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Biomedical subjects

H Mulec

Publications and source records attributed to H Mulec.

At least 19 recordsLinked to original sources
PubMed2006

Effect of fluvastatin on apolipoprotein-defined lipoprotein subclasses in patients with chronic renal insufficiency.

According to the concept of apolipoprotein (apo)-defined lipoproteins, apoA-I-containing lipoproteins consist of two subclasses referred to as lipoprotein A-I (LpA-I) and lipoprotein A-I:A-II (LpA-I:A-II), and apoB-containing lipoproteins of five subclasses, namely lipoprotein B (LpB), lipoprotein B:C (LpB:C), lipoprotein B:E (LpB:E), lipoprotein B:C:E (LpB:C:E), and lipoprotein A-II:B:C:D:E (LpA-II:B:C:D:E). The purpose of this study was to determine the levels of apoA-I- and apoB-containing lipoprotein subclasses before and after fluvastatin treatment of patients with chronic renal insufficiency. ApoA-I- and apoB-containing lipoprotein subclasses were measured in 15 patients with chronic renal failure and 15 asymptomatic subjects. The effect of fluvastatin on lipoprotein subclasses was determined in a randomized, double-blind, placebo-controlled, two-way, treatment period crossover study. Patients were administered fluvastatin 40 mg/day or placebo during 8 weeks in a randomized order. Patients were characterized by significantly higher levels of LpB (P < 0.001), LpB:C (P < 0.001), and LpB:E (P < 0.05), and slightly higher levels of LpB:C:E and LpA-II:B:C:D:E than controls. The levels of LpA-I:A-II were significantly lower (P < 0.01) in patients than controls. Fluvastatin treatment reduced all apoB-containing subclasses, but only the reduced level of LpB subclass was statistically significant (P < 0.02). The levels of LpA-I and LpA-I:A-II were not affected. Fluvastatin treatment reduced and normalized LpB and LpB:E subclasses. Although slightly reduced, the levels of markedly atherogenic LpB:C subclass were not normalized. The potential role of LpB:C on the progression of coronary artery disease in chronic renal insufficiency remains to be determined in future studies.

Aged↗
PubMed2000

Angiotensin I-converting enzyme gene polymorphism in non-diabetic renal disease.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene determines the concentration of ACE in serum and local tissues. The role of this polymorphism in progressive chronic renal disease is still not fully clear. METHODS: We analysed the impact of the D/D polymorphism on the rate of decline in renal function in patients with non-diabetic, chronic progressive renal insufficiency. Seventy non-diabetic patients, aged 21-69 years at baseline, with moderately advanced renal insufficiency due to primary chronic renal disease were followed for an average of 3 years with repeated measurements of their glomerular filtration rate (GFR). Their mean GFR at baseline was 41 ml/min/1.73 m(2) body surface area (BSA). The polymerase chain reaction (PCR) amplification method was used to detect the I/D polymorphism of the ACE gene. GFR was measured as the clearance of (51)Cr-EDTA and the individual rate of progression was calculated using linear regression. RESULTS: The distributions of the genotypes were: D/D 30%, I/D 49%, and I/I 21%. The rates of progression in the three ACE genotype groups were an annual decline in renal function of -4.2 (SD 4.6) ml/minx1.73 m(2) BSA in the D/D group, -2.7 (SD 3. 4) in the I/D group and -1.7 (SD 3.4) in the I/I group (ANOVA P=0. 12). In patients with proteinuria below 3.5 g/24 h, the D/D group had a significantly higher rate of progression than patients with the I allele. The same was found in a separate analysis when only patients with normal apoliprotein B (below 155 mg/dl) levels were analysed. Furthermore, the D/D genotype was a significant predictor of a more rapid decline in renal function in male, but not female, patients. CONCLUSION: The results in this study in non-diabetic patients with chronic renal disease indicate that the presence of the D allele in the ACE genotype may be of particular importance as a predictor of a high rate of progression in male patients who otherwise do not have a major burden of documented and important prognostic factors for progressive renal insufficiency.

