What is the clinical evidence from this study?

Study design: Observational. Population: Renal disease. Intervention: Renal magnetic resonance imaging (DTI). Primary outcome: Medullary DTI parameters (MD, AD, RD), eGFR, and complement C3.

What question did this study set out to answer?

To investigate the effects of Sglt2 deletion on cardiorenal damage, stroke incidence, and mortality in Dahl salt-sensitive hypertensive rats.

March 28, 2026Open Access

WCN26-8459 Sglt2 deletion attenuates cardiorenal damage but not stroke or mortality in Dahl salt-sensitive hypertensive rats

Key Result

Medullary diffusion tensor imaging parameters exhibited a statistically significant biphasic course over 1 year, whereas eGFR and complement C3 normalized by 6 months.

Key Points

To investigate the effects of Sglt2 deletion on cardiorenal damage, stroke incidence, and mortality in Dahl salt-sensitive hypertensive rats.
Conducted renal MRI at various time points (baseline, 2 weeks, 6 months, 1 year) using a 1.5-T scanner.
Quantified DTI parameters (mean diffusivity, axial diffusivity, radial diffusivity) in specific kidney regions.
Measured serum creatinine and complement C3, estimating glomerular filtration rate (eGFR).
Performed statistical analysis using Friedman test and Dunn's post-hoc correction.
eGFR and complement C3 levels normalized by 6 months and remained stable afterward.
Medullary DTI parameters showed a biphasic course, initially elevated, then decreased, and increased again by 1 year.
Cortical DTI parameters exhibited minor, transient changes over the same period.

Study Design

Type

Observational

Structured PICO

Does Sglt2 deletion reduce cardiorenal damage and improve survival in Dahl salt-sensitive hypertensive rats?

Population

Dahl salt-sensitive (DahlS) rats (male and female, 8 weeks of age)

Intervention

Sglt2 gene deletion (Sglt2 knockout)

Comparator

Wild-type (Sglt2+/+) DahlS rats

Outcome

Cardiorenal damage (heart weight, renal injury and fibrosis markers, histology) and survivalhard clinical

Sglt2 deletion in a hypertensive rat model attenuates cardiorenal damage but does not improve survival or prevent stroke, suggesting that hypertension remains the dominant risk factor for stroke.

Abstract

Methods: Renal magnetic resonance imaging was performed on a 1.5-T scanner at four time points: baseline (at biopsy), 2 weeks, 6 months, and 1 year.Diffusion tensor imaging (DTI) parameters-mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)-were quantified in cortical and medullary regions using manually placed regions of interest.Because the biopsy was performed on the right kidney, DTI parameters were consistently measured in the left kidney to avoid procedure-related artifacts.DTI metrics were processed and calculated using DSI Studio (http://dsi-studio.labsolver.org),ensuring reproducibility of parameter estimation.Serum creatinine-based estimated glomerular filtration rate (eGFR) and complement C3 were measured concurrently.Statistical analysis was performed with the Friedman test and Dunn's post-hoc correction.Results: eGFR and complement C3 normalized by 6 months and remained stable thereafter, while urinalysis was consistently normal.In contrast, medullary DTI parameters exhibited a biphasic course: MD, AD, and RD were elevated at baseline, decreased below baseline at 6 months, and increased again at 1 year, whereas cortical parameters showed only mild, transient alterations.Medullary results are summarized in Table 1, which integrates clinical (eGFR, C3) and imaging (MD, AD, RD) parameters.These biphasic changes were statistically significant compared with baseline values.

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