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Biomedical subjects

D Fliser

Publications and source records attributed to D Fliser.

At least 55 records · Page 3Linked to original sources
PubMed1996

Albuminuria in normotensive and hypertensive individuals attending offices of general practitioners.

OBJECTIVE: To investigate the rate of albumin excretion and the prevalence of albuminuria in hypertensive individuals relative to the normotensive population, and to clarify the quantitative importance of confounding variables. DESIGN AND METHODS: We examined the morning urines of all consecutive non-diabetic and diabetic hypertensive patients (n = 631; 371 women, 260 men) attending the offices of five general practitioners in a circumscribed geographical area during a 4-month period. To obtain a normotensive control population, all consecutive visitors (n = 375; 217 women, 158 men) were also examined. Urinary albumin excretion was assessed by kinetic nephrelometry in morning urine samples. RESULTS: The median albumin excretion rate was 4.3 micrograms/ml (range 1.9-112) in normotensive individuals; 3.4 micrograms/ml (1.9-1440) in hypertensive and 3.6 micrograms/ml (1.9-2790) in diabetic patients (n = 189; 115 women, 74 men). The overall prevalence of albuminuria above 20 micrograms/ml was 4% in normotensive individuals, 10% in hypertensive patients and 17% in diabetic patients. The proportion of patients with higher-grade albuminuria (> 50 micrograms/ml) was 1% among the normotensive subjects aged below 60 years and 2% in those aged above 60 years; the respective values in hypertensive patients were 3 and 6% and in diabetic patients 8 and 13%. The multivariate regression analysis showed a significant correlation between albuminuria and smoking (P < 0.0001), the presence of hypertension (P < 0.001), the current level of systolic blood pressure (P < 0.01) and age (0.031), but not sex or body mass index. CONCLUSIONS: The present study confirms a higher prevalence of albuminuria above 20 micrograms/ml in individuals with primary hypertension and diabetes mellitus compared with that in normotensive subjects, despite similar median albumin excretion rates. However, the excess of prevalence is moderate. Smoking, advanced age and current level of systolic blood pressure are the important determinants.

Adult↗
PubMed1996

Changes in plasma phosphate levels influence insulin sensitivity under euglycemic conditions.

The euglycemic clamp technique is a useful tool to evaluate insulin-mediated glucose uptake. The plasma phosphate concentration decreases during euglycemic clamp studies. Because insulin-dependent glucose uptake is closely related to phosphate uptake, we investigated whether modulation of plasma phosphate levels in the range observed during clamp studies influences insulin sensitivity. We studied 11 healthy (phosphate-replete) male volunteers (mean age, 27.5 +/- 1.8 yr;, mean body mass index, 23.9 +/- 1.6 kg/m2) in a double blind placebo-controlled cross-over study. The volunteers received in random order on two occasions either an infusion of sodium chloride (sham infusion) or an infusion of sodium phosphate. Insulin sensitivity was assessed under euglycemic conditions (clamp technique). The mean plasma phosphate concentration decreased with sham infusion from 1.09 +/- 0.17 to 0.64 +/- 0.13 mmol/L, whereas it increased with phosphate infusion from 1.06 +/- 0.19 to 1.32 +/- 0.13 mmol/L. In all volunteers except one the glucose disposal rate (M-value) was higher after phosphate infusion (mean M-value, 10.4 +/- 1.5 mg/kg.min) than that after sham infusion (mean M-value, 9.4 +/- 1.5 mg/kg.min; P < 0.01, by Wilcoxon's test for paired samples). There were no significant differences in mean plasma glucose, sodium, insulin, or arterialized standard bicarbonate levels with the two infusion protocols. Mean plasma calcium, albumin-corrected calcium, and potassium levels, however, were all significantly (P < 0.05) lower after phosphate infusion than after sham infusion. The mean PTH level decreased with sham infusion from 28 +/- 9 to 20 +/- 6 ng/L, whereas it increased with phosphate infusion from 26 +/- 9 to 36 +/- 8 ng/L, whereas it increased with phosphate infusion from 26 +/- 9 to 36 +/- 8 ng/L. The difference between the two infusion protocols was statistically significant (P < 0.01). The data presented illustrate that plasma phosphate (and calcium) levels may be confounders that should be at least monitored, and possibly controlled for, when performing euglycemic clamp studies.

