Renal protection by inhibition of the renin-angiotensinaldosterone
|
|
- Kevin Whitehead
- 6 years ago
- Views:
Transcription
1 Renal protection by inhibition of the renin-angiotensinaldosterone system Tomas Berl Key words: angiotensinconverting enzyme inhibitor, angiotensin receptor blocker, combination therapy, direct renin inhibitor, monotherapy, proteinuria Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, Denver, Colorado, USA. Correspondence to: Tomas Berl, MD Division of Renal Diseases and Hypertension, University of Colorado at Denver Health Sciences Center, 4200 East Ninth Avenue, Box C281, BRB 423, Denver, CO 80262, USA. Tel: Fax: uchsc.edu Abstract Renin-angiotensin-aldosterone system (RAAS) inhibition exerts a renoprotective effect independent of blood pressure reduction. Many studies using an end-point of proteinuria compared the effects of angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) monotherapy with combination ACE-I/ARB therapy. Despite methodological limitations, most studies suggest that combination therapy provides a greater antiproteinuric effect than monotherapy, perhaps because of more prolonged and complete RAAS inhibition. COOPERATE and ONTARGET used more robust end-points to study renoprotective effects. In COOPERATE, combination therapy resulted in significantly longer times to doubling serum creatinine or developing end-stage renal disease than trandolapril or losartan monotherapy. However, a secondary ONTARGET finding was that combination therapy significantly increased the risk for renal dysfunction compared with ramipril or telmisartan alone. Eventually, the VA NEPHRON-D trial should provide definitive data relating to patients with diabetic nephropathy. Results of AVOID suggest the renoprotective benefits of combination therapy extend to the direct renin inhibitors (DRI). In AVOID, combination therapy with aliskiren, a DRI, and losartan resulted in 20% greater protein excretion decrement than losartan monotherapy. Future trials should examine higher RAAS inhibitor doses, facilitate differentiation of renoprotective and antihypertensive effects of RAAS blockade, and use end-points that robustly demonstrate renoprotective effects. Introduction In the past 20 years, inhibitors of the reninangiotensin-aldosterone system (RAAS) have become a cornerstone for the treatment of hypertension. Similarly, RAAS inhibitors have been used increasingly in patients with underlying renal disease as mounting evidence has pointed to the agents having an antiproteinuric effect that is independent of blood pressure lowering. 1 This effect is considered important in light of two key observations. Several large interventional studies have uniformly found that proteinuria is a major risk factor for the progression of renal disease. 2-5 Furthermore, the reduction of proteinuria in patients with underlying diabetic nephropathy has been associated with a decreased risk for a renal end-point (e.g. doubling of serum creatinine, reaching end-stage renal disease). 3,4 A similar observation was seen in patients with nondiabetic kidney disease with lower levels of baseline proteinuria, 5 thereby demonstrating the importance of lowering protein excretion in a variety of renal disorders and across a broad spectrum of protein excretions. In view of these observations, it is not surprising that clinical studies have evaluated the effects of higher doses of angiotensin-converting enzyme inhibitors (ACE-I) 6,7 and angiotensin receptor blockers (ARB) 6,8 at doses exceeding those approved by the Food and Drug Administration for lowering blood pressure. Additionally, because RAAS intervention can be targeted at various points (figure 1), it has been postulated that combining more than one of these intervention points could lead to greater inhibition of the RAAS and a more robust decrement in protein excretion. Thus, there are four potential combinations of existing therapeutic agents. Furthermore, given that antagonists of aldosterone a downstream effector of angiotensin II (Ang II) have been shown to decrease protein excretion in patients with renal diseases, 9 the option of also using aldosterone inhibitors doubles the potential combinations to eight. In this review, a brief summary of the data is presented supporting the use of combination therapy with ACE-Is and ARBs compared with monotherapy using either /
2 Figure 1 RAAS and points at which pharmacologic intervention can inhibit it. ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; AT 1 = angiotensin II type 1; DRI = direct renin inhibitor. 2 class of agents. Also presented are some results of emerging studies with a recently approved direct renin inhibitor (DRI), aliskiren. Comparison of the effects of combination ACE-I plus ARB therapy with ACE-I or ARB monotherapy on proteinuria A large number of clinical studies have compared the effects of dual RAAS blockade and single blockade with an ACE-I or an ARB on protein excretion as a surrogate for renal protection. The reader is referred to tables 4 and 5 in the metaanalysis conducted on these studies by Kunz et al. 10 Details of some of these studies, which are representative of the group as a whole, are presented in table Mogensen et al. 11 were the first investigators to conduct a randomised, parallel-group, doubleblind study comparing lisinopril 20 mg, candesartan 16 mg, and combination lisinopril plus candesartan in 199 patients with type 2 diabetes. Combination therapy with lisinopril plus candesartan provided a significant decrease in protein excretion compared with ARB monotherapy (p=0.04); however, the difference was not significant when compared with ACE-I monotherapy. In a small follow-up study (n=20), Jacobsen et al. 12 compared the antiproteinuric effects of benazepril 20 mg, valsartan 80 mg, and combination therapy with benazepril plus valsartan in a randomised, double-blind, placebo-controlled, crossover trial in patients with type 1 diabetes. In contrast to the Mogensen et al. findings, 11 a significant decrease in protein excretion was reported in the patients treated with benazepril 20 mg plus valsartan 80 mg compared with patients treated with monotherapy of either agent (p<0.05). 12 In a study with similar design, Jacobsen et al. 13 evaluated the effect of enalapril 40 mg, irbesartan 300 mg, and combination therapy with enalapril plus irbesartan in 24 patients with type 1 diabetes. Repeatedly, the combination of the ACE-I and ARB provided a significantly greater antiproteinuric effect than therapy with the ACE-I alone (p<0.001). Although these often-cited studies support the clinical use of dual RAAS inhibition with an ACE-I and an ARB, two study limitations may impact this interpretation in clinical practice. The first limitation relates to the difference in achieved blood pressure measurements among the treatment groups. Specifically, in the study by Mogensen et al., 11 the authors clearly state that in the group of patients who received the combination treatment after 12 weeks, there was a measurable further reduction in systolic and diastolic blood pressure. Similarly, the two studies by Jacobsen et al. 12,13 report 7 mmhg to 9 mmhg lower systolic and diastolic ambulatory blood pressure in the group receiving ACE-I/ARB combination therapy. It is therefore difficult, if not impossible, to ascertain whether the changes observed in protein excretion
