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Background: Loop diuretics have well-described toxicities, and loss of response to these agents is common. Alternative strategies are needed for the maintenance of euvolemia in heart failure (HF). Nonrenal removal of sodium directly across the peritoneal membrane (direct sodium removal [DSR]) with a sodium-free osmotic solution should result in extraction of large quantities of sodium with limited off-target solute removal., Methods: This article describes the preclinical development and first-in-human proof of concept for DSR. Sodium-free 10% dextrose was used as the DSR solution. Porcine experiments were conducted to investigate the optimal dwell time, safety, and scalability and to determine the effect of experimental heart failure. In the human study, participants with end-stage renal disease on peritoneal dialysis (PD) underwent randomization and crossover to either a 2-hour dwell with 1 L DSR solution or standard PD solution (Dianeal 4.25% dextrose, Baxter). The primary end point was completion of the 2-hour dwell without significant discomfort or adverse events, and the secondary end point was difference in sodium removal between DSR and standard PD solution., Results: Porcine experiments revealed that 1 L DSR solution removed 4.1±0.4 g sodium in 2 hours with negligible off-target solute removal and overall stable serum electrolytes. Increasing the volume of DSR solution cycled across the peritoneum increased sodium removal and substantially decreased plasma volume ( P =0.005). In the setting of experimental heart failure with elevated right atrial pressure, sodium removal was ≈4 times greater than in healthy animals ( P <0.001). In the human proof-of-concept study, DSR solution was well tolerated and not associated with significant discomfort or adverse events. Plasma electrolyte concentrations were stable, and off-target solute removal was negligible. Sodium removal was substantially higher with DSR (4.5±0.4 g) compared with standard PD solution (1.0±0.3 g; P <0.0001)., Conclusions: DSR was well tolerated in both animals and human subjects and produced substantially greater sodium removal than standard PD solution. Additional research evaluating the use of DSR as a method to prevent and treat hypervolemia in heart failure is warranted. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03801226.

Systematic studies of relationships among depression, sexual function, and martial discord in hemodialysis patients and their spouses arelacking; existing studies focus upon only one of these three topics, or deal with patient or spouse as individuals rather than as a couple. We studied 17 chronic, medically stable hemodialysis patients and their husbands or wives. Although couples rated their degree of marital discord as low, the investigators rated it as high, based on the number and type of specific problems reported by the couple. The couples' evaluation may not represent denial, as has been commonly assumed. Instead their evaluation may imply that the disease and its treatment overshadow marital problems, even though couples recognize and react to these problems. Couples showed a high prevalence of sexual problems--in terms of overall satisfaction, frequency of intercourse, and specific dysfunctional symptoms (difficulty becoming excited, maintaining excitement, or having orgasm). We found a strong relationship between severity of depression and severity of sexual dysfunction in patients, but not in their mates. No strong relationship existed between a patient's depression score and marital discord, although spouses showed a trend toward correlation between severity of depression and martial discord. Younger couples, especially, seem not to want intercourse when severe martial discord exists. Patients' depression scores were comparable to thoseof psychiatric patients, while spouses' depression scores resembled those of normals. While psychosocial phenomena such as marital discord, sexual dysfunction, and depression are clear, causal chains are not. Despite disadvantages inherent in using questionnaires, short, self-administered, easily scored instruments may elicit problems with sex, marriage, and mood which might otherwise be overlooked by caretaking personnel.