Abstract: TH-PO499

On Top of Standard Treatment Selective Endothelin-A Receptor Antagonism Improves Lipid Profile in CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Author

  • Dhaun, Neeraj, University of Edinburgh, Edinburgh, United Kingdom
Background

CKD patients have an increased risk of cardiovascular disease (CVD) that is partly explained by conventional CVD risk factors. Current guidelines recommend the use of HMG-CoA reductase inhibitors (statins) to improve lipid profile in patients with pre-dialysis CKD. Despite their use many patients continue to have elevated lipids and remain at increased CVD risk. Endothelin-A (ETA) receptor antagonism is currently being investigated as a novel therapeutic approach to reduce proteinuria and blood pressure (BP), and to improve outcomes in pre-dialysis CKD. Here, we investigated the effects of ETA antagonism on circulating lipids in these patients.

Methods

In a randomized double-blind, 3-way crossover study, 27 subjects with proteinuric, pre-dialysis CKD received 6 weeks treatment with placebo, sitaxentan 100mg, an ETA antagonist, and nifedipine 30mg. Those with nephrotic syndrome were excluded. Serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides were measured at baseline and week 6 of each treatment period, alongside the primary endpoints of proteinuria, BP, and arterial stiffness.

Results

18 of 27 subjects were prescribed statin therapy. Baseline lipid profile was similar in the 3 phases of the study (mean±SEM – total cholesterol: 4.9±0.1mmol/L; HDL: 0.9±0.1mmol/L; LDL: 2.8±0.2mmol/L; triglycerides: 1.7±0.3mmol/L). Whereas placebo and nifedipine did not affect total cholesterol, LDL or triglycerides, treatment with the ETA antagonist reduced all three – baseline vs. week 6 – cholesterol: -11% (95% CI 8.7-13.2%, p <0.001); LDL: -21% (95% CI 17.8-27.3%, p <0.001); triglycerides: -26% (95% CI 15.1-36.5%, p <0.001). These effects were independent of the reductions seen in proteinuria, BP and arterial stiffness and were greatest in those receiving statin treatment. HDL was unaffected by all treatments.

Conclusion

In addition to currently recognized effects on proteinuria and BP, ETA antagonism may modify lipid profile and so have broader cardioprotective effects in CKD. Larger and longer-term trials with this specific endpoint are now warranted.