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A Remuzzi

Publications and source records attributed to A Remuzzi.

At least 19 recordsLinked to original sources
PubMed2007

Vitamin D, insulin resistance, and renal disease.

Chonchol and Scragg report the results of a population study on levels of 25-hydroxyvitamin D in patients with renal dysfunction. They demonstrate that these patients do not show vitamin D deficiency unless renal function is severely affected (GFR<29 mL/min/1.73m2), while vitamin D and renal function loss are independently associated with insulin resistance. These data provide more solid evidence than previous available studies on small patient groups, and pose new questions about the mechanisms responsible for progressive renal disease as well as potential effects of vitamin D supplementation.

Humans↗
PubMed2006

ACE inhibition reduces glomerulosclerosis and regenerates glomerular tissue in a model of progressive renal disease.

Today angiotensin II inhibition is primarily used to slow the rate of progression of kidney diseases. There is evidence that these therapies can induce a partial regression of glomerular lesions. However, we do not know yet the extent of sclerotic lesion regression and whether new glomerular tissue is formed to help support the renal function. We used male Munich Wistar Fromter (MWF) rats, an experimental model for progressive kidney disease, to quantify kidney structural lesions upon angiotensin-converting enzyme (ACE) inhibition therapy. Animals were studied at 50 weeks of age, when renal function and structure are severely altered, and after a 10-week observation period, without or with treatment with lisinopril (80 mg/l in drinking water). A group of untreated Wistar rats was used as controls. With age, proteinuria, and serum creatinine worsen, but lisinopril almost normalized proteinuria and stabilized serum creatinine. Serial section analysis of whole glomerular tufts showed that at baseline, glomerulosclerosis affected the entire glomerular population, and that these changes further increased with age. Lisinopril significantly reduced incidence and extent of glomerulosclerosis, with the presence of glomerular tufts not affected by sclerosis (23% of glomeruli). Glomerular volume was not significantly affected by treatment, and glomerular mass spared from sclerosis increased from 46.9 to 65.5% upon treatment, indicating consistent regeneration of glomerular tissue. Lisinopril normalized baseline glomerular transforming growth factor-beta and alpha-smooth muscle actin overexpression, and prevented worsening of interstitial changes. Hence, ACE inhibition, which is widely used in human kidney disease, may not only halt the progression of renal failure, but also actually induce the regeneration of new renal tissue.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic environment.

Natural cartilage remodels both in vivo and in vitro in response to mechanical forces and hence mechanical stimulation is believed to have a potential as a tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis on animal cells. A well-defined hydrodynamic environment is required to study the biochemical response to shear of three-dimensional engineered cell systems. We have developed a perfused-column bioreactor in which the culture medium flows through chondrocyte-seeded porous scaffolds, together with a computational fluid-dynamic model of the flow through the constructs' microstructure. A preliminary experiment of human chondrocyte growth under static versus dynamic conditions is described. The median shear stress imposed on the cells in the bioreactor culture, as predicted by the CFD model, is 3 x 10(-3) Pa (0.03 dyn/cm(2)) at a flow rate of 0.5 ml/min corresponding to an inlet fluid velocity of 44.2 mum/s. Providing a fluid-dynamic environment to the cells yielded significant differences in cell morphology and in construct structure.

Bioreactors↗
PubMed2002

The response of endothelial cells to fluid shear stress using a co-culture model of the arterial wall.

