AGT and hypertensive disorder: Indeed, well-known consequences of too much RAS blockade are renal dysfunction (reflected by a rise in creatinine) and hyperkaliemia.52 Combined AGT siRNA-ARB treatment of SHR did upregulate serum potassium, yet without affecting glomerular filtration rate.17 Also in other hypertension models (5/6th nephrectomy and DOCA-salt), AGT siRNA, either alone or in combination with an ARB, did not reduce glomerular filtration rate.16,18 Clearly, more work is needed to carefully assess this aspect, particularly in diabetic kidney disease.