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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of kidney disease, manifested by low glomerular filtration rates (GFR) and/or large amounts of protein in the urine, is independently associated with increased rates of cardiovascular disease (CVD). The severity of kidney disease is associated with graded increases in risk for CVD and death. Chronic kidney disease (CKD) should be recognized and treatment initiated early to maximize the chances for slowing nephropathy progression and reducing proteinuria. We recommend screening for CKD in all patients with CVD, including computing an estimated GFR and evaluating for proteinuria using a spot urine albumin:creatinine ratio. Aggressive management of traditional cardiovascular risk factors should be employed in this high-risk population, specifically rigorous hypertension control (including the use of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blocking agents (ARB)), management of hyperglycemia, hyperlipidemia and smoking cessation. Further studies are needed to identify the unique renal failure-related (non-traditional) risk factors that contribute to accelerated atherosclerosis in this population and performance of randomized trials to assess the effects of cardiovascular interventions in individuals with CKD.
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PMID:Cardiovascular disease in chronic kidney disease. 1912 39

The renin-angiotensin system (RAS) plays an important role in the pathogenesis of cardiovascular disease. One of the effects of the activated RAS is target-organ damage, in part due to their effects on causing hypertension. Blocking angiotensin-converting enzyme (ACE) with inhibitors has been shown to attenuate the pathological effects of the RAS. Clinical trials have shown that ACE inhibition improves outcomes in the prevention of acute myocardial infarction, lowering the morbidity and mortality in congestive heart failure, and attenuates renal dysfunction. There is recent evidence to show that angiotensin receptor blockers (ARBs) have similar efficacy to ACE inhibitors in reducing cardiovascular outcomes. The wealth of information obtained regarding the beneficial effects of RAS inhibition on clinical outcome has been focused on monotherapy with either ARB or ACE inhibition. Evidence from some trials suggests that better overall inhibition of RAS by dual therapy may improve clinical outcomes. Combination therapy has been shown to be beneficial in patients with congestive heart failure or renal disease. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial showed equal benefit of either ARB or ACE inhibition with reduction in primary end points in postmyocardial infarction patients, but there was no further benefit from dual therapy in reducing outcomes. In the recent ONTARGET study, there was further evidence that ARBs are equal to ACE inhibitors in reducing cardiovascular events. In Ongoing Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events (ONTARGET), combined RAS blockade did not have any added benefit but resulted in increased risk of adverse outcomes. In the Candesartan in Heart Failure (CHARM) and the Valsartan Heart Failure Trial (Val-HeFT) trials of patients with severe heart failure, the addition of an ARB to an ACE inhibitor reduced cardiac mortality and lowered hospital admissions. Whether or not dual therapy is beneficial in patients with diabetic renal failure should be clarified by future studies. Overall, patients receiving dual therapy, if clinically justified, should be monitored closely for potential adverse effects.
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PMID:Blocking the renin-angiotensin system: dual- versus mono-therapy. 1950 82

HCV-related membranoproliferative glomerulonephritis is the most common cause of hepatitis C-associated renal disease. Its treatment is still under debate and based on scant experimental evidence. The recommended therapeutic strategy depends on the severity of the kidney disease. The first-line treatment for patients with mild to moderate clinical and histological kidney damage is antiviral therapy with pegylated interferon alpha and ribavirin for 48 weeks combined with symptomatic treatment (diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers). In case of severe renal involvement (nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy), the initial treatment may consist of sequential administration of immunosuppressive therapies (plasmapheresis, corticosteroids and cyclophosphamide) and antiviral agents, although no definitive data are yet available from the literature. B-cell depleting agents such as rituximab may be an alternative to conventional therapy in refractory or intolerant patients. Large randomized and controlled clinical trials are needed to establish guidelines for the treatment of HCV-related cryoglobulinemic glomerulonephritis.
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PMID:[Treatment of HCV-associated cryoglobulinemic glomerulonephritis]. 1955 29

