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Introduction: We aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR)., Methods: We performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m 2 in the period 2010-2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88-0.97), SYSADOA (0.87;0.83-0.91) and acetaminophen (0.84;0.79-0.89), and an high risk for metamizole (1.07;1.03-1.12), and antiplatelet drugs (1.07;1.03-1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88-0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03-1.15) and Coxibs (1.19;1.08-1.30). Medium and high use of major opioids shows a high risk (1.15;1.03-1.29). Triflusal showed high risk at medium (1.23;1.02-1.48) and high use (1.68;1.40-2.01)., Conclusion: We observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results., (© 2024. The Author(s).)