Published online before print July 15, 2002, doi: 10.1161/01.CIR.0000024416.33113.0A
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:672.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Microalbuminuria Reduction With Valsartan in Patients With Type 2 Diabetes Mellitus
A Blood Pressure–Independent Effect
From the Department of Diabetes, Endocrinology, and Internal Medicine, GKT School of Medicine, Guy’s Hospital, King’s College London (G.V.), London, UK, and South Yorkshire Cardiothoracic Centre (N.M.W.), Sheffield, UK.
Correspondence to Professor Giancarlo Viberti, MD, FRCP, Unit for Metabolic Medicine, Division of Medicine, GKT School of Medicine, 5th Floor, Thomas Guy House, KCL Guy’s Hospital, London SE1 9RT, UK. E-mail giancarlo.viberti{at}kcl.ac.uk
 |
Abstract |
|---|
 Top Abstract IntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
Background— Elevated urine albumin excretion (UAER) is a modifiable risk factor for renal and cardiovascular disease in type 2 diabetes. Blockade of the renin-angiotensin system lowers UAER, but whether this effect is independent of blood pressure (BP) reduction remains controversial. The MicroAlbuminuria Reduction With VALsartan (MARVAL) study was designed to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with microalbuminuria.
Methods and Results— Three hundred thirty-two patients with type 2 diabetes and microalbuminuria, with or without hypertension, were randomly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks. A target BP of 135/85 mm Hg was aimed for by dose-doubling followed by addition of bendrofluazide and doxazosin whenever needed. The primary end point was the percent change in UAER from baseline to 24 weeks. The UAER at 24 weeks was 56% (95% CI, 49.6 to 63.0) of baseline with valsartan and 92% (95% CI, 81.7 to 103.7) of baseline with amlodipine, a highly significant between-group effect (P<0.001). Valsartan lowered UAER similarly in both the hypertensive and normotensive subgroups. More patients reversed to normoalbuminuria with valsartan (29.9% versus 14.5%; P=0.001). Over the study period, BP reductions were similar between the two treatments (systolic/diastolic 11.2/6.6 mm Hg for valsartan, 11.6/6.5 mm Hg for amlodipine) and at no time point was there a between-group significant difference in BP values in either the hypertensive or the normotensive subgroup.
Conclusions— For the same level of attained BP and the same degree of BP reduction, valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria, including the subgroup with baseline normotension. This indicates a BP-independent antiproteinuric effect of valsartan.
Key Words: diabetes mellitus • kidney • angiotensin • blood pressure • valsartan
|
Introduction |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
The development of microalbuminuria in type 2 diabetes increases the risk for renal and cardiovascular disease.1–3 The incidence of end-stage renal disease in type 2 diabetes has risen in many regions of the world.4,5 There is growing evidence that reduction and normalization of proteinuria is a key treatment goal for renal protection and possibly cardioprotection.6 Inhibition of the renin-angiotensin system (RAS), either by ACE inhibitors or angiotensin II antagonists (AIIAs), prevents the development or reduces the level of proteinuria in the diabetic animal model, resulting in less renal structural damage.7,8 In type 2 diabetic patients with microalbuminuria, ACE inhibitor treatment lowers albumin excretion rate (UAER) and prevents the progression of renal disease as measured by serum creatinine.9 Selective blockade of the AT1 receptor by AIIAs also lowers microalbuminuria in these patients to the same extent as ACE inhibition.10 Because of the blood pressure (BP)-lowering effect of blockade of the RAS, it has been difficult in all these studies to establish whether the antiproteinuric effect was specific to this type of drug or simply the results of lower BP. A reduction of proteinuria over and above that which is afforded by BP lowering would be important because it may confer added cardiorenal protection.6
See p 643
The purpose of this study, therefore, was to investigate whether the effect of the highly selective AIIA, valsartan, on UAER was independent of its BP-lowering properties. To fully test this hypothesis, microalbuminuric patients with baseline arterial normotension were allowed to enter the study. The third-generation calcium channel blocker (CCB) amlodipine was chosen as a comparator in view of its similar dosing schedule and the expectation that it would confer similar control of BP.11 Moreover, in patients with microalbuminuria, dihydropyridine CCBs appear to affect UAER in a pressure-dependent way.12
|
Participants |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
Patients 35 to 75 years of age with type 2 diabetes mellitus and evidence of persistent microalbuminuria (median UAER of 3 nonconsecutive timed overnight urine collections in the range of 20 to 200 µg/min during a 5-week period before entry) were recruited from 31 centers in the United Kingdom. Other inclusion criteria were normal serum creatinine and BP at baseline <180/105 mm Hg. Exclusion criteria were type 1 diabetes (onset <35 years and requiring insulin within the first year), use of ACE inhibitors, AIIAs, and CCBs in the 5 weeks before random assignment; child-bearing potential for women; heart failure within the preceding 6 months requiring ACE inhibitor therapy; history of myocardial infarction, PTCA or cerebrovascular accident within the preceding 3 months; severe diabetic neuropathy; history of hypertensive or hepatic encephalopathy; and evidence of hepatic disease.
Patients could be withdrawn from the study because of intolerable adverse events (AEs), exclusion criteria, noncompliance, or protocol violations. Patients were not excluded if they failed to reach the target BP.
