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Biomedical subjects

A Remuzzi

Publications and source records attributed to A Remuzzi.

At least 55 records · Page 3Linked to original sources
PubMed1991

Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy.

Clearances of uncharged dextrans of broad size distribution were used to evaluate the effects of a 30 day course of enalapril on glomerular barrier function in 10 patients with IgA nephropathy and proteinuria (from 1.4 to 5.6 g/day). Dextran clearance experiments were repeated three times: before enalapril therapy, after 30 days of enalapril and again 30 days after enalapril withdrawal. GFR, but not RPF, was significantly reduced by enalapril (basal 38.3 +/- 11.9, enalapril 30.2 +/- 12.6 ml/min/1.73 m2) and returned to basal values after enalapril withdrawal. Urinary protein excretion and fractional clearance of albumin were both significantly reduced by enalapril (basal 2.3 +/- 1.1 g/day and 102 +/- 90 x 10(-5), enalapril 1.2 +/- 0.6 g/day and 51 +/- 23 x 10(-5), respectively) and returned to basal values after enalapril withdrawal. Transglomerular passage of large dextrans (radii 54 to 62 A), but not of lower size (26 to 42 A) were significantly lowered by enalapril. When enalapril was withdrawn the dextran-sieving profile returned comparable to the baseline levels. A theoretical analysis of dextran-sieving profiles indicated that enalapril lowered the radius of largest membrane pores. This effect was independent from glomerular hemodynamic changes. We conclude that angiotensin converting enzyme inhibitors (CEI) in humans with IgA nephropathy reduces urinary protein excretion by a primary action on the intrinsic glomerular membrane properties enhancing barrier size-selective function. The hypofiltration associated with enalapril therapy in these patients, which was eliminated by its withdrawal, has to be taken into account as a possible undesired effect of CEI in long-term treatment.

Adult↗
PubMed1991

Nature and extent of glomerular injury induced by cyclosporine in heart transplant patients.

We sought to clarify whether low-dose cyclosporine (5.0 +/- 2.2 mg/kg/day) given for more than two years to prevent cardiac graft rejection induced glomerular injury and to quantify the extent of the lesions. After renal hemodynamic studies, renal biopsy specimens were obtained from 10 patients on cyclosporine and analyzed by a novel morphometric technique consisting of a tridimensional reconstruction of the glomerular tuft. Autopsy kidney specimens from three patients with no clinical history of renal disease, and from four patients who died with dilatative cardiomyopathy served as controls. The glomerular filtration rate and renal plasma flow were significantly depressed below normal values in transplant recipients given cyclosporine, averaging 35 +/- 8 and 325 +/- 94 ml/min/1.73 m2, respectively. Conventional light microscopy of specimens from controls and from patients who died with dilatative cardiomyopathy did not reveal renal structural abnormalities. By contrast kidney specimens from cyclosporine-treated patients had obliterative arteriolopathy and ischemic-type changes, with thickening and wrinkling of glomerular capillary wall. Morphometrical analysis of 28 control glomeruli and 40 glomeruli from patients with dilatative cardiomyopathy showed glomerular capillary tuft volumes (VCT) ranging between 1.2 and 2.3 microns 3 x 10(-6), whereas of 102 glomeruli from cyclosporine-treated patients 42.1% had VCT lower than 1.2 microns 3 x 10(-6) and 24.4% VCT higher than 2.3 microns 3 x 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Renoprotective effect of low iron diet and its consequence on glomerular hemodynamics.

