Pegylated interferon (alone or with ribavirin) for chronic hepatitis C in haemodialysis population.

BACKGROUND/AIMS: Hepatitis C virus infection remains prevalent among patients undergoing long-term haemodialysis and has a detrimental impact on survival in this population. Antiviral therapy for chronic hepatitis C in haemodialysis patients is still a challenge to clinicians. The aim of the current study is to evaluate the efficacy and safety of therapy with pegylated interferon, alone or combined with ribavirin, for chronic hepatitis C among patients undergoing long-term hemodialysis. METHODS: We conducted a retrospective, multicenter cohort trial with monotherapy (pegylated interferon) (n=21) or combined antiviral therapy (pegylated interferon plus ribavirin) (n=5) for chronic hepatitis C in patients undergoing long-term haemodialysis. RESULTS: Sustained virological response was obtained in eleven (42%) patients. Seven (26.9%) patients interrupted prematurely the antiviral treatment due to serious side-effects, the most frequent cause of treatment withdrawal being hematological (n=3). HCV RNA load was lower in responder than non-responder patients, 5.44 (3.45; 6.36) vs. 5.86 (4.61; 6.46) log10 copies/mL, even if the difference was not significant (P=0.099). Blood transfusion requirement was greater in patients on combined antiviral therapy than those on pegylated interferon alone, 100% (5/5) vs. 0% (0/21), P=0.0001. No difference in sustained viral response occurred between patients on combined antiviral therapy and those on pegylated interferon monotherapy [40% (2/5) vs. 42.8% (9/21), P=0.90]. CONCLUSIONS: Results from this study showed that pegylated interferon alone or with ribavirin is unsatisfactory in terms of efficacy and safety. Prospective trials based on interferon-free regimens (i.e., sofosbuvir plus ribavirin or sofosbuvir plus daclatasvir) are under way in patients with hepatitis C receiving long-term hemodialysis.

Inhibition of JAK2 protects renal endothelial and epithelial cells from oxidative stress and cyclosporin A toxicity.

Cyclosporin A is an immunosuppressant drug widely used in solid organ transplantation, but it has nephrotoxic properties that promote oxidative stress. The JAK2/STAT pathway has been implicated in both cell protection and cell injury; therefore, we determined a role of JAK2 in oxidative stress-mediated renal cell injury using pathophysiologically relevant oxidative challenges. The AG490 JAK2 inhibitor and overexpression of a dominant negative JAK2 protein protected endothelial and renal epithelial cells in culture against peroxide, superoxide anion and cyclosporin A induced cell death while reducing intracellular oxidation in cells challenged with peroxide and cyclosporin A. The decrease in Bcl2 expression and caspase 3 activation, induced by oxidative stress, was prevented by AG490. In mouse models of ischemia/reperfusion and cyclosporin A nephrotoxicity, AG490 decreased peritubular capillary and tubular cell injury. Our study shows that JAK2 inhibition is a promising renoprotective strategy defending endothelial and tubular cells from cyclosporin A- and oxidative stress-induced death.

A novel methodology for the analysis of membrane and cytosolic sub-proteomes of erythrocytes by 2-DE.

With the aim of studying a wide cohort of erythrocyte samples in a clinical setting, we propose here a novel approach that allows the analysis of both human cytosolic and membrane sub-proteomes. Despite their simple structure, the high content of hemoglobin present in the red blood cells (RBCs) makes their proteome analysis enormously difficult. We investigate here different strategies for isolation of the membrane and cytosolic fractions from erythrocytes and their influence on proteome profiling by 2-DE, paying particular attention to hemoglobin removal. A simple, quick and satisfactory approach for hemoglobin depletion based on HemogloBind reagent was satisfactorily applied to erythrocyte cells, allowing the analysis of the cytosolic sub-proteome by 2-DE without major interference. For membrane proteome, a novel combined strategy based on hypotonic lysis isolation and further purification on minicolumns is described here, allowing detection of high molecular weight proteins (i.e. spectrin, ankyrin) and well-resolved 2-DE patterns. An aliquot of the membrane fraction was also in solution digested and analyzed by nano-LC coupled to an LTQ-Orbitrap mass spectrometer. A total of 188 unique proteins were identified by this approach. This study sets the basis for future clinical studies where the erythrocyte cell may be implicated.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Alkalinization potentiates vascular calcium deposition in an uremic milieu.

