A systematic review on renal effects of SGLT2 inhibitors in rodent models of diabetic nephropathy

Ashfaq, Aqsa; Meineck, Myriam; Pautz, Andrea; Arioglu-Inan, Ebru; Weinmann-Menke, Julia; Michel, Martin C.

doi:10.1016/j.pharmthera.2023.108503

Cited by 5 publications

(3 citation statements)

References 145 publications

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“…By performing a systematic review on SGLT2 inhibitors in diabetic nephropathy in rodent models, Ashfaq et. al have shown that only four studies, out of 105, included females; the limited number of studies that did showed that SGLT2 inhibitors lacked effect more often than not [16]. To our knowledge, there were no studies conducted in females to evaluate the impact of CANA in the kidney of diabetic mice.…”

Section: Plos Onementioning

confidence: 94%

“…Clinical studies do not report sex-dependent differences in T2DM treated with CANA [14,15]. Furthermore, a recent systematic review (SR) has highlighted the lack of studies involving SGLT2 inhibitors in females rodents, as well as emphasized the importance of understanding the sensitivity of that class of drugs in both male and female animals [16]. Thus, stressing the need for further understanding the impact of CANA in type 1 diabetes and/or sex-dependent outcomes in such cohort.…”

Section: Introductionmentioning

confidence: 99%

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Sex-dependent effects of Canagliflozin on kidney protection in mice with combined hypertension-type 1 diabetes

Trentin-Sonoda,

Cheff,

Gutsol

et al. 2023

PLoS ONE

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Canagliflozin (CANA) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor with blood glucose lowering effects. CANA also promotes kidney protection in patients with cardiovascular diseases and type 2 diabetes (T2D), as well as in normoglycemic patients with hypertension or heart failure. Clinical studies, although conduct in both sexes, do not report sex-dependent differences in T2DM treated with CANA. However, the impact of CANA in type 1 diabetes, as well in sex-dependent outcomes in such cohort needs further understanding. To analyze the effects of CANA in mice with combined hypertension and type 1 diabetes, diabetes was induced by STZ injection (5 days, 50mg/kg/day) in both male and female 8 weeks old genetic hypertensive mice (Lin), whereas the control (Lin) received 0.1M sodium citrate injections. 8 weeks after STZ. Mice were fed either regular or CANA-infused diet for 4 weeks. 8 weeks after STZ, hyperglycemia was present in both male and female mice. CANA reversed BG increase mice fed regular diet. Male LinSTZ mice had elevated water intake, urine output, urinary albumin to creatinine ratio (ACR), kidney lesion score, and creatinine clearance compared to the Lin control group. Kidney injury was improved in male LinSTZ + CANA group in male mice. Water intake and urine output were not statistically significantly different in female LinSTZ compared to female LinSTZ+ CANA. Moreover, CANA did not improve kidney injury in female mice, showing no effect in creatinine clearance, lesion score and fibrosis when compared to LinSTZ fed regular diet. Here we show that Canagliflozin might exert different kidney protection effects in male compared to female mice with hypertension and type 1 diabetes. Sex-dimorphisms were previously found in the pathophysiology of diabetes induced by STZ. Therefore, we highlight the importance of in-depth investigation on sex-dependent effects of CANA, taking in consideration the unique characteristics of disease progression for each sex.

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Section: Plos Onementioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Sex-dependent effects of Canagliflozin on kidney protection in mice with combined hypertension-type 1 diabetes

Trentin-Sonoda,

Cheff,

Gutsol

et al. 2023

PLoS ONE

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“…The renal beneficial actions of SGLT2 inhibitors in diabetic rats and mice have been extensively reviewed [ 19 ].…”

Section: Sglt2 Inhibitors In Experimental Models Of Non-diabetic Kidn...mentioning

confidence: 99%

Sodium Glucose Cotransporter-2 Inhibitors in Non-Diabetic Kidney Disease: Evidence in Experimental Models

Castoldi,

Carletti,

Barzaghi

et al. 2024

Pharmaceuticals

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Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering agents widely used for the treatment of type 2 diabetes mellitus. A number of clinical trials in type 2 diabetic patients with different degrees of renal impairment have clearly demonstrated that SGLT2 inhibitors reduce the progression rate of diabetic kidney disease. Furthermore, recent studies have shown that SGLT2 inhibitors also exert a protective effect in the case of non-diabetic kidney disease. Consequently, it has been hypothesized that the nephroprotective activity of these drugs could exceed the canonical impact on glycemic control and that the resulting beneficial effects could be the consequence of their pleiotropic properties (proven reduction of inflammation, fibrosis, oxidative stress and sympathetic nervous activity) both at systemic and tissue levels, suggesting that the efficacy of these drugs could also be extended to non-diabetic nephropathies. This review focuses on the nephroprotective effects of SGLT2 inhibitors in different experimental models of non-diabetic kidney disease. The different glucose-independent mechanisms potentially implemented by SGLT2 inhibitors to ultimately protect the non-diabetic kidney are described in detail, and conflicting results, when present, are discussed.

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RAGE/DIAPH1 and atherosclerosis through an evolving lens: Viewing the cell from the “Inside – Out”

Ramasamy,

Shekhtman,

Schmidt

2024

Atherosclerosis

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A systematic review on renal effects of SGLT2 inhibitors in rodent models of diabetic nephropathy

Cited by 5 publications

References 145 publications

Sex-dependent effects of Canagliflozin on kidney protection in mice with combined hypertension-type 1 diabetes

Sex-dependent effects of Canagliflozin on kidney protection in mice with combined hypertension-type 1 diabetes

Sodium Glucose Cotransporter-2 Inhibitors in Non-Diabetic Kidney Disease: Evidence in Experimental Models

RAGE/DIAPH1 and atherosclerosis through an evolving lens: Viewing the cell from the “Inside – Out”

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