It has been reported that anemia limits renal injury in rats with reduced renal mass. We studied the effect of a low iron diet, given to reduce hematocrit, on urinary protein excretion and glomerular function in male MWF/Ztm rats, which spontaneously develop proteinuria and glomerular sclerosis. At 20 weeks of age, micropuncture and glomerular volume measurements were performed in untreated rats fed standard chow and in rats fed an isocaloric diet with low iron (5 mg/kg) content. Two additional groups of rats were used for total kidney function and glomerular volume evaluation at 35 weeks of age. At 20 weeks of age animals on low iron diet showed significantly (P less than 0.01) reduced hematocrit (46 +/- 5% vs. 54 +/- 2%) and proteinuria (60 +/- 15 vs. 225 +/- 34 mg/24 hr) than control animals, and no statistically significant differences were observed in single nephron hemodynamics. At 35 weeks of age rats on low iron diet had significantly lower proteinuria than age matched controls (222 +/- 68 vs. 411 +/- 71 mg/24 hr, P less than 0.01) and developed less glomerular sclerosis (mean percentage of sclerotic glomeruli was respectively 14 +/- 7% and 31 +/- 17%, P less than 0.05). Glomerular volume was comparable in animals on the low iron diet and in controls both at 20 and 35 weeks of age. These data indicate that low iron diet protected male MWF/Ztm rats against glomerular injury without significant effects on glomerular hemodynamics and on glomerular volume.

Anemia, Hypochromic↗
PubMed1991

Platelet-activating factor alters glomerular barrier size selectivity for macromolecules in rats.

The effect of platelet-activating factor (PAF) on glomerular permeability to macromolecules was investigated in the isolated kidneys from normal male Sprague-Dawley rats perfused at constant pressure. Compared with basal values, infusion of PAF (10 nM final concentration) into the isolated kidneys induced a progressive and significant increase in protein excretion (6.7 +/- 2.7 vs. 40.7 +/- 10.4 micrograms/min, P less than 0.01), completely reversible 20 min after PAF infusion was discontinued (8.5 +/- 1.3 micrograms/min). In additional experiments, during PAF infusion the fractional clearance of small neutral dextrans (radius 24-48 A), defined as the ratio of the clearance of neutral dextrans to the clearance of creatinine, was comparable to preinfusion values, whereas fractional clearance of large dextrans (greater than 50 A) was significantly elevated (P less than 0.005) above preinfusion values. The specific PAF receptor antagonist L 652731 completely prevented the increased fractional clearance of large dextrans induced by PAF. Finally, lowering Ca2+ concentration in the perfusion medium from 2.5 to less than 0.1 mM markedly reduced proteinuria in isolated kidneys exposed to PAF (80.0 +/- 10.3, 42.8 +/- 3.1, and 22.0 +/- 7.6 micrograms/min, respectively, for 2.5, 1.25, and less than 0.1 mM). These results indicate that in isolated perfused kidneys 1) PAF-induced proteinuria is a functional phenomenon reversible on discontinuing PAF infusion, 2) PAF modifies glomerular size-selective properties by increasing transmural passage of large dextran molecules, and 3) PAF-induced change in glomerular permselective properties is dependent on Ca2+ concentration in the extracellular medium.

Animals↗
PubMed1991

In vitro platelet adhesion to dialysis membranes.

This work describes an in vitro system developed to quantitate platelet deposition on different dialysis membranes. The system is based on the use of small dialysis filters and reproduces the haemodynamic pattern of blood flowing through hollow fibres during in vivo dialysis. We have determined the in vitro platelet adhesion to cuprophan and to a non-cellulosic membrane, polymethylmethacrylate. When albumin concentration in the platelet suspension was low (0.35%) platelet deposition to cuprophan and to polymethylmethacrylate was comparable. When albumin concentration was increased to a physiological value (3.5%) platelet adhesion to both cuprophan and to polymethylmethacrylate membranes significantly decreased. This effect of albumin was greatest for the high-permeable polymethylmethacrylate membrane (BK). These data suggest that platelet membrane interaction is significantly influenced by circulating albumin.

Albumins↗
PubMed1990

Three-dimensional morphometric analysis of segmental glomerulosclerosis in the rat.

