[Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis]. / Trombosis recurrente del acceso vascular asociada a la mutación G202 10A del gen de la protrombina en un paciente adulto en hemodiálisis.

Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.

[Cytomegalovirus esophagitis in a patient on peritoneal dyalisis]. / Esofagitis por citomegalovirus en un paciente en diálisis peritoneal.

Symptomatic cytomegalovirus (CMV) infection usually affects immunocompromised patients, such as transplant recipients. From that point of view, the patient with endstage renal disease under maintenance dialysis is considered as immunocompetent. Thus, opportunistic infections, such as CMV infection, is not systematicaly searched in these patients, despite that an impaired cellular immunity has been reported in dialysis patients. We report a case of CMV esophagitis, clinically symptomatic, in a patient endstage renal disease under peritoneal dialysis, without other known immunosuppressive factors and with a good clinical response to gancyclovir treatment.

Erythropoietin improves signaling through tyrosine phosphorylation in platelets from uremic patients.

Erythropoietin has shown to be effective in the correction of the hemostatic defect present in uremic patients. We have investigated the possible effect of recombinant human erythropoietin (rHuEPO) on the signaling processes occurring in platelets. Platelet suspensions were obtained from hemodialyzed patients before and after at least one month of initiating treatment with rHuEPO. Aliquots of non-activated or thrombin-activated platelets were treated to obtain platelet lysates or processed to extract platelet cytoskeleton. Samples were resolved by 8% SDS-polyacrylamide gel electrophoresis followed by Western blotting. After thrombin activation, proteins p120, p85, p78, p75, pp62, pp60, p59, p58, p56, p54 and p52 associated with the Triton-insoluble cytoskeletal fraction appeared phosphorylated in control profiles. In profiles from platelets obtained from uremic patients before treatment with rHuEPO, only proteins p58 and p56 appeared clearly and p54 was slightly phosphorylated. However, in platelets from the same patients under rHuEPO treatment, thrombin-induced phosphorylation improved to levels even above those observed in control profiles. Specially, the band at 54KDa appeared consistently more phosphorylated in all the patients under rHuEPO treatment. Although it is accepted that part of the hemostatic effect of erythropoietin is mediated by an increase in hematocrit, our study suggests that it enhances platelet signaling in uremic platelets which may explain the improvement of platelet response to activating stimulus before clinically noticeable elevation of hematocrit.

Uremic medium disturbs the hemostatic balance of cultured human endothelial cells.

We have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effects of uremic medium on the morphology of endothelial cells (ECs), and their resistance to flow was analyzed. The influence of uremic media on the reactivity of the extracellular matrix (ECM) generated by ECs towards normal platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic medium resulted in abnormal cell morphology and signs of an accelerated growth. Detachment of ECs exposed to circulating blood was increased when cells had been grown with media supplemented with uremic serum (21% vs. 14% non exposed). Platelet deposition was significantly elevated on ECMs generated in the presence of uremic media (uremicECMs) (p<0.01 vs. control studies). Effects of uremic serum were not observed at short incubation periods (5 h) but were evident after 24 or 72 h of incubation. Northern blot analysis revealed increased expression of tissue factor (TF) mRNA in ECs exposed to uremic conditions. Immunocytochemical methods detected an augmented expression of TF antigen on uremic ECMs. Incubation of ECMs with an antibody to human tissue factor prevented the increase in platelet deposition observed in uremic ECMs, suggesting that the presence of TF in ECM could be responsible for the enhanced platelet deposition. Results from our study indicate that uremic medium impairs the antithrombotic functions of cultured endothelial cells.

Platelet activation on hemodialysis: influence of dialysis membranes.

During hemodialysis, platelets are activated and release alpha-granule-specific proteins. GMP-140 is a glycoprotein stored in the alpha-granules of platelets, which is selectively expressed on the plasma membrane of activated platelets. Using a specific monoclonal antibody against this protein (CD 62), we have evaluated the influence of different dialysis membranes on hemodialysis-induced platelet activation in vivo by flow cytometry in nine patients with end-stage renal disease on maintenance hemodialysis. Five membranes were evaluated: Cuprophane, cellulose acetate, polymethylmethacrylate, polysulphone and polyacrylonitrile (AN-69). Blood samples were obtained before hemodialysis and from the inlet and outlet lines five minutes after the beginning of hemodialysis. A significant increase in the GMP-140 expression was observed in samples obtained from the outlet line compared with samples obtained from the inlet line for all membranes evaluated, but the extent of this increase depended on the type of membrane used: Cuprophane 13.95 +/- 3.94%, cellulose acetate 7.4 +/- 4.52%, polymethylmethacrylate 6.93 +/- 4.6%, polysulphone 3.83 +/- 2%, and AN-69 2.14 +/- 2.19% (mean +/- SD). Cuprophane induced the highest degree of platelet activation (P < 0.05). Cellulose acetate and polymethylmethacrylate induced more platelet activation than polysulphone or AN-69 (P < 0.05). These data demonstrate that all hemodialysis membranes induce platelet activation but to a variable extent, cuprophane being the most activating membrane, cellulose acetate and polymethylmethacrylate showing an intermediate potential of activation, while the more biocompatible membranes, polysulphone and AN-69, inducing the lowest degree of platelet activation.

