Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD

Abstract

Background and objectives Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, muscle, and bone. We tested the efficacy and safety of TRC101, a novel, sodium-free, nonabsorbed hydrochloric acid binder, to increase serum bicarbonate in patients with CKD and metabolic acidosis.Design, setting, participants, & measurements One hundred thirty-five patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter, in-unit study (designated the TRCA-101 Study). Patients had a mean baseline eGFR of 35 ml/min per 1.73 m 2 , a mean baseline serum bicarbonate of 17.7 mEq/L, and comorbidities, including hypertension (93%), diabetes (70%), and heart failure (21%). Patients ate a controlled diet and were treated for 14 days with placebo or one of four TRC101 dosing regimens (1.5, 3, or 4.5 g twice daily or 6 g once daily). After treatment, patients were discharged and followed for 7-14 days.Results All TRC101 treatment groups had a mean within-group increase in serum bicarbonate of $1.3 mEq/L (P,0.001) within 72 hours of the first dose and a mean increase in serum bicarbonate of 3.2-3.9 mEq/L (P,0.001) at the end of treatment compared with placebo, in which serum bicarbonate did not change. In the combined TRC101 treatment group, serum bicarbonate was normalized (22-29 mEq/L) at the end of treatment in 35% of patients and increased by $4 mEq/L in 39% of patients. After discontinuation of TRC101, serum bicarbonate decreased nearly to baseline levels within 2 weeks. All adverse events were mild or moderate, with gastrointestinal events most common. All patients completed the study.Conclusions TRC101 safely and significantly increased the level of serum bicarbonate in patients with metabolic acidosis and CKD.

Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease

“…Two very strong rationale for treating acid overload are retardation of progression of CKD and prevention of extrarenal complications. The availability of alkali therapy without sodium or potassium load in the form of hydrochloric acid binding polymer has added an entirely new exciting dimension to alkali therapy in CKD never before achievable 19 . The addition of a robust monitoring test to this regimen will greatly enhance this approach.…”

“…The traditional limitation imposed by the use of sodium and potassium salts of alkali (bicarbonate, carbonate, citrate, acetate) has limited alkali administration in clinical practice, especially in patients with more advanced CKD. A recent novel mode of therapy tantamount to HCl binding in the gastrointestinal tract and removal in the stool 19 has greatly revolutionized alkali therapy in terms of feasibility and safety in treatment of metabolic acidosis in CKD. This highly promising mode of therapy still requires robust monitoring of therapeutic efficacy.…”

Renal Failure Patients in Disasters

“…72 Sodium-free alkali preparations are under development to avoid the sodium load associated with sodium bicarbonate administration. 73 Electrocardiogram (ECG) changes of hyperkalemia or muscle paralysis 67 indicate severe degrees of hyperkalemia. 66 However, ECG changes for hyperkalemia are not always seen in patients because ECGs have a low sensitivity to detect hyperkalemia when advanced renal failure is present.…”

Oral alkali therapy and the management of metabolic acidosis of chronic kidney disease: A narrative literature review

“…TRC 101, a novel sodium-free, non-absorbed hydrochloric acid binder, has shown efficacy in alleviating MA-CKD without effecting blood pressure, and may become widely available in the near future[ 40 ].…”