The study was approved by the South Thames Multicentre Research Ethics Committee and undertaken in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. All patients gave written informed consent.
|
Study Design |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
This was a multicenter, randomized, double-blind, active control, parallel group, 24-week study of 80 mg/d valsartan versus 5 mg/d amlodipine. The study duration was based on the observation that inhibition of the RAS lowers albuminuria with full effect after 24 weeks.9,13
At screening, CCBs (n=27), ACE inhibitors, or AIIAs (n=48) were withdrawn from patients 5 weeks before study entry and replaced with non–potassium-sparing diuretics to maintain BP control. Other antihypertensive drugs were continued during the run-in (n=14). Hypertension was defined as BP 
140/90 mm Hg and/or antihypertensive therapy at baseline. All antihypertensive medications were withdrawn and replaced by study drug, before random assignment by a computer-generated, random allocation, concealed sequence.
The target BP was 135/85 mm Hg, based on evidence at the time of study design that these BP values slow progression of renal disease in type 2 diabetes.14 If adequate BP control was not achieved with study drug by week 4, the valsartan or amlodipine dose was doubled. If necessary, 2.5 mg/d bendrofluazide could be added from week 8 and doxazosin from week 12.
Patients were followed up at weeks 4, 8, 12, 18, and 24. At baseline and follow-ups, urinary albumin concentrations were measured with immunoturbidimetry centrally at Guys Hospital.15 Three consecutive urine collections for albumin concentration were made at baseline and 24 weeks and two collections at the other time points. The median value was used for calculation. At each time point the lowest arterial blood pressure during a 24-hour period (trough BP) was measured (Korotkoff phase I/V) by automatic oscillometry (OMRON 705CP, OMRON Healthcare) in the dominant arm, with the patient in the sitting position after at least 5 minutes of rest. Three measurements were taken 2 minutes apart, and the mean value was used for calculation. Glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography centrally at Pool Laboratories Ltd, UK, at baseline and 12 and 24 weeks. Full blood count, electrolytes, serum creatinine, liver function tests, and cholesterol were measured by routine biochemical methods at the local laboratory.
The primary end point was the percentage change in UAER from baseline to week 24. The secondary end point was the proportion of patients returning to normoalbuminuria status (UAER <20 µg/min as the median of the last visit measurements). At each visit, all new AEs were recorded.
|
Statistical Methodology |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
With 150 patients in each group, the study had 90% power at 5% significance (2-sided) to detect a clinically significant (15%) between-group difference in the primary end point.16 This sample size would also provide
80% power to detect a 15% difference in the primary end point in the hypertensive subgroup, estimated at 70% of study population. Efficacy analyses were carried out on the intention-to-treat population, all randomly assigned patients receiving medication and having at least 1 postdose assessment. For all variables analyzed, the end point measurement was the last post–random assignment measurement carried forward (for the primary efficacy parameter this was required for 14% and 15% in the valsartan and amlodipine groups, respectively). In addition, sensitivity analyses were carried out for the primary and secondary efficacy parameters on completers (all patients completing the study and having both baseline and end of study assessments). An additional sensitivity analysis was carried out for the primary efficacy parameter by using predicted mean imputation performed using an ordinary least squares regression (Solas version 2.0, Statistical Solutions). In all cases, the analyses gave results very similar to the intention-to-treat population and are not shown. Safety analyses were carried out on all randomly assigned patients who received study medication.
Changes from baseline in UAER, BP, HbA1c level, and serum creatinine was assessed with the use of ANOCOVA models (including terms for treatment, center, and treatment by center interactions) to adjust for any baseline differences. Baseline UAER was also included as a covariate for the primary analysis of UAER. Because of its skewed distribution, UAER raw data were log-transformed for calculation and expressed as the ratio from baseline. Summary statistics for UAER are provided as geometric mean with 95% CI. An additional analysis for UAER included baseline hypertensive status in the model. To further investigate whether changes in BP might explain the differences in UAER between treatments, an exploratory general linear model was carried out including center and treatment as factors and change in BP as a covariate. Model assumptions of normality and constant variance were both upheld. Treatment differences in blood pressure at each visit were analyzed by ANOVA, allowing for the effects of center and treatment and are shown for the whole group as well as the hypertensive and normotensive subgroups.
The proportion of patients returning to normoalbuminuria was analyzed with the use of Fisher’s exact test. For safety evaluation and binary efficacy parameters, between-treatment differences (valsartan minus amlodipine) together with exact binomial 95% CI are shown.
All analyses were performed with the use of version 6.12 of the SAS statistical package except for exact binomial confidence intervals, which were calculated with the StatXact statistical package (version 4.0). All hypothesis tests were 2-tailed, with 
=0.05.
|
Results |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
Patients were recruited between March 1998 and December 1999. Of 683 patients screened, a total of 332 were randomly assigned (valsartan 169, amlodipine 163). All randomly assigned patients received study medication: mean daily doses at end of study were 122 mg valsartan and 8 mg amlodipine. A total of 291 patients completed the study (valsartan 146, amlodipine 145). Main reasons for withdrawal were AEs (valsartan 8, amlodipine 7), protocol violations (valsartan 7, amlodipine 5), withdrawn consent (valsartan 4, amlodipine 4), and others (valsartan 4, amlodipine 2).
