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G Penno

Publications and source records attributed to G Penno.

At least 19 recordsLinked to original sources

Iohexol as a marker of glomerular filtration rate in patients with diabetes: comparison of multiple and simplified sampling protocols.

AIMS: To report on the reproducibility of iohexol glomerular filtration rate (GFR) estimation, to compare the plasma clearance of iohexol with that of[51Cr]EDTA and to evaluate the reliability of reduced sampling schedules in estimating GFR in Type 1 and Type 2 diabetes mellitus. METHODS: Agreement was assessed in 15 Type 1 and 26 Type 2 diabetics with creatinine ranging from 53 to 564 micromol/l. RESULTS: The regression between multiple-sample iohexol and[51Cr]EDTA clearances was 0.999 in Type 1 and 0.987 in Type 2 diabetes (P < 0.0001 for both). A seven-sample design and the three-sample approach by Brøchner-Mortensen were validated by comparison with the full-sample schedule in 87 patients (51 Type 1, 36 Type 2). Full-sample GFR was 80.3 +/- 43.8, seven-sample 79.5 +/- 43.9 (r = 0.990) and three-sample 79.8 +/- 45.2 ml.min-1.1.73 m-2 (r = 0.972). The coefficients of variation of GFR were 2.7 +/- 1.4% and 3.8 +/- 1.9% for the full-sample and the seven-sample approaches, respectively, and significantly higher for the three-sample design (6.9 +/- 3.4%, P = 0.0001). CONCLUSIONS: After iohexol injection, the Brøchner-Mortensen schedule does not provide an accurate estimate of GFR. The seven-sample approach gives acceptable errors and allows a good estimate of GFR throughout a wide range of renal function.

Adult↗

Plasma lipids and urinary albumin excretion rate in Type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIMS: To examine the relationship between increased urinary albumin excretion rate and fasting plasma lipids among male and female respondents to the EURODIAB IDDM Complications Study, and attempt to explain inconsistencies in previous reports. METHODS: A cross-sectional study of 3250 randomly selected Type 1 diabetic patients from 31 diabetes clinics in 16 European countries was carried out between 1989 and 1990. Plasma lipids and urinary albumin were measured centrally. The present analysis was confined to the subgroup of 2205 patients attending after a 10-12 h overnight fast. Mean age was 33 years (SD 10) and mean duration of Type 1 diabetes mellitus was 15 years (SD 9). RESULTS: The prevalence of microalbuminuria (24-h urinary albumin excretion rate 20-200 microg/min) was 21.7% (95% confidence interval 19.9-23.5) and macroalbuminuria (24-h urinary albumin excretion rate > 200 microg/min) 7.8% (6.6-9.0). In comparison to patients with normal urinary albumin excretion rate (< 20 microg/min), and after controlling for age, sex, glycaemic control, duration of diabetes and current smoking, macroalbuminuria was associated with significantly (P<0.01) increased fasting plasma triglycerides, cholesterol, LDL-cholesterol, cholesterol:HDL-cholesterol ratio and, in women, reduced HDL-cholesterol. In men and women with microalbuminuria, the only significant association was with increased plasma triglycerides. CONCLUSIONS: These data confirm that there is an association between fasting plasma lipids and increasing urinary albumin excretion rate in European Type 1 diabetic patients. In microalbuminuric patients, however, the association was weaker than previously reported and partly explained by confounding factors.

Adult↗

Microalbuminuria in type 1 diabetes: rates, risk factors and glycemic threshold.