An endothelial cell (EC) smooth muscle cell (SMC) co-culture model of the arterial wall was used to study the effect of fluid shear stress on EC behavior. This model, in addition to being a more realistic tissue analogue, is a valuable research tool for studying the effects of mechanical stimulation upon the behavior of both SMCs and ECs. In the present study, a 10% cyclic strain was used to alter the characteristics of an SMC-seeded collagen gel. This form of strain preconditioning resulted in a rearrangement of the vessel wall that yielded circumferentially oriented cells and collagen fibrils. The preconditioned collagen gel was subsequently seeded with ECs and exposed to fluid-induced shear stress (10 dynes/cm2) for 48 hr. In the absence of flow, ECs seeded on slab constructs were oriented with the underlying collagen fibrils. Sheared constructs exhibited ECs oriented in the flow direction. Shear stress also affected EC proliferation, reducing the total number of dividing ECs by as much as 48 percent compared to unsheared constructs. The shear-induced reduction in proliferation was further enhanced when constructs were first strain-preconditioned (64% reduction). Moreover, conditioned media from shear stress experiments inhibited proliferation of ECs seeded on tissue culture plastic. These results suggest that EC response to fluid shear stress in a collagen co-culture model is influenced by the underlying substrate, and one that in this study is modified by strain preconditioning.

Arteries↗
PubMed2001

Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress.

Verotoxin-1 (VT-1)-producing Escherichia coli is the causative agent of postdiarrheal hemolytic uremic syndrome (D+HUS) of children, which leads to renal and other organ microvascular thrombosis. Why thrombi form only on arterioles and capillaries is not known. This study investigated whether VT-1 directly affected endothelial antithrombogenic properties promoting platelet deposition and thrombus formation on human microvascular endothelial cell line (HMEC-1) under high shear stress. Human umbilical vein endothelial cells (HUVECs) were used for comparison as a large-vessel endothelium. HMEC-1 and HUVECs were pre-exposed for 24 hours to increasing concentrations of VT-1 (2-50 pM) and then perfused at 60 dynes/cm(2) with heparinized human blood prelabeled with mepacrine. Results showed that VT-1 significantly increased platelet adhesion and thrombus formation on HMEC-1 in comparison with unstimulated control cells. An increase in thrombus formation was also observed on HUVECs exposed to VT-1, but to a remarkably lower extent. The greater sensitivity of HMEC-1 to the toxin in comparison with HUVECs was at least in part due to a higher expression of VT-1 receptor (20-fold more) as documented by FACS analysis. The HMEC-1 line had a comparable susceptibility to the thrombogenic effect of VT-1 as primary human microvascular cells of the same dermal origin (HDMECs). The adhesive molecules involved in VT-induced thrombus formation were also studied. Blocking the binding of von Willebrand factor to platelet glycoprotein Ib by aurintricarboxylic acid (ATA) or inhibition of platelet alpha(IIb)beta(3)-integrin by chimeric 7E3 Fab resulted in a significant reduction of VT-1-induced thrombus formation, suggesting the involvement of von Willebrand factor-platelet interaction at high shear stress in this phenomenon. Functional blockade of endothelial beta(3)-integrin subunit, vitronectin receptor, P-selectin, and PECAM-1 with specific antibodies was associated with a significant decrease of the endothelial area covered by thrombi. Confocal microscopy studies revealed that VT-1 increased the expression of vitronectin receptor and P-selectin and redistributed PECAM-1 away from the cell-cell border of HMEC-1, as well as of HDMECs, thus indicating that the above endothelial adhesion molecules are directly involved and possibly determine the effect of VT-1 on enhancing platelet adhesion and thrombus formation in microvascular endothelium. These results might help to explain why thrombi in HUS localize in microvessels rather than in larger ones and provide insights on the molecular events involved in the process of microvascular thrombosis associated with D+HUS.

Blood Platelets↗
PubMed2001

Automatic generation of glomerular capillary topological organization.

