Volume overload is an important, but often hidden risk factor for all-cause and cardiovascular death in end stage renal disease (ESRD) patients. Monitoring lung water could be used as a biomarker for detecting and monitoring lung congestion in populations at risk for pulmonary edema, as substantial lung water accumulation may occur before clinical symptoms of heart failure and in other conditions appear, explains the author of the present Italian study. Until recently, measuring lung water meant using costly radioactive compounds, X-rays or placing catheter into the pulmonary artery. But as the present study shows, ultrasound (US) could also allow valid, reproducible estimates of lung water.
Why ultrasound? Water accumulates in the lung interstitium, thickening the interlobular septa and thereby generating visible bundles in the ultrasound. These bundles are a US equivalent of B lines (BL-US) detected in chest radiographs – which means that simply counting BL-US could offer an estimate of lung water. Studies have also shown that the number of BL-US is associated with parameters such as LV filling pressure, larger LV end-diastolic and end-systolic diameters, LV mass index, left atrial volume index, tricuspid regurgitation velocity and estimated pulmonary artery systolic pressure in heart failure (HF) patients. And: Ultrasound could also be particularly valuable in intensive care patients, where it could be used to discriminate moderate and severe lung congestion.
Ultrasound (US) is a well-validated technique that allows reliable estimates of lung water in the care of hemodialysis patients at high cardiovascular risk, summarizes the author.
Volume overload is a hidden, pervasive complication in dialysis patients with dyspnea and pulmonary edema being its main clinical manifestations. Measuring lung water has clinical potential because it allows timely treatment of lung congestion at a preclinical stage. Chest ultrasound (US) is a novel, well-validated technique that allows reliable estimates of lung water in clinical practice. The application of this technique in dialysis patients has shown that an unsuspectedly high proportion of these patients have moderate to severe lung congestion which is usually asymptomatic. Furthermore, lung congestion in these patients is only loosely associated with fluid excess as measured by bioimpedance (BIA). Lung congestion is associated with a high death risk in dialysis patients and therefore represents a potential treatment target. The “Lung water by Ultra-Sound guided Treatment to prevent death and cardiovascular complications in high risk ESRD patients with cardiomyopathy” (LUST) study will provide important information about the clinical value of this technique in the care of hemodialysis patients at high cardiovascular risk.
Estimates of fluid volume in dialysis patients are being increasingly applied to guide the prescription of ultrafiltration and dietary sodium intake in dialysis patients. These estimates include the measurement of total and extracellular fluid volume by bio-impedance (BIA) , inferior vena cava diameter, plasma volume changes across dialysis by the Crit-Line system and circulating levels of cardiac natriuretic peptides. All these biomarkers still have a low evidentiary basis supporting their systematic use in ESRD. Though small trials based on surrogates seem to support the use of BIA [6, 7] we still lack trials based on clinical endpoints documenting the usefulness of this technique. Inferior vena cava diameter does not provide useful information for probing dry weight . As with BIA, there are no clinical trials using valid clinical endpoints which test the value of this measurement in clinical practice. In a clinical trial testing the application of Crit-Line to guide UF, the Crit-Line Intradialytic Monitoring Benefit (CLIMB) study, adverse events in the active arm of the trial were significantly higher than in the control arm . Finally, cardiac natriuretic peptides, ANP, BNP and Pro-BNP, largely reflect left ventricular (LV) myocardial mass and LV end-diastolic pressure rather than circulating volume [10, 11].
It should be noted that, however, reliable and accurate a technique might be, the derived estimates of global fluid volumes may be insufficient to guide clinical decisions about fluid volume optimization in ESRD patients. Fluid accumulation in critical organs like the lung is of particular importance. Until recently, no easily applicable method for measuring fluid accumulation in this organ was available. Overall, notwithstanding the large majority of nephrologists who have no doubt about the paramount importance of body fluid volume optimization in the care of dialysis patients, most dialysis centers have no established clinical policy for evaluating and monitoring fluid volume status .
Fluid Excess, Hemodynamic, and Pulmonary Congestion
Together with the heart, the lung is the organ where fluid excess poses the major health hazards. Accumulation of fluid in a dialysis patient’s lungs entails a high risk for pulmonary edema [13, 14]. Superficially, pulmonary edema might be equated with volume overload. However, fluid overload apart, lung water content also depends on two additional, quite relevant factors: left ventricular (LV) function and lung permeability. In both LV systolic and diastolic dysfunction, LV end-diastolic pressure and hence left atrial pressure are high; retrograde transmission of this pressure to pulmonary veins and lung capillaries results into high pulmonary capillary wedge pressure — “hemodynamic congestion”. Hemodynamic congestion sets the stage for extravasation of fluid into the lung interstitium and into the alveoli, resulting into “pulmonary congestion”.
Even though pulmonary congestion is, in most cases, attributable to high pulmonary capillary pressure concomitant with fluid overload, this alteration may also occur without fluid overload pointing to fluid redistribution triggered by systemic arterial and/or venous vasoconstriction. In this regard, it cannot be overemphasized that fluid removal in patients with decompensated heart failure has just a loose relationship with the improvement of dyspnea . In the same vein, application of continuous intrathoracic impedance monitoring in these patients showed that pulmonary congestion may antedate by 2 weeks frank pulmonary edema in these patients. Of note, a high degree of tolerance to fluid accumulation in the lung without superimposed dyspnea is well-documented in patients with nephrotic syndrome where an estimated average lung water excess as high as 1.7 l can remain asymptomatic . Yet, in the vast majority of cases, particularly in patients with LV disorders, congestion eventually triggers clinical lung congestion, i.e., dyspnea, a symptom most often leading to hospitalization.