BACKGROUND: The occurrence of microalbuminuria in type 1 diabetes is strongly predictive of renal and cardiovascular disease and is still likely to occur despite improvements in glycemic control. A better understanding of microalbuminuria is required to inform new interventions. We determined the incidence and risk factors for microalbuminuria [albumin excretion rate (AER) 20 to 200 microg/min] in the EURODIAB Prospective Complications Study. METHODS: This is a seven-year follow-up (between 1988 and 1991) of 1134 normoalbuminuric men and women (aged 15 to 60) with type 1 diabetes from 31 European centers. Risk factors and AER were measured centrally. RESULTS: The incidence of microalbuminuria was 12.6% over 7.3 years. Independent baseline risk factors were HbA1c (7.1 vs. 6.2%, P = 0.0001) and AER (9.6 vs. 7.8 microg/min, P = 0.0001) and, independent of these, fasting triglyceride (0.99 vs. 0.88 mmol/L, P = 0.01), low-density lipoprotein cholesterol (3.5 vs. 3.2 mmol/L, P = 0.02), body mass index (24.0 vs. 23.4 kg/m2, P = 0.01), and waist to hip ratio (WHR; 0.85 vs. 0.83, P = 0.009). Triglyceride and WHR risk factors were nearly as strong as AER in predicting microalbuminuria (standardized regression effects of 1.3 for triglyceride and WHR and 1.5 for AER). Blood pressure at follow-up, but not at baseline, was also raised in those who progressed. There was no evidence of a threshold of HbA1c on microalbuminuria risk. CONCLUSIONS: The incidence of microalbuminuria in patients with type 1 diabetes remains high, and there is no apparent glycemic threshold for it. Markers of insulin resistance, such as triglyceride and WHR, are strong risk factors. Systemic blood pressure is not raised prior to the onset of microalbuminuria.

Adolescent↗

Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular disease.

Subclinical increases in albuminuria (microalbuminuria) predict morbid events, but the reasons for that are still not understood in full. This paper reviews the existing evidence regarding the relationships of non-diabetic microalbuminuria and cardiovascular disease, the underlying assumption being that endothelial dysfunction contributes both to atherosclerotic macrovascular disease and renal microvascular disease of which albuminuria is a marker. Much data support that concept, and suggest a preferential link with endothelial activation in response to acute and subclinical inflammatory stimulation, although further studies are needed to establish the exact cause-effect mechanisms. Epidemiological studies also show associations with cardiovascular events, and some recent prospective results also indicate the power of microalbuminuria to predict risk independently from conventional atherogenic factors. Thus, microalbuminuria might be considered as an integrated marker of cardiovascular risk sensitive to systemic vascular status in addition to other parameters such as blood pressure levels, glucose metabolism, smoking habits, a profile rather unique among the prognostic predictors available to stratify risk in hypertensive patients.

Albumins↗

Transvascular albumin leakage and forearm vasodilatation to acetylcholine in essential hypertension.

The impact of hypertension on microvascular permeability and nitric oxide-mediated endothelial vasomotion in humans has been studied by measuring either the transcapillary albumin escape rate (TERalb, a measure of permeability through systemic capillary endothelium where most of the albumin permeation takes place) and forearm vasodilatation to locally infused acetylcholine (used as a probe for the nitric oxide-releasing potential of arteriolar endothelial cells). It is unknown, however, how the two parameters relate to each other in the same hypertensive subject. This piece of evidence may enhance our understanding about the relative effect of hypertension on two biological functions (ie, permeability and nitric oxide-mediated vasomotion), both dependent on vascular endothelium, and also may allow to appreciate in greater detail the profile of parameters frequently used as markers of microvascular dysfunction in human hypertension. For these reasons, TERa1b (the 1-h decline rate of intravenous 125I-albumin) and forearm vasodilatation (strain gauge venous plethysmography) to graded intraarterial acetylcholine infusion were measured in 44 never-treated men with uncomplicated essential hypertension, and 15 male normotensive controls with comparable age, lipids, and proportion of current smokers. TERalb was increased in patients, whereas acetylcholine-mediated vasodilatation did not differ significantly between the two groups, indicating a heterogeneous impact of elevated blood pressure on capillary permeability and endothelial vasomotion in still uncomplicated mild to moderate essential hypertensive patients. The dissociation between TERalb and forearm responsiveness to acetylcholine also demonstrates that different endothelial-dependent biologic parameters do not behave uniformly in human hypertension.

Acetylcholine↗

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men.