In idiopathic nephrotic syndrome, and in experimental models of nephrosis, changes of visceral epithelial cells involve the entire glomerular population while segmental sclerotic changes are reported to affect only a certain number of glomeruli. Because conventional determination of the percentage of glomeruli affected by sclerotic lesions is usually based on the examination of randomly selected sections, we wondered whether glomeruli appearing normal in a given section could be affected by sclerosis in other regions of the capillary tuft (CT). To assess the real incidence and the spatial extension of sclerotic changes at the level of single glomerulus, we used serial-section morphological analysis to measure the volume of the glomerulus and that of sclerosis lesions. In glomeruli from control rats and in glomeruli from adriamycin (ADR) treated rats surface area of Bowman's capsule (BC), CT and sclerotic regions were measured using stereology techniques in all the consecutive sections containing each individual glomerulus, and corresponding volumes were then calculated. Mean volume of BC and CT were not significantly different between control and ADR rats (0.71 +/- 0.03 and 0.53 +/- 0.03 vs. 0.76 +/- 0.04 and 0.53 +/- 0.02 microns 3 x 10(-6), respectively). The distribution of glomerular volume parameters in the ADR rats were more spread out than in control animals, indicating that some glomeruli became smaller while other became larger. No sclerotic changes were found in control rats, while in the three ADR rats 94, 90 and 92% of glomeruli, respectively, were affected by sclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Glomerular response to hyperglycemia in human diabetic nephropathy.

We have studied the effect of acute hyperglycemia on glomerular function in seven insulin-dependent diabetics with overt nephropathy during hyperglycemic or euglycemic clamp. In all patients glomerular filtration rate (GFR) was higher during hyperglycemia than during euglycemia (35.0 +/- 15.5 vs. 21.4 +/- 10.3 ml.min-1.1.73 m-2, P less than 0.01), whereas renal plasma flow did not change significantly. To establish which determinant of GFR is altered by hyperglycemia, fractional clearances of neutral dextrans of graded molecular size were determined in both glycemic states, and data were analyzed by a theoretical model of hindered transport of macromolecules through a porous membrane. Hyperglycemia significantly increased sieving coefficients of small dextran molecules (28-40 A in radius), whereas fractional clearances of large macromolecules (greater than 44 A) did not change. Theoretical analysis suggested that the ultrafiltration coefficient (Kf) and membrane permeability to small dextrans (less than 40 A) increased in hyperglycemia in respect to euglycemia. Because these results have been obtained in patients with severe renal failure and hypertension, our conclusions do not necessarily apply to the early phase of diabetic nephropathy.

Body Water↗
PubMed1990

Angiotensin converting enzyme inhibition ameliorates glomerular filtration of macromolecules and water and lessens glomerular injury in the rat.

The effect of enalapril on glomerular hemodynamics and permselectivity and on subsequent sclerosis was studied in male MWF/Ztm rats which spontaneously develop proteinuria and glomerular structural damage. Untreated group 1 and enalapril-treated group 2 (50 mg/liter, in the drinking water) underwent micropuncture studies after 2 mo of observation. After the same period of treatment, group 3 (untreated) and group 4 (enalapril treated) were used for determination of whole-kidney function and neutral dextran clearances. Group 5 (untreated) and group 6 (enalapril treated) were followed for an additional 4 mo and used for kidney function and morphological studies. Enalapril significantly lowered systolic blood pressure, which was elevated in untreated groups, and significantly reduced proteinuria (295 +/- 64 vs. 128 +/- 24 mg/24 h by the end of the study). Despite the reduced renal perfusion pressure, whole-kidney glomerular filtration rate was higher in enalapril-treated than in untreated rats (0.96 +/- 0.14 vs. 0.81 +/- 0.10 ml/min, P less than 0.05) as was the single nephron glomerular filtration rate (54 +/- 7.1 vs. 46 +/- 4.0 nl/min, P less than 0.05). The single glomerular afferent plasma flow was comparable in both groups. Enalapril reduced mean glomerular capillary hydraulic pressure from the normal value of 51 +/- 1 mmHg (untreated rats) to a value lower than normal (44 +/- 1 mmHg, P less than 0.001). These hemodynamic changes were associated with a significant reduction in afferent (approximately 23%) and efferent (approximately 26%) arteriolar resistance. The mean ultrafiltration coefficient was two times higher in the enalapril (0.126 +/- 0.027 nl/s per mmHg) than in the untreated group (0.061 +/- 0.023 nl/s per mmHg). The clearance of dextran macromolecules relative to that of inulin was significantly reduced for all molecular sizes studied (26-64 A) in enalapril-treated vs. untreated rats. Theoretical analysis of dextran fractional clearances using a heteroporous model of neutral solute transport across the glomerular capillary wall indicated that enalapril affected glomerular membrane size selective properties, reducing uniformly the radius of hypothetical membrane pores. Enalapril treatment also significantly limited (P less than 0.01) the development of glomerular structural lesions (mean percentage of sclerotic glomeruli was 4.2 +/- 3.5% [treated] vs. 28 +/- 15% [untreated] rats at the end of the study) as well as tubulo-interstitial damage. These results suggest that the protective effect of enalapril on the development of proteinuria and glomerular sclerosis in this model is due to its property of ameliorating size selectivity and hydraulic permeability of the glomerular capillaries.