Adult↗
PubMed1999

The plasma levels of homocysteine are elevated in moderate renal insufficiency but do not predict the rate of progression.

BACKGROUND: Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It is also characterized by elevated plasma levels of total homocysteine (tHcy). Hyperhomocysteinemia has been shown to be a risk factor for atherosclerosis in both the general population and in patients with end-stage renal disease. AIM: To analyze whether elevated tHcy levels also may contribute to a higher rate of progression of renal insufficiency in patients with moderately advanced renal failure. METHODS: To investigate whether tHcy concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of tHcy with the progressive decline of renal function in an observational study of human chronic renal disease. RESULTS: Sixty-three nondiabetic patients (49 men, 14 women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.0 years, and the mean rate of decline in glomerular filtration rate ((51)Cr- EDTA clearance) was -3.2 +/- (SD) 3.9 ml/min x 1.73 m(2) body surface area. The mean plasma concentration of tHcy at the beginning of the study was 28.3 +/- 12.0 micromol/l. Plasma tHcy concentrations correlated significantly with the glomerular filtration rate (r = -0. 32, p < 0.01). However, there was no association between the initial plasma level of tHcy and the rate of progression as assessed by linear regression analysis (r = 0.02; NS). In contrast, increased levels of apolipoprotein B, low-density lipoprotein cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. CONCLUSIONS: Patients with moderately advanced chronic renal insufficiency have elevated plasma levels of homocysteine. The tHcy plasma levels increase in parallel with the degree of reduction in renal function. However, the hyperhomocysteinemia is not prospectively associated with a higher rate of progression of the renal functional impairment. Hence, there is no indication that elevated homocysteine levels play a contributing role for an accelerated glomerulosclerotic process.

Adult↗
PubMed1998

Effects of ticlopidine in AV-fistula surgery in uremia. Fistula Study Group.

Two hundred and fifty-eight patients with uremia who were offered surgery for placement of an arteriovenous fistula for hemodialysis were recruited in nine regional dialysis centers. The patients were randomized to receive the platelet aggregation inhibitory compound ticlopidine, 250 mg b.d., or matching placebo. Study medication was targeted at 7, minimum 3, days before scheduled surgery and continued for 28 days after surgery. The overall rate of occlusion was 41/260 evaluable operations (16%), 25/131 (19%) in the placebo group and 16/129 (12%) in the ticlopidine group. The risk of early occlusion was a non-significant 35% lower in the ticlopidine group. Limited risk factor analysis did not clearly identify any subgroup other than females at greater risk of early thrombosis nor any subgroup deriving particular benefit from ticlopidine treatment.

Adult↗
PubMed1998

The effect of metabolic control on rate of decline in renal function in insulin-dependent diabetes mellitus with overt diabetic nephropathy.

BACKGROUND: Strict glycaemic control has been shown to reduce the risk of developing diabetic nephropathy. In established nephropathy, however, the impact of glycaemic control on prognosis is less clear. Therefore we investigated the effect of long-term glycaemic control on the decline in renal function in insulin-dependent diabetic patients with overt nephropathy. METHODS: The study was performed at two hospital-based diabetes centres in western Sweden. The study was an observational retrospective follow-up study in 158 insulin-dependent diabetics with proteinuria with a mean (+/-SD) age of 36+/-9 years and a diabetes duration of 22+/-8 years. The change in glomerular filtration rate was measured as 51Cr EDTA clearance for a median of 8 years (range 1-17). Glycaemic control was determined with measurements of glycated haemoglobin A1c. RESULTS: The decline in glomerular filtration rate was 3.8+/-3.7 ml/min/year. The blood pressure was 143/82+/-15/7 mmHg and the mean glycated haemoglobin was 8.7+/-1.6%. The correlation coefficient between glycated haemoglobin and decline in glomerular filtration rate was -0.39 (P<0.0001 ) and between decline in glomerular filtration rate and systolic and diastolic blood pressure -0.17 (P=0.03) and -0.29 (P=0.003) respectively. In patients with glycated haemoglobin <8.0% and diastolic blood pressure <85 mmHg the decline in glomerular filtration rate was 1.7+/-2.3 ml/min/year. CONCLUSIONS: In this retrospective observational study, effective blood-pressure control was associated with a low rate of decline in renal function and a low urinary albumin excretion. The correlation between glycaemic control and decline in renal function indicates that poor glycaemic control can accelerate the loss of renal function in diabetic nephropathy.