3 Table 1 Combination of ACE-I plus ARB versus ACE-I or ARB. Combination better than monotherapy Blood pressure No. of patients lower in Reference End-point Condition Drugs ACE-I ARB combination Mogensen et al. 11 UACR n=199 Lisinopril 20 mg or candesartan No Yes Yes Type 2 diabetes 16 mg vs. lisinopril 20 mg + candesartan 16 mg Jacobsen et al. 12 Urinary n=20 Benazepril 20 mg or valsartan Yes Yes Yes albumin Type 1 diabetes 80 mg vs. benazepril 20 mg + valsartan 80 mg Jacobsen et al. 13 Urinary n=24 Enalapril 40 mg vs. enalapril Yes Yes albumin Type 1 diabetes 40 mg + irbesartan 300 mg Luno et al. 14 UACR n=45 Lisinopril to 40 mg or candesartan Yes Yes No Proteinuric to 32 mg vs. lisinopril nephropathy 20 mg + candesartan 16 mg Campbell et al. 15 UACR n=24 Benazepril 20 mg or valsartan Yes Yes No Nondiabetic 160 mg vs. benazepril proteinuria 10 mg + valsartan 80 mg Nakao et al. 16 Doubling n=263 Trandolopril 3 mg or losartan Yes Yes No serum Nondiabetic 100 mg vs. trandolopril creatinine proteinuria 3 mg + losartan 100 mg ESRD The ONTARGET Doubling serum n=25,620 Telmisartan 80 mg or ramipril No No Yes Investigators 17 creatinine 10 mg vs. telmisartan ESRD Death 80 mg + ramipril 10 mg Key: ESRD = end-stage renal disease; UACR = urinary albumin/creatinine ratio. were a consequence of more complete RAAS inhibition or decreased blood pressure. The second study limitation was the dosing used, which may in fact be partially responsible for the observed changes in blood pressure. Therefore, all three of these studies and two other studies 18,19 administered the same doses of ACE-I and ARB as monotherapy and as combination therapy, which might have resulted in more complete inhibition of RAAS with combination therapy than was achieved with either drug administered as monotherapy. This factor is particularly important because some studies have reported that the use of megadoses of monotherapy with ACE-Is or ARBs are associated with positive changes in protein excretion comparable to those reported using combination therapy with an ACE-I plus an ARB. 6-8 Several recent studies have avoided these design limitations. In a study of 45 patients with primary proteinuric nephropathies (>2 g protein/d), Luno et al. 14 described a significant decrease (p=0.023) in protein excretion with combination therapy of lisinopril (up to 20 mg) plus candesartan (up to 16 mg) versus monotherapy with either drug given at up to twice the original dose (lisinopril [up to 40 mg]; candesartan [up to 32 mg]; table 1). This dosing approach is more appropriate than the study design used in the earlier reports because it may provide equivalent RAAS inhibition in all treatment groups ,18,19 The study by Luno et al., 14 though limited in the number of patients enrolled, had merit in that it achieved equivalent blood pressure levels in all three treatment groups. Combination therapy with an ACE-I and an ARB resulted in a greater decrease in proteinuria than did monotherapy. A similar observation was reported by Campbell et al. 15 in a prospective, randomised, crossover study of 24 nondiabetic patients with proteinuria. Similar to the study design used by Luno et al., 14 Campbell et al. 15 administered twice the dose of an ACE-I (benazepril 20 mg) or an ARB (valsartan 160 mg) as monotherapy compared with the doses used for combination therapy (benazepril 10 mg plus valsartan 80 mg). This study design resulted in identical decreases in blood pressure reported as mean arterial pressure: 95 mmhg (benazepril 20 mg), 95 mmhg (valsartan 160 mg), and 94 mmhg 3
4 4 Figure 2 Percentage change from baseline for 24-hour urinary protein excretion rate, mean arterial pressure, and creatinine clearance. p<0.025 with Bonferroni adjustment. Data are mean±sem; n=24. Dosages: valsartan 160 mg; benazepril 20 mg; benazepril + valsartan 10 mg + 80 mg. 15 Reprinted with permission from Campbell R, Sangalli F, Perticucci E et al. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int 2003;63: (benazepril 10 mg plus valsartan 80 mg). Although monotherapy with benazepril or valsartan lowered the albumin/creatinine ratio by 45.9% or 41.5%, respectively, combination therapy lowered the albumin/creatinine ratio by 56.0%, which was statistically greater than was achieved with either monotherapy (figure 2). 15 These blood pressure-lowering independent effects of combination therapy at comparable doses were subsequently reported by others. 20 It must be noted that not all clinical studies uniformly report a positive response from combination treatment with an ACE-I plus an ARB, even when proper dose adjustments have been made. For example, Esnault et al. 21 found no greater decrement in protein excretion in 18 proteinuric patients given ramipril 5 mg plus valsartan 80 mg compared with ramipril 10 mg or valsartan 160 mg. However, this study suggests, as has been previously proposed by others, 22,23 that the concomitant sodium balance may be another important determinant of the response to inhibitors of RAAS. Thus, patients who received ACE-I/ARB combination therapy displayed marked reductions in protein excretion when they were also given the diuretic furosemide. However, in the study by Esnault et al., 21 furosemide was not given to the monotherapy groups and was associated with significant decrements in systolic blood pressure. Most studies of RAAS blockers comparing the antiproteinuric effect of monotherapy with combination therapy lack sufficient power to establish a difference between the regimens. Therefore, a meta-analysis of existing studies was undertaken by Doulton et al. 24 The meta-analysis included analysis of eight independent clinical studies; it found that combination ACE-I/ARB therapy decreased protein excretion by 30% compared with ACE-I monotherapy and by 39% with ARB monotherapy. A more recent and exhaustive meta-analysis compared the antiproteinuric effect in the early phase (1 4 months) and the later phase (5 12 months) of treatment. 10 In the early phase of treatment, 14 studies were analysed to compare the antiproteinuric effects of combination therapy with an ACE-I plus ARB with those of ARB monotherapy. The ratio of means (95% confidence interval [CI]) favoured combination treatment (0.76 [ ]). A similar result was observed in 21 studies when the comparator was ACE-I monotherapy (0.78 [ ]). In the later phase of treatment, a smaller group of studies was available for analysis. Nonetheless, combination therapy was found to be superior to ARB monotherapy in seven studies (0.75 [ ]). In the same studies, the ratio of means was 0.82 ( ) when the comparator was ACE-I monotherapy. Evaluated together, these data suggest that combining an ACE-I and an ARB may provide a superior antiproteinuric effect than monotherapy with either agent. However, the superiority may be limited to conventional doses of ACE-Is and ARBs because higher than conventional doses of these agents also decrease protein excretion. 6-8,25 For example, in one of these studies, Hollenberg et al. 8 found that 320 mg and 640 mg of valsartan provide further antiproteinuric effect when compared to conventional dose of 160 mg. Thus, in the appropriate clinical setting, this approach may yield results that are comparable to combination therapy. No studies have been published comparing the two approaches. The underlying, unifying mechanism for inhibition of the RAAS may be the degree of inhibition of the system and of the generation of Ang II. This is strongly suggested by the observations of a study by Forclaz et al., 26 who investigated the antihypertensive response of monotherapy and combination therapy of two ARBs (losartan and telmisartan) on angiotensin I (Ang I) infusion (figure 3) in normotensive persons. 26 As expected, blockade of Ang II generation was not observed with standard doses of either ARB, but inhibition of blood pressure response to Ang I was seen when the dose of losartan (a short-acting ARB) was increased to 100 mg twice a day or when a standard dose of telmisartan (a long-acting ARB) was combined with the ACE-I. As Linas 27 suggests, these results support the view that the critical determinant of blood pressure response is longer (a full 24 hours) and more complete inhibition of the RAAS rather than physiologic interaction between an ACE-I and an ARB, as supported by the data depicted in figure 3.
