In the News: Vonoprazan and the Kidney

A new agent has been found to cause AKI and AIN—Vonoprazan.  A recent paper in Kidney International is the first to describe this from Japan. The authors used the National reporting database of drug toxicities in Japan to assess this and compared it to PPIs—JADER database.  See visual ab from the recent paper. 

What is vonoprazan? 

Vonoprazan, a potassium-competitive acid blocker possessing a new mechanism of action. Vonoprazan inhibits acid secretion in the cells of the gastric wall. The inhibitory effect of vonoprazan on H+, K+-ATPase is perhaps over 300 times greater than that of lansoprazole. 

In Japan, this drug was approved for use for acid reflux in 2015. In the US, this drug has been FDA approved for esophageal esophagitis in association with H pylori recently in May 2022.  A recent meta-analysis also found that vonoprazan is non inferior to PPIs as therapy for GERD but in the subgroup for severe erosive esophagitis- it was more effective.

In this recent study in KI, authors compared PPI related renal adverse events to this new agent. The total numbers of renal adverse events associated with PPIs and vonoprazan were 14149 and 2465, respectively. Surprisingly, a safety signal for vonoprazan and a drug associated AIN —was detected, which was similar to that obtained for PPI. Interestingly. a safety signal for AKI caused by PPIs and vonoprazan were not detected.

The mechanism of action of vonoprazan is that it competes with potassium ions for the reversible inhibition of H+- K+-ATPase, whereas PPIs act by binding covalently to the gastric H+, K+-ATPase via disulfide bonds.  Having a H+, K+-ATPASe in the kidney have any impact? Not sure?

Another interesting finding from another study showed increase tacrolimus levels when this agent is used- a caution in our GN and transplant patients.

As we learn more about this agent in the US, we need to be vigilant!