TI: Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.

AU: Nielsen-FS; Rossing-P; Gall-MA; Skott-P; Smidt-UM; Parving-HH

AD: Steno Diabetes Center, Gentofte, Denmark.

SO: Diabetes. 1994 Sep; 43(9): 1108-13

ISSN: 0012-1797

PY: 1994

LA: ENGLISH

CP: UNITED-STATES

AB: Diabetic nephropathy is characterized by hypertension and a relentless decline in kidney function. Angiotensin-converting enzyme inhibitors have been claimed to preserve kidney function better than an equal blood pressure (BP) reduction with conventional antihypertensive treatment (renoprotection). We compared the effect on kidney function of lisinopril (10-20 mg/day) and atenolol (50-100 mg/day) in hypertensive NIDDM patients (mean age 60 +/- 8 years) with diabetic nephropathy. Forty-three (21 lisinopril and 22 atenolol) patients were enrolled in a 1-year randomized double-blind parallel study. Eight patients dropped out, and the results for the remaining 35 patients (16 lisinopril and 19 atenolol) are presented. Diuretics were required in 10 of 16 lisinopril patients and 12 of 19 atenolol patients. The following variables were measured: 24-hour ambulatory BP (Takeda TM2420), albuminuria (enzyme-linked immunosorbent assay), fractional albumin clearance, and glomerular filtration rate (GFR) ([51Cr]EDTA technique). The average reduction in mean arterial BP during the 12 months was identical in the two groups 12 +/- 2 vs. 11 +/- 1 mmHg in the lisinopril and atenolol group, respectively. Albuminuria was on average reduced 45% in the lisinopril group vs. 12% in the atenolol group (P < 0.01), and fractional albumin clearance was on average reduced 49% in the lisinopril group vs. 1% in the atenolol group (P < 0.05). GFR declined identically in the two groups 11.7 +/- 2.3 vs. 11.6 +/- 2.3 ml.min-1.year-1 in the lisinopril and atenolol groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

MESH: Albuminuria-; Apolipoproteins-analysis; Atenolol-adverse-effects; Blood-Pressure-drug-effects; Circadian-Rhythm; Double-Blind-Method; Follow-Up-Studies; Glomerular-Filtration-Rate-drug-effects; Hypertension-physiopathology; Kidney-drug-effects; Lisinopril-adverse-effects; Middle-Age; Potassium-blood; Renin-blood; Serum-Albumin-metabolism; Sodium-blood; Time-Factors; Triglycerides-blood

MESH: *Atenolol-therapeutic-use; *Diabetes-Mellitus,-Non-Insulin-Dependent-physiopathology; *Diabetic-Nephropathies-physiopathology; *Hypertension-drug-therapy; *Kidney-physiopathology; *Lisinopril-therapeutic-use

TG: Comparative-Study; Female; Human; Male

PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; RANDOMIZED-CONTROLLED-TRIAL

RN: EC 3.4.23.15; 0; 0; 0; 0; 29122-68-7; 7440-09-7; 7440-23-5; 83915-83-7

NM: Renin; apolipoprotein-Lp(a+); Apolipoproteins; Serum-Albumin; Triglycerides; Atenolol; Potassium; Sodium; Lisinopril

AN: 94350150

UD: 9412

SB: AIM

TI: Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group [see comments]

CM: Comment in: ACP J Club 1994 Jul-Aug;121 Suppl 1:11. Comment in: JAMA 1994 Oct 5;272(13):1005

AU: Viberti-G; Mogensen-CE; Groop-LC; Pauls-JF

AD: Unit for Metabolic Medicine, United Medical, School-Guy's Hospital, London, England.

