# Association between caffeine and the eGFR dip after initiation of SGLT2 inhibitors in adult patients

**Authors:** Zach Kisley, Amanda J. Kalishman, Aliza A. Memon, Sandeep S. Dhindsa, John C. Edwards, Amy Mosman, Krista L. Lentine, Paul Kunnath, Emily Wood, Kana N. Miyata

PMC · DOI: 10.14814/phy2.70638 · 2025-10-27

## TL;DR

High caffeine intake may reduce the initial kidney function decline seen when starting a specific heart and kidney medication.

## Contribution

This study is the first to show a link between caffeine consumption and a smaller eGFR dip after SGLT2 inhibitor initiation.

## Key findings

- Caffeine intake was negatively correlated with eGFR dip at 1 month (r = -0.31, p = 0.02).
- Caffeine and baseline creatinine were independently associated with the eGFR dip in multivariable regression.
- High caffeine consumption may help reduce early kidney function decline with SGLT2 inhibitors.

## Abstract

Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) are cornerstone therapies for heart failure and chronic kidney disease. Clinical trials have demonstrated that the estimated glomerular filtration rate (eGFR) typically declines within the first few weeks after SGLT2i initiation. One proposed mechanism of the acute eGFR dip is the reduced intraglomerular pressure through tubuloglomerular feedback (TGF). Adenosine is a key mediator in TGF signaling, and caffeine, a nonselective adenosine receptor antagonist, may influence this process. We conducted a retrospective cohort study at SSM Health Saint Louis University Hospital to examine whether caffeine intake influences the initial eGFR dip following SGLT2i initiation. Eligible patients completed a caffeine consumption survey, and chart reviews assessed creatinine and proteinuria at baseline and 1 month post‐initiation. Data from 62 patients (mean age 60.1 ± 12.4 years; median eGFR 50.0 [IQR 37.2–66.9] mL/min/1.73 m2) revealed a negative correlation between caffeine intake and eGFR dip at 1 month (r = −0.31, p = 0.02). Multivariable regression showed caffeine intake and baseline creatinine were independently associated with the eGFR dip. These findings suggest high caffeine consumption may attenuate the early eGFR decline seen with SGLT2i therapy. Further research is warranted to explore its impact on long‐term renal outcomes.

A retrospective study showed that high caffeine intake was associated with an attenuated initial eGFR dip following the initiation of an SGLT2 inhibitor.

## Linked entities

- **Chemicals:** caffeine (PubChem CID 2519)
- **Diseases:** heart failure (MONDO:0005252), chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Diseases:** heart failure (MESH:D006333), proteinuria (MESH:D011507), chronic kidney disease (MESH:D051436)
- **Chemicals:** creatinine (MESH:D003404), Adenosine (MESH:D000241), caffeine (MESH:D002110)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12559023/full.md

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Source: https://tomesphere.com/paper/PMC12559023