BACKGROUND: The reasons why microalbuminuria (albuminuria > or = 15 microg/min), an expression of a renal microcirculatory abnormality, predicts cardiovascular disease in essential hypertension are unsettled. To test the hypothesis that microalbuminuria represents a marker of subclinical atherosclerosis, we evaluated its association with common carotid artery (CCA) intima media thickness (IMT), a measure of preclinical atherosclerosis and an independent predictor of cardiac and cerebrovascular events, in uncomplicated essential hypertensive individuals. MATERIALS AND METHODS: Albuminuria, ultrasonographic CCA IMT (the mean of six bilateral far wall measurements within 1.5 cm proximally to the flow divider), brachial blood pressure (BP), smoking habits and lipids were evaluated in 136 stage 1-3 untreated essential hypertensive men free of cardiovascular disease. RESULTS: CCA IMT did not differ between normo- (n = 99) and microalbuminuric (n = 37) patients. The correlation between CCA IMT and albuminuria was not significant, and the prevalence of microalbuminuria across IMT quartiles was not different. Microalbuminuric patients showed higher systolic BP and that parameter was the only independent correlate in a multivariate logistic regression model including also age, CCA IMT, diastolic BP, lipids and smoking habits as independent variables and microalbuminuria as the dependent one. CONCLUSION: This cross-sectional study in hypertensive subjects free of cardiovascular disease has shown a dissociation between microalbuminuria and CCA IMT, a surrogate measure of subclinical atherosclerosis, and a parameter linearly related to cardiovascular events. The data do not support the theory of microalbuminuria as a surrogate measure of subclinical atherosclerosis, while confirming the importance of systolic BP levels as an independent correlate of increased albuminuria in essential hypertension. Journal of Human Hypertension (2000) 14, 831-835

Adult↗

Simvastatin, capillary permeability, and acetylcholine-mediated vasomotion in atherosclerotic, hypercholesterolemic men.

OBJECTIVES: The aim of this study was to test the effect of high-dose simvastatin therapy on vascular permeability, a key variable in the atherogenic process, and endothelial-mediated vasodilator responses in patients with hypercholesterolemic atherosclerosis. METHODS: The transcapillary albumin escape rate (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of macromolecular permeability of capillary endothelium) and forearm vasodilatation (venous plethysmography) to intraarterial acetylcholine and sodium nitroprusside (7.5, 15, 30 microg/min and 0.8, 1.6, and 3.2 microg/min respectively, 5 minutes at each rate) to account for endothelium-dependent and independent mechanisms, were measured at baseline and after 1-month simvastatin (40 mg once daily) in 16 hypercholesterolemic (low-density lipoprotein cholesterol >130 mg/dL), atherosclerotic men. Thirteen healthy, untreated subjects were the controls. RESULTS: Baseline TERalb was higher and responsiveness to both acetylcholine and sodium nitroprusside was depressed in patients compared with controls. One-month high-dose simvastatin reduced low-density lipoprotein cholesterol by 39%, normalized TERalb, and improved local vasomotor responses to acetylcholine, without modifying those to sodium nitroprusside. Changes in TERalb and acetylcholine-mediated vasodilatation were dissociated and unrelated to lipid modifications. CONCLUSIONS: Low-density lipoprotein cholesterol reduction through 1 month of high-dose simvastatin normalized the exaggerated transvascular albumin leakage of patients with hypercholesterolemic atherosclerosis, perhaps by restoring an exaggerated endothelial permeability, apparently through mechanisms independent of circulating lipids. Improvements in acetylcholine-mediated vasomotion were also evident, but were dissociated from TERalb, demonstrating a heterogeneous behavior of the 2 indices of endothelial function in response to high-dose statin treatment.

Acetylcholine↗

Microalbuminuria and pulse pressure in hypertensive and atherosclerotic men.

To identify the biological covariates of microalbuminuria (albuminuria >/=15 microg/min) in nondiabetic subjects, brachial blood pressure, echocardiographic left ventricular mass, and other cardiovascular and metabolic parameters were evaluated in 211 untreated males (38 normal controls, 109 uncomplicated stage 1 to 3 essential hypertensives, and 64 patients with clinically stable atherosclerotic peripheral vascular disease either with [n=44] or without [n=20] essential hypertension) with normal cardiac and renal function. Compared with normoalbuminuric subjects, microalbuminuric subjects (n=67) were characterized by higher systolic blood pressure, comparable diastolic blood pressure, and, therefore, wider pulse pressure. Greater prevalence of hypertension, peripheral vascular disease, left ventricular hypertrophy, and reduced HDL cholesterol values further distinguished microalbuminuric from normoalbuminuric subjects in univariate comparisons. The risk of microalbuminuria increased by ascending pulse pressure quintiles in age-corrected logistic regression models, in which pulse pressure was more predictive than systolic pressure and was independent of mean pressure. When microalbuminuric status was regressed against a series of dichotomous (vascular and active smoker status) and continuous (age, pulse and mean pressure, left ventricular mass index, and HDL and LDL cholesterol) variables, only pulse pressure, left ventricular mass index, and smoking status were independent predictors. The association of increased albuminuria with wider pulse pressure, a correlate of the pulsatile hemodynamic load and conduit vessel stiffness as well as an important cardiovascular risk factor, may explain why microalbuminuria predicts cardiovascular events in nondiabetic subjects. The independence from concomitant vascular disease also suggests that wider pulse pressure, rather than representing a simple marker for atherosclerotic disease, influences albuminuria directly.