Adult↗
PubMed1996

Renal findings in patients with short-term type 2 diabetes.

Under semiambulatory conditions, 85 consecutive patients with the diagnosis of Type 2 diabetes of short duration (excluding patients with islet cell antibodies or maturity onset diabetes of the young) were admitted to a self-control training program and were examined in this study. A comprehensive renal assessment was performed, including evaluation of albumin excretion rate (AER), renal hemodynamics, blood pressure (BP) profile, and indicators of genetic risk. AER > or = 30 mg/24 h was found in 13 (15%) of patients; in two of these patients, AER was > or = 300 mg/24 h. By logistic regression, high HbA1, current smoking, and BP parameters were significantly correlated with an increased risk of microalbuminuria (MA). In a multiple linear regression model, accounting for 57% of total variance, HbA1, ERPF, and current smoking were significantly correlated with AER. Median GFR (Cin(inulin clearance) 136 mL/min per 1.73m2; range, 94 to 194) and ERPF (Cpah(para-aminohippuric acid clearance) 733; range, 451 to 1328) were significantly higher in patients than in control subjects (upper 95th percentile, 131 and 706 mL/min per 1.73m2, respectively). In a multiple linear regression model, explaining 27% of total variance, age, AER, gender, and fasting blood glucose were significantly correlated to GFR. According to the criteria of average daytime BP > or = 135/85 mm Hg or 24-h BP > or = 130/80 mm Hg, 60% of patients were hypertensive (HT). Sixty-one percent of all patients (including 50% of the untreated normotensive patients) were "nondippers", i.e., < 15% nighttime decrease of mean arterial pressure. Either HT or nondipping was found in 79% of all patients, so that only 21% had a completely normal blood pressure profile. Ninety-four percent of untreated hypertensive patients had no MA. First-degree relatives of patients with MA compared with patients without MA had more frequent cardiovascular events (69% versus 31%). The risk of MA in diabetic patients with positive family history was amplified by poor glycemic control. MA, but not hypertension, was marginally related to K(m) of Na+/Li+ countertransport. It was concluded that (1) microalbuminuria is found in 15% of patients newly presenting with Type 2 diabetes; (2) a high proportion of patients exhibit hyperfiltration; (3) according to ambulatory BP only, 21% of patients have a completely normal circadian BP profile; (4) a family history of cardiovascular events interacts with glycemic control to increase the risk of MA.

Adult↗
PubMed1995

Effect of moxonidine on urinary electrolyte excretion and renal haemodynamics in man.

Moxonidine and related compounds have been recently introduced into antihypertensive therapy. It is thought that these drugs exert their blood pressure lowering effect through interaction with non-adrenergic receptors in the central nervous system, i.e. imidazoline receptors, although the contribution of specific interaction with alpha 2-receptors is still under debate. Imidazoline receptors have recently been documented in the renal proximal tubule. In experimental studies, interaction of imidazolines with these receptors decreased the activity of the Na+/H+ antiporter and induced natriuresis. To quantitate the effect of the imidazoline receptor agonist moxonidine on renal sodium handling and renal haemodynamics in man, we examined ten healthy normotensive males (age 25 +/- 4 years) in a double blind placebo-controlled study using a crossover design. Subjects were studied on a standardized salt intake (50 mmol per day). On the 7th and 10th study day they were randomly allocated to receive either i.v. placebo or i.v. 0.2 mg moxonidine. Urinary electrolyte excretion, lithium clearance (as an index of proximal tubular sodium handling), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal vascular resistance (RVR), mean arterial blood pressure (MAP), plasma renin activity (PRA) and plasma noradrenaline (NA) levels were assessed. Injection of moxonidine did not increase fractional sodium excretion or lithium clearance. Specifically, antinatriuresis was not observed after injection of moxonidine despite a significant decrease in MAP from 91 to 85 mmHg and a significant increase in PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The effect of dietary salt on insulin sensitivity.