The relevance of the second factor that may facilitate lung congestion in patients with kidney diseases, lung permeability, is obvious in acute kidney injury a condition where, independently of fluid overload, systemic inflammation may dramatically increase alveolo-capillary permeability and trigger life-threatening congestion . Furthermore, pulmonary capillaries are recognized as a vulnerable segment of the cardiopulmonary circulation in patients with heart disease  which has obvious implications in dialysis patients, a population where cardiomyopathy is almost universal .
Measuring Lung Congestion
Because substantial lung water accumulation may occur before clinical symptoms in heart failure and in other conditions, monitoring lung water has prima facie credibility as a biomarker for detecting and monitoring lung congestion in populations at risk for pulmonary edema. However, until recently measuring lung water entailed either the use of costly radioactive compounds , exposure to X-rays  or the placement of a catheter into the pulmonary artery to apply the thermo-dilution technique . The discovery that ultrasound (US) may allow valid, reproducible estimates of lung water as well as corollary information on other pulmonary alterations has been a breakthrough in pulmonary medicine .
The rationale for adopting ultrasound to measure lung water is that water accumulation in the lung interstitium thickens the interlobular septa. This thickening produces a reverberation of the US beam and generates visible bundles at narrow basis going from the probe to the edge of the echotomography screen. These bundles are a true US equivalent of B lines [BL-US] detected in chest roentgenograms and their simple count provides an estimate of lung water  (Fig. 1). The number of BL-US is associated with LV filling pressure  as well as with larger LV end-diastolic and end-systolic diameters, LV mass index, left atrial volume index, tricuspid regurgitation velocity and estimated pulmonary artery systolic pressure in heart failure (HF) patients with dyspnea as well as in those without overt cardiac decompensation . Beyond heart failure, the technique is of particular value in intensive care patients where it is a powerful instrument to discriminate moderate and severe lung congestion (areas under the ROC curves of 0.94 and 0.96 respectively) .
Lung Congestion in ESRD
Lung US has specifically been validated in ESRD patients where it holds high intra and interobserver reproducibility as well as high technical reproducibility, i.e. it provides reproducible results with different echo-tomography machines . Measuring the degree of lung congestion in dialysis patients has clinical potential for various reasons. Lung congestion is common both in hemodialysis [26-28] and in peritoneal dialysis  patients where it is usually asymptomatic. There is a dose–response relationship in dialysis patients between the number of US B lines and both the risk of mortality and cardiovascular complications which is largely independent of other risk factors ([27, 28]). In addition, the number of US-B lines is strongly associated with various echocardiography parameters including left atrial volume, pulmonary artery pressure, Ee’ ratio (an index of diastolic function) and, particularly, with the ejection fraction; these associations hold true both predialysis and postdialysis implying that the relationships are largely independent of volume overload .
Lung auscultation to detect crackles at the lung bases is a cornerstone for the diagnosis and the monitoring of congestion in patients with heart failure and in those with chronic kidney failure . However, as with several other time honored clinical signs , the reliability of auscultation for the diagnosis of lung congestion has not, until very recently, been specifically assessed in the dialysis population. Investigators of the “Lung water by Ultra-Sound guided Treatment to prevent death and cardiovascular complications in high risk ESRD patients with cardiomyopathy” (LUST) , a randomized trial testing whether the use of lung US in high risk hemodialysis patients may improve clinical outcomes and echocardiographic indicators of cardiomyopathy in these patients, adopted lung sonography as a reference test to examine the diagnostic reliability of crackles as a sign of pulmonary congestion  in over 1000 paired measurements of lung water by US with simultaneous standardized auscultation of the thorax. These analyses showed that crackles were quite insensitive in detecting interstitial lung edema found by lung US .
Lung congestion in heart failure is a gradual phenomenon and pulmonary edema may supervene after one or more weeks of insidious accumulation of fluid in the lung . This is of particular relevance in dialysis patients, a population where lung water (as measured US-B lines) only weakly correlated with total body water (by BIA) and interdialysis weight gain10. Furthermore, dialysis patients have increased alveolo-capillary permeability  and the average estimated interstitial lung water in ESRD patients is about 1.2 l, an unsuspectedly high degree of pulmonary congestion .
The application of lung US has relevant clinical potential. However, its usefulness in patients needs to be tested in a randomized trial comparing a treatment policy guided by this technique with that using the standard approach. Currently, the usefulness of targeting asymptomatic lung congestion remains unproven. The CLIMB study is a cautionary tale about accepting on purely physiologic grounds the use of medical devices and the lack of proper trials testing their impact on clinical endpoints.
Lung US is a well-validated, simple and low-cost technique which can be easily applied by nephrologists at the bedside by using virtually all, old and new, US machines  including affordable hand-held US devices. The LUST study is currently testing whether the use of lung US by nephrologists may improve clinical outcomes in high risk dialysis patients. It will provide important information about the clinical value of this technique in the care of hemodialysis patients at high cardiovascular risk.