Adult↗

Dissociation between albuminuria and insulinaemia in hypertensive and atherosclerotic men.

To better understand the links between circulating insulin and albuminuria in essential hypertension, the plasma insulin response t alpha a 75 gram glucose load and albuminuria were evaluated in 53 glucose-tolerant essential hypertensives and 12 controls. To allow any direct pressure-independent albuminuric effect of insulin to emerge more clearly, those same parameters were also evaluated in 20 glucose-tolerant normotensive patients with stable atherosclerotic peripheral vascular disease, a condition in which hyperinsulinaemia could be anticipated on the basis of previous reports. In response to glucose ingestion, hyperinsulinaemia was evident in both hypertensive and normotensive atherosclerotic patients, while, on average, urine albumin was elevated only in the former. When plasma insulin, systolic and diastolic blood pressure (BP) (by 24-h ambulatory BP monitoring), plasma glucose, triglycerides and body mass index were entered into a multiple regression analysis, only systolic BP appeared to exert an independent effect on urine albumin. Post-glucose load plasma insulin did not differ between hypertensive patients with (n = 14) and without (n = 39) microalbuminuria (albuminuria > 20 micrograms/min). In further analyses, insulin and systolic BP values were divided in quartiles: albuminuria did not differ across insulin quartiles, while it was significantly higher in the top (n = 21) vs the bottom (n = 21) systolic BP quartile. Thus, hyperinsulinaemia and microalbuminuria were unrelated variables in these hypertensive and atherosclerotic patients. Blood pressure, particularly systolic, emerged as a primary predictor of urinary albumin excretion, although the importance of this parameter needs to be proved prospectively.

Adult↗

Microalbuminuria and transcapillary albumin leakage in essential hypertension.

Microalbuminuria (an increased urinary albumin excretion that is not detectable by the usual dipstick methods for macroproteinuria) predicts cardiovascular events in essential hypertensive patients. A possible reason for this behavior is that albumin leaks through exaggeratedly permeant glomeruli exposed to the damaging impact of subclinical atherogenesis. To evaluate this possibility, the transcapillary escape rate of albumin (TER(alb), the 1-hour decline rate of intravenous (125)I-albumin), a parameter that estimates the integrity of systemic capillary permeability, albuminuria, blood pressure, echocardiographic left ventricular mass, lipids, and body mass index were measured in 73 uncomplicated, glucose-tolerant men with essential hypertension and normal renal function; 53 were normoalbuminuric, and 20 were microalbuminuric. Twenty-one normotensive age-matched male subjects were the controls. TER(alb) was higher in hypertensives, a behavior explained in part by a positive correlation with blood pressure values, although body mass index, lipids, and left ventricular mass showed no association. Transcapillary albumin leakage values did not differ between normoalbuminuric and microalbuminuric patients and were unrelated to albuminuria. Blood pressure, particularly systolic, and cardiac mass were higher in microalbuminuric patients in whom albuminuria correlated with both cardiovascular variables and indicated the influence of the hemodynamic load on urinary albumin levels. Thus, TER(alb), a parameter influenced by the permeability surface area product for macromolecules and the filtration power across the vascular wall, is altered in essential hypertensives. However, this abnormality is dissociated from the amount of albuminuria, which is contrary to the hypothesis that a higher albumin excretion reflects a greater degree of systemic microvascular damage in essential hypertension.

Albuminuria↗

Pronatriodilatin gene polymorphisms, microvascular permeability, and diabetic nephropathy in type 1 diabetes mellitus.

