Biomedical subjects

U M Smidt

Publications and source records attributed to U M Smidt.

12 recordsLinked to original sources

PubMed1995

Angiotensin-converting enzyme inhibition in diabetic nephropathy: ten years' experience.

The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive hypertensive insulin-dependent diabetes patients with nephropathy (mean age, 33 years) who had not been treated previously were all treated with captopril in combination with frusemide or bendrofluazide. The four patients who were refractory to this regimen also received nifedipine. Treatment was continued for a median of 8.9 years (range, 6.3 to 9.8, years). Renal function was assessed every 6 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and albuminuria by radioimmunoassay. Baseline values (+/- SE) were mean arterial blood pressure 146/93 +/- 3/1 mm Hg, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P < 0.01) and albuminuria (392 +/- 1.4 microns/min; P < 0.01), and the rate of decline in GFR was 4.4 +/- 0.7 mL/min/yr, in contrast to previous reports of 10 to 14 mL/min/yr (natural history). Univariate analysis revealed a significant correlation between the rate of decline in GFR and mean arterial blood pressure (r = 0.58, P = 0.01), albuminuria (r = 0.67, P < 0.01), hemoglobin A1c (r = 0.69, P < 0.01), and serum total cholesterol concentration (r = 0.51, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1988

Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy.

STUDY OBJECTIVE: To assess whether long term inhibition of angiotensin converting enzyme with captopril and frusemide or bendrofluazide protects kidney function in diabetic nephropathy. DESIGN: Non-randomised controlled before-after trial of matched hypertensive insulin dependent diabetics with nephropathy treated with captopril and frusemide or bendrofluazide. SETTING: Outpatient diabetic clinic in tertiary referral centre. PATIENTS: Treatment group of 18 hypertensive insulin dependent diabetics with nephropathy (mean age 33), who had not been treated previously. Control group of 13 patients (mean age 32) fulfilling the same entry criteria from a prospective study. INTERVENTIONS: Treatment group was given daily captopril 37.5-100.0 mg and frusemide (mean) 98 mg (10 patients) or bendrofluazide (mean) 4 mg (seven). Treatment was continued for about two and a half years. Controls were not treated. END POINT: Measurement of arterial blood pressure, albuminuria, and glomerular filtration. MEASUREMENTS AND MAIN RESULTS: Baseline values were identical in treated and untreated groups respectively: mean blood pressure 146/93 (SE 3/1) mm Hg v 137/95 (2/1) mm Hg; geometric mean albuminuria 982 (antilog SE 1.2) micrograms/min v 936 (1.2) micrograms/min; and mean glomerular filtration rate 98 (SE 5) ml/min/1.73 m2 v 96 (6) ml/min/1.73 m2. Mean arterial blood pressure fell by 8.7 (1.3) mm Hg with captopril and rose by 6.6 (1.5) mm Hg in controls, (p less than 0.001); Albumin excretion decreased to 390 (1.1) micrograms/min with captopril and rose to 1367 (1.3) micrograms/min in controls (p less than 0.001). The rate of decrease in glomerular filtration rate was lower with captopril (5.8 (0.7) ml/year v 10.0 (1.3) ml/year) (p less than 0.01). Rate of fall in glomerular filtration rate and mean arterial blood pressure were significantly correlated (n = 31, r = 0.37, p less than 0.05). CONCLUSIONS: Captopril is a valuable new drug for treating hypertension in insulin dependent diabetics with nephropathy.

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PubMed1987

Effect of antihypertensive treatment on kidney function in diabetic nephropathy.

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

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PubMed1985

Reduced transcapillary escape of albumin during acute blood pressure-lowering in type 1 (insulin-dependent) diabetic patients with nephropathy.

The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), and urinary albumin excretion rate (radial immunodiffusion). The study was performed twice within 2 weeks, with the patients receiving an intravenous injection of either clonidine (225 micrograms) or saline (0.154 mmol/l). The clonidine injection induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p less than 0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p less than 0.01), albuminuria diminished from 1434 to 815 micrograms/min (p less than 0.01), and plasma volume raised slightly from 2916 to 2995 ml (p less than 0.05). Our findings demonstrate that the enhanced albumin passage through the wall of the microvasculature characteristically found in long-term Type 1 diabetic patients with clinical microangiopathy is pressure-dependent to a large extent. This may be due to elevated hydrostatic pressure in the microcirculation.

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PubMed1985

Monitoring progression of diabetic nephropathy.

Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine and serum beta 2-microglobulin concentrations were measured simultaneously in 49 insulin-dependent diabetics with diabetic nephropathy. GFR ranged from 148 to 23 ml/min/1.73 m2. Inverse serum concentrations of creatinine and beta 2-microglobulin showed a significant correlation with GFR over the whole range of values, r = 0.87 and r = 0.90, respectively (p less than 0.001). In the 31 patients with a GFR less than 80 ml/min/1.73 m2, serum concentration of creatinine and beta 2-microglobulin were within the normal range in 12 and 9 patients, respectively. With GFR below 60 ml/min/1.73 m2, all patients had elevated serum beta 2-microglobulin concentrations, while 24% of the patients still had normal creatinine concentration. Linear regression analysis between log GFR and log serum beta 2-microglobulin showed a better relationship than between log GFR and log serum creatinine, slope -0.90 and -0.57, respectively, p less than 0.01. A prospective study for up to 70 months was performed in 18 of the patients. The study showed a closer relationship between the individual rate of decline in log GFR and log serum beta 2-microglobulin compared to log GFR versus log serum creatinine, p less than 0.01. Neither serum creatinine nor serum beta 2-microglobulin can be used as methods for screening of early impairment of renal function (GFR less than 80 ml/min/1.73 m2 in diabetic nephropathy. Our study suggests that serum beta 2-microglobulin is more ideal endogenous marker for GFR estimation than serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1984

Impaired autoregulation of glomerular filtration rate in type 1 (insulin-dependent) diabetic patients with nephropathy.

The effect of acute lowering of arterial blood pressure upon kidney function in nephropathy was studied in 13 patients with long-term Type 1 (insulin-dependent) diabetes. Ten normal subjects (six normotensive and four hypertensive) and five short-term Type 1 diabetic patients without nephropathy served as controls. Renal function was assessed by glomerular filtration rate (single bolus 51Cr-EDTA technique) and urinary albumin excretion rate (radial immunodiffusion). The study was performed twice within 2 weeks, with the subjects receiving an intravenous injection of either clonidine (225 micrograms) or saline (0.154 mmol/l). The arterial blood pressure was similar in the diabetic patients with nephropathy (mean 136 +/- 11 divided by 88 +/- mmHg) and in the non-diabetic control subjects (mean 140 +/- 25 divided by 92 +/- 15 mmHg). The clonidine injection induced similar reductions in mean arterial blood pressure in all three groups (16-18 mmHg). While glomerular filtration rate and urinary albumin excretion rate remained unchanged in both control groups after clonidine injection, glomerular filtration rate diminished from 78 to 71 ml/min per 1.73 m2 (p les than 0.01), and urinary albumin excretion declined from 1707 to 938 micrograms/min (p less than 0.01) in the patients with diabetic nephropathy. Our results suggest that an intrinsic vascular (arteriolar) mechanism underlying the normal autoregulation of glomerular filtration rate, i.e. the relative constancy of glomerular filtration rate that occurs in response to rather wide variations in perfusion pressure, is defective in diabetic nephropathy.

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PubMed1983

Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy.

The effect of early aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in ten insulin-dependent diabetics (mean age 29 years). During the mean pretreatment period of 29 (range 23-38) months the glomerular filtration rate (GFR) decreased significantly and the urinary albumin excretion rate and arterial blood pressure rose significantly. During the 39 month (range 28-48) period of antihypertensive treatment with metoprolol, hydralazine, and frusemide (furosemide) or thiazide, arterial blood pressure fell from 144/97 mm Hg (mean of all pretreatment values) to 128/84 mm Hg (mean of all post-treatment values), urinary albumin excretion from 977 micrograms/min to 433 micrograms/min, and GFR from 80 to 62 ml/min/1 . 73 m2. The rate of decline in GFR decreased from 0.91 ml/min/month before treatment to 0.39 ml/min/month (range 0.08 to 0.68 ml/min/month) during treatment.

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PubMed1983

Diabetic nephropathy and arterial hypertension.

The relationship between arterial blood pressure and diabetic nephropathy was examined in 61 Type 1 (insulin-dependent) diabetic patients (22 females and 39 males). All patients fulfilled the following criteria: persistent proteinuria (greater than 0.5 g/day), onset of diabetes before 31 years of age, age less than 42 years, serum creatinine less than 130 mumol/l, and no antihypertensive treatment. Thirty Type 1 diabetic patients without persistent proteinuria but matched for sex, age, ideal body weight and duration of diabetes, and 30 healthy subjects matched for sex, age and ideal body weight were also studied as controls. The diabetic patients with persistent proteinuria had elevated blood pressures (146/96 +/- 17/10 mmHg, mean +/- SD) compared with 123/75 +/- 11/8 mmHg in diabetic patients without persistent proteinuria, and normal subjects (120/77 +/- 6/6 mmHg; p less than 0.001 for each). Diastolic blood pressure greater than or equal to 95 mmHg was found in 51% of the group with persistent proteinuria. Elevated arterial blood pressure is frequently present in young Type 1 diabetic patients with diabetic nephropathy and normal serum creatinine.