Cytomegalovirus colitis in chronic renal failure.

Cytomegalovirus (CMV) is an ubiquitous agent and is recognized as a pathogen in all age groups. Although symptomatic infection by CMV (CMV disease) in normal adults is generally mild, the virus is known to produce severe symptoms, mostly in immunocompromised patients. In this group of patients, the primary involvement of the colon by CMV is reported to be rare. However, chronic renal failure patients are prone to CMV infection. Nevertheless, despite the high incidence of infection in these patients and the recognition of a defective immune response in some of them, clinical manifestations are an exception. Two chronic renal failure patients who developed acute colitis due to CMV infection are presented. Of interest are the rarity of the association, the favorable clinical course and the differential diagnosis with other gastrointestinal disorders which are more common in these patients.

[Increased adrenomedullin levels in hypertensive patients on maintenance hemodialysis]. / Niveles elevados de adrenomedulina en pacientes hipertensos en programa de hemodiálisis.

Hypertension is a frequent finding in uremic patients. The pathogenesis of this complication in uremia is complex and not fully elucidated. An imbalance between the vasoconstrictor and vasodilator systems may be involved in its pathogenesis. In this study we have evaluated the state of nitric oxide (NO) and adrenomedullin (ADM) in hemodialyzed patients, especially those with hypertension. We included a group of hypertensive hemodialyzed patients (n = 9) and a group of normotensive control patients (n = 10). We measured plasma renin activity, as well as plasma catecholamines, ADM, and nitrite/nitrate levels in basal conditions before starting the hemodialysis session. Plasma volume, as well as left ventricular ejection fraction were also measured. Hemodialysis patients showed plasma levels of nitrite/nitrates and ADM higher than the reference values in the normal population. We observed no differences in the plasma levels of nitrite/nitrates, but ADM levels were higher in hypertensive (278.2 +/- 15.5 pg/ml) patients than in normotensive patients (225 +/- 9.9 pg/ml) (p < 0.05). When considering all patients together, mean arterial pressure positively correlated with plasma ADM (r = 0.468, p < 0.05). Plasma volume and left ventricular ejection fraction were similar in the two groups of patients. In summary, plasma levels of nitrite/nitrates and ADM are increased in hemodialyzed patients, although only ADM levels were further increased in hypertensive patients. Our results do not suggest that a decreased production in the vasodilator factors evaluated is involved in the pathogenesis of hypertension in uremic patients.

[Uremic media affects hemostatic properties of human endothelial cells in culture and increases the production of von Willebrand factor]. / El medio urémico altera las propiedades hemostáticas de células endoteliales humanas en cultivo y aumenta la producción de factor von Willebrand.

We have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effect of the uremic media on the morphology of ECs, and their resistance to flow was analyzed. The reactivity of the extracellular matrix (ECM) generated by ECs towards normal platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic media resulted in abnormal morphology and signs of accelerated growth. Detachment of ECs exposed to circulating blood was increased when cells had been grown with media supplemented with uremic serum (22% vs 13%). Platelet deposition and formation of aggregates were significantly elevated on ECMs generated in the presence of uremic media (40.23 +/- 6.43% vs 25.42 +/- 2.69%, p < 0.05, n = 5). Immunocytochemical methods detected an enhanced expression of von Willebrand factor antigen on uremic ECMs (uremic 17.1 +/- 4.2% vs control 13.57 +/- 3.98%, p < 0.05) and its mRNA expression in endothelial cells (uremic 213.24 +/- 6.13 vs control 200.77 +/- 7.52, p < 0.05). These results suggest that uremic medium alters endothelial function and impairs the antithrombotic functions of cultured endothelial cells. This effect may contribute to the increased cardiovascular and thrombotic risk reported in ESRD patients.

[Superior vena cava thrombosis in a patient on hemodialysis]. / Trombosis de la vena cava superior en un paciente en hemodiálisis.

