The role of arterial hypertension in the progression of non-diabetic glomerular diseases

Abstract

Arterial hypertension (AH) per se is, together with diabetes mellitus, the most important cause of renal failure and of dialysis in the western world. AH is also a well known consequence of chronic renal disease, and at the same time one of the main factors which causes diabetic and/or non-diabetic chronic renal failure progression. AH is mostly registered in patients with focal segmental glomerulosclerosis and with membranoproliferative glomerulonephritis. The pathophysiology and the mechanism of AH within primary glomerular diseases are complex, including activation of the sympathetic nervous system, the renin-angiotensin system (RAS), sodium retention, volume expansion and decreased synthesis of vasodilatatory substances. As autoregulation of glomerular pressure in chronic glomerular disease is disturbed, the increment in systemic blood pressure leads to the rise in glomerular pressure. Glomerular hypertension results in glomerular capillary wall stretch, endothelial damage and a rise in protein glomerular filtration. These processes, in turn, cause changes of mesangial and proximal tubular cells, ultimately resulting in the replacement of functional by non-functional connective tissue and the development of fibrosis. One of the most important factors in the progression of chronic renal failure is activation of the RAS. Its effect is not only elevated blood pressure, but also the promotion of cell proliferation, inflammation and matrix accumulation. Many studies, first in experimental animals and later in humans, have shown that the lowering of blood pressure (and proteinuria) is associated with a slower progression of kidney disease. It seems that angiotensin-converting enzyme inhibitors (ACEIs) are more renoprotective than other antihypertensives (the protection beyond the antihypertensive effect), although some studies have also confirmed a comparatively beneficial effect of non-dihydropiridine calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs). Moreover, it seems that a combination of antihypertensives (e.g. ACEI + CCB, ACEI + ARB) has a more effective action than either of the drugs alone. However, the effects depend first on the degree of blood pressure reduction. According to comprehensive studies, the achievement of adequate blood pressure (not higher than 130/85 mmHg) is the most important factor. An even lower blood pressure (125/75 mmHg) has been suggested as the limit value in patients with proteinuria of >1 g/24 h and in Blacks.

Improvement of Blood Pressure Control in Hypertensive Patients with Renal Diseases

“…The improvement of BP control by using antihypertensive agents, such as ACE inhibitors or ARBs, has also been reported in previous studies (2,3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). A significant increase in the prescription of ARBs was observed in 2003 compared with 1996 in RD patients.…”

“…Several studies have suggested that the combined treatment with ACE inhibitors and ARBs may be more renoprotective than treatment with either agent alone (12,(20)(21)(22)24), and, indeed, in some RD patients, the combination of ACE inhibitors and ARBs was also prescribed in the present study. The improvement of BP control by using antihypertensive agents, such as ACE inhibitors or ARBs, has also been reported in previous studies (2,3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

“…Based on the findings obtained from the large-scale clinical trials (5,7), recent guidelines for the management of hypertension, such as JNC VI, JNC 7, WHO/ISH 1999, ESH-ESC 2003 and Japanese Society of Hypertension (JSH) 2004 recommend strict BP control in RD (8)(9)(10)(11). Moreover, the development of newer classes of antihypertensive drugs, such as angiotensin II receptor blockers (ARBs), has had a beneficial influence on the management of hypertension with RD (2,3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Thus, the aim of the present study was to assess the current status of BP control in hypertensive patients with RD, and whether BP control improved during the period between 1996 and 2003, i.e., before and after the introduction of recent hypertension guidelines.…”

Association of renal function with clinical parameters and conditions in a longitudinal population-based epidemiological study

“…Furthermore, sodium retention, volume expansion, and reduced synthesis of vasodilator substances subsequent to the rise in BP may exacerbate hypertension. Impairment of autoregulation of glomerular pressure may also lead to glomerular hypertension (20). Given that activation of the renin-angiotensin-aldosterone system not only causes a rise in BP, but also promotes cell proliferation, inflammation, and matrix accumulation, it may also lead to the progression of CKD (17).…”

Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

“…Some possible explanations for this may be the different model and the different starting time of atRA administration. Because hypertension is a risk factor for the progression of renal diseases [34] , a decrease in hypertension underlies the renoprotective effects of atRA.…”