Approximately 30% of diabetic patients develop nephropathy, the appearance of which is partially under genetic control. Atrial natriuretic peptide (ANP) has associated physiologic effects on the kidney. This study was conducted to examine the relationship between a newly identified and known polymorphism at the pronatriodilatin (PND) gene locus and renal involvement in type 1 diabetic subjects. Of 454 type 1 diabetic patients (219 men, 235 women), 323 showed no sign of nephropathy, 79 had incipient renal involvement, and 52 established nephropathy; 58 healthy control subjects were examined for comparison. Allele frequencies (C708 versus T708) were: 0.95 and 0.05 in normoalbuminuric patients, respectively; 0.88 and 0.12 in microalbuminuric patients; 0.96 and 0.04 both in those with overt nephropathy and in healthy control subjects (P = 0.011). Patients with incipient nephropathy were in disequilibrium compared with the total diabetic cohort (P = 0.02). In the same populations, an additional genotype for ScaI polymorphism of the PND gene was tested. The A1 and A2 allele frequencies were: 0.21 and 0.79 in normoalbuminuric patients; 0. 13 and 0.87 in microalbuminuric patients; 0.06 and 0.94 in type 1 diabetic subjects with overt nephropathy; and 0.20 and 0.80 in healthy control subjects, respectively (P < 0.0001). A subset of 55 normotensive patients with type 1 diabetes, well matched for clinical features, plasma ANP levels, and microvascular permeability to macromolecules, was investigated on the basis of the C708/T and A2/A1 polymorphisms. Both transcapillary escape rate of albumin (TERalb) and plasma ANP levels were significantly lower in patients with the T708 than with C708 allele, as well as in the A1 than in A2 allele (TERalb: T708 versus C708: 5.5+/-1.7 versus 7.8+/-2.0%/h, P = 0.0001; plasma ANP levels: 8.3+/-3.9 versus 15.3+/-7.7 pg/ml, P = 0.0003; A1 versus A2: 6.05+/-2.2 versus 7.3+/-2.1%/h, P = 0.044; 8.53+/-4.6 versus 14.5+/-7.4 pg/ml, P = 0.0024, respectively). Thus, in a large ethnically homogeneous cohort of diabetic subjects, our data show: (1) a significant association of C708/T polymorphism with microalbuminuria in long-term diabetes and with both lower plasma ANP levels and widespread albumin leakage; and (2) a strong association between ScaI polymorphism and both diabetic nephropathy and plasma ANP concentrations. These results suggest a possible role of PND gene in conferring protection from nephropathy and microvascular damage in type 1 diabetes.

Adult↗

Transvascular and urinary leakage of albumin in atherosclerotic and hypertensive men.

Increased urine albumin is associated with atherosclerotic disease and predicts cardiovascular morbidity and mortality in nondiabetic populations. This finding is frequently postulated to reflect the impact of atherosclerotic damage on glomerular and systemic capillary permeability, an interesting but as yet untested hypothesis. The transcapillary escape rate of albumin (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of capillary macromolecular permeability), albuminuria, lipid levels, echocardiographic wall thickness, and insulin responses to oral glucose were measured in 30 untreated dipstick-negative lean men and clinically stable atherosclerotic peripheral vascular disease; tolerance to oral glucose was a requirement for inclusion in the study. Because hypertension per se might influence TERalb, the sample included either normotensive (n=18, 118+/-6/72+/-7 mm Hg) or hypertensive (n=12, 141+/-7/84+/-6 mmHg by 24-hour blood pressure monitoring) arteriopathic patients; 11 normal age- and gender-matched subjects (121+/-7/76+/-5 mmHg) were used as control subjects. TERalb was higher in patients (10.7+/-3.2 versus 7.4+/-1.7%/h, P<0.013), a difference that persisted after postload glucose, insulin, and lipid levels were accounted for by covariance analysis; atherosclerosis and hypertension together did not further impair vascular permeation to albumin. In contrast with TERalb, albuminuria was elevated only in the hypertensive subgroup; the 2 variables showed no relationship, even when the data were analyzed separately in normotensive and hypertensive subgroups. Urine albumin correlated positively with 24-hour blood pressure and wall thickness. Thus, systemic capillary permeability is altered in nondiabetic atherosclerotic patients independently from blood pressure levels, but this abnormality is not reflected by proportionate changes in albuminuria.

Aged↗

Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

Adult↗

Iohexol plasma clearance in determining glomerular filtration rate in diabetic patients.