The demographic and clinical characteristics of the two treatment groups were comparable at baseline (Table 1). The majority of patients were white (88% valsartan and 85% amlodipine) and approximately 10% were Asian. Baseline UAER values were similar in the two groups, as was trough systolic (SBP) and diastolic BP (DBP). Five patients in the valsartan group had baseline UAER below (n=2) or above (n=3) the microalbuminuria range.
|
Efficacy
There was a statistically significant decrease in UAER with valsartan compared with amlodipine (P<0.001; 95% CI for ratio, 0.539, 0.729). Valsartan, in contrast to amlodipine, lowered UAER progressively over time to a nadir at 24 weeks (Table 2 and Figure 1A). The UAER at 24 weeks with valsartan was 56% (95% CI, 49.6 to 63.0) of baseline, equivalent to a 44% reduction. The UAER for amlodipine at week 24 was 92% (95% CI, 81.7 to 103.7) of baseline, a reduction of only 8%. The treatment effect was highly significant (P<0.001; 95% CI for ratio, 0.520, 0.710). When baseline hypertensive status was entered into the model, there was no change to the outcome of the analysis.
|
|
) or amlodipine (
). Error bars indicate 95% CI. Probability values indicate between-group differences in baseline to 24-week change. A, Whole population; B, subset of patients with hypertension at study entry; C, subset of patients with normotension at study entry.Subgroup analyses for patients who were hypertensive or normotensive at entry produced a similar pattern of results for change in UAER (hypertensive subgroup: P<0.001, 95% CI for ratio, 0.482, 0.737; normotensive subgroup: P<0.001, 95% CI for ratio, 0.486, 0.772). The time course of these changes is shown in Figure 1, B and C.
The mean reductions in trough BP from baseline to week 24 were similar in both treatment groups (SBP: valsartan, -11.2 mm Hg; amlodipine, -11.6 mm Hg, between-treatment adjusted mean change: -1.1 mm Hg, 95% CI, -5.1, 3.0, P=0.610; DBP: valsartan, -6.6 mm Hg, amlodipine -6.5 mm Hg, between-treatment adjusted mean change, -1.2 mm Hg, 95% CI, -3.3, 1.0, P=0.296). The time courses of the BP changes were similar in the two treatment groups for all patients as well as the hypertensive and normotensive subgroups (Figure 2, A through C). Table 3 shows the actual systolic and diastolic BP values attained at each time point during the study in the two treatment groups. Data are given for the whole group and the subgroups with baseline arterial hypertension or normotension. At no time point was there a significant difference in either systolic or diastolic BP between the valsartan and the amlodipine group. This was true for both the normotensive as well as the hypertensive subgroup.
|
|
In normotensive patients there were small decreases in BP with both treatments (valsartan: SBP/DBP, -2.8/-2.7 mm Hg; amlodipine, -1.9/-2.1 mm Hg) and no significant between-treatment differences (DBP, P=0.246; SBP, P=0.329). True equivalence of BP reduction was thus obtained between the two antihypertensive regimens, and this applied irrespective of normotensive or hypertensive status. The results of the analysis to assess whether changes in BP might explain the differences in UAER between treatments showed both change in DBP and SBP were statistically significant covariates (P=0.03 and <0.001, respectively). However, the treatment effect remained significant (P<0.001) in both models, indicating that the observed changes in UAER were independent of differences in BP reduction. The proportion of patients achieving target BP was similar in the two groups (valsartan, 53%; amlodipine, 45%) and not significantly different (P=0.196; difference 8.3%; 95% CI, -3.7%, 20.1%). In the valsartan group, 55% received bendrofluazide and 28% doxazosin; the proportions in the amlodipine group were 50% and 29%, respectively.
The secondary end point analysis showed a significantly greater percentage of patients returning to normoalbuminuria status by week 24 with valsartan (29.9%; n=49) than with amlodipine (14.5%; n=23) (between-treatment difference, 15.4%; 95% CI, 5.6, 25.8; P<0.001).
There was no significant difference in mean change in absolute values of HbA1c from baseline to week 24 between valsartan (0.04%) and amlodipine (0.16%) (P=0.427; 95% CI, -0.34, 0.15). HbA1c remained stable and did not differ throughout the study with either treatment (Table 4). Eighty-five percent of patients received oral hypoglycemic agents in both treatment groups. Insulin was used by the remainder.
|
Total cholesterol, serum potassium, and serum creatinine were similar at baseline between the two groups and did not change significantly during follow-up.
Safety
Treatment was well tolerated in both groups, but ankle edema occurred less frequently with valsartan (1.2% versus 7.4%; difference, -6.2%; 95% CI, -12.9%, -0.4%, P=0.006). There were no deaths related to study medication. There were 9 serious AEs with valsartan and 10 with amlodipine, of which 2 were suspected to be study drug-related. Both events resolved within 6 days.
|
Discussion |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
This study demonstrates that UAER was significantly reduced by valsartan in type 2 diabetic patients with microalbuminuria. Amlodipine had no significant effects on UAER over the time period of this trial. Valsartan also induced regression to normoalbuminuria in a significantly greater proportion of patients than amlodipine. Importantly, BP was reduced to a nearly identical extent by both drugs. Specific analysis of the relation between changes in BP and UAER confirmed that the differences in UAER reduction between treatment groups were not related to differences in BP reduction. This conclusion is strengthened further by the observation that in the normotensive subgroup valsartan but not amlodipine significantly lowered UAER despite similar minimal and nonsignificant changes in arterial pressure. We believe the results to be of importance because they suggest that blockade of the AT1 receptor might be used to prevent progression of albuminuria in the absence of arterial hypertension. Even in the subgroup that achieved BP targets, the between-treatment group differences in the reduction of UAER persisted (data not shown). These results strongly support the notion that the albuminuria-lowering effects of valsartan are in addition to and, to a large extent, divorced from its antihypertensive action.