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PubMed1983

Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment.

Our longitudinal study of urinary albumin excretion rate in long-term insulin-dependent diabetics without proteinuria (negative albustix) suggests that early detection of patients at high and low risk of developing persistent proteinuria, i.e., diabetic nephropathy, is possible by using a sensitive method for albumin determination. Our prospective studies in young insulin-dependent diabetics with diabetic nephropathy show that the rate of decline in glomerular filtration rate (GFR) varies considerably, with a mean of 0.75 ml/min/mo and a range from 0.1 to 1.50 ml/min/mo, and that an increase in arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy.

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PubMed1981

A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy.

Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (greater than 0.5 g/day) secondary to diabetic nephropathy. Twelve of the 14 patients had normal serum creatinine levels. None of the patients received antihypertensive treatment. During the mean observation period of 26 months (range 23 to 33 months) GFR decreased from 107 to 87 ml/min/1.73 m2 (p less than 0.001), serum creatinine remained unchanged: 107 and 112/mumol/l (NS), proteinuria increased from 1.8 to 3.3 g/day (p less than 0.001) and arterial blood pressure rose from 132/88 to 153/101 mmHg (p less than 0.001). Glomerular filtration rate decreased linearly with time (slope = -0.75, r = 0.99, p less than 0.001) by a mean of 0.75 ml/min/month (range 0.1 to 1.5 ml/min/month). The decrease in GFR did not correlate wih sex, age at onset, duration of diabetes, arterial blood pressure, proteinuria, insulin requirement, postprandial blood glucose or the initial GFR in each individual was constant, but varied considerably between patients. Increase in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy in young insulin-dependent diabetics.

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PubMedDate not supplied

Hypotensive therapy reduces microvascular albumin leakage in insulin-dependent diabetic patients with nephropathy.

The effect of hypotensive therapy on the transcapillary escape rate of albumin (TERalb) was studied in eight hypertensive insulin-dependent diabetic patients (mean age 29, range 19-42 years) with nephropathy and retinopathy. Transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), urinary albumin excretion rate (radial immunodiffusion), and glomerular filtrate rate (single bolus 51-Cr-EDTA technique) were measured. After hypotensive treatment (mean duration, 23 months, range 7-39 months) with combinations of metoprolol, hydralazine, and frusemide or thiazide diuretics, arterial blood pressure fell from 152/103 +/- 18/6 mmHg (mean +/- SD) to 133/81 +/- 12/10 mmHg (p less than 0.01), transcapillary escape rate of albumin from 10.2 +/- 1.8 to 8.1 +/- 1.8% of intravascular mass of albumin/h (p less than 0.01), albuminuria from 1803 (370-5066) micrograms/min to 940 (101-2676) micrograms/min (median and range, p less than 0.05), and glomerular filtration rate from 103 +/- 23 to 84 +/- 22 ml/min/1.73 m2 (p less than 0.01). Our study suggests that effective hypotensive treatment reduces the abnormally elevated albumin leakage characteristically found in insulin-dependent diabetic patients with clinical microangiopathy. This may be due to a reduction in the hydrostatic pressure in the microcirculation.

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PubMedDate not supplied

Reduced albuminuria during early and aggressive antihypertensive treatment of insulin-dependent diabetic patients with diabetic nephropathy.

Urinary albumin excretion rate (radial immunodiffusion), glomerular filtration rate (GFR) (single-shot 51Cr-EDTA technique), and arterial blood pressure (BP) were measured in 12 juvenile-onset, insulin-dependent diabetic patients with persistent proteinuria (greater than 0.5 g/day) due to diabetic nephropathy. Mean age of the patients was 30 yr. All patients had a diastolic blood pressure greater than or equal to 95 mm Hg. Metoprolol, hydralazine, and furosemide or thiazide were used as antihypertensives. During the 12-mo treatment period, BP decreased from 151/104 to 133/85 mm Hg (P less than 0.001), the urinary albumin excretion rate diminished from 1447 to 613 micrograms/min (P less than 0.005), and GFR declined from 96 to 89 ml/in/1.73 m2 (P less than 0.01). A linear relationship between mean blood pressure and the logarithm of the albuminuria was found (r = 0.48, P less than 0.01). Arterial hypertension is an early feature of diabetic nephropathy in young insulin-dependent patients. Early and aggressive treatment of that condition decreases albuminuria, probably due to reduced intraglomerular filtration pressure. Whether sustained reduction in arterial blood pressure to near-normal levels during several years also reduces the rate of decline in GFR in diabetic nephropathy remains to be established.

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