Despite reported renoprotection with angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and notwithstanding their increased use, we continue to experience an epidemic of acute renal failure (ARF)/chronic kidney disease/end-stage renal disease. Consequently, concerns about iatrogenic renal failure have resurfaced. Different analysis of these trials revealed flaws such as recruitment of relatively younger patients with preserved baseline renal function, common utilization of lower end doses of ACEIs/ARBs, high drug discontinuation rates, excessive use of surrogate endpoints, inadequate reporting of adverse effects, and short duration studies. Again, lower 24-hour ambulatory blood pressure among patients in the ramipril arm of the micro-HOPE (Heart Outcomes Prevention Evaluation) study raises doubts of renoprotection beyond blood pressure lowering. The disappointing results from the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study only compounded these doubts. We demonstrated significant renal salvage after ACEI/ARB was discontinued in chronic kidney disease patients recruited with increasing ARF while on ACEI/ARB. Apart from our reports, there are increasing reports incriminating the use of ACEI/ARB with ARF exacerbations. We conclude that close and indefinite monitoring of estimated glomerular filtration rate is an absolute must in these patients. The treating physician must be ready to consider trial discontinuation of ACEI/ARB, promptly. Combination ACEI + ARB therapy should be the exception, rather than the rule. Temporary withdrawal of ACEI/ARB before certain exposures, 'renoprevention', would only further improve the results of renoprotection.
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PMID:Analytical review of the evidence for renoprotection by renin-angiotensin-aldosterone system blockade in chronic kidney disease - a call for caution. 1960

Antihypertensive treatment is an essential, life-prolonging measure in primary hypertension. It prevents apoplexy, myocardial infarction, and hypertensive kidney failure. Chronic kidney failure is associated with hypertension and an accelerated form of arteriosclerosis. Demise from cardiovascular affliction is a leading cause of death in renal patients (chronic renal failure stages II-IV, renal failure requiring dialysis, renal transplantation). What, then, is the role of antihypertensive treatment in such patients, and, specifically, what is achieved by renin-angiotensin-aldosterone (RAA) system modifying agents? Two meta-analyses have recently investigated these issues. An article in The Lancet evaluated eight studies on dialysis patients (n = 1679). It concluded that antihypertensives are beneficial in reducing cardiovascular morbidity and mortality. However, we criticize these conclusions and show that the data are not convincingly in favor of antihypertensive treatment. A meta-analysis in the American Heart Journal assessed the role of antihypertensive agents and RAA system modifying drugs in 45,758 patients (from 25 studies), who were in stages I-III of renal failure, i.e., not (yet) requiring dialysis. The authors claim that angiotensin- -converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) significantly reduced cardiovascular outcomes. However, our analysis of the data is not consistent with their conclusions. It showed that the results were quite mixed, that the authors may have overemphasized the positive results, and that considering all the results, it should be concluded that antihypertensive treatments, including those with ACEI/ARB, may not be superior to placebo (sic!) in renal patients. Rather than doing meta-analyses, larger primary studies are needed to reveal the real role of antihypertensive treatments in renal patients.
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PMID:Should we prescribe blood pressure lowering drugs to every patient with advanced chronic kidney disease? A comment on two recent meta-analyses. 1984 40

Suppression of angiotensin II formation by angiotensin-converting enzyme inhibitors or blockade of the angiotensin II receptor by angiotensin receptor blockers is a powerful therapeutic strategy to slow the progression of renal disease. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers provide only imperfect protection against the progression of chronic kidney disease to end-stage renal failure. Hence, innovative approaches are needed to keep patients with chronic kidney disease off dialysis. Angiotensin II activates at least two receptors, namely the angiotensin II type 1 (AT( 1)) and angiotensin II type 2 (AT(2)) receptors. The majority of the effects of angiotensin II, such as vasoconstriction, inflammation, and matrix deposition, are mediated via the AT(1) receptor. It is thought that the AT(2) receptor counteracts these effects and plays a role in nephroprotection. However, recent data support the notion that the AT(2) receptor transduces pro-inflammatory effects and promotes fibrosis and hypertrophy. Therefore, the question of whether stimulation of the AT(2) receptor could represent a silver bullet for the treatment of chronic kidney disease or may, on the contrary, exert detrimental effects on renal physiology remains unresolved. Recent data from AT(2) receptor-knockout mice demonstrate that the loss of AT(2) receptor signalling is associated with increased renal injury and mortality in chronic kidney disease. This raises the expectation that pharmacological stimulation of the AT(2) receptor may positively influence renal pathologies. However, further research is needed to explore the question whether AT(2) receptor stimulation may represent a new therapeutic strategy for the treatment of chronic kidney disease.
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PMID:The angiotensin II type 2 receptor in renal disease. 1986 45

Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio > or =300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, -51.0%, -11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, -37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial.
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PMID:Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. 2053 2

The advancing chronic renal failure is at most the consequence of secondary haemodynamic and metabolic factors as intraglomerular hypertension and glomerular hypertrophy. Although tight blood pressure control is the major preventive mechanism for progressive renal failure, ACE inhibitors and angiotensin receptor blockers have some other renoprotective mechanisms beyond the blood pressure control. That is why these two groups of antihypertensive drugs traditionally have advantages in treating renal patients especially those with proteinuria over 400-1000 mg/day. Even if earlier experimental studies have shown renoprotective effect of calcium channel blockers, later clinical studies did not prove that calcium channel blockers have any advantages in renal protection over ACE inhibitors given as monotherapy or in combination with ACE inhibitors. It was explained by action of calcium channel blockers on afferent but not on efferent glomerular arterioles; a well known mechanism that leads to intraglomerular hypertension. New generations of dihydropiridine calcium channel blockers can dilate even efferent arterioles not causing unfavorable haemodynamic disturbances. This finding was confirmed in clinical studies which showed that renoprotection established by calcium channel blockers was not inferior to that of ACE inhibitors and that calcium channel blockers and ACE inhibitors have additive effect on renoprotection. Newer generation of dihydropiridine calcium channel blockers seem to offer more therapeutic possibilities in renoprotection by their dual action on afferent and efferent glomerular arterioles and, possibly by other effects beyond the blood pressure control.
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PMID:[Renoprotective effect of calcium channel blockers]. 2006 31

Hypertension is common and occurs in a majority of autosomal dominant polycystic kidney disease (ADPKD) patients before the loss of kidney function. Hypertension relates to progressive kidney enlargement and is a significant independent risk factor for progression to ESRD. The pathogenesis of hypertension in ADPKD is complex and dependent on many factors that influence each other. Pkd1 and Pkd2 expression levels are highest in the major vessels and are present in the cilia of endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin 1 or 2 expression is associated with abnormal vascular structure and function. Pkd1/Pkd2 deficiency results in reduced nitric oxide (NO) levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Ten percent to 20% of ADPKD children show hypertension and the majority of adults are hypertensive before any loss of kidney function. Cardiac abnormalities such as left ventricular hypertrophy and carotid intimal wall thickening are present before the development of hypertension in ADPKD. The activation of the renin-angiotensin-aldosterone system occurs in ADPKD because of decreased NO production as well as bilateral cyst expansion and intrarenal ischemia. With increasing cyst size, further activation of the RAAS occurs, blood pressure increases, and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to ESRD. The inhibition of the angiotensin aldosterone system is possible with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. However, interventional studies have not yet shown benefit in slowing progression to renal failure in ADPKD. Currently, large multicenter studies are being performed to determine the beneficial effects of RAAS inhibition both early and late in ADPKD.
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PMID:Hypertension in autosomal dominant polycystic kidney disease. 2021 18

Limited and discordant data are available on cyclosporine A (CsA) treatment for proteinuria in Alport syndrome (AS). To address this lack of consistent data, we have studied 15 AS patients (14 males; mean age 15.3 +/- 6.0 years) treated with CsA. Patient selection criteria included a urinary protein/creatinine ratio > or =1 mg/mg and a creatinine clearance >40 ml/min/1.73 m(2). CsA treatment was started at an initial dose of 5 mg/kg/day and subsequently adjusted to reach target C2 levels of 500 ng/ml. Renal function, proteinuria, and blood pressure were monitored. Blood pressure was treated to avoid the administration of angiotensin converting enzyme or angiotensin receptor blockers for the first 2 years of therapy. The average follow-up was 3.5 years. Five patients had chronic renal failure at the beginning of treatment, of whom three and one reached end-stage renal failure within 1 and 3 years, respectively. In the remaining 11 patients, the glomerular filtration rate declined by 11 +/- 6% within 6 months, but remained stable thereafter. Proteinuria decreased by 63 +/- 21% from baseline, but returned nearly to baseline after 2.5 years of follow-up. Based on these results, we suggest that CsA is effective in reducing proteinuria in patients with Alport syndrome but that this effect is temporary. Our data do not support the use of CsA therapy for proteinuric patients with AS, particularly if they have chronic renal failure.
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PMID:Cyclosporine A treatment in patients with Alport syndrome: a single-center experience. 2023 28


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