Endothelin Receptor Antagonism and Renin Inhibition as Treatment Options for Scleroderma Kidney

Scleroderma renal crisis (SRC) is an important complication of scleroderma associated with significant morbidity and mortality. Current treatment of patients with SRC focuses on renin-angiotensin-aldosterone system (RAAS) blockade, ideally using angiotensin-converting enzyme inhibitors. We present a case of SRC in a patient established on maximal tolerable RAAS-blocking treatment. Introduction of a selective endothelin-A receptor antagonist followed by a direct renin inhibitor provided excellent blood pressure control and complete abrogation of heavy proteinuria. This was associated with a decrease in kidney function, with serum creatinine level increasing by approximately 30%. This increase is considered acceptable after the introduction of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, is regarded as an indicator of drug efficacy, and confers longer term renal protection. Both endothelin receptor antagonism and direct renin inhibition offer alternate novel therapies for patients with SRC. Their ability to preserve or improve kidney function is unclear.