Glomerular structural changes are conventionally investigated by optical or electron microscopy on two-dimensional (2D) sections. To understand the relationship between functional and structural changes of glomerular capillary networks in more detail, three-dimensional (3D) investigation of the capillary tufts is required. Since confocal microscopy and scanning electron microscopy cannot completely show the 3D topological organization of the capillary tuft, we have developed an automatic method to obtain a 3D model of the glomerular capillary lumen structure and to derive its topological organization. Serial semithin sections of a glomerular tuft, from rat kidney tissue, were digitized at high resolution. Capillary lumens were digitally outlined and segmented images were automatically aligned. A 3D model of the capillary tuft was automatically generated using the Visualization Toolkit library and the Marching Cubes algorithm. We then developed an original algorithm for automatic 3D skeletonization of capillary lumen volume to identify capillary segments and bifurcations and to obtain the topological organization of the network and geometric parameters of capillary segments (length, radius, and spatial configuration). Capillary segment connectivity was graphically presented in a 2D layout with an automatic procedure, revealing the lobular organization of the network. This technique, successfully applied to serial sections of a glomerular capillary, can be used to study a population of glomerular capillaries to disclose the structural effects of pathological conditions. The methodology can be extended to other vascular structures, such as the microcirculation of neoplastic tissues.

Algorithms↗
PubMed2001

Angiotensin-converting enzyme inhibition prevents glomerular-tubule disconnection and atrophy in passive Heymann nephritis, an effect not observed with a calcium antagonist.

In proteinuric nephropathies tubular atrophy leads to glomerular-tubule disconnection through an unknown mechanism. Here we studied whether proteinuria promoted glomerular-tubule disconnection in individual nephrons and whether this phenomenon was prevented by an angiotensin-converting enzyme (ACE) inhibitor. Passive Heymann nephritis (PHN) and control rats were studied at 4 and 8 months. Two additional groups of PHN rats received lisinopril (40 mg/L) or a calcium channel blocker (lacidipine, 3 mg/kg) from day 7 after surgery to 8 months. At sacrifice, kidneys were serially sectioned to identify glomerular- tubule abnormalities in individual nephrons and changes in interstitial volume. In PHN rats, the time-dependent increase in proteinuria was paralleled by tubular atrophy leading to glomerular-tubule disconnection and interstitial volume enlargement. Marked apoptosis was invariably found in atrophic tubules in contrast to the absent or very mild terminal dUTP nick-end labeling staining in tubules normally connected to glomeruli in PHN animals. Treatment with an ACE inhibitor prevented hypertension, proteinuria, the formation of atrophic tubuli, glomerular-tubule disconnection and limited the fractional interstitial volume expansion. Although lacidipine limited hypertension, it did not reduce proteinuria or prevent tubular atrophy and disconnection. Multivariate analysis showed that the appearance of atubular glomeruli and the increase in interstitial volume were better predicted by proteinuria than blood pressure. This study suggests that ACE inhibitors effectively prevent glomerular-tubule disconnection possibly by their ability of reducing proteinuria, which in turn favors proximal tubular cell apoptosis. Agents that only reduced hypertension but not proteinuria do not affect tubular behavior.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Post-transplant renal artery stenosis: the hemodynamic response to revascularization.

BACKGROUND: Percutaneous transluminal angioplasty and stenting are relatively noninvasive approaches to treat post-transplant renal artery stenosis. However, the real impact of this procedure on renal function recovery has never been quantitated precisely to date. METHODS: In eight consecutive renal transplant patients with renal graft artery stenosis, blood pressure, body weight, and anatomical, functional, and Doppler ultrasound parameters were evaluated before and one month after renal artery transluminal angioplasty and stenting. On both occasions, glomerular filtration rate and renal plasma flow were evaluated by inulin and paraaminohippuric acid renal clearances, and glomerular size-selective function was evaluated by the fractional clearances of neutral dextran macromolecules. RESULTS: The correction of renal artery stenosis, by normalizing renal vascular resistances, fully restored kidney perfusion and decreased arterial blood pressure, relieved water and sodium retention, restored an almost laminar arterial blood flow, and normalized vascular shear stress without appreciable effects on glomerular barrier size-selective function and proteinuria. Preangioplasty and postangioplasty renal resistive indices and peak systolic blood velocity estimated by Doppler ultrasounds were significantly correlated with the effective renal plasma flow and the blood velocity calculated at the site of stenosis. All patients were discharged without sequelae one or two days after angioplasty. CONCLUSIONS: Percutaneous transluminal angioplasty and stenting are safe and effective procedures to normalize the functional changes sustained by hemodynamically significant artery stenosis after renal transplantation. Doppler ultrasound scanning is a reliable and reproducible technique to monitor the renal functional response to vascular reperfusion.