BACKGROUND: Vascular calcification is a serious complication of chronic kidney disease. Acid-base balance is a relevant, albeit somewhat forgotten factor in the regulation of calcium deposition. Hemodialysis patients undergo repeated episodes of alkaline loading from the dialysate, resulting in prolonged alkalinization. We have hypothesized that extracellular alkalinization may promote vascular calcification. METHODS: Primary cultures of vascular smooth muscle cells were induced to calcify by the phosphate donor beta-glycerophosphate, in the presence of normal or uremic sera from hemodialysis patients and at different pH conditions. The influence of sodium bicarbonate supplementation for 2 months on aorta calcification was studied in 5/6 nephrectomized uremic rats. RESULTS: Uremic serum increased vascular smooth muscle cell calcification (twofold over nonuremic human serum at day 12, p<0.001). Alkalinization of the extracellular medium also increased vascular smooth muscle cell calcification. Increasing the extracellular pH from 7.42 to 7.53 resulted in a 2.5-fold increase in calcium accumulation at day 12 (p<0.05). In vivo, arterial calcification was significantly higher in alkalinized uremic animals (aorta calcification index, uremic + sodium bicarbonate, 164 +/- 57 units, vs. uremic + vehicle, 56 +/- 14 units; p<0.01). CONCLUSIONS: Alkalinization increases vascular calcification in cultured cells and uremic rats. These data may be used to optimize dialysate composition and the degree of alkalinization in calcification-prone individuals with advanced renal disease.

An integrative approach to the anatomy of Syllis gracilis Grube, 1840 (Annelida) using micro-computed X-ray tomography.

BACKGROUND: The overall anatomy of the genus Syllis (Annelida: Syllidae) has been largely studied; however, an integrative approach considering different anatomical techniques has never been considered. Here, we use micro-computed X-ray tomography (micro-CT) to examine the internal anatomy of Syllis gracilis Grube, 1840, along with other widely available techniques. METHODS: We studied the anatomy of the marine annelid S. gracilis through an integrative approach, including micro-CT along with stereo and light compound microscopy (STM, LCM), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and histological sectioning (HIS). In this manner, we evaluated the applicability of micro-CT for the examination of annelid anatomy by testing whether the images obtained make it possible to visualize the main body structures, in comparison with other current techniques, of the various elements of its internal anatomy. RESULTS: Overall external and internal body elements are clearly shown by the integrative use of all techniques, thus overcoming the limitations of each when studied separately.Any given method shows disparate results, depending on the body part considered. For instance, micro-CT provided good images of the external anatomy, including relevant characters such as the shape, length and number of articles of dorsal parapodial cirri. However, it is especially useful for the examination of internal anatomy, thus allowing for 3D visualization of the natural spatial arrangement of the different organs. The features best visualized are those of higher tissue density (i.e., body musculature, anterior parts of the digestive tract), particularly in 3D images of unstained specimens, whereas less electrodense tissues (i.e., the peritoneal lining of septa and nervous system) are less clearly visualized. The use of iodine stain with micro-CT has shown advantages against non-staining for the adequate observation of delicate elements of low density, such as the segmental organs, the connective between the ganglia, the ventral nerve cord and segmental nerves. DISCUSSION: Main external anatomical elements of S. gracilis are well shown with micro-CT, but images show lesser optical resolution and contrast when compared to micrographs provided by SEM and CLSM, especially for fine structural features of chaetae. Comparison of micro-CT and HIS images revealed the utility and reliability of the former to show the presence, shape and spatial disposition of most internal body organs; the resolution of micro-CT images at a cellular level is, however, much lower than that of HIS, which makes both techniques complementary.

Hyperphosphatemia and hyperparathyroidism in incident chronic kidney disease patients.