Animals↗
PubMed1989

Angiotensin-converting enzyme inhibition ameliorates the defect in glomerular size selectivity in hyponatremic hypertensive syndrome.

The glomerular size-selective properties in a patient with "hyponatremic hypertensive syndrome" were investigated before and after administration of the angiotensin-converting enzyme inhibitor enalapril. Hyponatremic hypertensive syndrome is a rare condition of renovascular hypertension characterized by electrolyte abnormalities (hyponatremia, hypokalemia), polyuria, and high renin activity. In this patient a marked increase in urinary protein excretion was observed. Treatment with enalapril normalized BP, corrected electrolyte abnormalities, and reduced proteinuria. Glomerular filtration rate (GFR), renal plasma flow (RPF), and the clearance of neutral dextrans of graded sizes were measured before and after 6 months of enalapril (20 mg/d) administration. Theoretical analysis of dextran and inulin clearance data with a model of glomerular size selectivity were adopted to separate effects of hemodynamic changes on macromolecule filtration from changes of intrinsic membrane selective properties. After enalapril urinary protein excretion decreased, GFR was unchanged and RPF almost doubled. Fractional clearance values of dextran molecules were markedly elevated in comparison with the corresponding values measured in a group of normal controls and were normalized by enalapril. Theoretical calculation of membrane pore characteristics showed that enalapril treatment reduced the radius of all membrane pores by approximately 1 nm. Altogether these results indicate that enalapril normalized glomerular filtration of neutral macromolecules and circulating proteins in a human condition of angiotensin II-induced proteinuria. Enalapril effectively restored glomerular size-selective function, reducing dimensions of membrane pores, independently of its effect on renal hemodynamics.

Aged↗
PubMed1989

Theoretical effects of network structure on glomerular filtration of macromolecules.

A parallel network model was developed to examine the effects of a distribution of capillary lengths on the filtration of macromolecules by the glomerulus. When networks having different distributions of capillary lengths (but similar values of single nephron glomerular filtration rate) were compared, the filtrate-to-plasma concentration ratio (theta s) for neutral macromolecules was found to increase as the vessel lengths became less uniform. Because anatomical studies have demonstrated that the glomerulus is in fact a heterogeneous network, this implies that the conventional modeling assumption of identical capillaries in parallel leads to an overestimation of effective pore sizes. However, simulations employing various pore-size distributions demonstrated that the expected errors in estimating membrane-pore parameters are generally negligible. Furthermore, the dependence of theta s on hemodynamic inputs such as glomerular plasma flow rate and transmembrane hydraulic pressure difference was insensitive to the assumed distribution of capillary lengths. We conclude that models based on dimensionally uniform capillary networks remain valid for interpreting clearance data for macromolecules.

Capillaries↗
PubMed1988

Sex related differences in glomerular ultrafiltration and proteinuria in Munich-Wistar rats.

