Re: Methodological Limitations in SGLT2 Inhibitor Research for Nephrolithiasis Prevention
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Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies
Re: Methodological Limitations in SGLT2 Inhibitor Research for Nephrolithiasis Prevention
Dear Editor
McCormick et al. (2024) investigated the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout (1). This study revealed the renal protective effects of SGLT-2 inhibitors. The authors employed a target trial emulation framework that reduces biases common in observational studies.
However, the following methodological concerns behooves a discussion.
Firstly, the application of real-world data increases the chances of residual confounding (2). Variables such as dietary intake and over-the-counter drug use that are not synchronously captured in administrative health databases could significantly affect nephrolithiasis recurrence rate. Despite the authors acknowledging this limitation, it remains a potential source of bias as far as the study’s reliability goes (3). Integration of data sources that capture holistic lifestyle factors such as adherence and over-the-counter medications through actual surveys or wearable technology data would limit residual confounding.
Secondly, the absence of refined data on the severity of gout or nephrolithiasis is concerning. It is possible that patients with different severity of these conditions could respond differently to the SLGT-2 inhibitors, thus affecting the study’s conclusion. More granular stratifications in further studies would definitely address this concern. Such stratification could benefit from a multifaceted approach that considers significant properties such as stone composition and periodicity of gout flares.
Despite these methodological concerns, this study offers new opportunities to investigate the role of SGLT-2 inhibitors’ role in the prevention of nephrolithiasis. Nonetheless, healthcare practitioners should consider patient characteristics when extrapolating the findings to different clinical areas (4).
References
1. McCormick N, Chio Yokose, Lu N, Wexler DJ, J Antonio Aviña-Zubieta, De MA, et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies. BMJ. 2024 Oct 30; e080035–5.
2. Liu F, Demosthenes P. Real-world data: a brief review of the methods, applications, challenges and opportunities. BMC Medical Research Methodology. 2022 Nov 5;22(1).
3. Feng Q. Editorial: Causal inference in diet, nutrition and health outcomes. Frontiers in Nutrition. 2023 May 10;10.
4. Kani R, Watanabe A, Miyamoto Y, Kentaro Ejiri, Masao Iwagami, Takagi H, et al. Comparison of Effectiveness Among Different Sodium‐Glucose Cotransporter‐2 Inhibitors According to Underlying Conditions: A Network Meta‐Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2024 Jan 3
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Re: Methodological Limitations in SGLT2 Inhibitor Research for Nephrolithiasis Prevention
Dear Editor
McCormick et al. (2024) investigated the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout (1). This study revealed the renal protective effects of SGLT-2 inhibitors. The authors employed a target trial emulation framework that reduces biases common in observational studies.
However, the following methodological concerns behooves a discussion.
Firstly, the application of real-world data increases the chances of residual confounding (2). Variables such as dietary intake and over-the-counter drug use that are not synchronously captured in administrative health databases could significantly affect nephrolithiasis recurrence rate. Despite the authors acknowledging this limitation, it remains a potential source of bias as far as the study’s reliability goes (3). Integration of data sources that capture holistic lifestyle factors such as adherence and over-the-counter medications through actual surveys or wearable technology data would limit residual confounding.
Secondly, the absence of refined data on the severity of gout or nephrolithiasis is concerning. It is possible that patients with different severity of these conditions could respond differently to the SLGT-2 inhibitors, thus affecting the study’s conclusion. More granular stratifications in further studies would definitely address this concern. Such stratification could benefit from a multifaceted approach that considers significant properties such as stone composition and periodicity of gout flares.
Despite these methodological concerns, this study offers new opportunities to investigate the role of SGLT-2 inhibitors’ role in the prevention of nephrolithiasis. Nonetheless, healthcare practitioners should consider patient characteristics when extrapolating the findings to different clinical areas (4).
References
1. McCormick N, Chio Yokose, Lu N, Wexler DJ, J Antonio Aviña-Zubieta, De MA, et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies. BMJ. 2024 Oct 30; e080035–5.
2. Liu F, Demosthenes P. Real-world data: a brief review of the methods, applications, challenges and opportunities. BMC Medical Research Methodology. 2022 Nov 5;22(1).
3. Feng Q. Editorial: Causal inference in diet, nutrition and health outcomes. Frontiers in Nutrition. 2023 May 10;10.
4. Kani R, Watanabe A, Miyamoto Y, Kentaro Ejiri, Masao Iwagami, Takagi H, et al. Comparison of Effectiveness Among Different Sodium‐Glucose Cotransporter‐2 Inhibitors According to Underlying Conditions: A Network Meta‐Analysis of Randomized Controlled Trials. Journal of the American Heart Association. 2024 Jan 3
Competing interests: No competing interests