5 Figure 3 Summary of blockade of blood pressure (BP) response to exogenous angiotensin I at trough in study groups (n=5 10 according to study protocols). Data are mean±sd; *p<0.01; bid = twice a day; qd = every day. 26 Reprinted with permission from Forclaz A, Maillard M, Nussberger J, Brunner HR, Burnier M. Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor? Hypertension 2003;41:31-6. Renoprotection with combination ACE-I plus ARB therapy All the aforementioned studies used change in protein excretion as a surrogate for renal protection. A more robust end-point of renal protection is the ability of an intervention to alter the time to renal failure in patients with progressive renal disease. No review of this subject would be complete without a brief discussion of the COOPERATE trial, which compared ACE-I/ARB combination therapy with monotherapy and used a combined endpoint of time to doubling serum creatinine or development of end-stage renal disease (table 1). 16 In this study, 263 patients with moderately advanced renal insufficiency (glomerular flow rate, approximately 35 ml/min) were followed up for a median of 2.9 years (range, 3 months 3.3 years). The COOPERATE trial was terminated early because of the beneficial effect observed with combination therapy. Specifically, the hazard ratio of combination therapy compared with losartan monotherapy was 0.40 (95% CI, ; p=0.016); compared with trandolapril monotherapy it was 0.38 (95% CI, ; p=0.018). This effect occurred across the spectrum of baseline protein excretion and was independent of lowered blood pressure because it was similarly decreased in all three treatment groups. However, analysis of the ambulatory blood pressures in this study has raised questions about whether the effect was truly blood pressure independent. 28 Furthermore, serious concerns have been raised about the accuracy of the data and their analysis, 29 that if verified should lead to a negation of the trial. The effects of combination therapy on renal function were markedly different in the ONTARGET trial, whose final results have recently been published. 17 ONTARGET included 25,620 patients 85% with cardiovascular disease, 69% with hypertension, and 38% with diabetes who were randomly assigned to receive ramipril 10 mg, telmisartan 80 mg, or combination therapy. This was not a trial of patients with underlying renal disease because renal function at baseline was normal and only 13% of the patients had microalbuminuria. During the study, mean blood pressure was slightly lower in groups treated with telmisartan (a 0.9/0.6 mmhg greater reduction) and combination therapy (a 2.4/1.4 mmhg greater reduction) than in the group treated with ramipril (table 1). However, these did not result in a significant benefit in terms of the primary composite outcome (death from cardiovascular cause, myocardial infarction, or stroke or hospitalisation for heart failure). At a median follow-up of 56 months, the primary outcome had occurred in 16.5% of the ramipril group and 16.7% of the telmisartan group, indicating that telmisartan was noninferior to, but not superior to, ramipril (relative risk, 1.01; 95% CI, ). Similarly, the primary outcome occurred in 16.3% of the combination therapy group (relative risk vs. ramipril, 0.99; 95% CI, ). 17 Nephropathy was a secondary outcome of ONTARGET and the renal outcomes have been recently published. 30 The primary renal outcome was the composite of dialysis, doubling of serum 5
6 Figure 4 Kaplan-Meier curves for primary renal outcome (dialysis, doubling of serum creatinine, and death). 30 Reprinted with permission from Mann JF, Schmieder RE, McQueen M et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008;372: creatinine and death. While the telmisartan and ramipril arms did not differ from each other, the number of events was increased in the combination HR 1.09 [ ], p=0.037 (figure 4). The secondary outcomes of dialysis and doubling of serum creatinine were also higher in the combination group. It must be pointed out that the great majority of the patients in this trial had normal renal function and were free of proteinuria. In fact, a subgroup analysis suggests that the worse outcome with the combination therapy occurred in patients who were not diabetic, not hypertensive, had neither micro nor macroalbuminuria, and had no over diabetic nephropathy. A study primarily aimed at patients at risk for progressive renal disease is still needed. The VA NEPHRON-D study (NCT ) may eventually provide more definitive data on the effect of the combination of an ACE-I and an ARB on the progression of kidney disease. 31 This Department of Veterans Affairs-sponsored trial, which is open for recruitment, will enrol patients with type 2 diabetes, an estimated glomerular filtration rate (GFR) of 30 to <90 ml/min/1.73 m 2, and albuminuria >300 mg/g creatinine. Patients will receive open-label losartan 100 mg in combination with blinded lisinopril 40 mg or placebo for up to 5 years. The primary study end-point will be a composite of reduction in estimated GFR of >50% in patients with baseline estimated GFR <60 ml/min/1.73 m 2, reduction in estimated GFR of 30 ml/min/1.73 m 2 in patients with baseline estimated GFR? 60 ml/min/1.73 m 2, progression to end-stage renal disease, or death. Emergence of DRIs With the recent development of DRIs, there is now the possibility of inhibiting RAAS at its point of activation (figure 1), 32 while simultaneously abrogating the stimulation of plasma renin activity (PRA) that accompanies the use of ACE-Is and ARBs. This approach appears to be a particularly attractive method for treating hypertension. Additionally, two recent studies have established that a DRI (aliskiren) can be combined with an ACE-I 33 or an ARB. 34 In both studies, the combination of these agents produced a more profound decrement in blood pressure compared with monotherapy. Specifically, the combination of aliskiren 300 mg plus ramipril 10 mg resulted in a greater lowering of mean sitting diastolic blood pressure than did monotherapy with either drug (p=0.004), 33 whereas administration of aliskiren 300 mg with valsartan 320 mg produced significant decrement in all blood pressure parameters versus monotherapy with either drug (p<0.001). 34 Additionally, aliskiren monotherapy reduced PRA by 66% 33 and 73%. 34 In combination with ramipril or valsartan, PRA was reduced by 48% 33 and 44%, 34 respectively (p< for all values).
7 An exploratory study investigated the time course of the antiproteinuric and antihypertensive effects of direct renin inhibition by aliskiren in 15 evaluable patients with type 2 diabetes and microalbuminuria or macroalbuminuria. 35 After a 4-week washout of previous antihypertensive medications, patients received aliskiren 300 mg and furosemide daily for 28 days, followed by a 4-week withdrawal period. After initiation of treatment with aliskiren, there was a progressive reduction from baseline in urinary albumin/creatinine ratio (UACR): 17% after 2 to 4 days of treatment (p=0.04), 31% after 8 to 10 days (p<0.001), and 44% after days (p<0.001). Mean 24-hour systolic blood pressure was significantly lower than baseline after 7, 14, and 28 days of treatment. Mean 24-hour diastolic blood pressure was not significantly different from baseline during the treatment period, but the baseline diastolic blood pressure was low (75 mmhg). Importantly, there was no significant correlation between the relative change from baseline in UACR and in 24-hour blood pressure (r=0.298, p=0.347). In addition, the time course of changes in UACR and 24-hour blood pressure was not concordant. Significant changes in UACR occurred earlier (days 2 4) than changes in 24-hour systolic blood pressure (day 7), and, over the duration of treatment with aliskiren, there was a progressive reduction from baseline in UACR but not blood pressure. Findings of this exploratory study suggest that the antiproteinuric effect of aliskiren is, at least in part, blood pressure independent. The AVOID trial was a randomised, double-blind, placebo-controlled study that enrolled 599 hypertensive patients with type 2 diabetes and nephropathy. 