Extravascular Lung Water Assessment by Ultrasound to Guide Dry Weight Changes: Ready for Prime Time?

Related Article, p. 11 Related Article, p. 11 Chronic volume excess among long-term hemodialysis patients is common and if left untreated, leads to the development of heart failure and cardiac arrhythmias.1Sinha A.D. Agarwal R. Setting the dry weight and its cardiovascular implications.Semin Dial. 2017; 30: 481-488Crossref PubMed Scopus (19) Google Scholar Although potentially due to missed or shortened dialysis,2Tandon T. Sinha A.D. Agarwal R. Shorter delivered dialysis times associate with a higher and more difficult to treat blood pressure.Nephrol Dial Transplant. 2013; 28: 1562-1568Crossref PubMed Scopus (20) Google Scholar volume excess often occurs because of its protean manifestations and diagnostic challenges. Physicians often treat the resultant hypertension with antihypertensive medication, which can further limit the opportunity for ultrafiltration on dialysis. Often these patients present with acute volume overload, requiring emergent dialysis and therefore increasing costs.3Arneson T.J. Liu J. Qiu Y. Gilbertson D.T. Foley R.N. Collins A.J. Hospital treatment for fluid overload in the Medicare hemodialysis population.Clin J Am Soc Nephrol. 2010; 5: 1054-1063Crossref PubMed Scopus (61) Google Scholar Consequently, volume control is considered of primary importance for the rehabilitation of patients receiving dialysis.4Weiner D.E. Brunelli S.M. Hunt A. et al.Improving clinical outcomes among hemodialysis patients: a proposal for a “volume first” approach from the chief medical officers of US dialysis providers.Am J Kidney Dis. 2014; 64: 685-695Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar Although some measures such as relative blood volume monitoring may be helpful to assess volume, there are no gold standards to evaluate volume excess.5Sinha A.D. Light R.P. Agarwal R. Relative plasma volume monitoring during hemodialysis aids the assessment of dry weight.Hypertension. 2010; 55: 305-311Crossref PubMed Scopus (75) Google Scholar In a cross-sectional study6Agarwal 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 and a randomized trial,5Sinha A.D. Light R.P. Agarwal R. Relative plasma volume monitoring during hemodialysis aids the assessment of dry weight.Hypertension. 2010; 55: 305-311Crossref PubMed Scopus (75) Google Scholar physical signs such as pedal edema did not discriminate euvolumia from hypervolemia sufficiently to be of clinical value.7Agarwal R. Alborzi P. Satyan S. Light R.P. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial.Hypertension. 2009; 53: 500-507Crossref PubMed Scopus (267) Google Scholar,8Sinha A.D. Agarwal R. Can chronic volume overload be recognized and prevented in hemodialysis patients? The pitfalls of the clinical examination in assessing volume status.Semin Dial. 2009; 22: 480-482Crossref PubMed Scopus (70) Google Scholar Interest has therefore emerged in evaluating bedside techniques to determine volume status. Using lung ultrasound, a trained observer can rapidly assess excess extravascular lung water manifesting as sonographic B-lines, also known as lung comets.9Noble V.E. Murray A.F. Capp R. Sylvia-Reardon M.H. Steele D.J.R. Liteplo A. Ultrasound assessment for extravascular lung water in patients undergoing hemodialysis. Time course for resolution.Chest. 2009; 135: 1433-1439Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar Such extravascular lung water excess has been shown to associate with future cardiovascular morbidity and mortality.10Zoccali 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 (186) Google Scholar A recent randomized controlled trial from Loutradis et al11Loutradis C. Sarafidis P.A. Ekart R. et al.The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood pressure in hemodialysis patients: a randomized controlled trial.Kidney Int. 2019; 95: 1505-1513Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar tested the hypothesis that compared to usual therapy, a strategy of fluid removal guided by lung ultrasound water assessment results in better blood pressure control among patients with hypertension receiving long-term hemodialysis. The primary result of this trial was the finding of better 48-hour ambulatory blood pressure control in the intervention group. In this issue of AJKD, Loutradis et al12Loutradis C. Papadopoulos C.E. Sachpekidis V. et al.Lung ultrasound–guided dry weight assessment and echocardiographic measures in hypertensive hemodialysis patients: a randomized controlled study.Am J Kidney Dis. 2019; 75: 11-20Google Scholar report an