Our data add new information to previous studies suggesting that lowering of BP in diabetic patients by ACE inhibition or AT1 receptor antagonism results in greater reduction of albuminuria than that obtained with other antihypertensive agents.17–19 In virtually all these trials, however, the reduction in BP obtained by ACE inhibitor or AllA was greater than that of the comparator group, and this confounded interpretation. Our findings leave little doubt that AT1 receptor antagonism affects albuminuria also by mechanisms separate from systemic BP changes. These may involve distinct renal effects relating to microcirculation changes, 6,7 glomerular capillary wall permeability properties, and tissue remodeling.8,20,21 Angiotensin II receptor blockade also prevents the loss of nephrin in the glomeruli of the diabetic animal, 22 and recent data suggest that AIIAs may reduce levels of TGF-ß in type 2 diabetic patients with microalbuminuria.23
There are possible alternative interpretations of our results. Amlodipine per se, independent of its BP effect, could promote albuminuria, as suggested for other CCBs.24 If this was the case, one could still argue that because of the properties of the comparator, the effect of valsartan on proteinuria was entirely attributable to BP lowering. This interpretation, however, is unlikely. Several publications suggest that CCBs lower UAER through a systemic BP dependent mechanism,25–27 especially at BP reductions of the magnitude achieved in this study,12 though their effects may be delayed. There is no consistent evidence that dihydropyridine CCBs have an independent proteinuria-enhancing action.28 Thus, our conclusion that the prompt and profound effect of valsartan on UAER was independent of its antihypertensive effect.
Sixty-five percent of the whole group was found to be hypertensive at entry into the study. The observation that valsartan reduced microalbuminuria by >40% both in the hypertensive and particularly the normotensive subgroups is very important. Microalbuminuria in this patient population is an independent risk factor for both renal disease and cardiovascular disease. Our study was short-term and cannot establish whether the correction of microalbuminuria by valsartan will be translated into clinical benefit. Several studies, however, in patients with more advanced proteinuria, with and without diabetes, have shown a clear relation between proteinuria reduction and slowing of renal disease progression.6 Moreover, it is the type 2 diabetic subgroup with microalbuminuria that appears to benefit most from ACE inhibition in terms of cardioprotection.29 A recent trial in type 2 diabetic patients with microalbuminuria, 30 all of whom had hypertension, has shown that 300 mg/d (but not 150 mg/d) irbesartan significantly reduced UAER by 46% and lowered the risk of progression to persistent albuminuria by 70% over a 2-year period, compared with conventional antihypertensive therapy that excluded ACE inhibitors and dihydropyridine CCBs. These results were obtained in the face of similar average reductions in DBP, but mean SBP, throughout the trial, was highly significantly lower by 3 mm Hg in the 300 mg/d irbesartan group compared with placebo. This further underscores the importance of our findings in the normotensive subgroup in which the administration of valsartan was BP neutral but highly effective in lowering UAER.
Two other trials in type 2 diabetic patients with overt nephropathy have also recently shown a renoprotective effect of angiotensin receptor antagonism with losartan31 and irbesartan32 that appears largely though not entirely33 independent of BP reduction, underscoring the therapeutic relevance of other mechanisms of action, of which proteinuria lowering is likely to be an important one, of this class of compounds.
In conclusion, valsartan significantly reduces microalbuminuria in type 2 diabetic patients, an effect that appears to be independent of its BP-lowering action.
|
Acknowledgments |
|---|
This study was supported by a grant from Novartis Pharmaceuticals UK Ltd, Frimley, UK, which did not have access to unblinded information. We thank Dr G. McInnes for constructive suggestions in the design of the study and Tony Mossman from SQN for statistical analysis.
|
Footnotes |
|---|
*A full list of investigators and centers is given in the Appendix.
|
Appendix |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
List of Principle Investigators, Research Nurses, and Centers
Investigators
Dr J.C. Alcolado, East Glamorgan General Hospital; Dr W.J. Andrews and M. Andrews, Whiteabbey Hospital; Dr D.J. Barfordand and D. Mabbett, Northfield Surgery; Dr A.L.T. Blair and M. Gallen, Tyrone County Hospital; Dr A.C. Burden and S. Robertson, Leicester General Hospital; Dr A. Collier and V. McCann, Ayr Hospital; Dr Corrall, Bristol Royal Infirmary; Dr A. Dornhorst and U. Kirwan, Hammersmith Hospital; Dr K. Earle and L. Denver, Whittington Hospital; Dr B.M. Fisher and K. Raeburn, Royal Alexandra Hospital; Dr I. Gallen and C. Carter, Wycombe Hospital; Dr Harvey Rutherford and S. Rutherford, Maelor General Hospital; Dr D. Hepburn and C. Smith, Hull Royal Infirmary; Professor Hillhouse and P. Roper, Coventry and Warwickshire Hospital; Dr T. Jones and K. Birley, Barnsley District General; Dr C.M. Kesson and L. Cumming, Victoria Infirmary; Dr M. MacMahon and C. Ruthvern, Chiltern International Limited; Dr J. McKnight, Western General Hospital; Dr P. McNally and V. Johnston, Leicester Royal Infirmary; Dr K. Moles and R. Henderson, Altnagelvin Area Hospital; Dr R. Page and L. Everitt, City Hospital Nottingham; Dr D.E. Price, Morriston Hospital; Dr T. Purewal and S. Doolan, Royal Liverpool Hospital; Dr S.B.M. Reith and E. Davidson, Stirling Royal Infirmary; Dr P. Rowe, Derriford Hospital; Dr W.P. Stephens and M. Yates, Trafford General Hospital; Dr N. Sturrock, City Hospital Nottingham; Dr H. Tindall and H. Serghides, North Middlesex Hospital; Professor G.C. Viberti, J. Fray, and E. Chaney, Guy’s Hospital; Dr J.U. Weaver and L. Ingoe, Queen Elizabeth Hospital; Dr J. Wilding and L. Maudsley, Walton Hospital and Fazakerrley Hospital, respectively; Dr R.J. Young and L. Floyd, Hope Hospital.
