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Endothelin Receptor Antagonists in Diabetic Nephropathy

effects on renal and myocardial tissue? Would more selective ET receptor antagonists with a higher affinity for the ETA be equally renoprotective but induce fewer side effects?

Although we do not have the evidence-based answers to all these questions, the overwhelmingly positive findings in experimental studies are promising and should encourage the continuation of well-designed trials that take into consideration the selection of the right dose and of an appropriately subclass-specific ET receptor antagonist. Such studies should be performed in well-defined populations, excluding patients with major pre-existing cardiac problems (mainly heart failure). The study protocols should include advice on how to achieve low dietary sodium intake, possibly the

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co-administration of diuretics that are active in the collecting duct, and a strict weight-gain control. Beyond such indispensable clinical studies, we also need additional experimental data on the role of ET-receptor subtypes in the kidney, especially in the collecting duct.31

We are convinced that, in future, ET receptor antagonists will have a role to play in patients with renal and reno-cardiac disease. Predictably, the benefit will be greatest if these drugs are used at earlier stages of renal disease than in the above studies, mainly because, at these earlier stage, fluid retention is less of a problem. Betablockers, once contraindicated in heart failure patients because of their side effects, are now the cornerstone of therapy. Maybe one day ET receptor antagonists will know the same fate? n

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