This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

A 7-Year Follow-up Study

Mordchai Ravid, MD; Ruth Lang, MD; Rita Rachmani, MD; Michael Lishner, MD

Arch Intern Med. 1996;156(3):286-289.

Abstract
Background
Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. Duration of diabetes, blood pressure values, and metabolic status are the major determinants of the course of nephropathy, and microalbuminuria is the hallmark of its onset. Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non—insulin-dependent diabetes mellitus. Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy.

Methods
Double-blinded (first phase) and open (second phase) randomized controlled study of 7 years. Ninety-four normotensive patients with non—insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 µmol/L (1.4 mg/dL) and who had microalbuminuria (30 to 300 mg/24 h) were given enalapril maleate, 10 mg/d, or placebo, for 5 years. For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment.

Results
In the enalapril-treated patients, albuminuria remained stable for 7 years. An increase from (mean±SD) 123±58 to 310± 167 mg/24 h occurred in the untreated group after 5 years, and a further increase to (mean±SD) 393± 223 mg/24 h occurred after 7 years. Reciprocal creatinine was unchanged in treated patients for 7 years; in the untreated patients, the mean decline was 13% at 5 years and 16% at 7 years. Treatment with enalapril resulted in an absolute risk reduction of 42% for nephropathy to develop during 7 years (95% confidence interval, 15% to 69%; P<.001, Student's t test). Glycosylated hemoglobin and body mass index remained unchanged.

Conclusions
Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with non— insulin-dependent diabetes mellitus who have microalbuminuria, and it stabilizes renal function in previously untreated patients with impaired renal function. Discontinuation of treatment results in renewed progression of nephropathy.

Arch Intern Med. 1996;156:286-289)

Author Affiliations
From the Department of Medicine, Sackler Faculty of Medicine, Tel-Aviv (Israel) University.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Current Guidelines for Using Angiotensin-Converting Enzyme Inhibitors and Angiotensin II-Receptor Antagonists in Chronic Kidney Disease: Is the Evidence Base Relevant to Older Adults?
O'Hare et al.
ANN INTERN MED 2009;150:717-724.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2009
American Diabetes Association
Diabetes Care 2009;32:S13-S61.
FULL TEXT  

The role of SGK-1 in angiotensin II-mediated sodium reabsorption in human proximal tubular cells
Stevens et al.
Nephrol Dial Transplant 2008;23:1834-1843.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2008
American Diabetes Association
Diabetes Care 2008;31:S12-S54.
FULL TEXT  

Blockade of the renin-angiotensin system for renal future perspectives protection: from history to future perspective
Burnier
Journal of Renin-Angiotensin-Aldosterone System 2007;8:208-211.
 

Pharmacoeconomic Analysis of Angiotensin-Converting Enzyme Inhibitors in Type 2 Diabetes: A Markov Model
Campbell et al.
The Annals of Pharmacotherapy 2007;41:1101-1110.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2007
American Diabetes Association
Diabetes Care 2007;30:S4-S41.
FULL TEXT  

How Do You Define "Hypertension" in a Patient With Type 1 Diabetes?
Weir
Hypertension 2007;49:13-14.
FULL TEXT  

Efficacy and Safety of Angiotensin II Receptor Blockade in Elderly Patients With Diabetes
Winkelmayer et al.
Diabetes Care 2006;29:2210-2217.
ABSTRACT | FULL TEXT  

Heterogeneous Nuclear Ribonucleoprotein K Modulates Angiotensinogen Gene Expression in Kidney Cells
Wei et al.
J. Biol. Chem. 2006;281:25344-25355.
ABSTRACT | FULL TEXT  

Prevention and Treatment of Diabetic Renal Disease in Type 2 Diabetes: The BENEDICT Study
Remuzzi et al.
J. Am. Soc. Nephrol. 2006;17:S90-S97.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes-2006
American Diabetes Association
Diabetes Care 2006;29:S4-S42.
FULL TEXT  

Review: Dual blockade of the renin angiotensin system in diabetes -- rationale and risks
Kumar and Winocour
British Journal of Diabetes & Vascular Disease 2005;5:266-271.
ABSTRACT  

Cost-Effectiveness of Full Medicare Coverage of Angiotensin-Converting Enzyme Inhibitors for Beneficiaries with Diabetes
Rosen et al.
ANN INTERN MED 2005;143:89-99.
ABSTRACT | FULL TEXT  