36 After a 12- to 14-week, open-label phase of treatment with losartan 100 mg, patients were randomly assigned to receive aliskiren (increasing from 150 to 300 mg) or placebo. The primary end-point was UACR at 24 weeks. Despite marginal differences in reductions in blood pressure (systolic, 2 mmhg lower [p=0.07], and diastolic, 1 mm Hg lower [p=0.08], in patients who received aliskiren), the aliskiren group had a 20% greater reduction in UACR compared with the losartan plus placebo group (95% CI, 9 30; p<0.001). Whether a comparable antiproteinuric effect could have been obtained by increasing the dose of losartan to 200 mg was not explored. Aliskiren was well tolerated, but there was a higher incidence of hyperkalemia (6.0 meq/l) with aliskiren than with placebo (4.7% vs. 1.7%, respectively; p=0.06). Hyperkalaemia was transient, and none of the aliskiren-treated patients dis con tinued the study drug. This study showed that the addition of aliskiren provided an incremental antiproteinuric effect that appeared to be independent of blood pressure lowering in hyper tensive diabetic patients who had residual proteinuria despite treatment with an ARB. Further studies on the effect of DRIs on the progression of renal disease are eagerly awaited. Conclusion Increasing evidence indicates the inhibition of RAAS may exert a renoprotective effect that is independent of its effect on blood pressure reduction. Many studies that have used an end-point of proteinuria as a surrogate for renal protection have compared the effects of a single blockade of RAAS using an ACE-I or an ARB with a combined blockade using both an ACE-I and an ARB. Although some of these studies had methodological limitations, the results of most individual studies and two meta-analyses suggest that combining an ACE-I and an ARB may provide an antiproteinuric effect superior to that of monotherapy with either type of agent. It remains uncertain whether this effect is limited to conventional doses of ACE-Is or ARBs, or whether it also pertains to doses that exceed those approved for the treatment of hypertension. Available data suggest that the beneficial effect achieved with combination therapy derives from the more prolonged and complete inhibition of RAAS rather than from a physiologic interaction between an ACE-I and an ARB. The renoprotective effects of monotherapy with an ACE-I or an ARB compared with combination therapy have been examined more directly in the COOPERATE and ONTARGET trials. In COOPERATE, combination therapy with trandolapril and losartan slowed the progression of nondiabetic renal disease compared with either agent alone, but the veracity of the data has been questioned. However, a secondary finding of ONTARGET was that combination therapy significantly increased the risk for adverse renal outcomes compared with monotherapy with ramipril. Eventually, more definitive data are expected from the VA NEPHRON-D trial, in which patients with diabetic nephropathy will receive losartan monotherapy or losartan/lisinopril combination therapy. Data from the AVOID trial suggest that the addition of aliskiren to an ARB provides an antiproteinuric effect additional to that of the ARB alone. In AVOID, combination therapy with aliskiren and losartan resulted in a 20% greater decrease in UACR than losartan monotherapy, an effect independent of blood pressure reduction. Given the methodological limitations of existing studies, additional investigation is warranted. These trials should examine the efficacy and safety of 7
8 8 multiple doses of RAAS inhibitors, making it possible to differentiate more clearly between the renoprotective and antihypertensive effects of RAAS blockade, and to use end-points that demonstrate renal protection more robustly than does the surrogate end-point of proteinuria. References 1. Remuzzi G, Benigni A, Remuzzi A. Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest 2006;116: Peterson JC, Adler S, Burkart JM et al. Blood pressure control, proteinuria, and the progression of renal disease: the Modification of Diet in Renal Disease Study. Ann Intern Med 1995;123: De Zeeuw D, Remuzzi G, Parving HH et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int 2004;65: Atkins RC, Briganti EM, Lewis JB et al. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis 2005;45: Lea J, Greene T, Hebert L et al. The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease: results of the African American study of kidney disease and hypertension. Arch Intern Med 2005;165: Laverman GD, Navis G, Henning RH, de Jong PE, De Zeeuw D. Dual renin-angiotensin system blockade at optimal doses for proteinuria. Kidney Int 2002;62: Hou FF, Xie D, Zhang X et al. Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency. J Am Soc Nephrol 2007;18: Hollenberg NK, Parving HH, Viberti G et al. Albuminuria response to very high-dose valsartan in type 2 diabetes mellitus. J Hypertens 2007;25: Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int 2006;70: Kunz R, Friedrich C, Wolbers M, Mann JFE. Metaanalysis: effect of monotherapy and combination therapy with inhibitors of the renin-angiotensin system on proteinuria in renal disease. Ann Intern Med 2008;148: Mogensen CE, Neldam S, Tikkanen I et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000;321: Jacobsen P, Andersen S, Jensen BR, Parving HH. Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy. J Am Soc Nephrol 2003;14: Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving HH. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int 2003;63: Luno J, Barrio V, Goicoechea MA et al. Effects of dual blockade of the renin-angiotensin system in primary proteinuric nephropathies. Kidney Int 2002;62(suppl 82): Campbell R, Sangalli F, Perticucci E et al. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int 2003;63: Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-ii receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003;361: The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358: Segura J, Praga M, Campo C, Rodicio JL, Ruilope LM. Combination is better than monotherapy with ACE inhibitor or angiotensin receptor antagonist at recommended doses. J Renin Angiotensin Syst 2003;4: Rossing K, Jacobsen P, Pietraszek L, Parving HH. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 2003;26: Rutkowski P, Tylicki L, Renke M, Korejwo G, Zdrojewski Z, Rutkowski B. Low-dose dual blockade of the reninangiotensin system in patients with primary glomerulonephritis. Am J Kidney Dis 2004;43: Esnault VLM, Ekhlas A, Delcroix C, Moutel MG, Nguyen JM. Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents. J Am Soc Nephrol 2005;16: Heeg JE, de Jong PE, van der Hem GK, De Zeeuw D. Efficacy and variability of the antiproteinuric effect of ACE inhibition by lisinopril. Kidney Int 1989;36: Buter H, Hemmelder MH, Navis G, de Jong PE, De Zeeuw D. The blunting of the antiproteinuric efficacy of ACE inhibition by high sodium intake can be restored by hydrochlorothiazide. Nephrol Dial Transplant 1998;13: Doulton TWR, He FJ, MacGregor GA. atic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension 2005;45: Schmieder RE, Klingbeil AU, Fleischmann EH, Veelken R, Delles C. Additional antiproteinuric effect of ultrahigh dose candesartan: a double-blind, randomized, prospective study. J Am Soc Nephrol 2005;16: Forclaz A, Maillard M, Nussberger J, Brunner HR, Burnier M. Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor? Hypertension 2003;41: Linas SL. Are two better than one? converting enzyme inhibitors plus angiotensin receptor blockers for reducing blood pressure and proteinuria in kidney disease. Clin J Am Soc Nephrol 2008;3(suppl 1):S Bidani A. Controversy about COOPERATE ABPM trial data. Am J Nephrol 2006;26:629, Kunz R, Wolbers M, Glass T, Mann JF. The COOPERATE trial: a letter of concern. Lancet 2008;371: Mann JF, Schmieder RE, McQueen M et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, doubleblind, controlled trial. Lancet 2008;372: VA NEPHRON-D Study. NCT Accessed April 7, Staessen JA, Li Y, Richart T. Oral renin inhibitors. Lancet 2006;368: Uresin Y, Taylor AA, Kilo C et al. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Syst 2007;8: Oparil S, Yarows SA, Patel S, Fang H, Zhang J, Satlin A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet 2007;370: Persson F, Rossing P, Schjoedt KJ et al. Time course of the antiproteinuric and antihypertensive effects of direct renin inhibition in type 2 diabetes. Kidney Int 2008;73: Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK, for the AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008;358:
The CARI Guidelines Caring for Australasians with Renal Impairment. ACE Inhibitor and Angiotensin II Antagonist Combination Treatment GUIDELINES
ACE Inhibitor and Angiotensin II Antagonist Combination Treatment Date written: September 2004 Final submission: September 2005 Author: Kathy Nicholls GUIDELINES No recommendations possible based on Level
More informationAngiotensin-converting enzyme inhibitors (ACEI) and
Are Two Better Than One? Angiotensin-Converting Enzyme Inhibitors Plus Angiotensin Receptor Blockers for Reducing Blood Pressure and Proteinuria in Kidney Disease Stuart L. Linas Department of Internal
More informationReducing proteinuria
Date written: May 2005 Final submission: October 2005 Author: Adrian Gillin Reducing proteinuria GUIDELINES a. The beneficial effect of treatment regimens that include angiotensinconverting enzyme inhibitors
More informationProteinuria increases the risk for progression of chronic. Review
Review Annals of Internal Medicine Meta-analysis: Effect of Monotherapy and Combination Therapy with Inhibitors of the Renin Angiotensin System on Proteinuria in Renal Disease Regina Kunz, MD, MSc(Epi);
More informationAggressive blood pressure reduction and renin angiotensin system blockade in chronic kidney disease: time for re-evaluation?
http://www.kidney-international.org & 2013 International Society of Nephrology Aggressive blood pressure reduction and renin angiotensin system blockade in chronic kidney disease: time for re-evaluation?