Adult↗
PubMed1998

Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency.

Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It has been suggested that renal dyslipoproteinemia contributes to the progression of renal dysfunction. The objective of this study was to investigate the impact of different apoB-containing lipoprotein families on the progressive decline of renal function in patients with moderately advanced chronic renal failure. As part of a larger prospective study, 44 adult nondiabetic patients with primary chronic renal disease were followed with repeated GFR measurements for an average of 2.4 (SD 1.0) yr. Patients' characteristic variables, including plasma levels of lipids, apolipoproteins (apo), and apoA- and apoB-containing lipoprotein families (LP), were determined at the beginning of the observation period. The baseline variables were prospectively related, using linear regression, to the rate of progression (deltaGFR). The patient study group had a mean GFR at baseline of 40.3 (SD 16.7) ml/min per 1.73 m2 body surface area. The average rate of progression was a yearly decline in GFR of -3.2 (SD 5.1) ml/min per 1.73 m2 body surface area. A strong association was observed between the plasma concentration of complex, triglyceride-rich apoB-containing lipoproteins (LP-Bc) and the rate of progression (r=0.43, P < 0.01), whereas there was no association between the cholesterol-rich apoB-containing lipoproteins (LP-B) and deltaGFR. The association between the levels of LP-Bc and the rate of progression was not dependent on the baseline values of GFR, BP, and the degree of proteinuria. The results of this study extend earlier observations regarding the importance of renal dyslipoproteinemia for progressive renal insufficiency. In particular, elevated levels of intact or partially metabolized triglyceride-rich apoB-containing lipoproteins of intermediate- and low-density ranges seem to promote the progression of human renal insufficiency.

Adult↗
PubMed1997

Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency.

BACKGROUND: Chronic renal insufficiency is accompanied by specific alterations of the lipoprotein metabolism. It has been suggested that the renal dyslipoproteinaemia of renal insufficiency contributes to the progression of glomerular and tubular lesions, with subsequent deterioration of renal function. The objective of this prospective study was to investigate whether the specific lipoprotein abnormalities of renal insufficiency are associated with the rate of decline of renal function in patients with moderately advanced chronic renal failure. METHODS: A patient population of 73 adult non-diabetic patients with primary chronic renal disease were followed with repeated measurements of the glomerular filtration rate (GFR) for an average of 3.2 (SD 0.7) years. Forty-three of these patients had chronic glomerulonephritis as the underlying renal disease. Patient characteristics including plasma levels of lipids and apolipoproteins were determined at entry and were prospectively related, using linear regression, to the rate of progression. RESULTS: The mean GFR at entry was 41.3 (SD 15.3) ml/min x 1.73 m2 BSA. The average rate of progression was a decline in GFR of -2.8 (SD 3.7) ml/min x 1.73 m2 BSA per year. In the whole patient study group total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B (apoB) were all significantly associated with a more rapid decline in renal function, whereas triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein A (apoA) were not. In the more homogeneous subgroup of patients with chronic glomerulonephritis the association between dyslipidaemia and the rate of progression was even more pronounced. In this subgroup of patients also serum triglycerides and apoE were significantly associated with a higher rate of progression. Both the initial blood pressure and proteinuria were also significantly associated with a more rapid decline in renal function in the whole study group as well as in patients with chronic glomerulonephritis. The associations between these variables with the rate of progression were all independent of the entry GFR values. CONCLUSIONS: These results indicate that the lipoprotein abnormalities of renal insufficiency contribute to the progression of renal failure in human chronic renal disease.

