Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension

@article{Wesson2019LongtermSA,
  title={Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension},
  author={Donald Everett Wesson and Vandana S. Mathur and Navdeep Tangri and Yuri Stasiv and Dawn M Parsell and Elizabeth Li and Gerrit San Jose Klaerner and David A. Bushinsky},
  journal={The Lancet},
  year={2019},
  volume={394},
  pages={396-406}
}
Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial
TLDR
Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned.
Efficacy and Safety of Veverimer in the Treatment of Metabolic Acidosis Caused by Chronic Kidney Disease: A Meta-analysis
TLDR
Current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo, and further research comparing long-term veVerimer use with traditional alkali therapy is needed.
Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial
  • Miles D. Margaret Aimun Michael K. Gowrie Kolitha Deepak Witham Band Ahmed Almond Balasubramaniam Basnayake, M. Witham, A. Avenell
  • Medicine
    BMC Medicine
  • 2020
TLDR
Oral sodium bicarbonate did not improve physical function or renal function, increased adverse events and is unlikely to be cost-effective for use by the UK NHS for this patient group.
Effects of Veverimer in Older Adults With CKD and Metabolic Acidosis
Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease
TLDR
Veverimer binds and removes hydrochloric acid from the gastrointestinal tract, resulting in increased serum bicarbonate and the correction of metabolic acidosis, and is appropriate for patients with CKD with and without sodium-sensitive comorbidities.
Treatments for Chronic Kidney Disease: A Systematic Literature Review of Randomized Controlled Trials
TLDR
Clinically objective outcomes of kidney failure and all-cause mortality (ACM) were reported in 32 and 64 trials, respectively and contemporary data suggest that augmenting RAAS inhibitors with new drug classes has the potential to improve clinical outcomes in a broad range of patients with CKD.
Association of metabolic acidosis with fractures, falls, protein-calorie malnutrition and failure to thrive in patients with chronic kidney disease
TLDR
The presence and severity of metabolic acidosis was a significant, independent risk factor for failure to thrive, protein-calorie malnutrition and fall or fracture in this large community cohort of patients with stage 3–5 CKD.
Veverimer: An Emerging Potential Treatment Option for Managing the Metabolic Acidosis of CKD.
  • H. Adrogué, N. Madias
  • Biology
    American journal of kidney diseases : the official journal of the National Kidney Foundation
  • 2020
TLDR
Veverimer is a novel, non-absorbable polymer that binds H+ and Cl- in the gastrointestinal tract followed by fecal removal, thereby increasing serum [HCO3-] without administering sodium, and its mode of action and its potential interaction with colonic bacterial flora is raised.
New solutions to old problems-metabolic acidosis in chronic kidney disease.
TLDR
Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension.
...
...

References

SHOWING 1-10 OF 28 REFERENCES
Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD.
TLDR
TRC101 safely and significantly increased the level of serum bicarbonate in patients with metabolic acidosis and CKD and discontinuation of TRC101 decreased nearly to baseline levels within 2 weeks.
Correction of metabolic acidosis improves muscle mass and renal function in chronic kidney disease stages 3 and 4: a randomized controlled trial.
TLDR
Alkali supplementation to increase venous bicarbonate levels to 24-26 mEq/L is associated with preservation of LBM and kidney function in patients with CKD stages 3 and 4.
Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism.
TLDR
Combining results from 4 clinical trials, randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization, along with improvements in self-reported physical function and diminished pain.
Adverse Effects of the Metabolic Acidosis of Chronic Kidney Disease.
TLDR
Administration of base decreases muscle wasting, improves bone disease, restores responsiveness to insulin, slows progression of CKD, and possibly reduces mortality, and the target serum [HCO3-] remains unclear.
Tolerance to Sodium in Patients With CKD-Induced Metabolic Acidosis: Does the Accompanying Anion Matter?
  • D. Bushinsky
  • Medicine, Biology
    American journal of kidney diseases : the official journal of the National Kidney Foundation
  • 2019
TLDR
Unless patients with CKD can tolerate a diet virtually devoid of NaCl, additional sodium, regardless of the accompanying anion, appears to increase BP and sodium retention.
Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR.
TLDR
It appears that sodium citrate is an effective kidney-protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition in patients with hypertensive nephropathy and metabolic acidosis.
Bicarbonate supplementation slows progression of CKD and improves nutritional status.
TLDR
It is demonstrated that bicarbonate supplementation slows the rate of progression of renal failure to ESRD and improves nutritional status among patients with CKD and Nutritional parameters improved significantly with bic carbonate supplementation, which was well tolerated.
Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate.
TLDR
Dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.
The impact of selecting a high hemoglobin target level on health-related quality of life for patients with chronic kidney disease: a systematic review and meta-analysis.
TLDR
This study suggests that targeting hemoglobin levels in excess of 12.0 g/dL leads to small and not clinically meaningful improvements in HQOL, in addition to significant safety concerns, suggesting that targeting treatment to hemoglobinlevels that are in the range of 9.0 to 12.
...
...