Long-term use of proton pump inhibitors: from gastric protection to renal, nutritional and bone repercussions

Abstract

Introduction: Proton pump inhibitors (PPIs) have become essential drugs in the treatment of acid-peptic diseases due to their high efficacy and short-term safety. However, their prolonged use, often without formal indication or periodic reassessment, has raised increasing concerns about potential systemic repercussions, including renal, nutritional, and bone effects. Objective: To critically review the recent literature on adverse effects associated with long-term PPI use, with emphasis on repercussions on renal function, micronutrient metabolism, and bone health. Methodology: This is a narrative review with systematized characteristics, conducted in the PubMed, Embase, and Cochrane Library databases, complemented by a search in Google Scholar. Original studies, cohorts, clinical trials, systematic reviews, and meta-analyses published between 2018 and 2024 in Portuguese, English, and Spanish were included, addressing renal, nutritional, and bone outcomes related to long-term PPI use (≥12 weeks, with emphasis on periods longer than 1 year). Results: The analyzed studies show a consistent association between prolonged PPI use and increased risk of acute interstitial nephropathy, decline in glomerular filtration rate, progression to chronic kidney disease, and, in specific cases, evolution to end-stage renal disease. From a nutritional perspective, reduced absorption of magnesium, calcium, and vitamin B12 was observed, with relevant metabolic and clinical repercussions. Regarding bone health, the literature suggests an increased risk of osteopenia, osteoporosis, and fractures, although with heterogeneity among studies and variation according to population characteristics. Discussion: The available findings support biological plausibility for the described repercussions, including changes in the microbiota, immune-mediated renal inflammation, reduced gastric acidity, and consequent impairment of nutrient absorption. Despite the inherent limitations of observational studies, the consistency of results in different contexts strengthens the hypothesis of a causal association. Clinically, these findings reinforce the need for rational prescription, with periodic reassessment, laboratory monitoring, and deprescription strategies when appropriate. Conclusion: PPIs remain indispensable in the treatment of acid-peptic diseases, but their prolonged use should be approached with caution. Recent evidence points to significant risks of renal impairment, nutritional deficiencies, and bone alterations, which require continuous clinical and laboratory vigilance. The future of therapeutic management lies in individualized prescription, multidisciplinary integration, and the development of safer pharmacological alternatives.