Renoprotection and surrogate

PURPOSE: Residual renal function (RRF) contributes to dialysis adequacy, quality of life and survival of hemodialysis patients. There is an ongoing debate whether better preservation of residual renal function is the result of chronic fluid volume overload. Our prospective investigation analyzed the effects of different dialytic therapies on RRF and left ventricular hypertrophy, which may be considered--at least in part--a surrogate marker of chronic fluid overload. METHODS: Two cohorts of end-stage renal disease patients initiating renal replacement therapy (high efficiency post-dilution on-line hemodiafiltration (HDF) in 58 patients, conventional hemodialysis (HD) in 60 patients) were prospectively followed up...

Although there have been major advances in the understanding of the molecular mechanisms that contribute to the development of diabetic nephropathy, current best practice still leaves a significant treatment gap. The incidence of diabetes and associated nephropathy is increasing, with the main cause of mortality being related to cardiovascular causes. Novel therapies which are both 'cardio-renal'-protective seem the logical way forward. In the present review, we discuss the GLP-1 (glucagon-like peptide-1) receptor agonists and DPP-4 (dipeptidyl peptidase-4) inhibitors (incretin-based therapies), which are novel antidiabetic agents used in clinical practice and their role in diabetic nephropathy with specific focus on renoprotection and surrogate markers of cardiovascular disease...

Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT)...

Proteinuria is associated with adverse cardiovascular and renal outcomes that are not prevented by current treatments. Endothelin 1 promotes the development and progression of chronic kidney disease and associated cardiovascular disease. We, therefore, studied the effects of selective endothelin-A receptor antagonism in proteinuric chronic kidney disease patients, assessing proteinuria, blood pressure (BP), and arterial stiffness, key independent, surrogate markers of chronic kidney disease progression and cardiovascular disease risk...

BACKGROUND AND OBJECTIVES: Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma copeptin concentration (a marker of endogenous vasopressin levels) was measured in 102 ADPKD patients (diagnosis based on Ravine criteria) by an immunoassay...

Chronic kidney disease (CKD) is defined according to a decrease in the glomerular filtration rate and kidney damage such as proteinuria or albuminuria. Dip-stick proteinuria is only sensitive to albumin and correlates poorly with quantitative 24 h proteinuria, the most commonly used measure in renoprotective randomized controlled clinical trials (RCT). The amount of proteinuria correlates with the efficacy of angiotensin-converting enzyme inhibitors in non-diabetics in RCT. Random urine protein to creatinine ratio (PCR) or albumin to creatinine ratio (ACR) correlates with 24 h urinary excretion...

AIM: Angiotensin II type 1 receptor blockers (ARB) retard the progression of hypertensive diabetic kidney disease. Clinical evidence suggests that the dose of ARB required to correct hypertension is suboptimal for renoprotection evaluated by proteinuria. No systematic, prospective study has yet evaluated separately the effect of increasing doses of ARB on blood pressure and proteinuria. METHODS: Over a period of 8 weeks, the effect of seven constant doses of an ARB, valsartan (4-160 mg/kg per day), on blood pressure and proteinuria taken as a surrogate marker of nephropathy in a hypertensive, type 2 diabetic rat model, the spontaneously hypertensive/NIH-corpulent rat (SHR/NDmcr-cp), was assessed...

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...

Cardiovascular (CV) and renal complications associated with diabetes can be attenuated with antihypertensives that work on the renin-angiotensin-aldosterone system (RAAS),particularly angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and possibly direct renin inhibitors (DRIs). Cardioprotective and renoprotective benefits are independent of the blood pressure-lowering effect of the RAAS inhibitor. Given more complete RAAS blockade, evidence has suggested that the use of ACE inhibitor/ARB combination therapy may provide greater target organ protection...

Aliskiren is the first member of the new class of orally active direct renin inhibitors to receive approval from the United States Food and Drug Administration for the treatment of hypertension. In patients with hypertension, aliskiren can be used either as monotherapy or in combination with other antihypertensive agents. By inhibiting renin, aliskiren blocks the conversion of angiotensinogen to angiotensin I, which subsequently results in a reduction in angiotensin II concentrations. Unlike the angiotensin-converting enzyme inhibitors and the angiotensin II receptor blockers (ARBs), which reactively stimulate an increase in plasma renin activity, aliskiren suppresses the effects of renin and leads to a reduction in plasma renin activity...

