Research Progress on the Potential Mechanisms of Acute Kidney Injury and Chronic Kidney Disease Induced by Proton Pump Inhibitors

Abstract

Proton pump inhibitors (PPIs) are acid-suppressing medications widely used in peptic ulcers; however, their widespread use has led to many adverse renal events. Among these events, the most common form of acute kidney injury (AKI) is acute interstitial nephritis (AIN), which is the clinical manifestation. Several clinical trials and cohort studies have shown a significant relationship between PPIs and AKI induction; however, the pathogenesis of PPIs leading to AKI is unclear. In this paper, we reviewed the potential mechanisms by which PPIs cause AKI and proposed new conjectures. We considered that PPIs led to the development of AKI through a combination of mechanisms. By searching and reviewing PubMed and Embase, a total of 29 studies were finally included and reviewed, and the findings suggested that the mechanisms by which PPIs induce AKI are mainly related to oxidative stress, immune response, inflammatory response, mitochondrial damage, calcium overload, and the induction of cellular necrosis. In addition, tubular cell necrosis can cause tubulointerstitial fibrosis and progressive renal unit loss. Long-term follow-up observations also suggested that PPIs can contribute to AKI progression to chronic kidney disease (CKD). Therefore, we will also explore the potential link between PPIs and CKD.

The nuclear factor kappa B signaling pathway is a master regulator of renal fibrosis

“…Although numerous therapeutic strategies to prevent and treat renal fibrosis have been explored, the prognosis of patients is still poor ( Salvadori and Tsalouchos, 2022 ). Thus, there is an urgent need for the development of specific and efficacious antifibrotic drugs to improve AKI and CKD ( Tanemoto and Mimura, 2022 ; Allinson et al, 2023 ; Habshi et al, 2023 ; Song and Gong, 2023 ). Accordingly, renal fibrosis can be efficiently treated by inhibiting the NF-ƙB signaling pathway.…”