Tolvaptan and the incidence of contrast-induced acute kidney injury

Increased rates of coronary angiography and percutaneous coronary intervention (PCI) have resulted in a rising incidence of contrast-induced acute kidney injury (CI-AKI), also known as contrast-induced nephropathy (CIN). 

While there is no universally accepted definition of CI-AKI, it is closely associated with an increase in serum cystatin C (Cys-C) ≥10% within 24 hours of contrast agent use. In 2011, the European Society of Urogenital Radiology (ESUR) defined CIN as an increase in serum creatinine (SCr) >44.2 µmol/L or 25% within 3 days of administration. ESUR revised the definition in 2018 to state that CI-AKI is characterised by an increase in SCr >26.5 µmol/L or 1.5–1.9 times the baseline level within 48–72 hours.

Standard hydration therapy is a well-supported prevention strategy for those at high-risk of AKI. Tolvaptan (TOL) blocks vasopressin-mediated water reabsorption and provides a rapid oral hydration effect. Studies on TOL in AKI and CI-AKI are limited but show promise that it could be used in a preventive strategy in high-risk populations. The present study by Xu and colleagues investigated the effect of low-dose tolvaptan combined with standard hydration on the incidence of CI-AKI and prognosis in high-risk participants undergoing coronary angiography or intervention. 

In this prospective, randomised controlled trial, subjects were patients scheduled for elective coronary angiography or PCI, with an age–glomerular filtration rate–ejection fraction (AGEF) score >1.16. A total of 232 participants were included: 116 in the experimental group received low-dose TOL (7.5 mg before their procedure and 7.5 mg 24 hours later) plus standard intravenous hydration, and 116 in the control group received standard hydration alone.

Based on serum Cys-C criteria, the incidence of AKI in the TOL group was significantly lower than in the control group (10.3% vs 23.3%; P=0.008). According to both the 2011 and 2018 ESUR SCr criteria, there were slightly lower incidences of AKI in the TOL group compared to the control group, but the differences were not statistically significant.

Postoperative abdominal spectral CT scans of 30 participants showed that iodine concentration values in the renal medulla were significantly lower in the TOL group than in the control group (P<0.05).

A comparison of pre- and postoperative renal function indicators showed that the increases in SCr and Cys-C levels were significantly lower in the TOL group than in the control group (P<0.05). The decline in eGFR was also significantly smaller in the TOL group (P<0.05). 

A multivariate logistic regression model demonstrated that the use of TOL was associated with a significant reduction in the risk of CI-AKI (P=0.001), while lower preoperative eGFR and higher AGEF scores were independently associated with a higher risk of CI-AKI (P<0.05).

Kaplan–Meier analysis showed no significant difference in the cumulative 6-month, event-free survival rate for major adverse cardiovascular events between the TOL and control groups (93.9% vs 88.6%; P=0.142).

The authors conclude that TOL reduced the magnitude of the increase in postoperative SCr and blood Cys-C levels, and mitigated the decline in eGFR. TOL may be associated with less renal injury and may have a preventive effect on CI-AKI.

The full article can be read here.