SO: JAMA. 1994 Jan 26; 271(4): 275-9

ISSN: 0098-7484

PY: 1994

LA: ENGLISH

CP: UNITED-STATES

AB: OBJECTIVES--To study the effect of angiotensin converting enzyme inhibition on the rate of progression to clinical proteinuria and the rate of change of albumin excretion rates in patients with insulin-dependent diabetes mellitus and persistent microalbuminuria. DESIGN AND SETTING--Randomized, double-blind, placebo-controlled clinical trial of 2 years' duration at 12 hospital-based diabetes centers. PATIENTS--Ninety-two patients with insulin-dependent diabetes mellitus and persistent microalbuminuria but no hypertension. INTERVENTION--The patients were randomly allocated in blocks of two to receive either captopril, 50 mg, or placebo twice per day. MEASUREMENTS--Albumin excretion rate, blood pressure, glycosylated hemoglobin level, and fructosamine level every 3 months; urinary urea nitrogen excretion every 6 months; and glomerular filtration rate every 12 months. RESULTS--Twelve patients receiving placebo and four receiving captopril progressed to clinical proteinuria, defined as an albumin excretion rate persistently greater than 200 micrograms/min and at least a 30% increase from baseline (P = .05). The probability of progression to clinical proteinuria was significantly reduced by captopril therapy (P = .03 by log-rank test). Albumin excretion rate rose from a geometric mean (95% confidence interval) of 52 (39 to 68) to 76 (47 to 122) micrograms/min in the placebo group but fell from 52 (41 to 65) to 41 (28 to 60) micrograms/min in the captopril group, a significant difference (P < .01). Mean blood pressure was similar at baseline in the two groups and remained unchanged in the placebo group but fell significantly, by 3 to 7 mm Hg, in the captopril group. Glycosylated hemoglobin levels and glomerular filtration rate remained stable in the two groups. CONCLUSIONS--Captopril therapy significantly impeded progression to clinical proteinuria and prevented the increase in albumin excretion rate in nonhypertensive patients with insulin-dependent diabetes mellitus and persistent microalbuminuria.

MESH: Adolescence-; Adult-; Diabetic-Nephropathies-prevention-and-control; Double-Blind-Method; Middle-Age; Proteinuria-etiology; Proteinuria-prevention-and-control

MESH: *Albuminuria-etiology; *Albuminuria-prevention-and-control; *Captopril-therapeutic-use; *Diabetes-Mellitus,-Insulin-Dependent-drug-therapy; *Diabetes-Mellitus,-Insulin-Dependent-physiopathology

TG: Female; Human; Male; Support,-Non-U.S.-Gov't

PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY; RANDOMIZED-CONTROLLED-TRIAL

RN: 62571-86-2

NM: Captopril

AN: 94125500

UD: 9405

SB: AIM

TI: Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group [see comments]

CM: Comment in: BMJ 1998 Sep 12;317(7160):691-2. Comment in: BMJ 1998 Sep 12;317(7160):693-4

SO: BMJ. 1998 Sep 12; 317(7160): 713-20

ISSN: 0959-8138

PY: 1998

LA: ENGLISH

CP: ENGLAND

AB: OBJECTIVE: To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes. DESIGN: Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of <150/<85 mm Hg. SETTING: 20 hospital based clinics in England, Scotland, and Northern Ireland. SUBJECTS: 1148 hypertensive patients with type 2 diabetes (mean age 56 years, mean blood pressure 160/94 mm Hg). Of the 758 patients allocated to tight control of blood pressure, 400 were allocated to captopril and 358 to atenolol. 390 patients were allocated to less tight control of blood pressure. MAIN OUTCOME MEASURES: Predefined clinical end points, fatal and non-fatal, related to diabetes, death related to diabetes, and all cause mortality. Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography. RESULTS: Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively, with a similar proportion of patients (27% and 31%) requiring three or more antihypertensive treatments. More patients in the captopril group than the atenolol group took the allocated treatment: at their last clinic visit, 78% of those allocated captopril and 65% of those allocated atenolol were taking the drug (P<0.0001). Captopril and atenolol were equally effective in reducing the risk of macrovascular end points. Similar proportions of patients in the two groups showed deterioration in retinopathy by two grades after nine years (31% in the captopril group and 37% in the atenolol group) and developed clinical grade albuminuria >=300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg). CONCLUSION: Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.

MESH: Cerebrovascular-Disorders-prevention-and-control; Diabetic-Angiopathies-physiopathology; Diabetic-Retinopathy-prevention-and-control; Follow-Up-Studies; Hemoglobin-A,-Glycosylated-metabolism; Hypoglycemia-chemically-induced; Middle-Age; Myocardial-Infarction-prevention-and-control; Patient-Compliance; Peripheral-Vascular-Diseases-prevention-and-control; Prospective-Studies; Treatment-Outcome; Visual-Acuity; Weight-Gain-drug-effects

MESH: *Adrenergic-beta-Antagonists-therapeutic-use; *Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; *Antihypertensive-Agents-therapeutic-use; *Atenolol-therapeutic-use; *Captopril-therapeutic-use; *Diabetes-Mellitus,-Non-Insulin-Dependent-complications; *Diabetic-Angiopathies-prevention-and-control; *Hypertension-prevention-and-control

TG: Comparative-Study; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.

PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY; RANDOMIZED-CONTROLLED-TRIAL

RN: 0; 0; 0; 0; 29122-68-7; 62571-86-2

NM: Adrenergic-beta-Antagonists; Angiotensin-Converting-Enzyme-Inhibitors; Antihypertensive-Agents; Hemoglobin-A,-Glycosylated; Atenolol; Captopril

AN: 98404065

UD: 9901

SB: AIM

TI: Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus. A randomized, controlled trial.

AU: Ravid-M; Brosh-D; Levi-Z; Bar-Dayan-Y; Ravid-D; Rachmani-R

AD: Tel-Aviv University and Meir Hospital, Kfar-Sava, Israel. mravid@netvision.net.il

SO: Ann-Intern-Med. 1998 Jun 15; 128(12 Pt 1): 982-8

ISSN: 0003-4819

PY: 1998

LA: ENGLISH

CP: UNITED-STATES

AB: BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors attenuate the decline in renal function in diabetic patients with microalbuminuria. However, no data are available on the use of ACE inhibitors to prevent the decrease in renal function in normotensive, normoalbuminuric patients with type 2 diabetes. OBJECTIVE: To evaluate the effect of prolonged ACE inhibition on renal function and albuminuria in patients with type 2 diabetes. DESIGN: Randomized, double-blind, placebo-controlled trial with 6-year follow-up. SETTING: Eight outpatient clinics coordinated by a department of medicine in a university hospital. PATIENTS: 156 patients in whom type 2 diabetes was diagnosed after 40 years of age who had a baseline mean blood pressure less than 107 mm Hg and albuminuria (albumin excretion < or = 30 mg/24 h). INTERVENTION: Enalapril, 10 mg/d, or placebo. MEASUREMENTS: Degree of albuminuria at 24 hours, creatinine clearance, blood pressure, and hemoglobin A1c values. RESULTS: Enalapril therapy decreased albumin excretion from a mean +/- SD of 11.6 +/- 7 mg/24 h to 9.7 +/- 6 mg/24 h at 2 years. This was followed by a gradual increase to 15.8 +/- 8 mg/24 h at 6 years. In the placebo group, albumin excretion increased from 10.8 +/- 8 mg/24 h to 26.5 +/- 10 mg/24 h at 6 years (P = 0.001 for enalapril compared with placebo). Transition to microalbuminuria occurred in 15 of 79 (19%) placebo recipients and 5 of 77 (6.5%) enalapril recipients. Enalapril treatment resulted in an absolute risk reduction of 12.5% (95% CI, 2% to 23%; P = 0.042) for development of microalbuminuria. After 6 years, creatinine clearance decreased from 1.78 +/- 0.13 mL/s to 1.63 +/- 0.12 mL/s (mean decrease, 0.025 mL/s per year) in enalapril recipients and from 1.81 +/- 0.15 mL/s to 1.57 +/- 0.17 mL/s (mean decrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemoglobin A1c values decreased modestly in both groups. Mean blood pressure remained normal (< 107 mm Hg) in all patients. CONCLUSIONS: Enalapril attenuated the decline in renal function and reduced the extent of albuminuria in normotensive, normoalbuminuric patients with type 2 diabetes. Further research is needed to determine whether this treatment forestalls the development of overt nephropathy.

MESH: Adult-; Algorithms-; Blood-Pressure-physiology; Creatinine-urine; Diabetes-Mellitus,-Insulin-Dependent-physiopathology; Double-Blind-Method; Follow-Up-Studies; Hemoglobin-A-metabolism; Middle-Age; Placebos-

MESH: *Albuminuria-prevention-and-control; *Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; *Diabetes-Mellitus,-Insulin-Dependent-complications; *Diabetic-Nephropathies-prevention-and-control; *Enalapril-therapeutic-use

TG: Female; Human; Male; Support,-Non-U.S.-Gov't

PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY; RANDOMIZED-CONTROLLED-TRIAL

RN: 0; 0; 60-27-5; 75847-73-3; 9034-51-9

NM: Angiotensin-Converting-Enzyme-Inhibitors; Placebos; Creatinine; Enalapril; Hemoglobin-A

AN: 98273834

UD: 9808

SB: AIM

TI: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.

