Chronic Kidney Disease and Albuminuria in Arterial Hypertension

Abstract

Chronic kidney disease is a major public health problem worldwide: it is estimated that in the general population, 1 person in 10 has some degree of renal damage. Adequate blood pressure control represents the mainstay of treatment, to delay deterioration of renal function and prevent cardiovascular complications. Current evidence supports a target blood pressure value of 130/80 mm Hg or less (ie, <125/75 mm Hg) when proteinuria exceeds 1 g/L. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers represent the treatment of choice, especially in the presence of proteinuria. More complete blockade of the renin-angiotensin-aldosterone system (RAAS) has been advocated, using a combination of multiple RAAS blocker drugs or supramaximal doses to maximize renal protection. Achieving recommended blood pressure target values usually requires the use of multiple antihypertensive drugs, including diuretics and calcium channel blockers.

Diabetic nephropathy and long-term treatment effects of rosiglitazone and enalapril in obese ZSF1 rats

“…The use of a supra-maximal dose of enalapril raises questions about the clinical relevance of the detected renal effects (near elimination of albuminuria and prevention of glomerulosclerosis). Although beneficial renal effects of the observed magnitude should likely not be expected in humans, numerous studies on patients with both diabetic and non-diabetic chronic kidney disease suggest that supra-maximal doses of renin-angiotensin system inhibitors may provide additional renal protection over the doses used to reduce blood pressure (Leoncini et al 2010). In summary, this study indicates that, despite some limitations of the ZSF1 rat model, it is still the most appropriate rat model of DN, manifesting all of the features of human disease recommended by the Animal Models of Diabetic Complications Consortium (Fioretto et al 2008).…”

“…A number of studies have suggested that use of much higher doses of angiotensin converting enzyme (ACE) inhibitors (or angiotensin II receptor blockers) than those required to reduce blood pressure may further reduce proteinuria and provide additional renal protection (Leoncini et al 2010). Therefore, in this study, we used a high dose of enalapril to determine whether use of supra-maximal doses of ACE inhibitor may normalize blood pressure and prevent renal injury in diabetic ZSF1 rats.…”

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

“…This blocking has been postulated as the first choice for treatment of hypertension in CKD patients (7). However, some studies indicated that, even under appropriate ACE inhibitors or ARB use, the renal end point was reached during follow-up by approximately one third of all patients (4,6,61,62).…”

“…"Aldosterone escape" occurs in as many as half of all patients on chronic ACE inhibitor or under ARB treatment and this long-term inter-individual variability should be focused on the following pharmacogenetic studies. For this reason, the combined use of RAS-blocker drugs, higher dosages, and/or direct rennin inhibition has been proposed (4,46,72,73).…”

“…About 80% of CKD patients are hypertensive and kidney function and blood pressure are clearly related to both physiologic and pathologic conditions constituting a "vicious cycle" (4). In this pathologic scenario, there is a renin-angiotensin system (RAS) hyperactivity associated to progression of renal damage and current guidelines indicate as the first choice of treatment for hypertension in early-CKD patients, the pharmacologic blockade of the RAS (5).…”