More informationNew Treatment Options for Diabetic Nephropathy patients. Prof. M. Burnier, Service of Nephrology and Hypertension CHUV, Lausanne, Switzerland
New Treatment Options for Diabetic Nephropathy patients Prof. M. Burnier, Service of Nephrology and Hypertension CHUV, Lausanne, Switzerland Diabetes and nephropathy Diabetic nephropathy is the most common
More informationDiuretic uptitration with half dose combined ACEI + ARB better decrease proteinuria than combined ACEI + ARB uptitration
Nephrol Dial Transplant (2010) 25: 22 2224 doi: 10.1093/ndt/gfp776 Advance Access publication 26 January 2010 Diuretic uptitration with half dose combined ACEI + ARB better decrease proteinuria than combined
More informationAnastasia Chrysostomou, Eugenia Pedagogos, Lachlan MacGregor, and Gavin J. Becker
Original Articles Double-Blind, Placebo-Controlled Study on the Effect of the Aldosterone Receptor Antagonist Spironolactone in Patients Who Have Persistent Proteinuria and Are on Long-Term Angiotensin-Converting
More informationScientific conclusions and detailed explanation of the scientific grounds for the differences from the PRAC recommendation
Annex I Scientific conclusions, grounds for variation to the terms of the marketing authorisations and detailed explanation of the scientific grounds for the differences from the PRAC recommendation 1
More informationPrevention And Treatment of Diabetic Nephropathy. MOH Clinical Practice Guidelines 3/2006 Dr Stephen Chew Tec Huan
Prevention And Treatment of Diabetic Nephropathy MOH Clinical Practice Guidelines 3/2006 Dr Stephen Chew Tec Huan Prevention Tight glucose control reduces the development of diabetic nephropathy Progression
More informationNephrology. Safety and Tolerability of High-Dose Angiotensin Receptor Blocker Therapy in Patients with Chronic Kidney Disease: A Pilot Study
American Journal of Nephrology Original Report: Patient-Oriented, Translational Research Am J Nephrol 2004;24:340 345 DOI: 10.1159/000078950 Received: March 8, 2004 Accepted: April 5, 2004 Published online:
More informationEffect of aliskiren on proteinuria in non-diabetic chronic kidney disease: a double-blind, crossover, randomised, controlled trial
Int Urol Nephrol (2012) 44:1763 1770 DOI 10.1007/s11255-011-0110-z NEPHROLOGY ORIGINAL PAPER Effect of aliskiren on proteinuria in non-diabetic chronic kidney disease: a double-blind, crossover, randomised,
More informationKeywords albuminuria, hypertension, nephropathy, proteinuria
Should proteinuria reduction be the criterion for antihypertensive drug selection for patients with kidney disease? Rigas G. Kalaitzidis and George L. Bakris Department of Medicine, Hypertensive Diseases
More informationROLE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN TYPE I DIABETIC NEPHROPATHY DR.NASIM MUSA
ROLE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN TYPE I DIABETIC NEPHROPATHY DR.NASIM MUSA Type I IDDM is characterized by The abrupt onset of symptoms Insulinopenia
More informationTread Carefully Because you Tread on my Nephrons. Prescribing Hints in Renal Disease
Tread Carefully Because you Tread on my Nephrons Prescribing Hints in Renal Disease David WP Lappin,, MB PhD FRCPI Clinical Lecturer in Medicine and Consultant Nephrologist and General Physician, Merlin
More informationProteinuria as a Therapeutic Target in Patients with Chronic Kidney Disease
American Journal of Nephrology In-Depth Topic Review DOI: 10.1159/000101958 Received: March 25, 2007 Accepted: March 26, 2007 Published online: April 23, 2007 Biff F. Palmer Department of Medicine, Division
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. Blood Pressure Control role of specific antihypertensives
Blood Pressure Control role of specific antihypertensives Date written: May 2005 Final submission: October 2005 Author: Adrian Gillian GUIDELINES a. Regimens that include angiotensin-converting enzyme
More informationRenal Protection Staying on Target
Update Staying on Target James Barton, MD, FRCPC As presented at the University of Saskatchewan's Management of Diabetes & Its Complications (May 2004) Gwen s case Gwen, 49, asks you to take on her primary
More informationRANDOMIZED CONTROLLED trials
Combination Therapy With an Angiotensin Receptor Blocker and an ACE Inhibitor in Proteinuric Renal Disease: A Systematic Review of the Efficacy and Safety Data Martin MacKinnon, MD, Sabin Shurraw, MD,
More informationScientific conclusions and detailed explanation of the scientific grounds for the differences from the PRAC recommendation
Annex I Scientific conclusions, grounds for variation to the terms of the marketing authorisations and detailed explanation of the scientific grounds for the differences from the PRAC recommendation 1
More informationANGIOTENSIN II RECEPTOR BLOCKERS: MORE THAN THE ALTERNATIVE PRESENTATION BY: PATRICK HO, USC PHARM D. CANDIDATE OF 2017 MENTOR: DR.
ANGIOTENSIN II RECEPTOR BLOCKERS: MORE THAN THE ALTERNATIVE PRESENTATION BY: PATRICK HO, USC PHARM D. CANDIDATE OF 2017 MENTOR: DR. CRAIG STERN, PHARMD, MBA, RPH, FASCP, FASHP, FICA, FLMI, FAMCP RENIN-ANGIOTENSIN
More informationComparison between the efficacy of double blockade and single blockade of RAAS in diabetic kidney disease
International Journal of Advances in Medicine Gupta A et al. Int J Adv Med. 2018 Aug;5(4):931-935 http://www.ijmedicine.com pissn 2349-3925 eissn 2349-3933 Original Research Article DOI: http://dx.doi.org/10.18203/2349-3933.ijam20183122
More information(renoprotective (end-stage renal disease, ESRD) therapies) (JAMA)
[1], 1., 2. 3. (renoprotective (end-stage renal disease, ESRD) therapies) (JAMA) (multiple risk (renal replacement therapy, RRT) factors intervention treatment MRFIT) [2] ( 1) % (ESRD) ( ) ( 1) 2001 (120
More informationRENAAL, IRMA-2 and IDNT. Three featured trials linking a disease spectrum IDNT RENAAL. Death IRMA 2
Treatment of Diabetic Nephropathy and Proteinuria Background End stage renal disease is a major cause of death and disability among diabetics BP reduction is important to slow the progression of diabetic
More informationConclusion: Dual blockade of the RAAS is safe. and effective in reducing albuminuria in Asian. type 2 diabetic patients with nephropathy.
