sacubitril and Kidney-Failure--Chronic

The amount of evidence for guideline-directed new heart failure (HFrEF) disease-modifying drugs in the context of chronic kidney disease (CKD) is relatively modest, especially in end-stage CKD. We report a case of dramatic reverse remodelling and disease regression in a naïve HFrEF young woman on haemodialysis treated with sacubitril/valsartan and SGLT2i. At 10-month follow-up, the patient normalized left ventricle and atrial volumes and improved ejection fraction to the normal range, assessed both by echocardiography and cardiac magnetic resonance. Cardiac biomarkers and exercise performance improved consensually. The haemodialysis protocol and the loop diuretic dose were unchanged within the whole period.

Topics: Female; Heart Failure; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Stroke Volume; Tetrazoles; Valsartan

Sacubitril/valsartan was indicated for the treatment of heart failure and hypertension in patients with end-stage renal disease on peritoneal dialysis therapy. Herein, a rapid, sensitive and robust method based on ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination of the concentrations of valsartan, sacubitril and its major metabolite LBQ657 in plasma, urine and peritoneal dialysis fluid. Samples were extracted from various biological fluids using protein precipitation. Extracts were subjected to UPLC-MS/MS with electrospray ionization in positive-ion mode. The developed method was fully validated over a concentration range of 8.00-8000 ng/mL for valsartan, 2.00-2000 ng/mL for sacubitril and 30.0-30,000 ng/mL for LBQ657 in plasma, 2.00-1000 ng/mL for valsartan, 1.00-500 ng/mL for sacubitril and 20.0-10000 ng/mL for LBQ657 in urine, and 0.200-100 ng/mL for valsartan, 0.0400-20.0 ng/mL for sacubitril and 2.00-1000 ng/mL for LBQ657 in peritoneal dialysis fluid. The intra- and inter-day precisions for all analytes in various matrices were less than 12.3%, and the intra- and inter-day accuracies results were all between 88.0% and 109.2%. All analytes were stable for at least 8 h at room temperature (25°C), five freeze-thaw cycles, and 37 days at -40°C and -80°C in plasma, urine and peritoneal dialysis fluid. In conclusion, this developed method is reliable, sensitive and specific for determining the concentrations of valsartan, sacubitril and LBQ657 in plasma, urine and peritoneal dialysis fluid. The assay was available to pilot the pharmacokinetics study of sacubitril/valsartan in patients with end-stage renal disease on peritoneal dialysis, and it could provide evidence that peritoneal dialysis had an effect on the clearance of sacubitril/valsartan.

Topics: Aminobutyrates; Biphenyl Compounds; Chromatography, High Pressure Liquid; Chromatography, Liquid; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Tandem Mass Spectrometry; Valsartan

Topics: Aminobutyrates; Biphenyl Compounds; Cardiovascular Agents; Drug Combinations; Heart Failure; Humans; Kidney Failure, Chronic; Stroke Volume; Valsartan