What is the clinical evidence from this study?

Study design: Other. Population: Chronic kidney disease induced left ventricular hypertrophy (n=29). Intervention: Ramipril vs. Vehicle. Primary outcome: Left ventricular hypertrophy (LV mass) and KLF15 expression (p=<0.001).

July 3, 2018Open Access

Left ventricular hypertrophy in experimental chronic kidney disease is associated with reduced expression of cardiac Kruppel-like factor 15

Q: What are the key findings of this study?

In a rat model of chronic kidney disease, ramipril significantly reduced left ventricular hypertrophy and fibrosis while restoring cardiac KLF15 gene and protein expression.

Key Result

In a rat model of chronic kidney disease, ramipril significantly reduced left ventricular hypertrophy and fibrosis while restoring cardiac KLF15 gene and protein expression.

Structured PICO

Does ramipril reduce left ventricular hypertrophy and improve cardiac KLF15 expression in a rat model of chronic kidney disease?

Population

29 Sprague-Dawley rats (n=20 with chronic kidney disease induced by subtotal nephrectomy, n=9 sham-operated controls)

Intervention

Ramipril 1 mg/kg/day for 4 weeks

Comparator

Vehicle

Outcome

Cardiac structure and function and expression of Kruppel-like factor 15 (KLF15)surrogate

ACE inhibition with ramipril ameliorates the loss of cardiac KLF15 and reduces left ventricular hypertrophy and fibrosis in a rat model of chronic kidney disease.

Main Result

p-value: p=<0.001

Limitations

Investigators were not blinded to the disease groups or treatment administration.
It is unknown if KLF15 expression is directly influenced by ramipril independently of the fall in blood pressure.
It is unknown if other antihypertensive agents would have the same effect on KLF15.
Direct mechanistic studies on the effects of KLF15 on ANP, BNP, GATA4, and CTGF were not performed in this study.

Abstract

BACKGROUND: Left ventricular hypertrophy (LVH) increases the risk of death in chronic kidney disease (CKD). The transcription factor Kruppel-like factor 15 (KLF15) is expressed in the heart and regulates cardiac remodelling through inhibition of hypertrophy and fibrosis. It is unknown if KLF15 expression is changed in CKD induced LVH, or whether expression is modulated by blood pressure reduction using angiotensin converting enzyme (ACE) inhibition. METHODS: CKD was induced in Sprague-Dawley rats by subtotal nephrectomy (STNx), and rats received vehicle (n = 10) or ACE inhibition (ramipril, 1 mg/kg/day, n = 10) for 4 weeks. Control, sham-operated rats (n = 9) received vehicle. Cardiac structure and function and expression of KLF15 were assessed. RESULTS: STNx caused impaired kidney function (P < 0.001), hypertension (P < 0.01), LVH (P < 0.001) and fibrosis (P < 0.05). LVH was associated with increased gene expression of hypertrophic markers, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP, P < 0.01) and connective tissue growth factor (CTGF) (P < 0.05). Cardiac KLF15 mRNA and protein expression were reduced (P < 0.05) in STNx and levels of the transcription regulator, GATA binding protein 4 were increased (P < 0.05). Ramipril reduced blood pressure (P < 0.001), LVH (P < 0.001) and fibrosis (P < 0.05), and increased cardiac KLF15 gene (P < 0.05) and protein levels (P < 0.01). This was associated with reduced ANP, BNP and CTGF mRNA (all P < 0.05). CONCLUSION: This is the first evidence that loss of cardiac KLF15 in CKD induced LVH is associated with unchecked trophic and fibrotic signalling, and that ACE inhibition ameliorates loss of cardiac KLF15.

Ask AI

Helpful

Bookmark

View Full Paper