Adult↗
PubMed1997

Effect of gemfibrozil on lipoprotein abnormalities in chronic renal insufficiency: a controlled study in human chronic renal disease.

BACKGROUND: Renal dyslipoproteinemia is characterized by the accumulation of intact and partially metabolized triglyceride-rich lipoproteins. Reduced lipolytic enzyme activities may be one of the major pathophysiological mechanisms contributing to a retarded catabolism of these lipoproteins in patients with renal insufficiency. OBJECTIVE: To evaluate the effect of gemfibrozil treatment on renal dyslipoproteinemia. STUDY DESIGN: A randomized, controlled open study with 2 parallel groups. OUTCOME VARIABLES: Plasma concentrations of lipids, apolipoproteins and lipoprotein particles. PATIENTS AND METHODS: Fifty-seven non-nephrotic, non-diabetic patients with moderately advanced renal insufficiency were randomized to either treatment with gemfibrozil at dosages from 300 to 900 mg/day (n = 28) or dietary counseling (n = 29). The intervention period was 12 months. Plasma concentrations of lipids, apolipoproteins and apoA- and apoB-containing lipoprotein particles were determined at the entry and after 6 and 12 months of treatment. RESULTS: No serious adverse effects occurred during the study. Six patients experienced mild gastrointestinal symptoms and prematurely withdrew from the drug treatment. In the group treated with gemfibrozil the plasma concentrations of triglycerides, total cholesterol, very low density lipoprotein (VLDL) and low density (LDL) cholesterol decreased significantly by 47, 13, 43 and 14%, respectively, in comparison to baseline. High density lipoprotein (HDL) cholesterol increased significantly by 18%. ApoB, apoC-III, apoC-III in heparin-manganese precipitate (reflecting apoC-III in VLDL and LDL) and apoE decreased significantly by 21, 18, 26 and 49%, respectively. Furthermore, gemfibrozil treatment resulted in the reduction of plasma concentrations of complex (LP-Bc) and simple (LP-B) apoB-containing lipoprotein particles by 22 and 7%, respectively. However, these changes were not statistically significant. There was a slight, insignificant increase in the levels of LP-A-I:A-II particles and no change in the levels of LP-A-I particles. In contrast to the effect of the pharmacological intervention, the dietary counseling only resulted in minor changes in the plasma lipid and apolipoprotein profiles. The only significant changes were a 10% increase in HDL cholesterol and a 35% decrease in apoE. CONCLUSIONS: Gemfibrozil treatment significantly reduces both plasma lipids and apoB, apoC-III and apoE concentrations in patients with moderately advanced renal insufficiency. The results of this study indicate that gemfibrozil enhances the clearance of apoB-containing triglyceride-rich lipoproteins.

Apolipoproteins↗
PubMed1997

Deletion insertion polymorphism of the angiotensin converting enzyme gene and progression of diabetic nephropathy.