The plasma clearance of iohexol has recently been proposed as a new method for estimating GFR. The iohexol plasma clearance was compared with that of 51Cr-EDTA in 32 diabetic patients (12 IDDM, 20 NIDDM; age 23-70; diabetes duration 1-35 years) with normal to impaired renal function (serum creatinine: 0.8-6.4 mg/dL). Bolus i.v. injection of 51Cr-EDTA (1 muCi/kg) was followed by 5 mL slow i.v. injection of Omnipaque (Nycomed, Oslo, Norway). Samples for radioactivity and iohexol analysis were drawn at 0, 5, 10, 15, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 min (+360 and 420 min if serum creatinine > 2.0; +1440 min if > 5.0 mg/dL). Iohexol was assayed in duplicate by HPLC throughout a Nova-Pak C18 column (Waters-Millipore, USA). Only the second peak obtained during elution of iohexol (about 4.5 min) was used for calculation. Dilution tests show highly linear regressions for concentrations between 3.25-650 micrograms/mL (r = 0.99). Imprecision of iohexol assay (the whole procedure from deproteinization to chromatography) was: intra-assay 1.4 +/- 1.5%, mlsd (95% CI: 1.0-1.8%); inter-assay 3.0 +/- 2.7% (1.4-4.6%). Iohexol plasma clearance ranged between 12.9 and 150.9 mL/min, while 51Cr-EDTA plasma clearance between 11.9 and 149.8 mL/min with excellent correlation (iohexol = 0.95 51Cr-EDTA + 2.49; r = O.995). Mean CV between the two methods was 1.7% (range 0-4.9%) with a significant negative correlation (r = 0.5 I, p = 0.007) with the GFR levels. Correlation between repeated measurements, performed in eight patients, was excellent (r = O.994, P = 0.0001). In diabetes, GFR measured by plasma clearance of iohexol shows an excellent agreement with plasma clearance of 51Cr-EDTA throughout a wide range of renal function. Iohexol provides an accurate alternative method for measuring GFR.

Adult↗

Microalbuminuria and renal haemodynamics in essential hypertension.

The present study was designed to evaluate the renal haemodynamic pattern of never-treated microalbuminuric and normoalbuminuric patients with essential hypertension. A total of 19 never-treated essential hypertensive patients with microalbuminuria were selected and, as control subjects, 24 never-treated essential hypertensive patients without microalbuminuria (determined on three 24-h urine collections) were recruited. In the two groups, we compared blood pressure values, standing plasma noradrenaline, plasma renin activity, plasma aldosterone, urinary aldosterone, lipid profile, serum glucose and uric acid, glomerular filtration rate and renal plasma flow. In comparison with normoalbuminuric patients, microalbuminuric patients showed significantly higher systolic blood pressure values (P < 0.05), higher renal vascular resistances (P < 0.05) and lower plasma renin activity values (P < 0.01). Urinary albumin excretion showed a significant positive correlation with systolic (r = 0.46, P < 0.005) and mean blood pressure (r = 0.38, P < 0.05), serum uric acid (r = 0.43, P < 0.005) and triglyceride values (r = 0.36, P < 0.005), and a significant negative correlation with plasma renin activity (r = -0.34, P < 0.05). The present data are consistent with the occurrence of renal vasoconstriction in microalbuminuric never-treated essential hypertensive patients.

Adult↗

Transcapillary escape rate of albumin in type II diabetic patients. The relationship with microalbuminuria and hypertension.