Treatment of High-Risk Patients with Diabetes: Motivation and Teaching Intervention: A Randomized, Prospective 8-Year Follow-Up Study
Rachmani et al.
J. Am. Soc. Nephrol. 2005;16:S22-S26.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes
American Diabetes Association
Diabetes Care 2005;28:S4-S36.
FULL TEXT  

Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells
Hsieh et al.
J Endocrinol 2004;183:535-550.
ABSTRACT | FULL TEXT  

Preventing Microalbuminuria in Type 2 Diabetes
Ruggenenti et al.
NEJM 2004;351:1941-1951.
ABSTRACT | FULL TEXT  

Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria
Gaede et al.
Nephrol Dial Transplant 2004;19:2784-2788.
ABSTRACT | FULL TEXT  

The renoprotective effects of structured care in a clinical trial setting in type 2 diabetic patients with nephropathy
Leung et al.
Nephrol Dial Transplant 2004;19:2519-2525.
ABSTRACT | FULL TEXT  

Quality Improvement Initiatives: Issues in moving from diabetes guidelines to policy
Hayward et al.
Diabetes Care 2004;27:B54-B60.
ABSTRACT | FULL TEXT  

Blood Pressure Control and Nephroprotection in Diabetes
Abbott et al.
J Clin Pharmacol 2004;44:431-438.
ABSTRACT | FULL TEXT  

Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study)
Marre et al.
BMJ 2004;328:495.
ABSTRACT | FULL TEXT  

Treatment of the Patient With Diabetes Mellitus and Risk of Nephropathy: What Do We Know, and What Do We Need to Learn?
Hollenberg
Arch Intern Med 2004;164:125-130.
FULL TEXT  

Standards of Medical Care in Diabetes
Diabetes Care 2004;27:s15-35.
FULL TEXT  

High Glucose Stimulates Angiotensinogen Gene Expression and Cell Hypertrophy via Activation of the Hexosamine Biosynthesis Pathway in Rat Kidney Proximal Tubular Cells
Hsieh et al.
Endocrinology 2003;144:4338-4349.
ABSTRACT | FULL TEXT  

The importance of diabetic nephropathy in current nephrological practice
Locatelli et al.
Nephrol Dial Transplant 2003;18:1716-1725.
ABSTRACT | FULL TEXT  

ACE Inhibitors Improve Diabetic Nephropathy Through Suppression of Renal MCP-1
Amann et al.
Diabetes Care 2003;26:2421-2425.
ABSTRACT | FULL TEXT  

Addressing the Burden of Diabetes in the 21st Century: Better Care and Primary Prevention
Engelgau et al.
J. Am. Soc. Nephrol. 2003;14:S88-91.
ABSTRACT | FULL TEXT  

Review: ACE inhibition or angiotensin receptor blockade: which should we use in diabetic patients?
Ruilope et al.
Journal of Renin-Angiotensin-Aldosterone System 2003;4:74-79.
ABSTRACT  

The Case for "Outsourcing" Diabetes Care
Davidson
Diabetes Care 2003;26:1608-1612.
FULL TEXT  

Effect of Low-Dose Perindopril/Indapamide on Albuminuria in Diabetes: Preterax in Albuminuria Regression: PREMIER
Mogensen et al.
Hypertension 2003;41:1063-1071.
ABSTRACT | FULL TEXT  

Treatment of Hypertension in Type 2 Diabetes Mellitus: Blood Pressure Goals, Choice of Agents, and Setting Priorities in Diabetes Care
Vijan and Hayward
ANN INTERN MED 2003;138:593-602.
ABSTRACT | FULL TEXT  

Multifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes
Gaede et al.
NEJM 2003;348:383-393.
ABSTRACT | FULL TEXT  

Standards of Medical Care for Patients With Diabetes Mellitus
Diabetes Care 2003;26:S33-S50.
FULL TEXT  

The DIabetic Retinopathy Candesartan Trials (DIRECT) Programme, rationale and study design
The DIRECT Programme Study Group and Chaturvedi
Journal of Renin-Angiotensin-Aldosterone System 2002;3:255-261.
ABSTRACT  