exploratory analysis of echocardiographic parameters measured during the trial. There were 71 patients randomly assigned, 35 to the intervention group and 36 to the control group, for a trial that lasted 8 weeks or 24 dialysis sessions. Sample size was determined based on the expected effect size in ambulatory blood pressure monitoring. The initial study found improvements in lung water as assessed using ultrasound, and in the new report, the authors report that several echocardiographic measures of volume excess (such as left atrial volume indexed for body surface area, left atrial and right atrial diameter, and inferior vena cava diameter) improved, though not all (eg, left ventricular internal diameter). The authors conclude that this strategy of guiding fluid removal by using lung ultrasound water should now be used more widely given the results of this trial. To assess the effects of the intervention, the first step is to evaluate whether participants in the control group received the standard of care. For patients who are hypertensive receiving hemodialysis, the initial strategy is to probe the ideal dry weight. This was performed in just 5 of 36 (14%) patients in the control group. The control group gained 0.51 (95% confidence interval [CI], 0.19-0.83) kg over 8 weeks (P = 0.003). One would expect no statistically significant change in body weight—not a significant increase—in these patients even if nothing was done. Increases in echocardiographic markers within the control group confirmed an elevation in left atrial volume index (P = 0.008). In the intervention group, dry weight was reduced in 19 (54%) patients. During the 8 weeks of the trial, there was a mean reduction in body weight of 0.71 (95% CI, 0.52-1.17) kg in the intervention group. Echocardiographic diameters improved, and a comparison of between-group changes in the intervention group showed an impressive difference for various cardiac chamber diameters. Randomized trials are not common in nephrology and even less so among dialysis patients. Therefore, the authors should be congratulated for performing this study. The sample size for this study was determined based on ambulatory blood pressure; even so, the number of patients recruited was half that of the DRIP trial, a study to establish the value of probing dry weight among hypertensive hemodialysis patients.7Agarwal R. Alborzi P. Satyan S. Light R.P. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial.Hypertension. 2009; 53: 500-507Crossref PubMed Scopus (267) Google Scholar Sample size calculations were not based on echocardiographic parameters and they were not the primary end point in the study; therefore, all hypothesis tests are exploratory. Nonetheless, the study confirms changes in diameters of pressure chambers such as the atria and inferior vena cava, as have been reported previously in the DRIP trial.13Agarwal R. Bouldin J.M. Light R.P. Garg A. Inferior vena cava diameter and left atrial diameter measure volume but not dry weight.Clin J Am Soc Nephrol. 2011; 6: 1066-1072Crossref PubMed Scopus (61) Google Scholar However, perhaps because of larger numbers and universal probing of dry weight in the DRIP intervention group, a reduction of left ventricular internal diameter in diastole was seen in that larger study that was absent in the current study.14Agarwal R. Bouldin J.M. Light R.P. Garg A. Probing dry-weight improves left ventricular mass index.Am J Nephrol. 2011; 33: 373-380Crossref PubMed Scopus (36) Google Scholar Probing dry weight is necessary for an improvement in hypertension among dialysis patients15Agarwal R. Weir M.R. Dry-weight: a concept revisited in an effort to avoid medication-directed approaches for blood pressure control in hemodialysis patients.Clin J Am Soc Nephrol. 2010; 5: 1255-1260Crossref PubMed Scopus (120) Google Scholar,16Sarafidis 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).J Hypertens. 2017; 35: 657-676PubMed Google Scholar and results in better volume status, as demonstrated by the improved cardiac chamber volumes in both the current study and the larger DRIP trial. This study extends our findings to demonstrate that an 8-week trial is sufficient to show a differential improvement in lung water. Probing of dry weight also results in an improvement in interdialytic ambulatory blood pressure. However, the relationship between improvements in cardiac chamber diameters and interdialytic ambulatory blood pressure is poor.13Agarwal R. Bouldin J.M. Light R.P. Garg A. Inferior vena cava diameter and left atrial diameter measure volume but not dry weight.Clin J Am Soc Nephrol. 