BACKGROUND: The activity in the renin angiotensin system is important for the progression of diabetic nephropathy. Genetic abnormalities in this system have been suggested as a risk factor for the development and progression of diabetic nephropathy. The homozygous DD (deletion) genotype of the angiotensin-converting enzyme gene has been associated with increased circulating angiotensin converting enzyme and a more rapid progression of IgA nephritis. The aim of the present study was to investigate the relationship between the DD genotype and rate of decline in kidney function in patients with type 1 diabetes and nephropathy in relation to other risk factors for loss of renal function. METHODS: The insertion-deletion polymorphism was determined in patients with type 1 diabetes mellitus and diabetic nephropathy. Retrospective data were collected in 86 patients. The patients were studied by determining glomerular filtration rate during a mean (+/-SD) of 8.5 +/- 4.0 years (range 1.3-14.5 years) using the clearance of 51Cr EDTA. Measurements for glycaemic control, urinary albumin excretion, blood pressure, and serum lipids were available for the study period. RESULTS: The mean decline in glomerular filtration rate was 3.2 +/- 3.6 ml/min/year in all patients. Patients with the DD, ID and II genotype showed a rate of change in glomerular filtration of -3.5 +/- 3.5, -3.1 +/- 4.4 and -2.6 +/- 2.3 ml/min/year respectively. The tendency towards a more rapid decline in kidney function in the DD genotype was nonsignificant. The decline in renal function was significantly correlated to systolic and diastolic blood pressure, Hb AIc and serum triglycerides. Serum cholesterol was nearly significantly correlated to the decline in glomerular filtration rate (P = 0.057). Of these variables, glycaemic control and blood pressure control remained significant in multivariate analysis (P = 0.02 and P = 0.04, respectively). The patients with the DD genotype weighted significantly less. The body weight in patients with the DD genotype was 67.1 +/- 11.4 kg vs 74.9 +/- 9.2 kg in patients with the II genotype (P = 0.018). CONCLUSION: In this study, poor glycaemic and blood pressure control were associated with a more rapid loss of renal function in diabetic nephropathy while polymorphism of the angiotensin converting enzyme gene was not.

Adult↗
PubMed1996

Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure.

Chronic renal failure is frequently accompanied by elevated plasma levels of lipoprotein (a) [Lp(a)]. Elevated Lp(a) levels have been proposed to contribute not only to increased risk of atherosclerotic and thrombotic complications but also to the progression of renal insufficiency. To investigate whether higher Lp(a) plasma concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of Lp(a) with the progressive decline of renal function in an observational study of human chronic renal disease. Forty-nine non-diabetic patients (40 men, nine women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.1 years, and the mean rate of decline in glomerular filtration rate (51Cr-EDTA clearance) was -2.8 (SD 4.1) ml/min/1.73 m2. The mean plasma concentration of Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100 ml with a median value of 12.2 mg/100 ml. There was no association between the initial plasma concentration of Lp(a) and the rate of progression as assessed by linear regression analysis. Furthermore, the progression rate in patients within the highest quartile of the Lp(a) distribution (> or = 30 mg/100 ml) did not differ from that in patients with lower levels of Lp(a). In contrast, increased levels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Based on these results, it was concluded that elevated plasma levels of Lp(a) are not associated with an increased rate of progression of renal insufficiency in human chronic renal disease. However, the results of this study suggest that other apoB-containing lipoproteins may play a significant role in this process.

Adult↗
PubMed1995

Latent overhydration and nocturnal hypertension in diabetic nephropathy.

With the aim of studying the diurnal variation in blood pressure in relation to degree of fluid retention, 24-h ambulatory blood pressure monitoring was performed in 31 insulin-dependent diabetic patients with nephropathy. The extracellular volume was calculated from the distribution volume of 51Cr-EDTA after a single injection. The study population was arbitrarily divided into two groups, depending on their extracellular volume. Group 1 included 15 patients with a lower extracellular volume and group 2, 16 patients with a higher extracellular volume. Ambulatory blood pressure was measured with a portable monitor using an oscillometric technique. In all patients, the mean +/- SD 24-h ambulatory blood pressure was 135/79 +/- 14/7 mmHg. Day and night-time blood pressure were 136/81 +/- 14/7 and 133/75 +/- 17/8, respectively (p < 0.02). The ambulatory blood pressure was 135/80 +/- 14/7 in group 1 and 136/78 +/- 15/6 mmHg in group 2. The nocturnal change in blood pressure was significantly greater in group 1 than in group 2, -9/-9 +/- 10/5 mmHg and 1/-3 +/- 10/6 mmHg, respectively (p = 0.005/0.01). There were no other significant differences between the groups than the diurnal blood pressure pattern. There were significant correlations between day ambulatory blood pressure and night ambulatory blood pressure and 24-h ambulatory blood pressure and urinary albumin excretion. There was no correlation between ausculatatory clinic blood pressure on the one hand and albuminuria on the other. Latent fluid retention therefore may contribute to nocturnal hypertension in diabetic nephropathy.

