Literature analysis of renal injury caused by proton pump inhibitors based on real world database mining

SHANGGUAN Ke-ke; WANG Rong-huan

doi:10.3969/j.issn.1003-3734.2024.22.015

Abstract：Objective:To excavate drugs that cause acute kidney injury through the FAERS database,perform a retrospective literature analysis on the drugs with significant signals,and analyze the clinical manifestations,treatments and regressions of the cases,in order to provide references for the safe use of drugs in clinic.Methods:By using OpenVigil,an open drug data platform,the reports on drug-caused acute kidney injury from the first quarter of 2004 to the third quarter of 2023 were searched,the positive signals were analyzed to find potential risk drugs,the case reports were searched in PubMed,Web of science,Wanfang Data,China Knowledge and Wipu.com according to the drug name and kidney injury,and the patient's age,sex,nationality,drug usage,time of drug use,clinical manifestations,therapeutic measures,and regression were retrospectively analyzed.Results:There were 53 drugs with positive new signals from the initial screening,with four PPIs in the top five drugs.Literature search for this class of drugs was performed,and five PPIs had case reports in this class,involving 65 case reports and 152 cases.The highest number of cases were reported for omeprazole(113 cases,74.3％);reports were mainly concentrated in the year from 2010 to 2019(70 cases,46.1％).The United States had the highest number of cases(48 cases,31.6％).The male-to-female ratio of incidence was 1∶1.5.The age of onset was mainly concentrated in 60～80 years(96 cases,63.2％),with a mean age of 66.64 years and a median age of 70 years;the dosage of medication was basically conventional(84/85),and the time of onset mainly concentrated in 2～6 months(67 cases,44.1％)and was cumulative within 6 months(116 cases,76.3％).Renal biopsy was performed in 115 patients,and the main pathological findings were acute interstitial nephritis or exhibited interstitial nephritis(114 cases,75.0％).The clinical presentation was not significantly specific.The difference between baseline creatinine level and that after improvement was significant(P＜0.01).The primary treatment was discontinuation of medication in all cases,and glucocorticoids were administered to 60 patients for treatment.Twelve patients received secondary medication or re-initiation,and five of these patients required additional dialysis treatment.Conclusion:There is a higher risk of morbidity in the elderly population,especially in elderly female patients,where PPIs can cause interstitial renal injury at routine doses.It is recommended to focus on the presence of prodromal clinical symptoms such as fever,nausea,vomiting,and rash in the early stages of drug administration.For patients who have already developed renal injury from PPIs,discontinuation of the drug is the primary treatment,and hormonal treatment may be considered,as well as short-term haemodialysis treatment in severe cases.Renal function is worse after the onset of renal injury.Patients who have experienced such adverse event should avoid using PPIs again.