Central Laboratories
GKT School of Medicine, KCL Guys Hospital, London–UMM Collaborative Laboratory, Andrea Collins and GianCarlo Viberti; POOL Laboratories Ltd, Study Manager, Barbara Taylor.
Received April 11, 2002; revision received May 17, 2002; accepted May 17, 2002.
|
References |
|---|
|
TopAbstractIntroductionParticipantsStudy DesignStatistical MethodologyResultsDiscussionAppendixReferences |
|---|
1. Mogensen C. Microalbuminuria predicts clinical proteinuria and early mortality in maturity onset diabetes. N Engl J Med. 1984; 310: 356–360.[Abstract]
2. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med. 1997; 157: 1413–1418.
3. Mattock MB, Barnes DJ, Viberti GC, et al. Microalbuminuria and coronary heart disease in non-insulin-dependent diabetes: an incidence study. Diabetes. 1998; 47: 1786–1792.[Abstract]
4. USRDS Annual Data Report Chapter 2. Incidence and prevalence of ESRD. Am J Kidney Dis. 1999; 34: S40–S50.[Medline] [Order article via Infotrieve]
5. Pugh JA, Medina RA, Cornell JC, et al. NIDDM is the major cause of diabetic end-stage renal disease: more evidence for a tri-ethnic community. Diabetes. 1995; 44: 1375–1380.[Abstract]
6. Ruggenenti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal disease. Lancet. 2001; 357: 1601–1608.[CrossRef][Medline] [Order article via Infotrieve]
7. Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest. 1986; 77: 1993–2000.[Medline] [Order article via Infotrieve]
8. Remuzzi A, Perico N, Amuchastegui CS, et al. Short and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes. J Am Soc Nephrol. 1993; 4: 40–49.[Abstract]
9. Ravid M, Savin H, Jutrin I, et al. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med. 1993; 118: 577–581.
10. Muirhead N, Feagan BF, Mahon J. The effects of valsartan and captopril on reducing microalbuminuria in patients with type 2 diabetes mellitus: a placebo-controlled trial. Curr Therapeutic Res. 2000; 60: 650–660.
11. Corea L, Cardoni O, Fogari R, et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine. Clin Pharmacol Ther. 1996; 60: 341–346.[CrossRef][Medline] [Order article via Infotrieve]
12. Kloke HJ, Branten AJ, Huysmans FT, et al. Antihypertensive treatment of patients with proteinuric renal diseases: risks or benefits of calcium channel blockers? Kidney Int. 1998; 53: 1559–1573.[CrossRef][Medline] [Order article via Infotrieve]
13. Microalbuminuria Study Group. Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria: the Microalbuminuria Captopril Study Group. Diabetologia. 1996; 39: 587–593.[Medline] [Order article via Infotrieve]
14. Weidmann P, Schneider M Bohlen L. Therapeutic efficacy of different antihypertensive drugs in human diabetic nephropathy: an updated meta-analysis. Nephrol Dial Transplant. 1995; 10 (suppl 9): 39–45.
15. Kearney EM, Mant JN, Watts GF, et al. Simple immunoturbidimetric method for determining urinary albumin at low concentrations using Cobas-Bio centrifugal analyser. J Clin Pathol. 1987; 40: 465–468.
16. Dupont WD, Plummer WD Jr. Power and sample size calculations: a review and computer program. Control Clin Trials. 1990; 11: 116–128.[CrossRef][Medline] [Order article via Infotrieve]
17. The ACE Inhibitors in Diabetic Nephropathy Trialist Group. Should all type 1 diabetic patients with microalbuminuria receive ACE inhibitor treatment? A meta regression analysis. Ann Intern Med. 2001; 134: 370–379.
18. Velasco PLP, Martin FJM. Effects of losartan and diltiazem on blood pressure, insulin sensitivity, lipid profile and microalbuminuria in hypertensive type 2 diabetic patients. Clin Drug Invest. 1998; 5: 361–370.
19. Cooper ME. Renal protection and angiotensin converting enzyme inhibition in microalbuminuric type I and II diabetic patients. J Hypertens. 1996; 14: S11–S14.
20. Morelli E, Loon N, Meyer TW, et al. Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopathy. Diabetes. 1990; 39: 76–82.[Abstract]
21. Andersen S, Blouch K, Bialeh J, et al. Glomerular permselectivity in early stages of overt diabetic nephropathy. Kidney Int. 2000; 58: 2129–2137.[CrossRef][Medline] [Order article via Infotrieve]
22. Bonnet F, Cooper ME, Kawaci H, et al. Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension. Diabetologia. 2001; 44: 874–877.[CrossRef][Medline] [Order article via Infotrieve]
23. Esmatjes E, Fiores L, Iñigo P, et al. Effect of losartan on TGF-ß1 and urinary albumin excretion in patients with type 2 diabetes mellitus and microalbuminuria. Nephrol Dial Transplant. 2001; 161 (suppl 1): 90–93.
24. De Marre BK, Bakris GL. Effects of different classes of calcium antagonists on proteinuria in diabetic subjects. Ann Intern Med. 1990; 113: 987–988.
25. Fogari R, Zoppi A, Malamani G D, et al. Effects of amlodipine vs enalapril on microalbuminuria in hypertensive patients with type II diabetes. Clin Drug Invest. 1997; 11: 42–49.