Munich-Wistar rats (MWF/Ztm), originally selected for high number of superficial glomeruli, were used to correlate abnormal urinary protein excretion with glomerular hemodynamics and glomerular morphology. Two animal groups were used, one of male and one of female rats. They were kept periodically in metabolic cages to determine urinary protein excretion. All animals were fed standard rat chow. In male animals protein excretion, evaluated at seven weeks of age, was already significantly higher than in females (17 +/- 11 vs. 8 +/- 3 mg/24 hr), and then progressively increased averaging 291 +/- 51 mg/24 hr at week 21. In females urinary protein excretion was within the normal range up to week 18 and averaged 25 +/- 13 mg/24 hr at week 21. Body and kidney weight at the end of the experimental period were significantly higher in males than in females. Whole kidney inulin clearance (CIn) and single nephron glomerular filtration rate (SNGFR) were significantly higher in male than in female rats, while mean glomerular capillary hydraulic pressure (PGC) and transcapillary hydraulic pressure difference (delta P) were comparable. Single nephron glomerular plasma flow (QA) and afferent and efferent arteriolar resistance were comparable in male and female rats. The calculated glomerular ultrafiltration coefficient (Kf) was significantly higher in male than in female MWF/Ztm rats. No significant differences were detected between the two groups in the total number of glomeruli, and in glomerular size. These findings indicate that male MWF/Ztm rats develop spontaneous proteinuria, which progressively increases with the age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Glomerular size selectivity in nephrotic rats exposed to diets with different protein content.

Glomerular size-selective properties in animals made nephrotic by adriamycin (ADR) injection and fed standard (20% protein) or high-protein (35% protein) diets were investigated using dextran fractional clearances. To interpret filtration and dextran-sieving data, a theoretical approach previously developed for analysis of experimental data in healthy and nephrotic humans was used. Four types of hypothetical pore-radius distributions were compared in order to establish the best tool for describing membrane pore structure in normal and nephrotic rats. This analysis revealed that a spread distribution of pores, the lognormal probability distribution, is the most adequate in representing membrane intrinsic characteristics. ADR animals on standard diet developed massive proteinuria and a lower glomerular filtration rate (GFR) than control animals. High-protein feeding in ADR rats induced a further increase in urinary protein excretion and in GFR. Dextran fractional clearance was more elevated for larger dextran fractions (greater than 46 A) in ADR animals on the standard diet than in control rats. No differences were observed in dextran-sieving curves between ADR rats on the standard and high-protein diet. Theoretical analysis of filtration and fractional clearance data revealed comparable changes in the intrinsic parameters of glomerular size selectivity in the two groups of nephrotic animals. These observations indicate that increased traffic of plasma proteins through the glomerular capillary wall does not imply, in our experimental condition, a further loss of glomerular size-selective properties. The greater urinary protein excretion of ADR animals on high-protein diet than ADR animals on a standard diet cannot be explained by further impairment of glomerular size selectivity but more likely reflects hemodynamic changes.

Animals↗
PubMed1986

Theoretical effects of a distribution of capillary dimensions on glomerular ultrafiltration.

Simple network models were developed to examine the effects of a distribution of capillary dimensions on the filtration of fluid in the renal glomerulus. Two idealized networks were considered, one with parallel capillaries of varying length, and the other with parallel capillaries of varying radius. It was found that for a fixed value of the ultrafiltration coefficient (Kf), the product of hydraulic permeability and total capillary surface area per glomerulus, any assumed heterogeneity of capillary dimensions lowered the single nephron glomerular filtration rate (SNGFR) below that predicted for uniform capillaries in parallel. This implies that, to the extent that the capillaries are not identical, a given filtering surface area is used less efficiently. A consequence of this is that for a given set of measured glomerular pressures and flows, a model which assumes identical capillaries will underestimate the value of Kf for the actual (heterogeneous) glomerular network. The effects of a distribution in capillary lengths were found to be more pronounced, in general, than those of a distribution in radii. Considering only heterogeneity in capillary length, and characterizing the effective length distribution using available data in the literature, it was found that calculating Kf using the customary assumption of identical capillaries will underestimate the true value by approximately 30%, under typical micropuncture conditions in the rat. The predicted dependence of SNGFR on afferent plasma flow rate, transmural hydraulic pressure difference, and afferent protein concentration was quite similar, however, whether capillary dimensions were assumed to be uniform or heterogeneous.

Animals↗
PubMed1986

Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro.