Acute reduction of salt intake causes an increase in serum lipid and insulin levels in healthy volunteers and patients with essential hypertension, suggesting induction of insulin resistance by salt restriction. Direct measurements of insulin sensitivity using the euglycaemic clamp showed no significant change after 7 days of salt restriction. Our previous study showed a time dependent course of dyslipidaemia after institution of a low salt diet. We therefore assessed insulin sensitivity (M-value) under euglycaemic conditions (clamp technique) at discrete time points using a parallel group design. Two groups of healthy males were examined on high (200 mmol d-1) and low (20 mmol d-1) salt intake. One group (n = 7, 25 +/- 3 years, BMI 22.4 +/- 2.1 kg m-2) received high and low salt diet in random order each for 7 days. The other group (n = 7, 26 +/- 3 years, 22.1 +/- 1.9 kg m-2) received the respective diet in random order for 3 days. A significantly (P < 0.01) different mean M-value was noted in the group receiving the diets for 3 days, i.e. after low salt intake it was 7.4 +/- 1.2 mg kg-1 min-1 and after high salt intake 8.6 +/- 1.1 mg kg-1 min-1. In contrast, the mean M-value was similar after low and high salt periods in the group of individuals who had been studied after 7 days on either salt take (7.8 +/- 1.8 on low salt vs. 7.6 +/- 1.3 mg kg-1 min-1 on high salt).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Influence of ACE inhibition on glucose tolerance in patients with stable chronic renal failure.

ACE inhibitors improve glucose tolerance and insulin sensitivity in hypertensive patients with normal renal function. Hypertensive patients with renal failure are a high-risk group who are particularly glucose intolerant and insulin resistant. We have therefore studied whether ACE inhibition improve glucose tolerance in this group as well. In a double-blind placebo-controlled crossover study 10 patients with stable moderate chronic renal failure (mean endogenous creatinine clearance 40 +/- 16 ml/min/1.73 m2) were examined. Patients were randomly allocated to receive either placebo or the ACE inhibitor perindopril (2 mg/day per os) for 14 days. After 7 days of wash-out they received the alternative medications in random order for another 14 days. Before and after each of the two treatment periods (day 1 and day 15) an intravenous glucose tolerance test (i.v. GTT) with concomitant determination of insulin levels was performed. The glucose disappearance rate (K value) was calculated to express changes in glucose tolerance. An i.v. GTT was also performed in a group of healthy volunteers. The mean K value was significantly (P < 0.05) lower, i.e. glucose tolerance was impaired, in patients compared with healthy controls. In addition, baseline and peak insulin levels after the i.v. GTT were significantly higher (P < 0.05) in patients than in healthy subjects. The K values in patients before and after placebo treatment (1.33 +/- 0.31 and 1.41 +/- 0.45 respectively) were not significantly different from the values with perindopril treatment (1.35 +/- 0.37 and 1.41 +/- 0.48 respectively). Furthermore, no significant differences between placebo and perindopril treatment were found with respect to the insulin response to the glucose load. The peak (5 min) insulin concentrations after the i.v. glucose load were 49.0 +/- 19.2 microU/ml (day 1) and 50.0 +/- 24.9 (day 15) with placebo and 49.2 +/- 19.3 (day 1) and 46.8 +/- 17.9 (day 15) with perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Renal reserve in the elderly.

The increase in glomerular filtration rate after an amino acid load, the so-called renal reserve, was found to be impaired in the aged rat. Renal diseases progress more rapidly in the elderly. Whether the renal reserve predicts progression of renal disease is controversial, however, and generally little information on renal reserve in elderly subjects is available. We examined renal hemodynamics before and after an amino acid infusion in 15 healthy normotensive subjects of young age (median age, 26 years [23 to 32]) and in 10 of old age (70 years [61 to 82]). Median basal inulin (Cin) and paraaminohippurate (Cpah) steady-state clearances were significantly lower in the elderly (102 and 339 mL/min/1.73 m2) than in the young subjects (122 and 647 mL/min/1.73 m2), but virtually all GFR values of the elderly were still within the normal range. The median percent rise of Cin was +16% in young and +17% elderly subjects (independent of gender). A well-preserved renal reserve was also confirmed by two other studies; one in chronically ill elderly patients treated for various nonnephrological diseases using an amino acid load and the other in healthy elderly volunteers in which renal reserve was tested with a protein (meat) meal. The mean absolute renal reserve in the three cohorts studied was between 16 and 26 mL/min/1.73 m2, the oldest patient studied was 89 years. The results of these studies document that in humans renal functional reserve is preserved at least until age 90 years in women and men.