UNLABELLED: Disturbances in bone and mineral metabolism are common in chronic kidney disease (CKD) patients. Most studies have been performed in hemodialysis and there is less information on non-dialysis patients, on the coexistence of other risk factors and on the achievement of more recent and stringent guidelines. Cross sectional study of analytical mineral and bone parameters in 125 incident patients (creatinine clearance <60 ml/min) in a monographic CKD clinic. Evaluation after one year of follow-up in 69 patients. Progression of CKD was associated with significant increased levels of phosphate, calcium x phosphate and iPTH and decreased calcium and 1,25 dihydroxyvitamin D. Levels of 25-hydroxyvitamin D were unchanged, but lower than recommended. Phosphate correlated negatively with 1,25-dihydroxivitamin D and creatinine clearance, and positively with iPTH. At every stage of CKD, most patients had PTH values outside recommended limits. More than 69% CKD 3 and CKD 4 patients had higher than recommended PTH levels. Above recommended phosphate levels were present in 25% of CKD 4 and 47% of CKD 5 patients. Most of these had associated high LDL-cholesterol. Higher than recommended calcium levels were more prevalent than low calcium and there was a high prevalence (31%) of vascular calcification. One year of intervention improved the percentage of patients with controlled calcium or iPTH, but not phosphate. CONCLUSIONS: In incident CKD patients there is a high prevalence of out-of-target mineral and bone analytical parameters. The currently authorized therapeutic arsenal for these patients may not be adequate to deal with the problem.

Plasma amyloid-beta, Abeta1-42, load is reduced by haemodialysis.

Patients with chronic renal failure treated with haemodialysis have vascular risk factors that, in the general population, are associated with increased prevalence of Alzheimer's disease (AD). Patients in haemodialysis, however, present different kinds of dementia but they do not have an increased risk of AD. We have hypothesized that amyloid-beta (Abeta)1-42 is washed out from plasma during the dialysis and that this procedure enhances Abeta elimination and reduces the risk of AD. We have measured plasma Abeta1-42 levels in 11 patients with renal failure, before and after haemodialysis. A single procedure reduced the plasma Abeta levels in all subjects with a mean decrement of 30% of baseline. Since Abeta deposition could be altered by certain metals like Cu and Zn, we have also measured the effects of dialysis on the levels of these ions in plasma. We found no changes in levels of Cu and Zn after dialysis. Haemodialysis, therefore, reduces very effectively plasma Abeta without modifying Cu and Zn levels. The potential use of this strategy in patients with AD requires further investigation.

Cyclophilin-mediated pathways in the effect of cyclosporin A on endothelial cells: role of vascular endothelial growth factor.

The relative importance of cyclophilin (CyP) versus calcineurin (Cn)-mediated mechanisms in the effect of cyclosporin A (CsA) on endothelial cells (ECs) is largely unknown. In cultured ECs, CsA was cytotoxic/proapoptotic or cytoprotective/antiapoptotic at high or low concentrations, respectively. CsA analogs (MeVal-4-CsA and MeIle-4-CsA), which bind to CyP but do not inhibit Cn, closely reproduced the CsA effects. Based on our previous data, the role of vascular endothelial growth factor (VEGF) as a mediator of CsA-induced cytoprotection was further analyzed. The actions of CsA and CsA analogs were shifted from a protective to a cell-damaging pattern in the presence of a specific anti-VEGF monoclonal antibody (mAb). This positive interaction was further supported by a transient increase in cytosolic free calcium concentration ([Ca(2+)](i)) by VEGF after pretreatment with either CsA or MeVal-4-CsA and an increase in the expression and synthesis of VEGF receptor 2 (VEGFR2). Of functional importance, blockade of the interaction between VEGF and VEGFR2 by a VEGFR2 mAb abolished the cytoprotective effect of CsA. In addition, preconditioning with low concentrations of CsA or CsA analogs increased both cytoprotection and VEGFR2 mRNA expression when EC were exposed to higher concentrations of CsA. In summary, our results reveal that (1) the biphasic responses to CsA in EC are related to the interaction of CsA with CyP rather than with Cn and (2) VEGF is a critical factor in the cytoprotective effect of CsA, by a mechanism that involves VEGFR2.

