A Phase 1 dose-ranging study examining the effects of a superabsorbent polymer (CLP) on fluid, sodium and potassium excretion in healthy subjects.

BACKGROUND: CLP is an orally administered, non-absorbed, superabsorbent polymer being developed to increase fecal excretion of sodium, potassium and water in patients with heart failure and end-stage renal disease. This study was conducted to evaluate the safety of CLP, and to explore dose-related effects on fecal weight, fecal and urine sodium and potassium excretion, and serum electrolyte concentrations. METHODS: This Phase 1, open-label, dose-escalation study included 25 healthy volunteers, who were administered CLP orally immediately prior to four daily meals for 9 days at doses of 7.5, 15.0, and 25.0 g/day (n = 5/group). An additional dose group received 15.0 g/day CLP under fasting conditions, and an untreated cohort (n = 5) served as control. Twenty-four-hour fecal and urinary output was collected daily. Samples were weighed, and sodium, potassium, and other ion content in stool and urine were measured for each treatment group. Effects on serum cation concentrations, other standard laboratory values, and adverse events were also determined. RESULTS: At doses below 25.0 g/day, CLP was well tolerated, with a low frequency of self-limiting gastrointestinal adverse events. CLP increased fecal weight and fecal sodium and potassium content in a dose-related manner. Concomitant dose-related decreases in urinary sodium and potassium were observed. All serum ion concentrations remained within normal limits. CONCLUSIONS: In this study, oral CLP removed water, sodium and potassium from the body via the gastrointestinal tract in a dose related fashion. CLP could become useful for patients with fluid overload and compromised kidney function in conditions such as congestive heart failure, salt sensitive hypertension, chronic kidney disease and end stage renal disease. TRIAL REGISTRATION: NCT01944007.

Symptomatic intradialytic hypotension and mortality: an opinionated review.

The unchanging rate of symptomatic hypotension that attends maintenance hemodialysis and its link to sodium/volume overload are explored. Correlations between interdialytic weight gain, ultrafiltration rate, hypertension, and mortality are found to be strong. Suggestions/opinions for correcting this unfortunate clinical reality are offered.

Immunoaffinity removal of xenoreactive antibodies using modified dialysis or microfiltration membranes.

Hyperacute rejection following xenogeneic transplantation in primates is mediated by naturally occurring IgM antibodies, which are specifically directed to alpha-Galactosyl residues on many nonprimate mammalian cells. Current approaches to remove these anti-alphaGal IgM include plasmapheresis followed by immunoaffinity adsorption on bead columns using synthetic Gal epitopes, which requires two pieces of complex equipment. In this study, we explored the use of immunoaffinity adsorption with hollow fiber microporous or dialysis membranes to which a synthetic alphaGal trisaccharide ligand is bound. Covalent attachment of ligand directly to the surface produced negligible binding, but use of long-chain polyamines as reactive spacers yielded binding densities for anti-alphaGal IgM as high as 89 mg/mL membrane volume in breakthrough curve experiments with microporous nylon membranes having an internal surface area of 4.2 m(2)/mL membrane volume. A crossflow microfilter fabricated from the membranes described in this study and having about 0.4 m(2) luminal surface area would be able to carry out plasma separation and immunoadsorption in a single device with a large excess of binding capacity to ensure that all plasma that filters across the device and is returned to a human patient is essentially free of anti-alphaGal IgM. We conclude that immunoaffinity removal of xenoreactive antibodies using microfiltration hollow fiber membranes is feasible and has potential advantages of efficiency and simplicity for clinical application.