Original Article Singapore Med J 201 0; 51(2) : 1 51 Dual blockade of the renin-angiotensinaldosterone system is safe and effective in reducing albuminuria in Asian type 2 diabetic patients with nephropathy
More informationChronic Kidney Disease Management for Primary Care Physicians. Dr. Allen Liu Consultant Nephrologist KTPH 21 November 2015
Chronic Kidney Disease Management for Primary Care Physicians Dr. Allen Liu Consultant Nephrologist KTPH 21 November 2015 Singapore Renal Registry 2012 Incidence of Patients on Dialysis by Mode of Dialysis
More informationManagement of Hypertensive Chronic Kidney Disease: Role of Calcium Channel Blockers. Robert D. Toto, MD
R e v i e w P a p e r Management of Hypertensive Chronic Kidney Disease: Role of Calcium Channel Blockers Robert D. Toto, MD Both the prevalence and incidence of end-stage renal disease have been increasing
More informationManagement of Hypertension in Diabetic Nephropathy: How Low Should We Go?
Review Advances in CKD 216 Published online: January 15, 216 Management of Hypertension in Diabetic Nephropathy: How Low Should We Go? Hillel Sternlicht George L. Bakris Department of Medicine, Section
More informationProceedings of the 34th World Small Animal Veterinary Congress WSAVA 2009
www.ivis.org Proceedings of the 34th World Small Animal Veterinary Congress WSAVA 2009 São Paulo, Brazil - 2009 Next WSAVA Congress : Reprinted in IVIS with the permission of the Congress Organizers PROTEINURIA
More informationThe CARI Guidelines Caring for Australians with Renal Impairment. Specific effects of calcium channel blockers in diabetic nephropathy GUIDELINES
Specific effects of calcium channel blockers in diabetic nephropathy Date written: September 2004 Final submission: September 2005 Author: Kathy Nicholls GUIDELINES a. Non-dihydropyridine calcium channel
More information1. Albuminuria an early sign of glomerular damage and renal disease. albuminuria
1. Albuminuria an early sign of glomerular damage and renal disease albuminuria Cardio-renal continuum REGRESS Target organ damage Asymptomatic CKD New risk factors Atherosclerosis Target organ damage
More informationHypertension and diabetic nephropathy
Hypertension and diabetic nephropathy Elisabeth R. Mathiesen Professor, Chief Physician, Dr sci Dep. Of Endocrinology Rigshospitalet, University of Copenhagen Denmark Hypertension Brain Eye Heart Kidney
More informationCommonKnowledge. Pacific University. Holly A. Walkington Pacific University
Pacific University CommonKnowledge School of Physician Assistant Studies Theses, Dissertations and Capstone Projects 8-14-2010 Effects of Dual Blockade of the ReninAngiotensin System Compared to Single
More informationACE Inhibitors and Protection Against Kidney Disease Progression in Patients With Type 2 Diabetes: What s the Evidence?
Reviews ACE Inhibitors and Protection Against Kidney Disease Progression in Patients With Type 2 Diabetes: What s the Evidence? George L. Bakris, MD; 1 and Matthew Weir, MD 2 Although angiotensin-converting
More informationSince 1898, when renin was isolated from
NARRATIVE REVIEW Dual Blockade of the Renin-Angiotensin System for Cardiorenal Protection: An Update Mustafa Arıcı, MD, and Yunus Erdem, MD The renin-angiotensin system (RAS) has an important role in hypertension
More informationCombined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy
The new england journal of medicine original article Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy Linda F. Fried, M.D., M.P.H., Nicholas Emanuele, M.D., Jane H. Zhang, Ph.D.,
More informationAn acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function
original article http://www.kidney-international.org & 2011 International Society of Nephrology see commentary on page 235 An acute fall in estimated glomerular filtration rate during treatment with losartan
More informationBy Prof. Khaled El-Rabat
What is The Optimum? By Prof. Khaled El-Rabat Professor of Cardiology - Benha Faculty of Medicine HT. Introduction Despite major worldwide efforts over recent decades directed at diagnosing and treating
More informationSLOWING PROGRESSION OF KIDNEY DISEASE. Mark Rosenberg MD University of Minnesota
SLOWING PROGRESSION OF KIDNEY DISEASE Mark Rosenberg MD University of Minnesota OUTLINE 1. Epidemiology of progression 2. Therapy to slow progression a. Blood Pressure control b. Renin-angiotensin-aldosterone
More informationHYPERTENSION IN CKD. LEENA ONGAJYOOTH, M.D., Dr.med RENAL UNIT SIRIRAJ HOSPITAL
HYPERTENSION IN CKD LEENA ONGAJYOOTH, M.D., Dr.med RENAL UNIT SIRIRAJ HOSPITAL Stages in Progression of Chronic Kidney Disease and Therapeutic Strategies Complications Normal Increased risk Damage GFR
More informationInterventions to reduce progression of CKD what is the evidence? John Feehally
Interventions to reduce progression of CKD what is the evidence? John Feehally Interventions to reduce progression of CKD what is the evidence? CHALLENGES Understanding what we know. NOT.what we think
More informationALLHAT RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED INTO 4 GROUPS BY BASELINE GLOMERULAR FILTRATION RATE (GFR)
1 RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED INTO 4 GROUPS BY BASELINE GLOMERULAR FILTRATION RATE (GFR) 6 / 5 / 1006-1 2 Introduction Hypertension is the second most common cause of end-stage
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. Antihypertensive therapy in diabetic nephropathy GUIDELINES
Antihypertensive therapy in diabetic nephropathy Date written: September 2004 Final submission: September 2005 Author: Kathy Nicholls GUIDELINES a. Adequate control of blood pressure (BP) slows progression
More informationTherapeutic approaches to slowing the progression of diabetic nephropathy is less best?
www.drugsincontext.com The journal of interventions in clinical practice REVIEW Therapeutic approaches to slowing the progression of diabetic nephropathy is less best? FULL TEXT ARTICLE Eva Vivian, 1 Chelsea
More informationKDIGO Controversies Conference on Management of Patients with Diabetes and Chronic Kidney Disease
KDIGO Controversies Conference on Management of Patients with Diabetes and Chronic Kidney Disease February 5-8, 2015 Vancouver, Canada Kidney Disease: Improving Global Outcomes (KDIGO) is an international
More informationThe Ramipril Efficacy in Nephropathy (REIN) study was
Add-On Angiotensin Receptor Blocker in Patients Who Have Proteinuric Chronic Kidney Diseases and Are Treated with Angiotensin-Converting Enzyme Inhibitors Yoshihiko Kanno,* Tsuneo Takenaka,* Tsukasa Nakamura,
More informationPreventing the cardiovascular complications of hypertension
European Heart Journal Supplements (2004) 6 (Supplement H), H37 H42 Preventing the cardiovascular complications of hypertension Peter Trenkwalder* Department of Internal Medicine, Starnberg Hospital, Ludwig
More informationDiabetes and kidney disease.
