Treatment of Hypertensive Retinopathy

Heart, 1994

The advent of angiotensin converting enzyme (ACE) inhibitors has provided not only a new treatment for hypertension but also a specific treatment for hypertension in renal disease, which carries the promise of lessening the progression of renal disease and the risk of additional side effects. In this review we aim to cover the evidence for a role for ACE inhibition in the slowing or halting of progression of chronic renal disease, together with the possible consequences of the use of these drugs in patients with renovascular hypertension and other forms of renal disease. Progression of renal disease Despite the advent of effective renal replacement therapy, mortality and morbidity remain high in patients undergoing dialysis. Effective treatment to slow or halt the progression of renal failure in patients with mild to moderate chronic uraemia is of prime importance. Such treatment would delay the onset of renal replacement therapy, thereby reducing the incidence of associated complications and the limitations it places on the quality of life. Currently, apart from specific treatments for particular renal diseases, efforts to slow the progression of renal failure have focused on two factors: the control of hypertension and dietary protein restriction. Recent data have suggested that progression of renal disease in humans is not significantly improved by protein restriction, hence, the control of hypertension remains the mainstay of conservative measures.' Evidence is now accumulating that there may be a specific additional role for ACE inhibitors in the treatment of renal disease.

Hypertension, 2001

Nephrosclerosis constitutes a major cause of end-stage renal disease. Independently of blood pressure control, ACE inhibitors (ACEIs) are considered to be more nephroprotective than other antihypertensive agents. We have reviewed the long-term evolution of renal function in our series of essential hypertensive patients diagnosed as having nephrosclerosis when first seen in our unit. The analysis was performed depending on whether or not their antihypertensive therapy contained an ACEI alone or in combination for the whole follow-up. The end point was defined as the confirmation of a 50% reduction in creatinine clearance or entry in a dialysis program. A historical cohort of 295 patients was included in the analysis. Mean follow-up was 7.4Ϯ3.9 years. Diabetes prevalence was higher in ACEI-treated patients (25.7% versus 7.1%, Pϭ0.000), but the diagnosis of diabetic nephropathy could not be confirmed on clinical grounds, including renal biopsy. Twenty-three out of 183 (12.6%) patients in the ACEI group and 23 out of 112 (20.5%) patients in the non-ACEI group experienced a renal event (Pϭ0.0104 by log rank test). Similar results were observed when only nondiabetic patients were considered for the analysis. Cox regression analysis showed that baseline serum creatinine, absence of ACEI administration, mean proteinuria during follow-up, and age were independent predictors for the development of a renal event. In hypertensive nephrosclerosis, therapy containing an ACEI alone or in combination significantly reduces the incidence of renal events. This effect is independent of blood pressure control. (Hypertension. 2001;38[part 2]:645-649.)

Journal of Human Hypertension, 2001

European Journal of Nuclear Medicine and Molecular Imaging, 2002

Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much more sensitive than valsartan renography in detecting a clinically significant renal artery stenosis. Furthermore, our data suggest that other effects, such as that on the prostaglandin-bradykinin system, are of at least similar importance to ACE inhibition for the high diagnostic sensitivity of captopril renography regarding renovascular hypertension.

Drug Safety, 1991

International Urology and Nephrology, 2012

Purpose The activation of the renin-angiotensinaldosterone system caused by renal ischaemia in atherosclerotic renal artery stenosis (ARAS) may be responsible for serious cardiovascular and renal consequences. The aim of the study was to assess the longterm safety, tolerability and outcomes of the use of angiotensin I-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients with ARAS. Methods Thirty-six patients with angiographically defined ARAS (managed either with revascularization or only with medical treatment) were prospectively assessed for the safety, tolerability and outcomes of the use of ACEis or ARBs. Results The mean period of follow-up was 88.9 ± 37.8 months. A statistically significant reduction in systolic and diastolic blood pressure was recorded over time (P \ 0.001). While estimated glomerular filtration rate remained almost stable during the study period (0.816), nuclear EDTA-GFR showed a significant reduction over time (P = 0.03). Mean time from diagnosis/intervention to end-stage renal disease for the cohort of 36 patients was 165.38 ± 13.62 months. Mean overall patient survival was 135.36 ± 15.25 months, with fourteen deaths (38.8%) occurring during the observational period. ACEi/ARB therapy was discontinued transiently in only 4 subjects. Conclusions The use of ACEis/ARBs is safe and effective in patients with ARAS independently of any parameters.

Circulation, 2001

A ngiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs. Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies. Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of "functional renal insufficiency" and/or hyperkalemia. This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent. Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures. The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient. Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor-induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion. Renal and Systemic Effects of Ang II During Volume Depletion and CHF Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs. 1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system. When renal perfusion pressure falls (as in hypovolemia or CHF), the sympathetic nervous system is activated and renin is secreted from juxtaglomerular cells of afferent arterioles, with consequent Ang II production. At the level of the renal glomerulus, Ang II can be expected to cause vasoconstriction of postglomerular efferent to a much greater degree than preglomerular afferent arterioles. This imbalance of effect on the efferent arteriolar circulation restores glomerular capillary pressure and thereby maintains glomerular filtration despite reduced perfusion pressure. Under these circumstances, filtration fraction (GFR/ renal plasma flow) increases, which favors proximal tubular Na ϩ reabsorption. Ang II also independently promotes proximal tubule Na ϩ reabsorption and, through its effect on aldosterone synthesis, collecting duct Na ϩ reabsorption. 2 In the presence of excess Ang II, as in CHF, urinary Na ϩ excretion can be expected to fall dramatically, although other factors, such as low blood pressure, make important contributions to the antinatriuretic state that is characteristic of CHF. Ang II is also a proven dipsogen (that is, an agent that induces thirst) in experimental animals because of an effect on central thirst centers. An increase in water intake may be explained in part by the physiologically inappropriate thirst drive in CHF. 3 In volumedepleted normal individuals, these mechanisms preserve ECF volume by curbing additional losses, and taken together, they The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee in June 2001. A single reprint is available by calling 800-242-8721

Clinical journal of the American Society of Nephrology : CJASN, 2014

People with atherosclerotic renal artery stenosis may benefit from renin-angiotensin inhibitors, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers, but little is known about the factors associated with their use. The Cardiovascular Outcomes in Renal Atherosclerotic Lesions study (ClinicalTrials.gov identified: NCT00081731) is a prospective, international, multicenter clinical trial that randomly assigned participants with atherosclerotic renal artery stenosis who received optimal medical therapy to stenting versus no stenting from May 2005 through January 2010. At baseline, medication information was available from 853 of 931 randomly assigned participants. Kidney function was measured by serum creatinine-based eGFR at a core laboratory. Before randomization, renin-angiotensin inhibitors were used in 419 (49%) of the 853 participants. Renin-angiotensin inhibitor use was lower in those with CKD (eGFR&lt;60 ml/min per 1.73 m(2)) (58% versus 68%; P=0.004) and ...

The Journal of Clinical Hypertension, 2014