Adult↗
PubMed1994

OACE inhibition does not interfere with acute extrarenal or renal potassium disposal in chronic renal failure.

The influence of angiotensin converting enzyme (ACE) inhibition on acute extrarenal and renal potassium elimination in stable chronic renal failure has been examined in 10 male patients median age 44 y; mean CLCR 42 ml.min-1.1.73 m-2. In a double blind, placebo-controlled cross-over study, K+ 0.3 or 0.4 mmol.kg-1 body weight was infused IV on two occasions while the patients also received an infusion either of placebo or 0.5 mg of the ACE inhibitor perindoprilat in random order. Plasma K+ levels and urinary K+ excretion were measured at regular intervals. During the study patients adhered to an isocaloric diet providing a standardised daily intake of potassium and sodium (50 mmol K+ and 40 mmol Na+). The median rise in plasma K+ was not significantly different after placebo (delta K 0.66 mmol.l-1) compared with to the infusion of perindoprilat (delta K 0.66 mmol.l-1). The median baseline urinary K+ excretion rate was 6.5 mmol.3 h-1 before the placebo infusion and 5.9 mmol.3 h-1 before infusion of perindoprilat. During the potassium load, the urinary excretion rate rose to 16.1 mmol.3 h-1 (after placebo) and 15.1 mmol.3 h-1 after perindoprilat in the first 3 h, and it returned almost to the baseline value within the next 3 h (5.6 mmol.3 h-1 after placebo and 5.7 mmol.3 h-1 after perindoprilat); the differences were not statistically significant. With perindoprilat a decrease in mean arterial blood pressure and ACE activity, an increase in renin plasma activity and a decrease in aldosterone concentrations were observed compared to the placebo infusion. There was no significant differences plasma in adrenaline or insulin levels after either infusion. Thus, ACE inhibition did not interfere either with the extrarenal or the renal disposal of an acute potassium load in patients with chronic renal failure.

Adult↗
PubMed1994

Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure. Consequence of dose adjustment.

To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e.g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n = 8; endogenous creatinine clearance [CLCR]: 18 ml.min-1.1.73 m-2) and in healthy subjects with normal renal function (n = 16; CLCR: 107 ml.min-1.1.73 m-2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1-2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (Cmax) in patients was lower than in volunteers (30.7 vs 40.7 ng.ml-1, while the mean area under the concentration-time curve (AUC0-24 h) was higher (525 vs 473 ng.h-1.ml-1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9-2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Coadministration of thiazides increases the efficacy of loop diuretics even in patients with advanced renal failure.

It is commonly assumed that thiazide diuretics are ineffective in patients with advanced renal failure (GFR < 30 ml/min/1.73 m2). Thiazides act on the nephron segment distal to the ascending thick loop of Henle, that is, the site of action of loop diuretics. Blockade of sodium reabsorption in the thiazide-sensitive segment should therefore obliterate the compensatory increase in sodium reabsorption seen after administration of loop diuretics and thus potentiate the natriuretic efficacy of loop diuretics even in advanced renal failure. In a single-blind, randomized, placebo controlled crossover study we compared the natriuretic and chloruretic effect of the loop diuretic, torasemide, given alone or in combination with the thiazide diuretic, butizid, in 10 patients with advanced renal failure (mean CIn 13.1 +/- 5.9 ml/min/1.73 m2). For two weeks patients adhered to a diet containing a standardized amount of Na+ and K+. On the 6th and 13th study days, two sham infusions were given to patients in order to assess basal 24-hour urinary electrolyte excretion. On the 7th and 14th days they were randomly allocated to receive either 50 mg i.v. torasemide in combination with a sham infusion or torasemide in combination with 20 mg i.v. butizid. Administration of torasemide alone significantly (P < 0.01) increased mean cumulative 24-hour excretion of sodium (from 154 +/- 30 to 232 +/- 59 mmol/24 hr) and chloride (from 128 +/- 21 to 233 +/- 84 mmol/24 hr) as compared with baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pathophysiology and treatment of hypertension and oedema due to renal failure.