Renoprotection: A Matter of Blood Pressure Reduction or Agent-Characteristics?
Vogt et al.
J. Am. Soc. Nephrol. 2002;13:S202-207.
ABSTRACT | FULL TEXT  

Review: Calcium channel blockade in combination with angiotensin-converting enzyme inhibition or angiotensin II (AT1-receptor) antagonism in hypertensive diabetics and patients with renal disease and hypertension
Swales and Williams
Journal of Renin-Angiotensin-Aldosterone System 2002;3:79-89.
ABSTRACT  

The Impact of Clinical Trials on the Treatment of Diabetes Mellitus
Nathan
J. Clin. Endocrinol. Metab. 2002;87:1929-1937.
ABSTRACT | FULL TEXT  

Effect of a Chicken-Based Diet on Renal Function and Lipid Profile in Patients With Type 2 Diabetes: A randomized crossover trial
Gross et al.
Diabetes Care 2002;25:645-651.
ABSTRACT | FULL TEXT  

Diabetes in Ontario: Determination of prevalence and incidence using a validated administrative data algorithm
Hux et al.
Diabetes Care 2002;25:512-516.
ABSTRACT | FULL TEXT  

Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease
Garg and Bakris
Vasc Med 2002;7:35-43.
ABSTRACT  

Does Microalbuminuria Predict Diabetic Nephropathy?
Parving et al.
Diabetes Care 2002;25:406-407.
FULL TEXT  

Targeting the renin-angiotensin system in patients with renal disease
Devonald and Karet
JRSM 2002;95:391-397.
FULL TEXT  

Standards of Medical Care for Patients With Diabetes Mellitus
Diabetes Care 2002;25:213-229.
FULL TEXT  

A Practical Approach to Achieving Recommended Blood Pressure Goals in Diabetic Patients
Bakris
Arch Intern Med 2001;161:2661-2667.
ABSTRACT | FULL TEXT  

Renal function and structure in albuminuric type 2 diabetic patients without retinopathy
Christensen et al.
Nephrol Dial Transplant 2001;16:2337-2347.
ABSTRACT | FULL TEXT  

The Diabetes Quality Improvement Project: Moving science into health policy to gain an edge on the diabetes epidemic
Fleming et al.
Diabetes Care 2001;24:1815-1820.
FULL TEXT  

Serum Type IV Collagen in Diabetic Patients at Risk for Nephropathy
Cohen et al.
Diabetes Care 2001;24:1324-1327.
ABSTRACT | FULL TEXT  

Angiotensin-Converting Enzyme Inhibitors and Progression of Nondiabetic Renal Disease: A Meta-Analysis of Patient-Level Data
Jafar et al.
ANN INTERN MED 2001;135:73-87.
ABSTRACT | FULL TEXT  

The Effect of Angiotensin-Converting Enzyme Inhibitors on the Progression of Nondiabetic Renal Disease: A Pooled Analysis of Individual-Patient Data from 11 Randomized, Controlled Trials
Schrier and Estacio
ANN INTERN MED 2001;135:138-139.
FULL TEXT  

Diabetics with Hypertension Not Controlled with ACE Inhibitors: Alternate Therapies
Cleophas et al.
ANGIOLOGY 2001;52:469-475.
ABSTRACT  

Increased Collagen IV Excretion in Diabetes: A marker of compromised filtration function
Cohen et al.
Diabetes Care 2001;24:914-918.
ABSTRACT | FULL TEXT  

Diabetes, Hypertension, and Cardiovascular Disease : An Update
Sowers et al.
Hypertension 2001;37:1053-1059.
ABSTRACT | FULL TEXT  

Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats
Wienen et al.
Journal of Renin-Angiotensin-Aldosterone System 2001;2:31-36.
ABSTRACT  

Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors
Wehbi et al.
Am. J. Physiol. Renal Physiol. 2001;280:F254-F265.
ABSTRACT | FULL TEXT  

High Blood Pressure and Diabetes Mellitus: Are All Antihypertensive Drugs Created Equal?
Grossman et al.
Arch Intern Med 2000;160:2447-2452.
ABSTRACT | FULL TEXT  

Urinary excretion of podocytes in patients with diabetic nephropathy
Nakamura et al.
Nephrol Dial Transplant 2000;15:1379-1383.
ABSTRACT | FULL TEXT  