The effects of hemodynamic forces upon vascular endothelial cell turnover were studied by exposing contact-inhibited confluent cell monolayers to shear stresses of varying amplitude in either laminar or turbulent flow. Laminar shear stresses (range, 8-15 dynes/cm2; 24 hr) induced cell alignment in the direction of flow without initiating the cell cycle. In contrast, turbulent shear stresses as low as 1.5 dynes/cm2 for as short a period as 3 hr stimulated substantial endothelial DNA synthesis in the absence of cell alignment, discernible cell retraction, or cell loss. The results of these in vitro experiments suggest that in atherosclerotic lesion-prone regions of the vascular system, unsteady blood flow characteristics, rather than the magnitude of wall shear stress per se, may be the major determinant of hemodynamically induced endothelial cell turnover.

Animals↗
PubMed1986

Role of renal prostaglandins in normal and nephrotic rats with diet-induced hyperfiltration.

Changes in glomerular hemodynamics have been observed in animals and humans after a high-protein feeding. It has been postulated that these changes can induce progressive deterioration of renal function favoring loss of glomerular permselectivity properties and subsequent glomerulosclerosis, especially when the renal mass is already reduced surgically or by a disease process. We studied the consequence of long-term protein supplementation on renal function parameters in normal animals and in animals affected by adriamycin nephrosis, a model of renal damage that closely mimics human "minimal change". We also wanted to investigate whether vasodilatory prostaglandins (PGs) generated at the renal level are responsible for the adaptive hemodynamic changes that follow dietary manipulation in normal animals and in animals with experimental nephrosis. The model of glomerular damage we used is characterized by heavy and persistent proteinuria induced in the rat by adriamycin (ADR). Two isocaloric diets were selected containing 20% and 35% protein. High-protein feeding induced a significant increase in glomerular filtration rate in both normal and nephrotic animals. In normal animals the high-protein diet did not modify the urinary excretion of 6-keto-PGF1 alpha, the stable breakdown product of prostacyclin (PGI2), but significantly reduced urinary excretion of prostaglandin E2. In nephrotic rats, the high-protein diet increased urinary excretion of 6-keto-PGF1 alpha, without modifying urinary excretion of prostaglandin E2. Glomerular synthesis of vasodilatory prostaglandins paralleled the urinary excretion pattern. The cyclooxygenase inhibitor indomethacin effectively inhibited urinary excretion of vasodilatory PGs but did not prevent hyperfiltration in normal animals fed the high-protein diet. At variance, when given to nephrotic animals fed the high-protein diet, indomethacin at a dose that reduced 6-keto-PGF1 alpha and prostaglandin E2 urinary excretion by 84% and 93%, respectively, inhibited hyperfiltration. We conclude that the same hemodynamic changes that occur in normal animals given a high-protein diet also take place when glomeruli are uniformly damaged by a disease process as in ADR nephrosis. However, whereas hyperfiltration in normal animals appears to be independent of renal PGs, in nephrotic animals an enhanced renal synthesis of PGI2 appears to play a crucial role in the adaptive changes responsible for hyperfiltration.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Platelet adhesion to subendothelium--effect of shear rate, hematocrit and platelet count on the dynamic equilibrium between platelets adhering to and detaching from the surface.

The adherence of human 3H-adenine-labeled platelets to rat subendothelium was quantitated using a rotating probe device. Platelet adhesion increased in relation to the rotation time, reaching a plateau value in about 4-6 min without any further increase. A non-linear fitting analysis of experimental data allowed calculations of initial rate and plateau value of platelet adhesion. Increasing the shear rates (from 35 to 150 sec-1) or the hematocrit (from 10% to 40%), both the adhesion rate and the plateau value were increased. When different platelet concentrations were used the adhesion rate and the plateau calculated increased with platelet concentration. Different plateau values were obtained in the experimental conditions considered. This suggests that the plateau was not reached for the complete occupation of the subendothelial surface by the adherent platelets. Experiments using two different vessels rotated in the same platelet suspension or, viceversa, the same vessel rotated successively in two fresh platelet suspensions, showed that the plateau was not determined by reduced platelet reactivity. Rotating the same vessel first in radiolabeled platelets, until the plateau was reached, and secondly in non labeled platelets, or viceversa, showed that the plateau was indeed a dynamic condition where the number of platelets adhering and detaching reached equilibrium. These observations suggest that the platelet adhesion to subendothelium is the final equilibrium of two platelet fluxes, one adhering to the surface and another detaching from the surface.

Animals↗