Adult↗
PubMed2001

Computational fluid dynamics of a vascular access case for hemodialysis.

Vascular accesses (VA) for hemodialysis are usually created by native arteriovenous fistulas (AVF) or synthetic grafts. Maintaining patency of VA continues to be a major problem for patients with end-stage renal disease, since in these vessels thrombosis and intimal hyperplasia often occur. These lesions are frequently associated with disturbed flow that develops near bifurcations or sharp curvatures. We explored the possibility of investigating blood flow dynamics in a patient-specific model of end-to-end native AVF using computational fluid dynamics (CFD). Using digital subtraction angiographies of an AVF, we generated a three-dimensional meshwork for numerical analysis of blood flow. As input condition, a time-dependent blood waveform in the radial artery was derived from centerline velocity obtained during echo-color-Doppler ultrasound examination. The finite element solution was calculated using a fluid-dynamic software package. In the straight, afferent side of the radial artery wall shear stress ranged between 20 and 36 dynes/cm2, while on the inner surface of the bending zone it increased up to 350 dynes/cm2. On the venous side, proximal to the anastomosis, wall shear stress was oscillating between negative and positive values (from -12 dynes/cm2 to 112 dynes/cm2), while distal from the anastomosis, the wall shear stress returned within the physiologic range, ranging from 8 to 22 dynes/cm2. Areas of the vessel wall with very high shear stress gradient were identified on the bending zone of the radial artery and on the venous side, after the arteriovenous shunt. Secondary blood flows were also observed in these regions. CFD gave a detailed description of blood flow field and showed that this approach can be used for patient-specific analysis of blood vessels, to understand better the role of local hemodynamic conditions in the development of vascular lesions.

Arteriovenous Anastomosis↗
PubMed2000

Influence of donor age on bovine pancreatic islet isolation.

BACKGROUND: Pancreatic islets from pigs are largely used for experimental studies. However, pancreas harvesting requires modification of conventional slaughtering to reduce ischemia time. It has been shown that bovine pancreatic islets can be more easily obtained and they show satisfactory in vitro and in vivo function. To improve the isolation procedure we compared the effect of bovine donor age on islet isolation. METHODS: Islets were isolated by collagenase digestion and sequential sieving from calves (6 months of age) and from adult bovine (> 16 months of age). After isolation the number of islet equivalents was calculated and histological and immunohistochemical studies performed. The purity and viability of islet for each preparation was also estimated. In vitro function of islets was evaluated by static insulin secretion assay, and alginate encapsulated islets were transplanted in streptozotocin-induced diabetic rats for in vivo functional evaluation. RESULTS: A significantly higher number of islets were obtained from calf pancreas, compared with adult bovine pancreas. Hystological examination showed intact morphologic features of islets. The purity of islet preparations was higher from calf pancreas than from adult pancreas. Cell viability, and insulin production in presence of high glucose concentration, were not affected by donor age. All animals receiving microencapsulated islets from calves showed normoglycemia for prolonged periods (17-40 days). CONCLUSIONS: These results indicate that pancreatic islet isolation is more efficient from juvenile bovine than from adult. Calf pancreas is a good and convenient source of tissue for massive islet isolation for experimental studies.

Aging↗
PubMed2000

Shear stress downregulation of platelet-derived growth factor receptor-beta and matrix metalloprotease-2 is associated with inhibition of smooth muscle cell invasion and migration.