2011; 6: 1066-1072Crossref PubMed Scopus (61) Google Scholar This suggests that improved volume is an intermediate step in improving blood pressure but is not sufficient in itself. Autoregulatory mechanisms such as reduction in systemic vascular resistance may be important to provoke a reduction in blood pressure. For example, in patients in whom autoregulatory changes are impaired, the reduction in blood pressure may not be seen. Dietary sodium intake and dialysate sodium prescription, as well an adequate duration of dialysis—at least 4 hours, 3 times a week—may play an important role in controlling blood pressure among patients receiving hemodialysis. Despite the tremendous efforts of the investigative team in this study, the intervention group was compared with a group of patients who had hypertension and presumably volume excess. The recommended treatment in such patients is to probe dry weight, which was not implemented in this trial. Because the control group was not treated by what can be considered standard of care, the interventional strategy of lung ultrasound assessment to guide dry weight reduction is difficult to evaluate. Somewhat inexplicably, despite dry weight reductions in 14% of the control and 54% of the intervention group, there were numerically more patients in the control group who experienced hypotension (56% vs 34%), but this was not statistically significant (P = 0.07). Although this study does not change practice, it provides the basis for conducting the next trial that may help patients receiving dialysis. In our opinion, lung ultrasound may still be a valuable tool to help gauge volume overload in dialysis patients but would need a different approach. Lung ultrasound is clearly safe and simple without a danger or burden for the patients. One approach to test the utility of this novel technique is as follows: in a larger trial, the control group would be targeted to probe dry weight as was performed as an intervention in the DRIP trial or as done more gently in this trial. In the intervention group, dry weight would be probed but would be guided by lung ultrasound. The end point would be symptoms receiving dialysis. The expectation would be that fewer symptoms will occur in the intervention group. Until such a trial is done, we should continue to follow the standard of care, which is to probe dry weight when the long-term hemodialysis patient is hypertensive, and to guide therapy by symptoms.15Agarwal R. Weir M.R. Dry-weight: a concept revisited in an effort to avoid medication-directed approaches for blood pressure control in hemodialysis patients.Clin J Am Soc Nephrol. 2010; 5: 1255-1260Crossref PubMed Scopus (120) Google Scholar Rajiv Agarwal, MD, MS, Robert D. Toto, MD, and Matthew R. Weir, MD. This editorial was produced without any direct financial support. Dr Weir is supported by grants R01HL127422, R01HL132372, U01DK106102, and U01DK116095. Dr Agarwal reports personal fees from Relypsa, Inc (a Vifor Pharma Group Company), Abbvie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly & Co, Gilead, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Sandoz, ZS Pharma, Akebia, Takeda, Sanofi, Reata, Ironwood Pharmaceuticals, Otsuka, Opko, and Birdrock Bio, all outside the submitted work; has served as an Associate Editor of the American Journal of Nephrology and Nephrology, Dialysis, and Transplantation and an author for UpToDate; and has received research grants from the US Veterans Administration and National Institutes of Health. Dr Toto reports serving as consultant for Amgen, Astra-Zeneca, Bayer, Boehringer-Ingelheim, Quest Diagnostics, Quintiles, Relypsa, and Reata. Dr Weir reports serving as consultant for Abbvie, Astra-Zeneca, Boehringer-Ingelheim, Merck, Janssen, Relypsa, Vifor, Boston Scientific, and Bayer. Received August 12, 2019, in response to an invitation from the journal. Direct editorial input from an Associate Editor and a Deputy Editor. Accepted in revised form September 8, 2019. Lung Ultrasound–Guided Dry Weight Assessment and Echocardiographic Measures in Hypertensive Hemodialysis Patients: A Randomized Controlled StudyAmerican Journal of Kidney DiseasesVol. 75Issue 1PreviewLeft ventricular (LV) hypertrophy and dysfunction are associated with adverse outcomes in hemodialysis patients. Hypertension and hypervolemia play important roles in these cardiac abnormalities. We report on the prespecified secondary outcome, echocardiographic indexes of LV function, from a previously reported study of the effect of lung ultrasound (US)-guided dry weight reduction on systolic blood pressure. Full-Text PDF