Bruce Hendry
The Renal Association, UK
Title: T-type calcium channel inhibition: A novel therapy in renal disease
Biography
Biography: Bruce Hendry
Abstract
There is a lack of effective therapeutic options for patients with chronic kidney disease (CKD) related to IgA nephropathy and proteinuric nephropathies. Treatment with inhibitors of the renin angiotensin system (RAS) is standard but residual risk of progression of CKD remains high. In this context this lecture will explore an innovative strategy for therapy in CKD targeting T-type calcium channels. T-type calcium channels (TTCC) are closely related to the more familiar L-type calcium channels (LTCC). We have extended work on the role of TTCC in smooth muscle proliferation by demonstrating that TTCC have a role in mesangial cell function. TTCC are also expression in the efferent arteriole and TTCC inhibition reduces glomerular capillary pressure. In vitro human and rat mesangial cell proliferation is dependent on TTCC and not LTCC. Moreover, in models of glomerular cell proliferation, inhibition of TTCC reduces glomerular damage, reduces cell proliferation and inhibits monocyte infiltration, with improved renal function. In parallel with this work a series of studies in Japan has demonstrated that TTCC inhibition reduces glomerular proteinuria in animal studies and in small clinical studies of diabetic nephropathy. Taken together these studies provide the basis for optimism about TTCC inhibition as a new therapy in renal diseases where mesangial cell proliferation is coupled with significant proteinuria. Such diseases include IgA Nephropathy, Diabetic Nephropathy and lupus nephritis.