26. Velussi M, Brocco E, Frigato F, et al. Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. Diabetes. 1996; 45: 216–222.[Abstract]
27. Fogari R, Zoppi A, Carradi I, et al. Long-term effects of ramipril and nitrendipine on albuminuria in hypertensive patients with type II diabetes and impaired renal function. J Hum Hypertens. 1999; 13: 47–53.[CrossRef][Medline] [Order article via Infotrieve]
28. Gansevoort RT, Sluiter WJ, Hemmelder MH, et al. Antiproteinuric effect of blood-pressure-lowering agents, meta-analysis of comparative trials. Nephrol Dial Transplant. 1995; 10: 1963–1974.
29. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000; 355: 253–259.[CrossRef][Medline] [Order article via Infotrieve]
30. Parving H-H, Lehnert H, Brochner-Mortensen J, et al, for the irbesartan in patients with type 2 diabetes and microalbuminuria study group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001; 345: 870–878.
31. Brenner BM, Cooper ME, De Zeeuw D, et al, for the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001; 345: 861–869.
32. Lewis EJ, Hunsicker LG, Clarke WR, et al, for the Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001; 345: 851–860.
33. Opie LH. Renoprotection by angiotensin-receptor blockers and ACE inhibitors in hypertension. Lancet. 2001; 358: 1829–1831.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  R. R. Wenzel, T. Littke, S. Kuranoff, C. Jurgens, H. Bruck, E. Ritz, T. Philipp, A. Mitchell, and for the SPP301 (Avosentan) Endothelin Antagonist E Avosentan Reduces Albumin Excretion in Diabetics with Macroalbuminuria J. Am. Soc. Nephrol., March 1, 2009; 20(3): 655 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Karalliedde, A. Smith, L. DeAngelis, V. Mirenda, A. Kandra, J. Botha, P. Ferber, and G. Viberti Valsartan Improves Arterial Stiffness in Type 2 Diabetes Independently of Blood Pressure Lowering Hypertension, June 1, 2008; 51(6): 1617 - 1623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Galle, E. Schwedhelm, S. Pinnetti, R. H. Boger, C. Wanner, and on behalf of the VIVALDI investigators Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy Nephrol. Dial. Transplant., May 1, 2008; (2008) gfn230v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Izuhara, M. Nangaku, S. Takizawa, S. Takahashi, J. Shao, H. Oishi, H. Kobayashi, C. van Ypersele de Strihou, and T. Miyata A novel class of advanced glycation inhibitors ameliorates renal and cardiovascular damage in experimental rat models Nephrol. Dial. Transplant., February 1, 2008; 23(2): 497 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kunz, C. Friedrich, M. Wolbers, and J. F.E. Mann Meta-analysis: Effect of Monotherapy and Combination Therapy with Inhibitors of the Renin-Angiotensin System on Proteinuria in Renal Disease Ann Intern Med, January 1, 2008; 148(1): 30 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]
|
|
|
|
 |
|
 The Shiga Microalbuminuria Reduction Trial (SMART) Reduction of Microalbuminuria in Patients With Type 2 Diabetes: The Shiga Microalbuminuria Reduction Trial (SMART) Diabetes Care, June 1, 2007; 30(6): 1581 - 1583. [Full Text] [PDF]
|
|
|
|
|
|
F. F. Hou, D. Xie, X. Zhang, P. Y. Chen, W. R. Zhang, M. Liang, Z. J. Guo, and J. P. Jiang Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: A Randomized Controlled Study of Benazepril and Losartan in Chronic Renal Insufficiency J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1889 - 1898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Dzau, E. M. Antman, H. R. Black, D. L. Hayes, J. E. Manson, J. Plutzky, J. J. Popma, and W. Stevenson The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part II: Clinical Trial Evidence (Acute Coronary Syndromes Through Renal Disease) and Future Directions Circulation, December 19, 2006; 114(25): 2871 - 2891. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lubrano, F. Soscia, M. Elli, F. Ventriglia, C. Raggi, E. Travasso, S. Scateni, V. Di Maio, P. Versacci, R. Masciangelo, et al. Renal and Cardiovascular Effects of Angiotensin-Converting Enzyme Inhibitor Plus Angiotensin II Receptor Antagonist Therapy in Children With Proteinuria Pediatrics, September 1, 2006; 118(3): e833 - e838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Johnson, E. F. Tierney, K. U. Onyemere, C.-W. Tseng, M. M. Safford, A. J. Karter, A. Ferrara, O. K. Duru, A. F. Brown, K.M. V. Narayan, et al. Who Is Tested for Diabetic Kidney Disease and Who Initiates Treatment?: The Translating Research Into Action for Diabetes (TRIAD) study Diabetes Care, August 1, 2006; 29(8): 1733 - 1738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Miyata and C. van Ypersele de Strihou Renoprotection of angiotensin receptor blockers: beyond blood pressure lowering Nephrol. Dial. Transplant., April 1, 2006; 21(4): 846 - 849. [Full Text] [PDF]
|
|
|
|
|
|