BACKGROUND: After endovascular injury, smooth muscle cells (SMCs) may be exposed to hemodynamic shear stress (SS), and these forces modulate neointima accumulation. The effect of SS on SMC migration and invasion is unknown, and it was examined in the present study. METHODS AND RESULTS: Bovine aortic SMCs were exposed to laminar SS of 12 dyne/cm(2) for 3 (SS3) or 15 (SS15) hours; control (C3 and C15) SMCs were kept under static conditions. Platelet-derived growth factor (PDGF)-BB-directed SMC migration and invasion were evaluated by a modified Boyden chamber assay with filters coated with either gelatin or reconstituted basement membrane proteins (Matrigel), respectively. SS15 inhibited both SMC migration and invasion (P<0.0001). There was no significant difference between SS3 and C3 cells. Media conditioned with SS15 cells exhibited a reduction in matrix metalloprotease-2 (MMP-2) by zymography and Western analysis. Northern blot analysis revealed no effect of SS15 on MMP-2 mRNA. In contrast, SS15 decreased MMP-2 activator and membrane-type MMP (MT-MMP or MMP-14) mRNA and protein. Furthermore, SS15 decreased PDGF receptor-beta (PDGF-Rbeta) mRNA and protein (P<0.05), and the SS-dependent decrease in PDGF-BB-directed cell migration was rescued by overexpressing PDGF-Rbeta. CONCLUSIONS: SS inhibits SMC migration and invasion via diminished PDGF-Rbeta expression. This effect of SS is associated with decreased MMP-2 secretion and MT-MMP downregulation.

Animals↗
PubMed2000

ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome.

Patients with idiopathic membranous nephropathy (IMN) and persistent nephrotic-range proteinuria are at risk for progression to end-stage renal failure. Whether angiotensin-converting enzyme (ACE) inhibitors are also renoprotective in these patients remains elusive. In 14 patients with IMN (patients) and persistent proteinuria (protein > 3 g/24 h for >6 months), we studied mean arterial pressure (MAP), urinary protein excretion, glomerular filtration rate (GFR), renal plasma flow (RPF), and albumin and neutral dextran fractional clearance after 2 months washout from previous antihypertensive treatment (basal), after 2 months of enalapril (2.5 to 20 mg/d) therapy (posttreatment), and 2 months after enalapril withdrawal (recovery). MAP, proteinuria, and GFR were also measured at the same time points in 6 patients with IMN and persistent overt proteinuria maintained on conventional treatment throughout the study period (controls). Basal MAP, proteinuria, and GFR were similar in the two study groups. However, in patients at the end of the treatment period, MAP (posttreatment, 99.6 +/- 11.2 versus basal, 103.3 +/- 12.1 mm Hg; P < 0.05), proteinuria (posttreatment protein, 5.0 +/- 2.9 versus basal, 7.1 +/- 4.9 g/24 h; P < 0.05), albumin fractional clearance (posttreatment median, 1.7 x 10(-3); range, 0.2 to 22.7 x 10(-3) versus basal median, 4.1 x 10(-3); range, 0.4 to 22. 1 x 10(-3); P < 0.05), and fractional clearance of largest neutral dextrans (radii from 62 to 66 A) were significantly less than basal values. At recovery, MAP significantly increased to 106.6 +/- 11.7 mm Hg (P < 0.001 versus enalapril), but all other parameters remained less than basal values. GFR and RPF were similar at each evaluation. Changes in proteinuria after treatment withdrawal positively correlated (r = 0.72; P < 0.01) with baseline GFR. Theoretical analysis of dextran-sieving data indicated that ACE inhibitor treatment significantly improved glomerular membrane size-selective dysfunction. This effect persisted more than 2 months after treatment withdrawal. No patient had symptomatic hypotension, acute renal function deterioration, or hyperkalemia during enalapril treatment. Thus, in patients with IMN and long-term nephrotic syndrome, ACE inhibitor treatment, but not conventional therapy, improves glomerular barrier size selectivity. The antiproteinuric effect of ACE inhibition is long lasting, especially in patients with more severe renal insufficiency. This is the premise of a long-term renoprotective effect that may limit the need for treatment with more toxic drugs.

Adult↗
PubMed2000

A novel interpretation of the role of von Willebrand factor in thrombotic microangiopathies based on platelet adhesion studies at high shear rate flow.

Clinical manifestations of thrombotic microangiopathies (TMA) are secondary to platelet aggregation and thrombotic occlusion of the microvasculature of the affected organs. Abnormalities in von Willebrand factor (vWF) in these patients were considered instrumental in promoting the process leading to microvascular thrombosis. We evaluated the capacity of plasma in these patients to induce adhesion of normal platelets and thrombus formation under conditions of controlled fluid shear stress. We also studied vWF multimeric distribution to establish whether abnormalities of this glycoprotein correlate with platelet adhesion and thrombus formation. Plasma from patients in the acute phase and remission showed the same capacity to induce platelet adhesion and thrombus formation at a low level of shear rate (600 sec(-1)) as plasma from control subjects. At a high shear rate (1,500 sec(-1)), platelet adhesion and thrombus dimensions were significantly increased (P: < 0.05) by plasma from patients with TMA compared with controls. The capacity to enhance thrombus formation at high shear stress was present during the acute phase and disease remission and did not correlate with the presence of unusually large vWF multimers. Increased thrombus formation with patient plasma is completely normalized by blocking the interaction of vWF with the platelet receptors, glycoprotein (GP)Ib and GPIIb-IIIa, suggesting that the phenomenon is completely mediated by vWF. Our results suggest the possibility of an intrinsically altered vWF molecule in these patients that is probably more effective than normal vWF in mediating platelet adhesion and thrombus formation.

Adult↗
PubMed2000

Localization of cerebral arterovenous malformations using digital angiography.

Since 1989 we performed stereotactic radiotherapy treatments of cerebral arterovenous malformations (AVM), estimating three-dimensional (3-D) localization and shape of target volumes by the Leksell stereotactic helmet on two orthogonal radiographic projections. Due to the limitations of this method, we developed a new technique for the localization of the target volume using digital subtraction angiography (DSA) and digital image processing. To achieve this result we first developed a method to correct nonlinear distortion of DSA images using spatial relocation of image pixels based on a calibration grid. We then developed an algorithm for localization of the target volume using two independent DSA projections. Target volume coordinates in the helmet system are calculated using two DSA acquisitions taken with a free angle (approximately 90 degrees), one in the AP and the other in the LL direction. The helmet can be freely positioned between the x-ray source and the image plane. The projections of eight reference points inserted in the helmet at a known location, are used to calculate the transformation matrix between the two coordinate systems. We performed numerical and experimental validation of the system. A hypothetical random error (up to 2 mm) on image coordinates of the reference points allowed to determine that the error in target localization was less than 0.2 mm. Using DSA images of target points with a known location within a phantom, the error between calculated and actual location was, on average, 0.30+/-0.13 mm (mean+/-SD), with a maximum error of 0.49 mm. The results of numerical and experimental validations show that the system we have developed allows fast and accurate localization of the center of the target volume and it is suitable for efficient guiding during stereotactic radiosurgery of AVM.

Algorithms↗
PubMed2000

Ringtail in suckling Munich Wistar Fromter rats: a histopathologic study.

Ringtail is a pathologic condition of the tail of rats and other rodents that is traditionally attributed to low environmental humidity, although dietary deficiencies, genetic susceptibility, environmental temperature, and degree of hydration of the animal also have been suggested as possible causes. To the authors' knowledge, a detailed histopathologic study that may serve to shed light on the etiopathogenesis of this disease has not yet been published. We describe the histologic findings of ringtail observed in 12 suckling Munich Wistar Fromter (MWF) rats from two litters. Epidermal hyperplasia characterized by orthokeratotic and parakeratotic hyperkeratosis and acanthosis was observed in all affected rats. Numerous often dilated vessels were present in the dermis of tails that appeared of red/brown color at gross examination. In severe cases, the dilated vascular structures were thrombotic and accompanied by dermal hemorrhages and focal coagulative necrosis of the overlying epidermis. These findings suggest that epidermal acanthosis and hyperkeratosis are the main and primary events in the development of ringtail. To clarify the cause of this disease, future studies should be focused on the numerous factors that can induce such epidermal changes.

