In prior clinical studies of secondary prevention in diabetes with pre-existing CKD, direct VDR agonists (calcitriol and paracalcitol) reduced proteinuria [7,42-45]; whether this effect was mediated by the RAS, or could be extrapolated for the primary prevention of diabetic nephropathy, are questions that the VALIDATE-D study will clarify. The gene discussed is VDR; the disease is chronic kidney disease.