T. Konoshita, S. Wakahara, S. Mizuno, M. Motomura, C. Aoyama, Y. Makino, Y. Kawai, N. Kato, I. Koni, I. Miyamori, et al. Tissue Gene Expression of Renin-Angiotensin System in Human Type 2 Diabetic Nephropathy Diabetes Care, April 1, 2006; 29(4): 848 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sugaru, T. Nakagawa, M. Ono-Kishino, J. Nagamine, T. Tokunaga, M. Kitoh, W. E. Hume, R. Nagata, and M. Taiji SMP-534 ameliorates progression of glomerular fibrosis and urinary albumin in diabetic db/db mice Am J Physiol Renal Physiol, April 1, 2006; 290(4): F813 - F820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Volpe, G. Tocci, and E. Pagannone Fewer Mega-Trials and More Clinically Oriented Studies in Hypertension Research? The Case of Blocking the Renin-Angiotensin-Aldosterone System. J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S36 - S43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Remuzzi, M. Macia, and P. Ruggenenti Prevention and Treatment of Diabetic Renal Disease in Type 2 Diabetes: The BENEDICT Study J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S90 - S97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Barnett Preventing Renal Complications in Type 2 Diabetes: Results of the Diabetics Exposed to Telmisartan and Enalapril Trial J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S132 - S135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogawa, T. Mori, K. Nako, T. Kato, K. Takeuchi, and S. Ito Angiotensin II Type 1 Receptor Blockers Reduce Urinary Oxidative Stress Markers in Hypertensive Diabetic Nephropathy Hypertension, April 1, 2006; 47(4): 699 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Kopyt Chronic Kidney Disease: The New Silent Killer J Am Osteopath Assoc, March 1, 2006; 106(3): 133 - 136. [Full Text] [PDF]
|
|
|
|
|
|
H. Ibsen, M. H. Olsen, K. Wachtell, K. Borch-Johnsen, L. H. Lindholm, C. E. Mogensen, B. Dahlof, S. M. Snapinn, Y. Wan, and P. A. Lyle Does Albuminuria Predict Cardiovascular Outcomes on Treatment With Losartan Versus Atenolol in Patients With Diabetes, Hypertension, and Left Ventricular Hypertrophy?: The LIFE study. Diabetes Care, March 1, 2006; 29(3): 595 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Hall Prevention of Progression in Diabetic Nephropathy Diabetes Spectr, January 1, 2006; 19(1): 18 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Montalescot and J.-P. Collet Preserving cardiac function in the hypertensive patient: why renal parameters hold the key Eur. Heart J., December 2, 2005; 26(24): 2616 - 2622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Izuhara, M. Nangaku, R. Inagi, N. Tominaga, T. Aizawa, K. Kurokawa, C. van Ypersele de Strihou, and T. Miyata Renoprotective Properties of Angiotensin Receptor Blockers beyond Blood Pressure Lowering J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3631 - 3641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Bakris, V. Fonseca, R. E. Katholi, J. B. McGill, F. Messerli, R. A. Phillips, P. Raskin, J. T. Wright Jr, B. Waterhouse, M. A. Lukas, et al. Differential Effects of {beta}-Blockers on Albuminuria in Patients With Type 2 Diabetes Hypertension, December 1, 2005; 46(6): 1309 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamada, M. Komatsu, I. Komiya, Y. Miyahara, Y. Shima, M. Matsuzaki, Y. Ishikawa, R. Mita, M. Fujiwara, N. Furusato, et al. Development, Progression, and Regression of Microalbuminuria in Japanese Patients With Type 2 Diabetes Under Tight Glycemic and Blood Pressure Control: The Kashiwa Study Diabetes Care, November 1, 2005; 28(11): 2733 - 2738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Araki, M. Haneda, T. Sugimoto, M. Isono, K. Isshiki, A. Kashiwagi, and D. Koya Factors Associated With Frequent Remission of Microalbuminuria in Patients With Type 2 Diabetes Diabetes, October 1, 2005; 54(10): 2983 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Schmieder, A. U. Klingbeil, E. H. Fleischmann, R. Veelken, and C. Delles Additional Antiproteinuric Effect of Ultrahigh Dose Candesartan: A Double-Blind, Randomized, Prospective Study J. Am. Soc. Nephrol., October 1, 2005; 16(10): 3038 - 3045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Hermida, C. Calvo, D. E. Ayala, and J. E. Lopez Decrease in Urinary Albumin Excretion Associated With the Normalization of Nocturnal Blood Pressure in Hypertensive Subjects Hypertension, October 1, 2005; 46(4): 960 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Hypertension in type 2 diabetes - targeting angiotensin DTB, June 1, 2005; 43(6): 41 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H Boger, E. Schwedhelm, R. Maas, S. Quispe-Bravo, and C. Skamira ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study Vascular Medicine, May 1, 2005; 10(2_suppl): S97 - S102. [Abstract] [PDF]
|
|
|
|
|
|
N. P. Kopyt Slowing Progression Along the Renal Disease Continuum J Am Osteopath Assoc, April 1, 2005; 105(4): 207 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nagai, L. Yao, H. Kobori, K. Miyata, Y. Ozawa, A. Miyatake, T. Yukimura, T. Shokoji, S. Kimura, H. Kiyomoto, et al. Temporary Angiotensin II Blockade at the Prediabetic Stage Attenuates the Development of Renal Injury in Type 2 Diabetic Rats J. Am. Soc. Nephrol., March 1, 2005; 16(3): 703 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Fioretto and A. Solini Antihypertensive Treatment and Multifactorial Approach for Renal Protection in Diabetes J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S18 - S21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Krimholtz, J. Karalliedde, S. Thomas, R. Bilous, and G. Viberti Targeting Albumin Excretion Rate in the Treatment of the Hypertensive Diabetic Patient with Renal Disease J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S42 - S47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Gradman, R. E. Schmieder, R. L. Lins, J. Nussberger, Y. Chiang, and M. P. Bedigian Aliskiren, a Novel Orally Effective Renin Inhibitor, Provides Dose-Dependent Antihypertensive Efficacy and Placebo-Like Tolerability in Hypertensive Patients Circulation, March 1, 2005; 111(8): 1012 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Gross, M. J. de