[Response to hypoxia. A systemic mechanism based on the control of gene expression]. / Respuesta a la hipoxia. Un mecanismo sistemico basado en el control de la expresion genica.

New, critically important data have been recently generated about the response to hypoxia. This response can be schematized in three main systems or functions, ie, detectional or oxygen sensing, regulatory, which controls gene expression and effector. The principal organizer of the regulatory branch is a specific transcription factor, the hypoxia-inducible factor 1 (HIF-1). In the presence of oxygen, the alpha subunit of HIF-1 (HIF-1alpha) is modified by hydroxylases, that represent the central point of the oxygen sensing mechanism. This type of hydroxylation induces HIF-1alpha catabolism by the proteosome. On the contrary, in hypoxia, or in the presence of certain growth factors that increase HIF-1alpha synthesis, HIF-1alpha translocates to the nucleus, where it binds HIF-1beta, and thence acts on transcription of genes carrying hypoxia responsive elements (HRE) on their promoters. These genes regulate the synthesis of an ample series of proteins, which span from respiratory enzymes and transporters to hormones regulating circulation and erythropoiesis. The role of HIF-1alpha is not restricted to the mere induction of adaptation to decreased oxygen: instead, it significantly participates in cell repairing mechanisms. A simple list of some of the stimulatory or inhibitory alterations of pathophysiological importance involving the HIF-1 system, would include: chronic lung disease, smoking adaptation, anemia/hemorrhage, ischemia/reperfusion, growth, vascularization and cell resistance of tumors, preeclampsia and intrauterine growth retardation, retinal hyper o hypovascularization, drug intoxications, bowel inflammatory disease and wound repair. This list illustrates by itself the importance of the mechanism herein reviewed.

Tubular cell apoptosis and cidofovir-induced acute renal failure.

Cidofovir is an antiviral drug with activity against a wide array of DNA viruses including poxvirus. The therapeutic use of cidofovir is marred by a dose-limiting side effect, nephrotoxicity, leading to proximal tubular cell injury and acute renal failure. Treatment with cidofovir requires the routine use of prophylactic measures. A correct knowledge of the cellular and molecular mechanisms of cidofovir toxicity may lead to the development of alternative prophylactic strategies. We recently cared for a patient with irreversible acute renal failure due to cidofovir. Renal biopsy showed tubular cell apoptosis. Cidofovir induced apoptosis in primary cultures of human proximal tubular cells in a temporal (peak apoptosis at 7 days) and concentration (10-40 microg/ml) pattern consistent with that of clinical toxicity. Apoptosis was identified by the presence of hypodiploid cells, by the exposure of annexin V binding sites and by morphological features and was associated with the appearance of active caspase-3 fragments. Cell death was specific as it was also present in a human proximal tubular epithelial cell line (HK-2), but not in a human kidney fibroblast cell line, and was prevented by probenecid. An inhibitor of caspase-3 (DEVD) prevented cidofovir apoptosis. The survival factors present in serum, insulin-like growth factor-1 and hepatocyte growth factor, were also protective. The present data suggest that apoptosis induction is a mechanism contributing to cidofovir nephrotoxicity. The prophylactic administration of factors with survival activity for tubular epithelium should be further explored in cidofovir renal injury.

Modulation of the effect of vascular endothelial growth factor on endothelial cells by heparin: critical role of nitric oxide-mediated mechanisms.

BACKGROUND: In spite of intensive research, the actual role of heparin in endothelial cell (EC) biology remains incompletely understood. In particular, further insight is needed into the interaction of heparin with the potent heparin-binding angiogenic factor, vascular endothelial growth factor (VEGF). This study aimed to examine the effect of heparin on VEGF-mediated EC responses. METHODS: Confluent bovine aorta EC were treated with high (HMWH) and low molecular weight heparin (LMWH). 3H-Thymidine (3H-Thy) uptake, flow cytometry, 51Cr-release, nitrites accumulation, and cytosolic free Ca2+ ([Ca2+]i), endothelial nitric oxide synthase (eNOS) mRNA expression and tissue factor (TF) concentration were measured. RESULTS: HMWH and LMWH blocked VEGF proliferative actions and blunted VEGF-induced [Ca2+]i transients. However, the heparins did not block the VEGF protective effects on EC. These changes occurred in parallel with a potentiation of the VEGF-related NO production by both heparins. The Akt/PI3K inhibitor, LY 294002, blocked this potentiation, related to increased eNOS activity rather than eNOS expression. Connecting both effects, the NO antagonist, L-NAME, shifted the protective effects of VEGF to a cytotoxic mode. CONCLUSION: HMWH and LMWH block the proliferative and [Ca2+]i-mobilizing effects of VEGF on EC, by a NO-dependent mechanism. On the contrary, VEGF-induced NO production is stimulated. The Akt/PI3K pathway at least in part mediates this effect. By changing the way the VEGF intracellular signaling is driven, heparin could act as a stabilizing factor for the endothelium, without stimulating vessel proliferation.