We present a patient with end-stage renal disease on maintenace hemodialysis through a permanent catheter (Permcath) on the right subclavian vein. One month after the catheter placement the patient exhibited a superior vena cava syndrome due to a pericatheter thrombosis. The patient was initially managed with anticoagulation with early clinical improvement. Nevertheless, the reappearance of the symptoms forced the removal of the catheter and percutaneous angioplasty of the superior vena cava. After those measures and anticoagulation with coumarin the patient remains stable with complete clinical resolution and angiographical improvement.

[Vascular access in Spain: analysis of its distribution, morbidity, and monitoring systems]. / El acceso vascular en España: análisis de su distribución, morbilidad y sistemas de monitorización.

Vascular access disfunction causes a therapeutic emergency with different implications in patients and care givers. The aim of this study was to know the distribution of different kinds of vascular access between prevalent hemodialysis patients, the proportion of incident patients that holds a permanent vascular access, the monthly hospital ratio for access repair and the use of surveillance systems of vascular access adequacy in the different Centers. This is a National survey that shows results of a questionnaire sent to all hemodialysis units in Spain on september 1999. Eighty-eight units answered the questionnaire (42%) providing information about 5,476 prevalent patients. Of these patients, 81% receives treatment through an arteriovenous fistula, 10% uses a central catheter and 9% a graft. Only 56% of incident patients have a permanent vascular access. Reasons for catheter use between prevalent patients were exhaustion of vascular sites in 42%, maduration of permanent access in 24%, thrombosis of the access in 14% and another reasons in 19%. Patients monthly hospitalization ratio for vascular repair was 3%, that might represent more than 5,600 hospital ingress by year. More than 80% of the Units releases different surveillance programs of access adequacy, 69% by fiscal detection problems, 47% by dynamic alterations and 18% by dilution and imaging procediments. The conclusions of this survey are that arteriovenous fistula is the most used vascular access in Spain. Almost half of the patients do not have vascular access in use for the beginning of hemodialysis. Exhausted vascular sites is the primary reason for central catheter using. A great proportion of Units are employing programs for access monitoring.

[Non-convulsive status epilepticus secondary to adjusted cefepime doses in patients with chronic renal failure]. / Estatus epiléptico no convulsivo secundario a cefepima a dosis ajustadas en enfermos con insuficiencia renal crónica.

Fever is one of the most frequent causes of hospital admission in patients with end-stage renal disease. Lack of an identified source of infection and/or lack of clinical response to the first empirical antibiotic treatment favour the use of broader spectrum antibiotics. The availability of fourth-generation cephalosporins (e.g. cefepime) and the increasing incidence of bacterial resistances to classical antibiotics has increased their use in the clinical practice. We present two cases of non-convulsive status epilepticus in patients with advanced chronic renal failure who received cefepime at doses corrected for the degree of renal function according to the manufacturer's instrument as. The clinical symptoms included shouthough, processes, disorientation, loss of attention, and the later appearance of myoclonus. In both cases the electroencephalogram (EEG) was compatible with non-convulsive epileptic status. After cefepime withdrawal there was a clinical remission of symptoms and normalization of the EEG. It is concluded that cefepime treatment can induce a non-convulsive epileptic status in patients with advanced chronic renal failure. Pharmacokinetic studies are urgently needed to clearly define the appropriate dose of cefepime in patients with advanced chronic renal failure.

[Autonomic dysfunction in chronic hypotension associated with uremia]. / Disfunción autonómica en la hipotensión crónica asociada a la uremia.

BACKGROUND: Chronic hypotension is a not uncommon complication among hemodialyzed patients which is responsible of an important morbidity. The autonomic nervous system (ANS) dysfunction seems to play a key role in the pathogenesis of chronic hypotension. METHODS: In order to study whether ANS dysfunction is responsible for chronic hypotension in hemodialyzed patients, the authors evaluated the integrity of the whole baroreflex arc by the Valsalva's manoeuver, of parasympathetic efferent pathway by the deep-breathing test and of sympathetic efferent pathway by the hand-grip test in 16 hemodialyzed patients with chronic hypotension, 17 normotensive hemodialyzed patients and 17 normal control subjects. Plasma catecholamine levels were also measured in these patients. RESULTS: In normotensive patients, Valsalva's manoeuver response (p < 0.005) and deep-breathing test response (p < 0.05) were lowered, while hand-grip test response was preserved. In chronic hypotensive patients, in addition to an impaired deep-breathing test (p < 0.05), a further reduced Valsalva's manoeuver response and a lower pressor response to hand-grip test were observed (p < 0.001). Catecholamine levels were higher in both groups of patients (p < 0.01) with respect to control subjects, specially in chronic hypotensive patients. CONCLUSIONS: In hemodialyzed patients (both normotensive and hypotensive) the whole baroreflex function and parasympathetic response are impaired. The lower pressor response to hand-grip test observed in hypotensive patients, in spite of the higher catecholamine levels, suggest that in these patients the cardiovascular dysfunction cannot be ascribed to a reduced sympathetic "outflow" but to a resistance of the target organs (heart and vessels) to the sympathetic stimulation.

