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Abstract: FR-PO397

Role of Ca++ Calmodulin-Dependent Kinase II in Cardiac Pathological Remodeling in Uremia

Session Information

  • Hypertension and CVD: Basic
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1601 Hypertension and CVD: Basic


  • Denby, Laura, The University of Edinburgh School of Biological Sciences, Edinburgh, Edinburgh, United Kingdom
  • Chinnappa, Shanmugakumar, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, Doncaster, Doncaster, United Kingdom
  • Maqbool, Azhar, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, United Kingdom
  • Viswambharan, Hema, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, United Kingdom
  • Mooney, Andrew, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
  • Drinkhill, Mark John, University of Leeds Faculty of Medicine and Health, Leeds, West Yorkshire, United Kingdom

Left ventricular hypertrophy is a ubiquitous finding in advanced chronic kidney disease associated (CKD) associated with high risk of heart failure. Our understanding of such pathological hypertrophy in CKD is still evolving. In this study, we set out to test the hypothesis that Ca++- Calmodulin Dependent Kinase II (CAMKII) pathway, a well-recognised downstream mechanism in the genesis of myocardial pathological remodelling, is activated in uremia using a rodent model of experimental uremia.


Wistar rats had subtotal nephrectomy (STNx, n=10) or sham surgery (sham, n=8) and were followed up for 10 weeks. In vivo and in vitro cardiac assessments were performed. Cardiac tissue was extracted and protein expression of CAMKII, phosphorylated-CAMKII, and myocyte enhance factor 2 (MEF2), the target transcription factor of CAMKII, were quantified using immunoblotting. Data was analysed using an independent sample t-test with Welch's correction and expressed as mean± SEM.


Serum creatinine was elevated in the STNx group (55.00±3.06 vs 32.50±1.44 µmol/L, P<0.01). Echocardiographic left ventricular mass (896.37±54.59 vs 629.81±24.27 mg) and heart weight to tibia length ratio (0.035±0.002 vs 0.027±0.001) were higher in the STNx group (both P<0.01). Furthermore, there was more myocardial fibrosis in the STNx group (4.29±0.79 vs 0.91±0.16 %, P<0.01) (Figure 1). CaMKII signalling was activated in the heart following STNx. An increase in both phosphorylated-CaMKII and total CaMKII was observed. The expression of MEF2 was also increased (Figure 1).


The study shows that experimental uremia induces cardiac pathological hypertrophy and there is associated activation of CAMKII-MEF2 pathway. This novel finding not only offers a mechanism of pathological hypertrophy in uremia but also a potential treatment target to prevent such hypertrophy and the subsequent myocardial dysfunction in CKD.