This state is presumed to arise from decreased sympathetic drive to renin secretion (in diabetic autonomic neuropathy), decreased capacity to synthesise renin because of injury to the juxtaglomerular apparatus (in afferent arteriolar hyalinosis and diabetic nephropathy) and a decreased volume stimulus to renin release because of chronic renal salt retention [53, 54]. This evidence concerns the gene REN and diabetic kidney disease.