[Prospective study of 75 episodes of sepsis in hemodialysed patients]. / Estudio prospectivo de 75 episodios de sepsis en pacientes hemodializados.

During a 38-month period the bacteremias developing in patients on hemodialysis from three centers of the Barcelona area were evaluated to assess their incidence, characteristics, and response to therapy. In the overall 13376 months of hemodialysis of the study, 75 episodes of bacteremia were detected in 64 patients; this amounts to an incidence of 5.6 episodes per 1000 hemodialysis months. The most common sources of becteremia were intravenous catheters (44%), which were mainly used as temporary vascular access, followed by the definitive vascular access (26%), the genitourinary system (10%), and the lung (6%). Twenty-seven episodes of bacteremia developed in 24 patients in whom dialysis had been started in the two previous months (11% of the overall number of new patients), and, in them, 77% originated in an intravenous catheter, while this was the origin of bacteremia in only 23% of the remaining patients. 72% of bacteremias were caused by gram positive organisms, particularly Staphylococcus aureus and Staphylococcus epidermidis (60%), followed, in frequency order, by aerobic gram negative bacilli (25%), particularly Escherichia coli and Pseudomonas. Stpahylococci were significantly associated with the vascular access, either if this was a catheter or not (81% of instances), while gram negative bacilli were associated with sources different from the vascular access (48% of instances). Severe complications included 2 cases of aortic valve endocarditis, one hemorrhagic shock caused by rupture of an infected vascular access, and one suppurative phlebitis associated with a hemodialysis catheter. Staphylococcal sepsis was randomly treated with vancomycin or vancomycin plus gentamicin, without differences in the results.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of the treatment with human recombinant erythropoietin on primary hemostasis in uremic patients]. / Efecto del tratamiento con eritropoyetina recombinante humana sobre la hemostasia primaria en pacientes urémicos.

The effect of human recombinant erythropoietin (r-EPO) on primary hemostasia was studied in 9 patients undergoing hemodialysis. The analysis was performed before and after the hematocrit reached a value of 30%. The most important complications observed during the study period were a death for acute myocardial infarction in a patient with previous severe ischemic cardiopathy and a thrombosis of the venous line. The bleeding time shortened in four patients although the mean value did not change significantly. Platelet count showed a non significant increase. There was a significant improvement in in vitro platelet aggregability with ADP (p less than 0.05), arachidonic acid (p less than 0.05), adrenaline (p less than 0.05), and ristocetin (p less than 0.05) as well as in the parameters that quantify the interaction between platelets and subendothelium in in vitro experiments using perfused models (p less than 0.05). There were no significant changes in coagulation and fibrinolysis tests. The treatment with r-EPO improved primary hemostasia in uremic patients. This beneficial effect was due to the increased hematocrit and to the improvement of platelet function induced by r-EPO.

[Hemodialysis and complement (author's transl)]. / Hemodiálisis y complemento.

After observing alterations in the activity of the serum complement in patients undergoing periodic hemodialysis, the authors performed a preliminary study to determine repeatedly the activity of C3, C4, and CH50 in 44 patients. They discovered a consistent drop in C3 and CH50 while C4 remained normal. An attempt to explain these findings with information from the literature offered no more than a hypothesis for further study. While the possibility of a decline in the synthesis of the complement factors cannot be disregarded, the authors believe it is much more probable that they are consumed at a rate higher than normal. Since the C4 factor does not appear to be involved, activation is probably along the alternative pathway. Defective synthesis cannot be attributed to liver disease because the latter is not always present and because there is no relationship between C3 levels and levels of albumin or the presence of hepatopathy. The literature was reviewed for data that might support the idea that the complements in these patients are activated continuously by some process in connection with dialysis, by chemical products employed for to clean the machines, by commonly administered drugs, etc. Because so few data could be found on the subject, the authors consider that is necessary to study these mechanisms and their repercussions over a longer period of time.

[Ototoxicity of desferrioxamine in hemodialyzed patients]. / Ototoxicidad por desferrioxamina en pacientes hemodializados.

A prospective study performed on 37 patients with end-stage renal disease who required treatment with deferoxamine is presented. Three patients presented a sudden sensorineural hearing loss, with tinnitus in one case, which was demonstrated to be of cochlear origin. All patients recovered auditory function completely after treatment was discontinued.