Adult↗
PubMed1994

Lipoprotein abnormalities without hyperlipidaemia in moderate renal insufficiency.

To characterize lipoprotein metabolism during early renal insufficiency, plasma lipid and apolipoprotein profiles were determined in normotriglyceridaemic (NTG, n = 31) and hypertriglyceridaemic (HTG, n = 30) middle-aged patients with primary renal disease and with moderately impaired renal function (GFR 20-55 ml/min, mean: 37.2). Mean GFR was similar in the two patient groups. They were compared with 102 normolipidaemic control subjects. In comparison with controls the NTG patients (plasma triglycerides TG < or = 1.7 mmol/l, mean TG: 1.16 mmol/l) had significantly increased plasma concentrations of apo C-III and apoB. The apoA-I levels tended to be lower and as a consequence the apoA-I/apoC-III ratio, considered to represent the hallmark of the altered apolipoprotein profile in renal dyslipoproteinaemia, was markedly lower in NTG patients (8.7 versus 16.8, P < 0.001). There was also a reduction of the antiatherogenic ratio apoA-I/apoB and an increase of the apoC-III/apoE ratio. The HTG patients (mean TG: 3.22 mmol/l) showed the same, but even more accentuated, qualitative changes as the NTG patients. There was a fourfold increase of apoC-III in VLDL-LDL lipoprotein fractions with little change in HDL in the HTG patients. In NTG patients the increase of apoC-III was found in VLDL-LDL and in HDL. Plasma insulin and PTH levels both correlated with the apoA-I/apoC-III ratio independently of GFR and BMI. This suggests a pathogenetic relationship between PTH-mediated alterations of insulin metabolism and the lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1994

Long-term enalapril treatment in diabetic nephropathy.

A randomized comparison of enalapril and metoprolol in patients with type 1 diabetes and nephropathy showed that the decline in kidney function was 5.6 +/- 5.9 ml/min/year in the metoprolol-treated and 2.0 +/- 3.2 ml/min/year in the enalapril-treated patients (P = 0.02). In the present study, the enalapril treated patients have been studied for two additional years. In the metoprolol-treated group, only the endpoints of death or uremia have been recorded, and six of the patients have reached end-stage renal failure and three are dead, compared to three and two, respectively in the enalapril treated group. The mean fall in glomerular filtration rate in 18 enalapril-treated patients is 8.4 +/- 9.4 ml/min/1.73 m2 after four years; 7.5 +/- 9.8 ml/min/1.73 m2, occurred during the first six months treatment. The mean decline in kidney function was 1.7 +/- 2.4 ml/min/year over the whole study period and 0.3 +/- 3.9 ml/min/year after exclusion of the first six months. In this study, long-term enalapril treatment in diabetic nephropathy was associated with a low rate of decline in kidney function.

Adult↗
PubMed1993

Cholesterol: a renal risk factor in diabetic nephropathy?

