group did not show significant BP changes for any of these periods. To further examine the impact of lung congestion on dry weight and 48-hour ambulatory BP, we assessed simple linear correlations between changes during the study in US-B lines and dry weight, 48-hour SBP and DBP in the total population (Figure 3). A positive correlation between US-B line score changes and dry-weight changes was noted (whole dataset, r = 0.305, P = 0.010; without the outlier, r = 0.274, P = 0.022; Figure 3a). Positive correlations also were evident between changes in US-B lines score and 48-hour SBP (whole dataset, r = 0.253, P = 0.033; without the outlier, r = 0.234, P = 0.051) and DBP (whole dataset, r = 0.309, P = 0.009; without the outlier, r = 0.287, P = 0.016). Table 3 presents the number of interventions needed and hypotensive or vascular access thrombosis episodes in the 2 groups. During the 8-week follow up, the percentage of patients who had dry-weight decrease was significantly higher in the active group compared with the control group (54.3% vs. 13.9%, P < 0.001), whereas the percentage of patients who had per-protocol drug treatment initiation or intensification was insignificantly higher in the control group (2.9% vs. 8.3%, P = 0.614). Despite higher dry-weight reduction, the percentage of patients experiencing ≥1 intradialytic hypotensive episodes were marginally lower in the active group (34.3% vs. 55.6%, P = 0.072). The mean number of intradialytic hypotensive episodes were similar in the two groups (P = 0.894). No vascular access thrombosis episodes were evident in either of the groups studied. During follow-up one patient from the active group and one from the control group died due to central nervous system infection and lung infection, respectively. Other adverse events requiring hospitalization included 2 patients (one from each group) hospitalized for hematuria (resulting from polycystic kidney disease and prostate cancer, respectively), one patient from the control group hospitalized for possible gastrointestinal bleeding, one patient from the control group hospitalized for lung infection, and one patient from the active group hospitalized for tunneled central venous catheter change due to material failure (clip break).Table 3Interventions needed, hypotensive episodes, and vascular access episodes in the 2 study groupsParameterActive group, n (%)Control group, n (%)P valuePatients with dry-weight reduction19 (54.3)5 (13.9)<0.001Patients requiring time extension in at least 1 dialysis session4 (11.4)3 (8.3)0.710Per protocol drug treatment initiation or intensification1 (2.9)3 (8.3)0.614Patients experiencing ≥1 intradialytic hypotensive episodes12 (34.3)20 (55.6)0.072No. of intradialytic hypotensive episodes1.23 ± 2.171.17 ± 1.720.894Vascular access thrombosis0 (0.0)0 (0.0)1.000Statistically significant P values are in bold type. Open table in a new tab Statistically significant P values are in bold type. This study aimed to investigate whether a lung-ultrasound–guided strategy to guide dry-weight probing would affect ambulatory BP levels in patients with hypertension undergoing hemodialysis who were already on their dry weight by standard clinical criteria. Although only 54% of patients in the active arm required dry-weight reduction (on average –0.7 kg) on the basis of lung US criteria, intradialytic, 44-hour, 48-hour, daytime, and nighttime ambulatory BP levels were significantly lower after 8 weeks. In contrast, in patients in the control arm (dry weight changes guided by conventional clinical criteria), no changes in BP were registered. Overall, 48-hour BP reductions throughout the study were significantly greater in the active group (average between-group difference 6/3.3 mm Hg for SBP/DBP). Moreover, significant correlations between changes in lung water content, indicated by US-B lines score and changes in dry weight, 48-hour SBP, or 48-hour DBP were observed in the total population studied. The main pathogenic mechanism of hypertension in patients undergoing hemodialysis is water and sodium overload.13Loutradis C.N. Tsioufis C. Sarafidis P.A. The clinical problems of hypertension treatment in hemodialysis patients.Curr Vasc Pharmacol. 2017; 16: 54-60Crossref PubMed Scopus (11) Google Scholar The pathogenesis of hypertension in patients with end-stage renal disease who are undergoing hemodialysis is multifactorial, including sodium and water overload, sympathetic nervous system overdrive, renin-angiotensin system activation, arterial stiffness, endothelin-1 increase and nitric oxide decrease causing endothelial dysfunction, sleeping disorders and apnea provoking nocturnal hypoxemia and sympathetic overactivity, and use of medications inducing BP increase, such as recombinant erythropoietin.8Sarafidis P.A. Persu A. Agarwal R. et al.Hypertension in dialysis patients: a consensus document by the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension (ESH).Nephrol Dial Transplant. 2017; 32: 620-640PubMed Google Scholar, 9Agarwal R. Flynn J. Pogue V. et al.Assessment and management of hypertension in patients on dialysis.J Am Soc Nephrol. 2014; 25: 1630-1646Crossref PubMed Scopus (113) Google Scholar Volume overload is also a major driver for the high risk of death and cardiovascular events in predialysis and dialysis patients, and the need for treatment policies guided by metrics of fluid status, including lung water measured by lung US, is perceived to be a priority in clinical research in these populations.25Zoccali C. Mallamaci F. Mapping progress in reducing cardiovascular risk with kidney disease: managing volume overload.Clin J Am Soc Nephrol. 2018; 13: 1432-1434Crossref PubMed Scopus (9) Google Scholar The achievement of the “ideal” dry weight is perhaps the most challenging problem in everyday clinical practice in patients undergoing hemodialysis. Dry weight is classically defined as the lowest tolerated postdialysis weight, achieved through a gentle and gradual reduction in postdialysis weight, at which patients experience minimal signs or symptoms of either hypovolemia or hypervolemia.26Sinha A.D. Agarwal R. Can chronic volume overload be recognized and prevented in hemodialysis patients? The pitfalls