Pharmacotherapeutic Treatments for Hypertension Complicated with Proteinuria
Brenner, Michael; Manning, Justin, Drug Topics
Hypertension affects over 50 million Americans. It is a risk factor for heart disease, stroke, and kidney disease. The incidence of hypertension increases with age, but the onset most often occurs during the third, fourth, and fifth decades of life.
Hypertension can be classified into two categories: primary and secondary hypertension. Primary or essential hypertension is the most prevalent, making up more than 90% of all cases and has no specific cause or symptoms. secondary hypertension results from a known cause, which includes: chronic renal disease, renal artery stenosis, primary hyperaldosteronism, stress, sleep apnea, hyper/hypothyroidism, pheochromocytoma, pre-eclampsia, coarctation of the aorta, and it can be drug-induced. In secondary hypertension, treatment of the underlying cause is warranted before antihypertensive therapy is given.
Proteinuria is one of the clinical features of renal disease and may also be secondary to diabetes. Proteinuria is classified as nephropathy (microalbuminuria with reduced renal function) and overt nephropathy (macroalbuminuria with reduced renal function). This will be discussed in further detail after the section on padiophysiology. Patients with chronic kidney disease (CKD) and proteinuria exceeding 1gm per day are at high risk for further renal deterioration and cardiovascular disease. Reducing proteinuria will reduce progression to end-stage renal disease (ESRD), and decrease the morbidity and mortality associated with cardiovascular events.
Hypertension is a well-known cause of chronic kidney disease. Blood pressure (BP) is directly proportional with proteinuria. As the BP rises, the incidence of developing proteinuria increases. Reducing BP in the presence of proteinuria and mild to moderate renal insufficiency has consistently decreased progression of kidney disease. According to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative Working Group (NKF K/DOQI) guidelines, the goal of antihypertensive therapy for hypertension in conjunction with CKD is to decrease BP and reduce the incidence of cardiovascular disease.
The pathogenesis of hypertension remains uncertain. There are various physiological mechanisms that may lead to essential hypertension. BP may be modulated by the kidneys, the central nervous system (CNS), peripheral nervous system (PNS), and the vascular endothelium.
Normal BP is dependent on a balance between cardiac output and peripheral resistance. In essential hypertension, there is a higher level of vascular resistance and usually a normal cardiac output. This may lead to excessive vasoconstriction of the smooth muscle, inducing structural changes to the arteriolar vessel.
Renin, a hormone secreted by the kidneys, is produced when there is a lack of perfusion in the glomerulus, reduced salt intake, or in response to stimulation of the sympathetic nervous system (SNS). Renin plays an important role in the renin-angiotensin-aldosterone system (RAAS). RAAS plays a significant role in regulating BP and blood volume. In the presence of renin, angiotensinogen converts to angiotensin I. Angiotensin I converts to angiotensin II via angiotensin converting enzyme. The action of angiotensin II is mediated by the activation of the ATI receptor. Angiotensin II is a potent vasoconstrictor elevating BP. Aldosterone is also secreted from the adrenal gland in the presence of angiotensin II. Aldosterone causes sodium (Na+) and water retention, leading to elevated BP.
Excess stimulation of the SNS may result in peripheral vasoconstriction, elevated heart rate (HR), and release of norepinephrine resulting in elevated BR Sympadietic stimulation can also lead to vasoconstriction in the renal efferent artery, decreasing renal blood flow and increasing vascular resistance.
Hypertension may also be caused by environmental factors such as excess sodium intake, obesity, stress, and genetic factors, such as family history and race. …