Azevedo, S. P. Silveiro, L. H. Canani, M. L. Caramori, and T. Zelmanovitz Diabetic Nephropathy: Diagnosis, Prevention, and Treatment Diabetes Care, January 1, 2005; 28(1): 164 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sironi, P. Gelosa, U. Guerrini, C. Banfi, V. Crippa, M. Brioschi, E. Gianazza, E. Nobili, A. Gianella, M. de Gasparo, et al. Anti-Inflammatory Effects of AT1 Receptor Blockade Provide End-Organ Protection in Stroke-Prone Rats Independently from Blood Pressure Fall J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 989 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Lim, A. D. Blann, A. Y. Chong, B. Freestone, and G. Y.H. Lip Plasma Vascular Endothelial Growth Factor, Angiopoietin-1, and Angiopoietin-2 in Diabetes: Implications for cardiovascular risk and effects of multifactorial intervention Diabetes Care, December 1, 2004; 27(12): 2918 - 2924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gaede, L. Tarnow, P. Vedel, H.-H. Parving, and O. Pedersen Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria Nephrol. Dial. Transplant., November 1, 2004; 19(11): 2784 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D Coyle, S. F Gardner, and C M. White The Renal Protective Effects of Angiotensin II Receptor Blockers in Type 2 Diabetes Mellitus Ann. Pharmacother., October 1, 2004; 38(10): 1731 - 1738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Sowers Treatment of Hypertension in Patients With Diabetes Arch Intern Med, September 27, 2004; 164(17): 1850 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Lim, R. J. MacFadyen, and G. Y. H. Lip Diabetes Mellitus, the Renin-Angiotensin-Aldosterone System, and the Heart Arch Intern Med, September 13, 2004; 164(16): 1737 - 1748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Nickenig Should Angiotensin II Receptor Blockers and Statins Be Combined? Circulation, August 24, 2004; 110(8): 1013 - 1020. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Sharma Is There a Rationale for Angiotensin Blockade in the Management of Obesity Hypertension? Hypertension, July 1, 2004; 44(1): 12 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Cohn, A. A. Quyyumi, N. K. Hollenberg, and K. A. Jamerson Surrogate Markers for Cardiovascular Disease: Functional Markers Circulation, June 29, 2004; 109(25_suppl_1): IV-31 - IV-46. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yasunari, K. Maeda, T. Watanabe, M. Nakamura, J. Yoshikawa, and A. Asada Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular hypertrophy J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2116 - 2123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Delles, A. U. Klingbeil, M. P. Schneider, R. Handrock, T. Schaufele, and R. E. Schmieder The role of nitric oxide in the regulation of glomerular haemodynamics in humans Nephrol. Dial. Transplant., June 1, 2004; 19(6): 1392 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Hollenberg Treatment of the Patient With Diabetes Mellitus and Risk of Nephropathy: What Do We Know, and What Do We Need to Learn? Arch Intern Med, January 26, 2004; 164(2): 125 - 130. [Full Text] [PDF]
|
|
|
|
|
|
G. D. Laverman, G. Remuzzi, and P. Ruggenenti ACE Inhibition versus Angiotensin Receptor Blockade: Which Is Better for Renal and Cardiovascular Protection? J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S64 - 70. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Schafer, W. Linz, A. Bube, M. Gerl, J. Huber, G. U. Kurzel, M. Bleich, H.-L. Schmidts, A. E Busch, and H. Rutten Vasopeptidase inhibition prevents nephropathy in Zucker diabetic fatty rats Cardiovasc Res, November 1, 2003; 60(2): 447 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden The Endocrine Society Meeting: Topics in Insulin Sensitivity and Hypertension Diabetes Care, September 1, 2003; 26(9): 2679 - 2688. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Torp-Pedersen, C. Rask-Madsen, I. Gustafsson, F. Gustafsson, and L. Kober Diabetes mellitus and cardiovascular risk: just another risk factor? Eur. Heart J. Suppl., August 1, 2003; 5(suppl_F): F26 - F32. [Abstract] [PDF]
|
|
|
|
|
|
G. Wolf and E. Ritz Diabetic Nephropathy in Type 2 Diabetes Prevention and Patient Management J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1396 - 1405. [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden American Association of Clinical Endocrinologists (AACE) Consensus Conference on the Insulin Resistance Syndrome: 25-26 August 2002, Washington, DC Diabetes Care, April 1, 2003; 26(4): 1297 - 1303. [Full Text] [PDF]
|
|
|
|
|
|
M.A. Weber Angiotensin receptor blockers and the cardiovascular continuum: what future is indicated by recent successes? Eur. Heart J. Suppl., April 1, 2003; 5(suppl_C): C1 - C4. [Abstract] [PDF]
|
|
|
|
|
|
L. Ruilope Proven benefits of angiotensin receptor blockers in the progression of renal disease Eur. Heart J. Suppl., April 1, 2003; 5(suppl_C): C9 - C12. [Abstract] [PDF]
|
|
|
|
|
|
R.M. Califf Insulin resistance: a global epidemic in need of effective therapies Eur. Heart J. Suppl., April 1, 2003; 5(suppl_C): C13 - C18. [Abstract] [PDF]
|
|
|
|
|
|
E. M Vivian Slowing the progression of renal disease in patients with diabetes mellitus Ann. Pharmacother., February 1, 2003; 37(2): 303 - 303. [Full Text] [PDF]
|
|
|
|
|
|
L. H. Opie and H.-H. Parving Diabetic Nephropathy: Can Renoprotection Be Extrapolated to Cardiovascular Protection? Circulation, August 6, 2002; 106(6): 643 - 645. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||