Effect of a Pharmacist-Managed Diabetes Care Program in a Free Medical Clinic
Davidson et al.
American Journal of Medical Quality 2000;15:137-142.
ABSTRACT  

Effect of Angiotensin II Antagonist Eprosartan on Hyperglycemia-Induced Activation of Intrarenal Renin-Angiotensin System in Healthy Humans
Osei et al.
Hypertension 2000;36:122-126.
ABSTRACT | FULL TEXT  

The Risk of Cardiovascular Disease Mortality Associated With Microalbuminuria and Gross Proteinuria in Persons With Older-Onset Diabetes Mellitus
Valmadrid et al.
Arch Intern Med 2000;160:1093-1100.
ABSTRACT | FULL TEXT  

Direct and indirect randomized trials of screening: the A's and D's of evidence-based clinical practice guidelines
Mahon
CMAJ 2000;162:1002-1004.
FULL TEXT  

1999 Canadian recommendations for the management of hypertension
Feldman et al.
CMAJ 1999;161:S1-17.
ABSTRACT | FULL TEXT  

Insulin Inhibits Angiotensinogen Gene Expression via the Mitogen-Activated Protein Kinase Pathway in Rat Kidney Proximal Tubular Cells
Zhang et al.
Endocrinology 1999;140:5285-5292.
ABSTRACT | FULL TEXT  

The Paradox of the Low-Renin State in Diabetic Nephropathy
PRICE et al.
J. Am. Soc. Nephrol. 1999;10:2382-2391.
ABSTRACT | FULL TEXT  

Angiotensin II Activation of Insulin-Like Growth Factor 1 Receptor Transcription Is Mediated by a Tyrosine Kinase–Dependent Redox-Sensitive Mechanism
Du et al.
Arterioscler. Thromb. Vasc. Bio. 1999;19:2119-2126.
ABSTRACT | FULL TEXT  

Expansion of Cortical Interstitium Is Limited by Converting Enzyme Inhibition in Type 2 Diabetic Patients with Glomerulosclerosis
CORDONNIER et al.
J. Am. Soc. Nephrol. 1999;10:1253-1263.
ABSTRACT | FULL TEXT  

Factors Associated With Implementation of Preventive Care Measures in Patients With Diabetes Mellitus
Streja and Rabkin
Arch Intern Med 1999;159:294-302.
ABSTRACT | FULL TEXT  

Current Strategies for Management of Hypertensive Renal Disease
Moore et al.
Arch Intern Med 1999;159:23-28.
ABSTRACT | FULL TEXT  

Hyperglycemia and Angiotensin-Mediated Control of the Renal Circulation in Healthy Humans
Osei et al.
Hypertension 1999;33:559-564.
ABSTRACT | FULL TEXT  

Chronic Renal Insufficiency: A Diagnostic and Therapeutic Approach
Rahman and Smith
Arch Intern Med 1998;158:1743-1752.
ABSTRACT | FULL TEXT  

Main Risk Factors for Nephropathy in Type 2 Diabetes Mellitus Are Plasma Cholesterol Levels, Mean Blood Pressure, and Hyperglycemia
Ravid et al.
Arch Intern Med 1998;158:998-1004.
ABSTRACT | FULL TEXT  

Angiotensin-Converting Enzyme Inhibitors
Brown and Vaughan
Circulation 1998;97:1411-1420.
ABSTRACT | FULL TEXT  

The Effect of Nisoldipine as Compared with Enalapril on Cardiovascular Outcomes in Patients with Non-Insulin-Dependent Diabetes and Hypertension
Estacio et al.
NEJM 1998;338:645-652.
ABSTRACT | FULL TEXT  

Evolution of the Joint National Committee Reports, 1988-1997: Evolution of the Science of Treating Hypertension
Fagan
Arch Intern Med 1997;157:2401-2402.
ABSTRACT  

The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
Arch Intern Med 1997;157:2413-2446.
ABSTRACT  

Renal Hemodynamic Response to an Angiotensin II Antagonist, Eprosartan, in Healthy Men
Price et al.
Hypertension 1997;30:240-246.
ABSTRACT | FULL TEXT  

ACE Inhibitors as a Shield Against Diabetic Nephropathy
Materson
Arch Intern Med 1996;156:239-240.
ABSTRACT