Probing Dry Weight: A New Path, or a Dead End for Dialysis Patients?

By Peter Laird, MD

The DRIP trial from 2009 looked at patient outcomes over an 8 week randomized trial of intensified ultrafiltration and the subsequent ambulatory blood pressure measurements. Patients in the study group underwent no additional time or duration of dialysis, but instead they increased the intensity of ultrafiltration which did show a significant decrease in ambulatory blood pressure readings. In a recent secondary analysis of this study, Agarwal and his colleagues measured echocardiographic indices for LVH immediately following dialysis and likewise showed a significant reduction in Left Ventricular Mass Index during their 8 week study. However, an accompanying editorial correctly points out that the reduction of LVMI in the Agarwal study was of the intracavatary size and not the actual muscle wall, a key difference from prior studies on LVH evaluated by MRI by Culleton et al and the FHN:

Left Ventricular Mass Index as an Outcome Measure in Clinical Trials in Dialysis Patients: A Word of Caution

Actually, the reduction in LV mass mainly depended on a decrease in the LV end-diastolic diameter (cavitary component). Volume removal has a relevant influence on the measurement’s LV mass which shows a substantial fall across a single dialysis session, an effect entirely attributable to the decrease of the end-diastolic diameter ( fig. 1 ). Predictably, UF intensification in the DRIP study reduced blood volume and the cavitary component of LV mass but failed to modify the muscular component.

In simpler terms, all Agarwal really measured with his echocardiagraphic measurements post dialysis is the volume of fluid removed during dialysis which was greater in the study group of intensified ultrafiltration. The Left Ventricular Mass Index is not reliably measured by post dialysis as shown in prior studies comparing pre-dialysis and post dialysis MRI measurements. There are significant changes immediately following dialysis that are completely related to the extent of volume of fluids removed during dialysis:

Myocardial Mass and Volume Measurement of Hypertrophic Left Ventricles by MRI - Study in Dialysis Patients Examined Before and After Dialysis

In conclusion, cine MRI is a reliable technique for LVMM measurement that is independent of LV loading status. This method allows for detection of small changes, which is crucial for accurate therapy monitoring in LVH. Left ventricular myocardial mass and volumes decrease significantly during hemodialysis.

In addition, the DRIP study achieved improved ambulatory blood pressures at the cost of at least three significant adverse events as well as significant increases in intradialytic hypotension, a known risk factor for increased episodes of myocardial ischemia, myocardial stunning and sudden cardiac death precipitated by intensified ultrafiltration paradigms.

Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP)

The end point of reducing weight in the intervention group was the appearance of symptoms that, in the opinion of the investigator, suggested that the goal was reached. The proportion of patients experiencing these symptoms is shown in Table SI. . . Cramps, dizziness, intradialytic hypotension, need for saline, or reduction in ultrafiltration rates were more commonly seen among patients allocated to the ultrafiltration group, as expeceted. . .

Probing for dry weight led to the predictable increase in muscle cramps, dizziness, and hypotensive episodes. (21) Even with careful supervision, we witnessed [greater than or equal to] 3 serious adverse events that were likely related to intervention: hypotension and seizures, dizziness requiring saling administration after dialysis, and chest pain followed by hypotension. It is also possible that lower BPs achieved as a result of challenging dry weight may increase the risk of access thromobosis.

Since intradialytic hypotension and its attendant consequences are well documented in the medical literature, a simple question is what is the underlying basis for studying intensified ultrafiltration rates in the first place. The answer is in parallel to the same questions posed with urea solute clearances in the NCDS and the HEMO study, how can they increase clearances without increasing duration or frequency of dialysis, the for-profit LDO motive that has resulted in our last place American dialysis survival compared to the rest of the developed nations. Interestingly, this is noted in the accompaning editorial:

Left Ventricular Mass Index as an Outcome Measure in Clinical Trials in Dialysis Patients: A Word of Caution

Given the high predictive power of LV mass for death and CV events, prima facie, the parallel decline in BP and in LV mass may suggest that UF intensification – a purely technical, easily implementable intervention – may translate into better clinical outcomes in ESRD patients. If this is the case, UF intensification could represent a clinically important, cheaper and much less demanding alternative to frequent dialysis to improve the ominous prognosis of these patients.

To date, since the publication of the Frequent Hemodialysis Network Trial Group results showing a significant improvement in LVH and all cause mortality, I have yet to see any major movement to implementing these results, instead we have articles like the one in question before us trying in my opinion to substitute an inferior alternative that is far from proven in any clinical outcome trial. In addition, Agarwal in my opion is impressing those that don’t understand the dynamics of fluid removal and LVMI measurements which are completely dependant on volume removal post dialysis and do not in the least give a true measure of actual LV muscle mass changes with his intervention.

Finally, according to the original DRIP study itself, significant complications occurred in this very short trial of only 8 weeks leaving me with the opinion that Agarwal, et al offer no new alternatives to the proven efficacy of longer duration and more frequent dialysis shown to us nearly 50 years ago by the venerable pioneers of dialysis. In addition, Agarwal’s protocol completely ignores the benefits found in more frequent and longer duration dialysis from improved PO4 clearances and middle molecule clearances which are time dependent. Unless Dry-Weight Probing is accomplished in the manner of Charra and his associates in Tassin with longer duration dialysis or more frequent hemodialysis as shown in the FHN, intensified ultrafiltration in my opinion is an already proven dead end that will not in the end analysis improve the dismal American dialysis survival rates.