Hypertension and oedema resulting from sodium retention are the main indications for diuretic treatment in patients with chronic renal failure. The pharmacokinetics of most loop diuretics and their active metabolites are altered in chronic renal failure, due both to reduced transtubular transport via the proximal tubular anion transporter and to protein binding within the tubule. In chronic renal failure, the reduced number of nephrons leads to adaptive reduction of tubular sodium reabsorption, i.e. high baseline fractional natriuresis and increased absolute distal tubular sodium reabsorption. These processes interfere with the pharmacodynamic actions of diuretics. Therapeutic strategies to overcome the partial resistance to the action of diuretics in patients with chronic renal failure include the use of high doses, continuous administration and the combination of loop and thiazide compounds.

Diuretics↗
PubMed1994

Proteinuria and hypertension.

Albuminuria is more prevalent in patients with primary hypertension than in normotensive subjects of the general population. The presence of albuminuria predicts the presence of more severe target organ damage and is related to the risk of cardiovascular events. Preliminary results show albuminuria even in some normotensive individuals with a genetic risk of hypertension and in association with insulin resistance. While albuminuria is generally more frequent in the elderly, it is also found in young patients with mild to moderate primary hypertension. It is uncertain whether in these circumstances albuminuria indicates some "renal component" in the etiology of primary hypertension. Massive albuminuria may occur in subjects with "benign" nephrosclerosis. Whether albuminuria is a predictor of hypertensive renal damage requires further study. Albuminuria is reduced by antihypertensive treatment, but diverse effects on albuminuria are seen with different antihypertensive agents.

Adult↗
PubMed1994

Treatment with high doses of loop diuretics in chronic renal failure.

In the late 60s, A. Heidland and his collaborators were amongst the first to characterize the renal action of frusemide in preterminal renal failure by giving quantitative information on dose requirements, fractional Na and K excretion, effects on renal haemodynamics, and by recognizing reversible inner ear dysfunction as the major dose-limiting side-effects. These early studies have been largely reconfirmed. They have been extended by more clearly characterizing (a) altered pharmacokinetics of frusemide, e.g. the importance of altered transepithelial transport in the proximal tubule and intratubular protein binding, and (b) the mechanisms underlying altered pharmacodynamics, particularly high baseline fractional Na rejection and increased absolute distal Na reabsorption. Apart from increasing the dose of frusemide, continuous administration by infusion and combination of frusemide with thiazide diuretics have emerged as rational therapeutic strategies in chronic renal failure.

Animals↗
PubMed1993

Effects of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection.

The goal of this study was to quantitate the effect of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection. The study was carried out on low and normal salt intake to assess potential interaction with salt balance. Eighteen healthy normotensive volunteers were examined in a double placebo-controlled parallel group design. Subjects were randomly put on either low-salt (20 mmol/day) or normal-salt (110 mmol/day) diet. In either arm of the diet volunteers were first treated orally with placebo for 1 week and subsequently with 2.5 mg/day of the angiotensin-converting enzyme inhibitor cilazapril for another 1 week. Cumulative 24-h urinary sodium excretion was measured on the 6th day of the respective week after sham injection and on the 7th day after injection of 40 mg furosemide. Compared to pretreatment with placebo, pretreatment with cilazapril resulted in a higher cumulative sodium excretion after furosemide injection (day 7) than after the sham injection (day 6) on both salt intakes. The difference in natriuresis (cilazapril versus placebo) was evident 2 and 3 h after injection of furosemide. Neither the time of onset nor the magnitude of antinatriuresis were affected by cilazapril. Following furosemide angiotensin II increased significantly even after cilazapril pretreatment. Cilazapril tended to reduce urinary furosemide excretion. At any given urinary furosemide concentration, the increment in urinary sodium excretion was significantly greater with cilazapril irrespective of salt intake. The study shows that (a) cilazapril increases furosemide-induced natriuresis irrespective of salt intake, (b) antinatriuresis is not affected by cilazapril, and (c) angiotensin II levels rise after furosemide on cilazapril in therapeutic doses.

Adult↗