In a prospective follow-up of 30 patients with type 1 diabetes and nephropathy, serum cholesterol, triglycerides, apolipoprotein Al and B, and lipoprotein(a) were determined to study their relationship to the rate of decline in glomerular filtration rate. The patients had proteinuria and advanced nephropathy with a mean +/- SD glomerular filtration rate of 39 mL/min/1.73 m2. The decline in glomerular filtration rate was determined during 2.5 +/- 0.5 years. High serum cholesterol, triglycerides, and apolipoprotein B were correlated to a more rapid deterioration in kidney function. The rate of decline in glomerular filtration rate was 1.0 +/- 2.5 mL/min/yr in the 10 patients with the lowest cholesterol level, compared with 4.5 +/- 3.2 mL/min/yr in the patients with the highest serum cholesterol (P = 0.015). The combined effect of the measured lipids, blood pressure, type of antihypertensive treatment, protein intake, proteinuria, and hemoglobin A1C on the rate of decline in glomerular filtration rate was assessed by multiple regression analysis. The measured factors together had a high explanatory power for the rate of decline in glomerular filtration rate. In this model, 73% of the variation in decline in glomerular filtration rate was explained by the measured variables (multiple r2 = 0.73). Low cholesterol and treatment with an angiotensin-converting enzyme inhibitor were the strongest predictors of a favorable renal prognosis. This suggests that hypercholesterolemia is an important risk factor for diabetic nephropathy.

Adult↗
PubMed1992

Renal protective effect of enalapril in diabetic nephropathy.

OBJECTIVE: To determine whether inhibition of angiotensin converting enzyme can reduce the rate of decline in kidney function more than reducing blood pressure with other antihypertensive treatment. DESIGN: Prospective, open randomised study lasting a mean of 2.2 years in patients with diabetic nephropathy. SETTING: Three outpatient nephrology clinics. PATIENTS: 40 patients with insulin dependent diabetes and diabetic nephropathy with reduced renal function. INTERVENTION: Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURE: Rate of decline in glomerular filtration rate measured as chromium-51 edetic acid clearance. RESULTS: Glomerular filtration rate declined a mean of 2.0 (SD 3.2) ml/min/year in the group given enalapril and 5.6 (5.9) ml/min/year in the control group. The mean arterial blood pressure during the study was 102 (5) mm Hg in the patients given enalapril and 103 (5) mm Hg in the patients given metoprolol. Urinary albumin excretion during treatment with enalapril was 60% lower than during treatment with metoprolol. CONCLUSIONS: Enalapril has an antiproteinuric effect independent of the effect on systemic blood pressure. Treatment with enalapril can reduce the rate of decline in kidney function in patients with diabetic nephropathy more than equally effective antihypertensive treatment with metoprolol. This points to a specific renal protective effect of angiotensin converting enzyme inhibitors in diabetic nephropathy.

Adult↗
PubMed1990

Contrasting effects of enalapril and metoprolol on proteinuria in diabetic nephropathy.

OBJECTIVE: To assess whether angiotensin converting enzyme inhibition reduces proteinuria in diabetic nephropathy more than blood pressure reduction with other antihypertensive treatment. DESIGN: Prospective, open randomised study lasting eight weeks in patients with diabetic nephropathy. SETTING: Outpatient nephrology clinics. PATIENTS: 40 Patients with type I diabetes and diabetic nephropathy with reduced renal function. INTERVENTION: Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURES: Arterial blood pressure and urinary excretion of albumin and protein. RESULTS: Arterial blood pressure after eight weeks was 135/82 (SD 13/7) mm Hg in the group given enalapril and 136/86 (16/12) mm Hg in the group given metoprolol. Proteinuria and albuminuria were similar in both groups before randomisation. After eight weeks' treatment, the geometric mean albumin excretion was 0.7 (95% confidence interval 0.5 to 1.2) g/24 h in the patients given enalapril and 1.6 (1.1 to 2.5) g/24 h in the patients given metoprolol (p less than 0.02). The proteinuria was 1.1 (0.7 to 1.7) and 2.4 (1.6 to 3.6) g/24 h respectively (p less than 0.02). CONCLUSIONS: Antihypertensive treatment with enalapril reduced proteinuria in patients with diabetic nephropathy more than an equally effective antihypertensive treatment with metoprolol. This points to a specific antiproteinuric effect of the angiotensin converting enzyme inhibitor independent of the effect on systemic blood pressure.

Adult↗