AU: Mogensen-CE

SO: N-Engl-J-Med. 1984 Feb 9; 310(6): 356-60

ISSN: 0028-4793

PY: 1984

LA: ENGLISH

CP: UNITED-STATES

AB: We studied whether microalbuminuria (30 to 140 micrograms of albumin per milliliter) would predict the later development of increased proteinuria and early mortality in Type II diabetics. During 1973, morning urine specimens of diabetic clinic patients 50 to 75 years of age whose disease had been diagnosed the age of 45 were examined for albumin level by radioimmunoassay. Seventy-six patients with albumin concentrations of 30 to 140 micrograms per milliliter were identified for long-term follow-up. They were compared with normal controls, diabetic patients with lower albumin concentrations (75 patients with concentrations less than 15 micrograms per milliliter and 53 with concentrations of 16 to 29 micrograms per milliliter), and 28 diabetic patients with higher concentrations (greater than 140). Age, duration of diabetes, treatment method, fasting blood glucose level, blood pressure, height, and weight were determined for the four diabetic groups. After nine years the group with albumin concentrations of 30 to 140 micrograms per milliliter was more likely to have clinically detectable proteinuria (greater than 400 micrograms per milliliter) than were the groups with lower concentrations. Mortality was 148 per cent higher in this group than in normal controls--comparable to the increase (116 per cent) in the group with heavy proteinuria (albumin levels greater than 140 micrograms per milliliter). In addition, mortality was increased 76 per cent in the group with albumin levels of 16 to 29 micrograms per milliliter and 37 per cent in the group with levels below 15. We conclude that microalbuminuria in patients with Type II diabetes is predictive of clinical proteinuria and increased mortality.

MESH: Aged-; Albuminuria-urine; Denmark-; Diabetic-Nephropathies-diagnosis; Follow-Up-Studies; Middle-Age; Mortality-; Prognosis-; Proteinuria-urine; Time-Factors

MESH: *Albuminuria-complications; *Diabetes-Mellitus,-Non-Insulin-Dependent-mortality; *Proteinuria-diagnosis

TG: Comparative-Study; Female; Human; Male; Support,-Non-U.S.-Gov't

PT: JOURNAL-ARTICLE

AN: 84093506

UD: 8404

SB: AIM

TI: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group [see comments] [published erratum appears in N Engl J Med 1993 Jan 13;330(2):152]

CM: Comment in: N Engl J Med 1993 Nov 11;329(20):1496-7. Comment in: N Engl J Med 1994 Mar 31;330(13):937; discussion 938. Comment in: N Engl J Med 1994 Mar 31;330(13):937-8

AU: Lewis-EJ; Hunsicker-LG; Bain-RP; Rohde-RD

AD: Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL.

SO: N-Engl-J-Med. 1993 Nov 11; 329(20): 1456-62

ISSN: 0028-4793

PY: 1993

LA: ENGLISH

CP: UNITED-STATES

AB: BACKGROUND. Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs. The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy. METHODS. We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was < or = 2.5 mg per deciliter (221 mumol per liter). Blood-pressure goals were defined to achieve control during a median follow-up of three years. The primary end point was a doubling of the base-line serum creatinine concentration. RESULTS. Two hundred seven patients received captopril, and 202 placebo. Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P = 0.007). The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole, 76 percent in the subgroup with a baseline serum creatinine concentration of 2.0 mg per deciliter (177 mumol per liter), 55 percent in the subgroup with a concentration of 1.5 mg per deciliter (133 mumol per liter), and 17 percent in the subgroup with a concentration of 1.0 mg per deciliter (88.4 mumol per liter). The mean (+/- SD) rate of decline in creatinine clearance was 11 +/- 21 percent per year in the captopril group and 17 +/- 20 percent per year in the placebo group (P = 0.03). Among the patients whose base-line serum creatinine concentration was > or = 1.5 mg per deciliter, creatinine clearance declined at a rate of 23 +/- 25 percent per year in the captopril group and at a rate of 37 +/- 25 percent per year in the placebo group (P = 0.01). Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation that was independent of the small disparity in blood pressure between the groups. CONCLUSIONS. Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone.

MESH: Adult-; Creatinine-metabolism; Diabetic-Nephropathies-metabolism; Diabetic-Nephropathies-physiopathology; Double-Blind-Method; Follow-Up-Studies; Kidney-drug-effects; Kidney-physiopathology; Middle-Age; Patient-Compliance; Prospective-Studies

MESH: *Captopril-therapeutic-use; *Diabetic-Nephropathies-drug-therapy

TG: Female; Human; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.

PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; MULTICENTER-STUDY; RANDOMIZED-CONTROLLED-TRIAL

CN: 5R01DK39826DKNIDDK; 5R01DK39908DKNIDDK; MO1RR00030RRNCRR

RN: 60-27-5; 62571-86-2

NM: Creatinine; Captopril

AN: 94019617

UD: 9401

SB: AIM