Diabetes and kidney disease. What are the implications? Can it be prevented? Nice 18 june 2010 Lars G Weiss. M.D. Ph.D. Department of Neprology Central Hospital Karlstad Sweden Diabetic nephropathy vs
More informationRenin-Angiotensin-Aldosterone System Blockade in Diabetic Nephropathy. Present Evidences
J. Clin. Med. 2015, 4, 1908-1937; doi:10.3390/jcm4111908 Review OPEN ACCESS Journal of Clinical Medicine ISSN 2077-0383 www.mdpi.com/journal/jcm Renin-Angiotensin-Aldosterone System Blockade in Diabetic
More informationRemission and Regression of Diabetic Nephropathy
515 Review Remission and Regression of Diabetic Nephropathy Hirofumi MAKINO, Yoshio NAKAMURA, and Jun WADA Diabetic nephropathy has become the single largest cause of end-stage renal disease (ESRD) worldwide.
More informationEffects of different ACE inhibitor combinations on albuminuria: results of the GUARD study
http://www.kidney-international.org & 28 International Society of Nephrology original article Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study GL Bakris 1, RD
More informationHypertension in Geriatrics. Dr. Allen Liu Consultant Nephrologist 10 September 2016
Hypertension in Geriatrics Dr. Allen Liu Consultant Nephrologist 10 September 2016 Annual mortality (%) Cardiovascular Mortality Rates are Higher among Dialysis Patients 100 10 1 0.1 0.01 0.001 25-34
More informationDiabetes has become the most common
P O S I T I O N S T A T E M E N T Diabetic Nephropathy AMERICAN DIABETES ASSOCIATION Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the U.S. and Europe; this is due
More informationDiabetic Nephropathy. Objectives:
There are, in truth, no specialties in medicine, since to know fully many of the most important diseases a man must be familiar with their manifestations in many organs. William Osler 1894. Objectives:
More informationWhat is the Role of Direct Renin Inhibitors in the Treatment of the Hypertensive Diabetic Patient?
Adv Ther (2011) 28(9):716-727. DOI 10.1007/s12325-011-0049-6 REVIEW What is the Role of Direct Renin Inhibitors in the Treatment of the Hypertensive Diabetic Patient? Alejandro de la Sierra Jorge Salazar
More informationClinical Pearls in Renal Medicine
Clinical Pearls in Renal Medicine Joel A. Gordon MD Professor of Medicine Nephrology Division Staff Physician Kidney Disease and Blood Pressure Clinic Disclosures None of my financial holdings will have
More informationHypertension management and renin-angiotensin-aldosterone system blockade in patients with diabetes, nephropathy and/or chronic kidney disease
Hypertension management and renin-angiotensin-aldosterone system blockade in patients with diabetes, nephropathy and/or chronic kidney disease July 2017 Indranil Dasgupta DM FRCP, Debasish Banerjee MD
More informationFirenze 22 settembre 2007
Istituto di di medicina dello sport di di Firenze AMES Prevenzione cardiovascolare e cambiamenti negli stili di vita Firenze 22 settembre 2007 Orientamenti attuali per un intervento farmacologico e non
More informationAntihypertensive efficacy of olmesartan compared with other antihypertensive drugs
(2002) 16 (Suppl 2), S24 S28 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh compared with other antihypertensive drugs University Clinic Bonn, Department of Internal
More informationLaunch Meeting 3 rd April 2014, Lucas House, Birmingham
Angiotensin Converting Enzyme inhibitor (ACEi) / Angiotensin Receptor Blocker (ARB) To STOP OR Not in Advanced Renal Disease Launch Meeting 3 rd April 2014, Lucas House, Birmingham Prof Sunil Bhandari
More informationHTN: 80 mg once daily 23,f 80 mg once daily 23,f Hypertension 40, 80 mg $82.66 (80 mg once daily) HTN: 8-32 mg daily in one or two divided doses 1
Detail-Document #260301 This Detail-Document accompanies the related article published in PHARMACIST S LETTER / PRESCRIBER S LETTER March 2010 ~ Volume 26 ~ Number 260301 Comparison of Angiotensin Receptor
More informationThe Road to Renin System Optimization: Renin Inhibitor
The Road to Renin System Optimization: Renin Inhibitor A New Perspective on the Renin-Angiotensin System (RAS) Yong-Jin Kim, MD Seoul National University Hospital Human and Economic Costs of Hypertension
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. Protein Restriction to prevent the progression of diabetic nephropathy GUIDELINES
Protein Restriction to prevent the progression of diabetic nephropathy Date written: September 2004 Final submission: September 2005 Author: Kathy Nicholls GUIDELINES a. A small volume of evidence suggests
More informationManagement of New-Onset Proteinuria in the Ambulatory Care Setting. Akinlolu Ojo, MD, PhD, MBA
Management of New-Onset Proteinuria in the Ambulatory Care Setting Akinlolu Ojo, MD, PhD, MBA Urine dipstick results Negative Trace between 15 and 30 mg/dl 1+ between 30 and 100 mg/dl 2+ between 100 and
More informationTELMISARTAN IN IN ISOLATED SYSTOLIC HYPERTENSION
Chapter 3 The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebocontrolled
More informationUniversity of Groningen. Evaluation of renal end points in nephrology trials Weldegiorgis, Misghina Tekeste
University of Groningen Evaluation of renal end points in nephrology trials Weldegiorgis, Misghina Tekeste IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish
More informationRATIONALE. chapter 4 & 2012 KDIGO
http://www.kidney-international.org chapter 4 & 2012 KDIGO Chapter 4: Blood pressure management in CKD ND patients with diabetes mellitus Kidney International Supplements (2012) 2, 363 369; doi:10.1038/kisup.2012.54
More informationDISCLOSURES OUTLINE OUTLINE 9/29/2014 ANTI-HYPERTENSIVE MANAGEMENT OF CHRONIC KIDNEY DISEASE
ANTI-HYPERTENSIVE MANAGEMENT OF CHRONIC KIDNEY DISEASE DISCLOSURES Editor-in-Chief- Nephrology- UpToDate- (Wolters Klewer) Richard J. Glassock, MD, MACP Geffen School of Medicine at UCLA 1 st Annual Internal
More informationDual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence?
Mallat Cardiovascular Diabetology 2013, 12:108 CARDIO VASCULAR DIABETOLOGY REVIEW Open Access Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials
More informationRecent Update in The Management of Hypertension
REVIEW ARTICLE Salim Lim ABSTRACT Hypertension is still the leading cause of death worldwide. Hypertension increases not only the risk for progression of chronic kidney disease (CKD) but also for cardiovascular
More informationSlide notes: References:
1 2 3 Cut-off values for the definition of hypertension are systolic blood pressure (SBP) 135 and/or diastolic blood pressure (DBP) 85 mmhg for home blood pressure monitoring (HBPM) and daytime ambulatory
More informationLong-Term Dual Blockade With Candesartan and Lisinopril in Hypertensive Patients With Diabetes
Clinical Care/Education/Nutrition O R I G I N A L A R T I C L E Long-Term Dual Blockade With Candesartan and Lisinopril in Hypertensive Patients With Diabetes The CALM II study NIELS H. ANDERSEN, MD, PHD
More informationThis clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.
abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the
More informationProf. Armando Torres Nephrology Section Hospital Universitario de Canarias University of La Laguna Tenerife, Canary Islands, Spain.
Does RAS blockade improve outcomes after kidney transplantation? Armando Torres, La Laguna, Spain Chairs: Hans De Fijter, Leiden, The Netherlands Armando Torres, La Laguna, Spain Prof. Armando Torres Nephrology
More informationCLINICIAN INTERVIEW A REVIEW OF THE CURRENT TREATMENT MODALITIES FOR DIABETIC NEPHROPATHY. Interview with Ralph Rabkin, MD
A REVIEW OF THE CURRENT TREATMENT MODALITIES FOR DIABETIC NEPHROPATHY Interview with Ralph Rabkin, MD Dr Rabkin is Professor of Medicine, Emeritus, Active, at Stanford University School of Medicine, Stanford,
More informationheart failure John McMurray University of Glasgow.
