Impact of urine cyclic AMP relative to plasma arginine vasopressin on response to tolvaptan in patients with chronic kidney disease and heart failure

• Published in: Clinical and experimental nephrology Vol. 27; no. 5; pp. 427 - 434
• Main Authors: Kakeshita, Kota, Koike, Tsutomu, Imamura, Teruhiko, Fujioka, Hayato, Yamazaki, Hidenori, Kinugawa, Koichiro
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.05.2023; Springer Nature B.V
• Subjects: Aged; Antidiuretic Hormone Receptor Antagonists - therapeutic use; Arginine Vasopressin - blood; Arginine Vasopressin - chemistry; Argipressin; Benzazepines - therapeutic use; Congestive heart failure; Cyclic AMP; Cyclic AMP - chemistry; Cyclic AMP - urine; Diuretics; Glomerular filtration rate; Heart failure; Heart Failure - diagnosis; Heart Failure - drug therapy; Humans; Kidney diseases; Male; Medicine; Medicine & Public Health; Nephrology; Original Article; Plasma; Prospective Studies; Renal failure; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - drug therapy; Tolvaptan - therapeutic use; UMIN; UMIN000022422; Urine; Urology; Vasopressin; Diuretics; Aquaporin-2; Congestive heart failure; Vasopressin type-2 receptor antagonist; Osmolality
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-023-02325-1

Background The clinical utility of tolvaptan in chronic kidney disease (CKD) patients with heart failure remains uncertain. The level of urine cyclic adenosine monophosphate (AMP) relative to plasma arginine vasopressin (AVP) indicates the residual function of the collecting ducts in response to AVP stimulation and might be a key to predicting response of tolvaptan. Methods CKD patients who were hospitalized to treat their congestive heart failure refractory to conventional loop diuretics were considered to receive tolvaptan and included in this prospective study. The impact of urine cyclic AMP/plasma AVP ratio for prediction of response to tolvaptan, which was defined as any increase in urine volume at day 7 from day 0, was investigated. Results A total of 30 patients (median 75 years old, 24 men, and median estimated glomerular filtration rate 14.4 mL/min/1.73 m 2 ) were included. As compared to baseline, urine volume increased at day 7 in 17 responders, whereas urine volume decreased at day 7 in 13 non-responders. Baseline urine cyclic AMP/plasma AVP ratio distributed between 0.25 and 4.01 with median 1.90. The urine cyclic AMP/plasma AVP ratio was a significant predictor of response to tolvaptan, which was adjusted for 6 potential confounders with a cutoff of 1.24. Conclusions Baseline urine cyclic AMP/plasma AVP ratio is an independent predictor of response to tolvaptan in advanced CKD patients with heart failure. Clinical trial registration UMIN000022422