OBJECTIVE: To study why in type II diabetes, microalbuminuria, a marker of generalized vascular dysfunction, and hypertension have been linked with both renal and cardiovascular organ damage. RESEARCH DESIGN AND METHODS: To investigate the effect of moderately elevated blood pressure on vascular damage, the transcapillary escape rate of albumin (TERalb) was measured by intravenous injection of purified 125I-human serum albumin in 9 healthy control subjects (group 1), 9 nondiabetic hypertensive subjects (group 2), and 73 nonobese type II diabetic patients stratified as follows: group 3: 17 normoalbuminuric-normotensive subjects; group 4: 22 normoalbuminuric-hypertensive subjects (systolic blood pressure [sBP] > or = 140 mmHg or diastolic blood pressure [dBP] > or = mmHg or both); group 5: 16 normotensive subjects with microalbuminuria (albumin excretion rate [AER]: 20-200 micrograms/min); and group 6: 18 microalbuminuric-hypertensive subjects. RESULTS: Groups 3-6 had similar age, sex, duration of diabetes (group 3: 7.8 +/- 5.5; group 4: 9.7 +/- 8.7; group 5: 12.1 +/- 8.1; and group 6: 10.7 +/- 8.3 years), BMI, HbA1c (7.8 +/- 1.1, 7.5 +/- 1.5, 8.7 +/- 1.5, and 7.7 +/- 1.1%, respectively), blood glucose, and lipid profile. Systolic and diastolic blood pressure did not differ in the three hypertensive group (group 2: 154 +/- 3/99 +/- 6; group 4: 149 +/- 13/95 +/- 6; group 6: 154 +/- 15/91 +/- 9 mmHg) and were significantly lower (P < 0.001) in group 3 (126 +/- 12/76 +/- 7), group 5 (128 +/- 11/77 +/- 5), and healthy control subjects (group 1: 133 +/- 7/81 +/- 4). TERalb was similar in control subjects (5.77 +/- 1.06%/h) and in normoalbuminuric-normotensive subjects (5.81 +/- 1.51%/h) but significantly higher (P < 0.0001) in microalbuminuric subjects with or without hypertension (9.11 +/- 1.65 and 8.60 +/- 1.50%/h, respectively) as well as in normoalbuminuric diabetic patients with hypertension (8.10 +/- 2.27%/h) and in essential hypertensive subjects (8.12 +/- 1.68%/h). CONCLUSIONS: By stepwise regression, TERalb was related (step 1) to log-AER (r = 0.30) or to the presence of microalbuminuria (r = 0.36) and (step 2) to dBP (multiple r = 0.40) or to the presence of hypertension (multiple r = 0.51) in the whole diabetic cohort (groups 3-6). TERalb was related to dBP (r = 0.47) or to the presence of hypertension (r = 0.56) only in normoalbuminuric diabetic patients (groups 3 and 4) and to log-AER (r = 0.56) or the presence of microalbuminuria (r = 0.68) only in normotensive patients (groups 3 and 5). In type II diabetic patients, TERalb was elevated in subjects with increased albuminuria, irrespective of blood pressure levels, but also was independently related to the presence of mild-to-moderate systemic hypertension.

Adult↗

Increased transcapillary escape rate of albumin in microalbuminuric type II diabetic patients.

OBJECTIVE: To evaluate microvascular permeability by the transcapillary escape rate of albumin (TERalb) in type II diabetic patients with normo- and microalbuminuria. RESEARCH DESIGN AND METHODS: The TERalb has been measured following intravenous injection of 125I-labeled human serum albumin in 32 normotensive type II diabetic patients and 9 healthy control subjects matched for sex and age. Type II diabetic subjects were grouped in normoalbuminuric, albumin excretion rate (AER) < 20 micrograms/min (n = 18), and microalbuminuric, AER 20-200 micrograms/min (n = 14) categories. RESULTS: In type II diabetic patients, no differences were noted between normo- and microalbuminuric groups for known diabetes duration (8.3 +/- 5.9 vs. 11.7 +/- 8.0 years), blood pressure (BP) (129/76 +/- 16/8 vs. 131/76 +/- 14/5 mmHg), current metabolic control (HbA1c: 8.0 +/- 1.4 vs. 8.5 +/- 1.6%), and serum lipids. However, previous 2-year mean HbA1c levels were significantly higher in microalbuminuric patients (8.7 +/- 1.45 vs. 7.6 +/- 1.29%; P < 0.05). The TERalb was similar in control subjects and normoalbuminuric patients (5.16 +/- 1.09 vs. 5.71 +/- 1.66 %/h) and significantly higher in the microalbuminuric group (8.98 +/- 1.35 %/h; P < 0.0001). The increased leak of albumin was not explained by differences in diabetes duration, BP, or metabolic control at the time of investigation and was independently related to the presence of microalbuminuria (r = 0.63, percent explained variance approximately 40) and mean "historical" HbA1c (multiple r = 0.705; total explained variance approximately 50%). CONCLUSIONS: Type II diabetic patients with microalbuminuria show an increased TERalb, i.e., a widespread microvascular damage that may be important in the pathogenesis of long-term complications. Our findings may contribute to the explanation of why albuminuria seems to be an independent cardiovascular risk factor in type II diabetes.

Albuminuria↗