A to Z of RAAS blockade in heart failure John McMurray BHF Cardiovascular Research Centre University of Glasgow. RAAS inhibition in CHF ACE inhibition in patients with low LVEF CHF CONSENSUS Enalapril
More informationCARDIO-RENAL SYNDROME
CARDIO-RENAL SYNDROME Luis M Ruilope Athens, October 216 DISCLOSURES: ADVISOR/SPEAKER for Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Esteve, GSK Janssen, Lacer, Medtronic, MSD, Novartis, Pfizer, Relypsa,
More informationHypertension Update 2009
Hypertension Update 2009 New Drugs, New Goals, New Approaches, New Lessons from Clinical Trials Timothy C Fagan, MD, FACP Professor Emeritus University of Arizona New Drugs Direct Renin Inhibitors Endothelin
More informationCardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes
T h e n e w e ngl a nd j o u r na l o f m e dic i n e original article Cardiorenal End Points in a Trial of for Type 2 Diabetes Hans-Henrik Parving, M.D., D.M.Sc., Barry M. Brenner, M.D., Ph.D., John J.V.
More informationDiabetes has become the most common
P O S I T I O N S T A T E M E N T Diabetic Nephropathy AMERICAN DIABETES ASSOCIATION Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the U.S. and Europe; this is due
More informationTreating Hypertension in Individuals with Diabetes
Treating Hypertension in Individuals with Diabetes Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any
More informationThe hypertensive effects of the renin-angiotensin
Comparison of Telmisartan vs. Valsartan in the Treatment of Mild to Moderate Hypertension Using Ambulatory Blood Pressure Monitoring George Bakris, MD A prospective, randomized, open-label, blinded end-point
More informationThe Remission Clinic approach to halt the progression of kidney disease
THOROUGH CRITICAL APPRAISAL JN EPHROL 24( DOI:10.5301/JN.2011.7763 The Remission Clinic approach to halt the progression of kidney disease The Remission Clinic Task Force * 1, 2, Clinical Research Center
More informationegfr > 50 (n = 13,916)
Saxagliptin and Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus and Moderate or Severe Renal Impairment: Observations from the SAVOR-TIMI 53 Trial Supplementary Table 1. Characteristics according
More informationVA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease in Primary Care (2008) PROVIDER REFERENCE CARDS Chronic Kidney Disease
VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease in Primary Care (2008) PROVIDER REFERECE CARDS Chronic Kidney Disease CKD VA/DoD Clinical Practice Guideline for the Management
More informationACEIs / ARBs NDHP dihydropyridine ( DHP ) ACEIs ARBs ACEIs ARBs NDHP. ( GFR ) 60 ml/min/1.73m ( chronic kidney disease, CKD )
005 16 175-180 1 1 ( chronic kidney disease, CKD ) 003 ( end-stage renal disease, ESRD ) Angiotensin-converting enzyme inhibitors ( ) angiotensin receptor blockers ( ) nondihydropyridine ( NDHP ) / NDHP
More informationStages of Chronic Kidney Disease (CKD)
Early Treatment is the Key Stages of Chronic Kidney Disease (CKD) Stage Description GFR (ml/min/1.73 m 2 ) >90 1 Kidney damage with normal or GFR 2 Mild decrease in GFR 60-89 3 Moderate decrease in GFR
More informationDoes renin angiotensin system blockade deserve preferred status over other anti-hypertensive medications for the treatment of people with diabetes?
Editorial Page 1 of 6 Does renin angiotensin system blockade deserve preferred status over other anti-hypertensive medications for the treatment of people with diabetes? Joshua I. Barzilay 1, Paul K. Whelton
More informationClinical Policy: ACEI and ARB Duplicate Therapy Reference Number: CP.PMN.61 Effective Date: Last Review Date: 05.18
Clinical Policy: Reference Number: CP.PMN.61 Effective Date: 08.01.14 Last Review Date: 05.18 Line of Business: Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory
More informationAnalysis of Factors Causing Hyperkalemia
ORIGINAL ARTICLE Analysis of Factors Causing Hyperkalemia Kenmei Takaichi 1, Fumi Takemoto 1, Yoshifumi Ubara 1 and Yasumichi Mori 2 Abstract Objective Patients with impaired renal function or diabetes
More informationDrugs acting on the reninangiotensin-aldosterone
Drugs acting on the reninangiotensin-aldosterone system John McMurray Eugene Braunwald Scholar in Cardiovascular Diseases, Brigham and Women s Hospital, Boston & Visiting Professor, Harvard Medical School
More informationSGLT2 inhibition in diabetes: extending from glycaemic control to renal and cardiovascular protection
SGLT2 inhibition in diabetes: extending from glycaemic control to renal and cardiovascular protection Hiddo Lambers Heerspink Department of Clinical Pharmacy and Pharmacology University Medical Center
More informationOutline. Outline CHRONIC KIDNEY DISEASE UPDATE: WHAT THE GENERALIST NEEDS TO KNOW 7/23/2013. Question 1: Which of these patients has CKD?
CHRONIC KIDNEY DISEASE UPDATE: WHAT THE GENERALIST NEEDS TO KNOW MICHAEL G. SHLIPAK, MD, MPH CHIEF-GENERAL INTERNAL MEDICINE, SAN FRANCISCO VA MEDICAL CENTER PROFESSOR OF MEDICINE, EPIDEMIOLOGY AND BIOSTATISTICS,
More informationSee Important Reminder at the end of this policy for important regulatory and legal information.
Clinical Policy: (Diovan, Diovan HCT, Exforge, Exforge HCT, Teveten) Reference Number: CP.HNMC.16 Effective Date: 11.16.16 Last Review Date: 11.17 Line of Business: Medicaid Medi-Cal Revision Log See Important
More informationThe relation between elevated blood pressure (BP) and
ACE Inhibitors and Appearance of Renal Events in Hypertensive Nephrosclerosis Julián Segura, Carlos Campo, José L. Rodicio, Luis M. Ruilope Abstract Nephrosclerosis constitutes a major cause of end-stage
More informationVariability in drug response: towards more personalized diabetes care Petrykiv, Sergei
University of Groningen Variability in drug response: towards more personalized diabetes care Petrykiv, Sergei IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you
More informationDual Therapy with ACE Inhibitors and Angiotensin II Receptor Blockers in Proteinuric IgA Nephropathy Patients
Brief Communication Dual Therapy with ACE Inhibitors and Angiotensin II Receptor Blockers in Proteinuric IgA Nephropathy Patients Kai-Ming Chow, Cheuk-Chun Szeto, Bonnie Ching-Ha Kwan, Chi-Bon Leung, Kwok-Yi
More informationEffective Health Care Program
Comparative Effectiveness Review Number 37 Effective Health Care Program Chronic Kidney Disease Stages 1 3: Screening, Monitoring, and Treatment Executive Summary Objectives This systematic review evaluates
More informationThe hypertensive kidney and its Management
The hypertensive kidney and its Management Dr H0 Chung Ping Hypertension Management Seminar 20061124 Hypertensive kidney Kidney damage asymptomatic till late stage Viscous cycle to augment renal damage
More information