Role of endogenous vascular endothelial growth factor in tubular cell protection against acute cyclosporine toxicity.

BACKGROUND: Recent studies have shown that exogenous administration of vascular endothelial growth factor (VEGF) is protective against cyclosporine A (CsA) renal toxicity. No data are available, however, on the possible role of endogenous VEGF. Our objective was to examine whether endogenous VEGF has a significant role in the renal response against CsA toxicity. METHODS: In vivo, we used high-dose (50-150 mg/kg/day) CsA +/- specific goat anti-mouse VEGF blocking monoclonal antibody (alpha-VEGF) in mice. In vitro, we exposed mouse tubular cells (MCT) to CsA +/- alpha-VEGF. RESULTS: alpha-VEGF markedly enhanced CsA renal toxicity, inducing severe tubular damage and increased blood urea nitrogen. In animals treated with CsA + alpha-VEGF, damage progressed to generalized tubular injury (histology) and apoptosis (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling) with associated anemia and reticulocytosis (18 days of treatment). CsA + alpha-VEGF treatments strikingly increased tubular VEGF and Bcl-xL proteins. In vitro, autocrine production of VEGF by MCT was identified by Western blot. Of specific interest, CsA toxicity in MCT increased significantly in the presence of alpha-VEGF. CONCLUSIONS: Endogenous VEGF has a relevant role in the renal tubular defense against CsA toxicity. Blockade of the VEGF effect by alpha-VEGF results in clear-cut intensification of the tubular injury and appearance of regenerative anemia in the CsA + alpha-VEGF-treated animals. The occurrence of both in vivo and in vitro effects of VEGF blockade provides evidence of a direct protective effect of VEGF on the tubular cell.

Peritoneal dialysis retardation of progression of advanced renal failure.

OBJECTIVES: The rate of decline of residual renal function is slower in peritoneal dialysis (PD) than in hemodialysis. However, it is unclear which and whether either of the two techniques modifies the natural course of renal failure. We tested whether PD influences the natural course of the progression of chronic renal failure in humans. DESIGN: Retrospective review of clinical charts. SETTING: Tertiary-care center. PATIENTS: Fourteen patients were selected from the 36 patients that were treated with PD in our center from January 1997 to June 2000, applying the following criteria: predialysis follow-up longer than 12 months, renal creatinine clearance 20 mL/minute or more at the start of predialysis follow-up, follow-up while on PD longer than 6 months, and renal creatinine clearance above 0 mL/minute at the start of PD. MAIN OUTCOME MEASURE: Residual renal function calculated as renal creatinine clearance obtained from 24-hour urine samples. RESULTS: A lower mean rate of decline of residual renal function was observed during PD than during the predialysis period (-0.06 +/- 0.16 vs -0.94 +/- 0.74 mL/min/month, p < 0.0005). The rate of decline in renal creatinine clearance was faster in every patient during the predialysis period than during his or her time on PD. CONCLUSIONS: These preliminary data support the hypothesis that PD may contribute to the slowing of the natural progression of renal disease in humans, as it does in rodents. Prospective studies involving a larger number of patients are needed to settle the question.

[Combined cardiorenal failure: a rapidly expanding clinical entity]. / Insuficiencia combinada cardiorrenal: una entidad clínica emergente.

