Comment on The impact of dynamic kidney function prior to using sodium–glucose cotransporter-2 inhibitors in type 2 diabetes patients with low-risk renal disease progression

Sep 28, 2026

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Letter to the editor evaluating a study by Chiu et al. examining whether dynamic trajectories of eGFR and urinary albumin-to-creatinine ratio (UACR) predict renal responses after SGLT2 inhibitor initiation in type 2 diabetes with low-risk renal disease progression. The correspondent highlights benefits for a “glomerular injury” subgroup, then calls for clarification on treatment initiation context, model diagnostics for eGFR slope estimation, justification of dichotomous cutoffs, adjustment for key confounders, and external validation across diverse cohorts and different SGLT2i agents.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

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Letter to the editor

Study interest and key findings

Requests for clarification to strengthen causal inference

Acknowledgments and disclosure

Author contributions and affiliations

References

LETTER TO THE EDITOR Comment on “The impact of dynamic kidney function prior to using sodium–glucose cotransporter-2 inhibitors in type 2 diabetes patients with low-risk renal disease progression” Dear Editor, We read with great interest the study by Chiu et al., which explored whether recent trajectories in estimated glomerular ﬁltration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) predict renal responses after the initiation of sodium–glucose cotransporter-2 inhibitors (SGLT2i)1. The effort to stratify patients with otherwise “low-risk” renal proﬁles using dynamic markers is timely and has clear translational potential for tailoring early preventive therapies. The authors provide persuasive evidence that the subgroup labeled as “glomerular injury” (rapid eGFR decline together with rising UACR) experienced lower adjusted hazards for a >30% eGFR decline (adjusted hazard ratio [HR] 0.384, 95% CI 0.199–0.740) and for UACR progression (adjusted hazard ratio 0.514, 95% CI 0.313–0.846) after SGLT2i exposure. This ﬁnding, together with the within-person improvement in eGFR slope after treatment (ﬁrst- and secondyear differences reaching statistical signiﬁcance in the rapid decline groups), is an important signal that early dynamic surveillance can identify individuals who derive measurable renal trajectory beneﬁts from SGLT2i. Correspondence Shyam Sundar Sah Tel: +912067116412 Fax: +912027420010 E-mail address: [shyam.sundar.sah@proton.me](shyam.sundar.sah@proton.me) Received 21 October 2025; revised 21 October 2025; accepted 4 November 2025 Several aspects require further clariﬁcation to strengthen the causal inference and facilitate clinical adoption. First, the study would beneﬁt from a more granular description of the clinical decision context for SGLT2i initiation; confounding by indication (e.g., initiation for cardiovascular risk, glycemic control, or perceived renal risk) may inﬂuence both baseline trajectories and subsequent outcomes2. Second, although the authors used a linear mixed model to estimate individual eGFR slopes, reporting model diagnostics (random-effects variance, number of measurements per subject, and sensitivity to nonlinearity) and an assessment of regression to the mean beyond the small subgroup with single post-treatment values would improve the conﬁdence in slope estimates. Third, the choice of dichotomous cutoff points (eGFR decline >2.5 mL/min/ 1.73 m2/year; UACR increase >30%) underpins group allocation and effect estimates. A brief justiﬁcation linking these thresholds to absolute risk or decision thresholds used in prior prognostic studies would aid readers in judging external applicability. Fourth, adjustment sets excluded measures of blood pressure control, smoking status, and longitudinal medication adherence, which plausibly inﬂuence both albuminuria and eGFR trajectory3; consideration of these confounders or an instrumental-variable approach could reduce residual bias. Finally, external validity beyond a single tertiary care registry in Taiwan deserves attention; replication in geographically and ethnically diverse cohorts and exploration of whether the predictive utility holds across different SGLT2i agents and doses will be important before recommending trajectorybased SGLT2i initiation in routine practice. In summary, Chiu et al.1 advanced a pragmatic framework that marries shortterm renal dynamics to therapeutic responsiveness, and their results merit prospective validation. We thank the authors for opening this clinically actionable line of inquiry and encourage follow-up work that addresses the above points to help translate these observations into personalized prevention strategies. ACKNOWLEDGMENTS No funding was received for this study. Generative AI use statement: Genera tive AI tools, including Paperpal and ChatGPT 5, were utilized solely for language, grammar, and stylistic reﬁnement. These tools had no role in the conceptualization, dat

FAQs

What main finding does the letter highlight from Chiu et al.?

It emphasizes that the “glomerular injury” subgroup had lower adjusted hazards for >30% eGFR decline and for UACR progression after SGLT2 inhibitor exposure, indicating measurable renal trajectory benefit.

Why does the letter ask for a clearer description of SGLT2 inhibitor initiation context?

It notes potential confounding by indication, since initiation may be driven by cardiovascular risk, glycemic control, or perceived renal risk, which could influence both baseline trajectories and outcomes.

What methodological details does the letter recommend reporting to improve confidence in eGFR slope estimates?

It requests model diagnostics for the linear mixed model, including random-effects variance, number of measurements per subject, sensitivity to nonlinearity, and assessment of regression to the mean beyond the small subgroup with limited post-treatment values.

Sep 28, 2026

Uploaded by Cipher