Animals↗
PubMed1999

Beneficial effects of calcium channel blockade on acute glomerular hemodynamic changes induced by cyclosporine.

Experimental and human studies have documented that cyclosporine (CsA) acutely reduces glomerular filtration rate (GFR). It has been reported that this effect can be partially prevented by calcium (Ca) channel blockade; however, the mechanisms by which this combination exerts its beneficial effects are unknown. We evaluated glomerular ultrafiltration determinants during acute CsA administration in the rat. First, we determined that maximal whole-kidney functional changes occur between 120 and 150 minutes after CsA administration and confirmed that pretreatment of MWF rats with the Ca channel blocker lacidipine effectively prevents a reduction in GFR. Micropuncture measurements in CsA-treated animals showed that a reduction in GFR (0.49 +/- 0.24 v 0.88 +/- 0.26 mL/min; P < 0.05; CsA-treated v untreated rats) is associated with a significant increase in glomerular capillary pressure (Pgc; 63.1 +/- 2.1 v 52.8 +/- 2.8 mm Hg; P < 0.01) and efferent arteriolar resistance, whereas single-nephron (SN) GFR and ultrafiltration coefficient (Kf) are both importantly reduced (34.0 +/- 11.7 v 68.9 +/- 23.8 nL/min; P < 0.05 and 1.04 +/- 0.33 v 4.40 +/- 2.36 nL/min/mm Hg; P < 0.01, respectively). Lacidipine partially prevented SNGFR (43.1 +/- 14.3 nL/min) and Kf decline (2.08 +/- 1.10 nl/min/mm Hg) despite the presence of elevated Pgc. This study further documents that Ca channel blockade has favorable effects on CsA-induced acute renal dysfunction. The mechanism of protection includes the prevention of glomerular hemodynamic changes induced by CsA, mainly GFR decline and reduction in glomerular Kf.

Acute Disease↗
PubMed1999

ACE inhibition induces regression of proteinuria and halts progression of renal damage in a genetic model of progressive nephropathy.

Experimental data consistently indicate that renal disease progression is fully prevented in proteinuric glomerulopathies by long-enough angiotensin-converting enzyme (ACE) inhibition therapy. Whether regression of established proteinuria to normal can be achieved is, however, ill defined. The current study was designed with the aim to clarify whether ACE inhibition may induce regression of established proteinuria and renal structural damage in MWF rats, a genetic model of progressive proteinuria and renal injury. Animals treated with the ACE inhibitor lisinopril from 20 weeks of age (time when proteinuria is already important) and age-matched untreated rats were followed for 10 weeks. ACE inhibition normalized systolic blood pressure and progressively reduced proteinuria (from 172 +/- 79 to 81 +/- 23 mg/24 hours). In these animals, a highly significant correlation was obtained between baseline proteinuria and antiproteinuric response. At variance in untreated rats, proteinuria showed a marked increase in the 10-week follow-up period (from 165 +/- 57 to 325 +/- 86 mg/24 hours). Lisinopril prevented the progression of renal damage, as documented by a significantly lower incidence of glomeruli affected by sclerotic lesions (P < 0.01) than in untreated animals after the 10-week study period. Kidney tissue damage was comparable in lisinopril-treated rats and in untreated animals at 20 weeks of age, indicating that structural changes were arrested by the treatment. Thus, in proteinuric MWF rats, late-onset ACE inhibition normalized blood pressure, effectively and progressively restored high protein excretion rate toward normal values, and arrested progression of tissue damage.

Angiotensin-Converting Enzyme Inhibitors↗