The cardiovascular diseases represent the chief cause of morbidity and mortality in Spain. The development of renal insufficiency has a definite prognostic value and modifies therapeutic options. Cardio-renal insufficiency (IC-R) is a differentiated entity, underestimated in our population, in which both cardiac and renal failure coexist. Patients with IC-R are genuine survivors of the application of diverse technologies and have a different hemodynamic and hydrosaline balance compared to that seen in patients with isolated cardiac or renal insufficiency. Early diagnosis and careful follow-up, both in hospital and at ambulatory level, along with a specific management, determine the prognosis of this entity. A key aspect in the control of these patients resides in the preservation of a delicate fluid balance, which is always individualized and personalized. This type of approach requires a particular type of training and mental attitude by healthcare professionals, with an integrated view of the multifactorial nature of IC-R. The design of a plan structured according to objectives and the full understanding of the individual equilibrium constitute the keystone in the management of IC-R. The present review, which is based on traditional concepts updated under a practical view, is aimed to call attention on a rapidly expanding clinical entitiy.

External sense receptors in microdrile oligochaetes (Annelida, Clitellata) as revealed by scanning electron microscopy: Typology and patterns of distribution in the main taxonomic groups.

This work summarizes the observations on 30 species of microdriles belonging to the families Naididae (Rhyacodrilinae, Pristininae, Naidinae, Phallodrilinae, and Tubificinae), Phreodrilidae, Lumbriculidae, and Enchytraeidae using scanning electron microscopy. The lumbricid Eiseniella tetraedra, a megadrile species common in typical microdrile habitats, was used for comparison. Microdriles display external ciliate sense structures along the entire body; even at the clitellum and in budding and regeneration zones. According to the shape of the cilia, these sense structures can be divided into receptors of blunt cilia, receptors of sharp cilia, and composed receptors. Sense receptors can be morphologically unconspicuous or clearly defined on sensory buds or papillae. All microdriles studied have receptors of blunt cilia. Enchytraeids have characteristic receptors of short cilia. Pristina (Pristininae), Chaetogaster, Ophidonais, and Stylaria (Naidinae) have receptors of long blunt cilia. Composed receptors were found only in some microdriles and E. tetraedra. Receptors of sharp cilia have been found in most microdriles. Enchytraeids might be the only exception, but sharp cilia are probably present in the amphibiotic Cognettia sphagnetorum. Sensory cells with long sharp cilia might play a rheoreceptor role, and their presence in E. tetraedra and C. sphagnetorum would imply the reappearing of an ancient character that was probably lost with the transit from aquatic to terrestrial habitats. Some lumbriculids have ciliated fields. Anatomically, these structures appear as intermediate between the typical isolate sensory structures of microdriles and the sensillae of the hirudineans. The general pattern in microdriles is that uniciliate receptors and multiciliate receptors are separated, which supports the presumed aquatic origin of the clitellates.

Cholesterol embolism evaluated by polarized light microscopy after primary renal artery stent placement with filter protection.

PURPOSE: Cholesterol microembolization may explain some treatment failures after renal artery stent placement. The identification of cholesterol crystals may provide significant help in diagnosing the real frequency and severity of this complication. The aim of the present study was to examine the efficacy of polarized light imaging in the detection of cholesterol emboli trapped in a protection device. MATERIALS AND METHODS: During a period of 18 months, 15 significant atherosclerotic stenoses of the ostium of the main renal artery were treated with primary stent placement with embolic protection. The filter device used was made of polyurethane, with a pore size of 115 ?m. The device was mounted over a 0.014-inch guide wire. For pathologic analysis, the recaptured filter basket was compressed between two slides and examined in a microscope under polarized light. RESULTS: All the stenoses were successfully treated without clinical complications. All the filters were deployed and recaptured without difficulty. Cholesterol crystals were detected in 12 filters and no cholesterol was found in three. In one case, trouble with filter manipulation precluded pathologic analysis. No worsening of renal function was detected in any patient during follow-up. CONCLUSIONS: Microscopic analysis with polarized light easily detects the cholesterol crystals trapped in the filter device. This provides evidence that renal cholesterol microembolism is highly prevalent during renal artery stent placement.