BACKGROUND: Evidence suggests that transforming growth factor-beta1 (TGF-beta(1)) is associated with target organ damage in hypertension. This study aimed to investigate the relationship between TGF-beta(1) levels and kidney damage and renoprotective effects of angiotensin-converting enzyme inhibitor and/or angiotensin II type 1 receptor blocker in patients with essential hypertension (EH). METHODS: A total of 156 patients with EH were enrolled and grouped according to albumin-to-creatinine ratio (ACR)...

BACKGROUND: N-Acetylcysteine, theophylline, and other agents have shown inconsistent results in reducing contrast-induced nephropathy. PURPOSE: To determine the effect of these agents on preventing nephropathy. DATA SOURCES: Relevant randomized, controlled trials were identified by computerized searches in MEDLINE (from 1966 through 3 November 2006), EMBASE (1980 through November 2006), PubMed, Web of Knowledge (Current Contents Connect, Web of Science, BIOSIS Previews, and ISI Proceedings for the latest 5 years), and the Cochrane Library databases (up to November 2006)...

In chronic kidney disease (CKD) sympathetic overactivity is stimulated by signals from the diseased kidney activating hypothalamic centers. In addition, breakdown of circulating catecholamines is decreased. Indications for beta-blockers are cardio- and renoprotection. Cardioprotection is important because cardiovascular (CV) death is two- to 20-fold more likely in CKD than end-stage kidney disease; consequently, beta-blockers, with their adverse effect on CV risk profile, should be avoided. Controlled prospective evidence for renoprotection by beta-blockers in nondiabetic CKD with hard end points is lacking, but renoprotection by antihypertensive agents was first documented by administering beta-blockers in patients with diabetic nephropathy...

Chronic kidney disease, stage 3 or higher, affects approximately 20 million people in the United States. Aggressive management of blood pressure is critical to slow the decline in renal function. Despite adequate control, however, patients continue to progress to end-stage renal disease. A surrogate marker for renal parenchymal injury is the presence of proteinuria. Blood pressure reduction per se has been shown to decrease proteinuria. However, certain classes of antihypertensive agents, namely the inhibitors of the renin-angiotensin-aldosterone system, exert antiproteinuric and renoprotective effects that are in addition to, but independent of, blood pressure lowering...

Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD) and is associated with elevated cardiovascular morbidity and mortality. Current renoprotective treatment for diabetic nephropathy includes strict glycemic and optimal blood pressure control, proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the renoprotection provided by these treatments is only partial, and many patients still have progressive disease, thus suggesting that a more effective approach is urgently needed...

In patients with primary as well as secondary chronic kidney disease (CKD), anemia has been identified as an independent risk factor for progression. In these patients anemia is thought to be a surrogate parameter for tissue hypoxia that perpetuates preexisting renal tissue injury, and treatment of anemia with recombinant human erythropoietin (rHuEPO) was therefore expected to retard progression. However, results of recently published large trials in patients with CKD did not fulfill these expectations. The reason for the discrepant findings may be distinct molecular pathways and/or EPO tissue receptor affinities that mediate the effect of EPO on erythropoiesis and tissue protection by EPO...

BACKGROUND: The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated. METHODS: Fourteen of 16 patients (nine male, five female), age 45...

BACKGROUND: We evaluated the renoprotective effects of dual blockade of renin-angiotensin system (RAS) by using a low-dose combination of ACE inhibiter and angiotensin II receptor blocker in type 2 diabetic patients with advanced kidney disease. The amount of proteinuria and the urinary levels of bioassayable TGF-beta1 were used as surrogate markers of renal injury and sclerosis. METHODS: We performed a prospective double-blinded randomized crossover trial consisting of three 16-week treatment periods with ramipril alone (10 mg/day), candesartan alone (16 mg/day), and ramipril (5 mg/day) plus candesartan (8 mg/day) combination therapy...

Prevention of contrast agent-induced nephropathy is of crucial importance for a number of diagnostic studies. N-Acetylcysteine (NAC) was recently reported to decrease serum creatinine levels in this setting, and its administration before radiocontrast medium administration has been widely recommended. The objective of this prospective study was to investigate whether there are effects of NAC on serum creatinine levels that are independent of alterations in GFR. Volunteers with normal renal function who did not receive radiocontrast medium were studied...

AIMS: The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors...