[Renal and systemic changes caused by non-steroidal anti-inflammatory agents].
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Acute Kidney Injury↗
Biomedical subjects
L Revert
Publications and source records attributed to L Revert.
[Neutrophil anticytoplasmic antibodies: their diagnostic utility in vasculitis and glomerulonephritis].
BACKGROUND: The prevalence and diagnostic usefulness of antineutrophil cytoplasmic antibodies (ANCA) were analyzed in a series of patients with different types of vasculitis, connective tissue diseases, nephropathies and lung diseases. METHODS: Six hundred seventy-six consecutive patients with systemic vasculitis, connective tissue diseases, nephropathies and different lung disturbances were included in the study. The ANCA were determined by indirect immunofluorescence (IIF) on neutrophils fixed in ethanol. For the detection of antimyeloperoxidase (MPO) antibodies (Ab) a new technique was developed consisting in the performance of IIF on neutrophils with a deficiency in MPO. The serologic samples were also analyzed by enzyme-linked immunosorbent assays with MPO and purified proteinase 3 (PR3). RESULTS: ANCA were demonstrated in 95 patients. A cytoplasmic pattern (c-ANCA) was detected in 25 cases (26%) and in 70 (74%) a perinuclear pattern (p-ANCA) was observed. Twenty-one of the 25 cases (84%) of c-ANCA corresponded to anti-PR3 Ab and 61 of the 70 (87%) of p-ANCA corresponded to anti-MPO Ab. The anti-PR3 Ab identified Wegener's granulomatosis, with a sensitivity and specificity for the generalized and clinically active forms being 65 and 88%, respectively. The anti-MPO Ab were principally detected in patients with rapidly progressive glomerulonephritis (RPGN) and hemorrhagic alveolar capillaritis. The sensitivity and specificity of the anti-MPO Ab for the RPGN and alveolar capillaritis were 75% and 98%. CONCLUSIONS: Two principal subtypes of ANCA may be detected, which also recognize two fundamental clinicopathologic entities. The high diagnostic sensitivity and specificity of these antibodies for each of the processes to which they are associated can justify the adoption of therapeutic measures in determined cases.
Antibodies, Antineutrophil Cytoplasmic↗
Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension.
To investigate the relationship between changes in intracellular calcium concentration ([Ca2+]i) and agonist-induced activation of the Na+/H+ exchanger in essential hypertension (EH), platelet [Ca2+]i and pHi were measured in 24 patients with EH (14 males) aged 48 +/- 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 +/- 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2+]i and BCECF for pHi. [Ca2+]i and pHi were measured in the resting condition and after stimulation in vitro with 0.1 U/ml human thrombin. The thrombin-induced rise in pHi was Na+ dependent and amiloride sensitive, indicating that it was mediated by the Na+/H+ exchanger. Unstimulated [Ca2+]i was higher in patients with EH than in NT (60 +/- 3 vs. 48 +/- 1 nmol/liter, P < 0.005), but there were no differences in resting pHi between both groups (7.16 +/- 0.01 vs. 7.16 +/- 0.008). In the presence of 1 mmol/liter external calcium (Ca2+o), thrombin-induced increment in [Ca2+]i was significantly greater in patients with EH than in NT (281 +/- 21 vs. 206 +/- 19; P < 0.05) as was the pHi increment (EH: 0.137 +/- 0.01; NT: 0.095 +/- 0.01; P < 0.05). Both agonist-induced increments in [Ca2+]i and in pHi were correlated with mean arterial pressure (MAP) only in the EH group (r = 0.58, P < 0.005 and r = 0.59, P < 0.005, respectively). The agonist-induced rise in pHi was positively correlated with the rise in [Ca2+]i both in the EH group (r = 0.65, P < 0.001) and in the NT (r = 0.55, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Platelets↗
Effect of antihypertensive treatment on intracellular calcium concentration and intracellular pH in essential hypertension.
The platelet intracellular calcium concentration ([Ca2+]i) and intracellular pH (pHi) were measured by spectrofluorimetry with the dyes Fura-2 and BCECF, respectively, in 19 patients with essential hypertension (10 males), aged 48 +/- 2 years, before and after 12 weeks of antihypertensive treatment and in 19 normotensive controls (11 males), aged 46 +/- 3 years. [Ca2+]i and pHi were measured in the resting state and after stimulation in vitro with 0.1 U/ml human thrombin. In patients with essential hypertension, both resting [Ca2+]i (61 +/- 4 nmol/l) and thrombin-induced maximal increase in [Ca2]i (291 +/- 26 nmol/l) were significantly (P < 0.01) greater than in the normotensive controls (resting 49 +/- 2 nmol/l and thrombin-induced 199 +/- 21 nmol/l). With respect to pHi, no difference in resting pHi between both groups was found (7.16 +/- 0.01 vs. 7.16 +/- 0.01). However, pHi increment at 300 seconds in response to thrombin was higher in the patients with essential hypertension than in the controls (0.131 +/- 0.02 vs. 0.083 +/- 0.01 pH units, P < 0.05). The increment in pHi was blunted by the amiloride derivative EIPA, indicating that it was mediated by the Na+/H+ exchanger. After antihypertensive therapy in the essential hypertensive patients, basal [Ca2+]i was significantly reduced (52 +/- 2 nmol/l, P < 0.01) and was not statistically different to the value found in the normotensive controls. Resting pHi suffered no significant modification after treatment (7.17 +/- 0.01, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Fatal rupture of a mycotic aneurysm of the subclavian artery: an unusual complication of methicillin-resistant Staphylococcus-aureus-related sepsis.
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Aged↗
Intracellular calcium mobilization and activation of the Na+/H+ exchanger in platelets.
The aim of the present study was to evaluate the regulatory relationship between the cytosolic free calcium concentration ([Ca2+]i and cytosolic pH (pHi). [Ca2+]i and pHi were measured using the fluorescent dyes fura-2 and BCECF [2',7'-bis-(carboxyethyl)-5,6-carboxyfluorescein] respectively. In a medium with 1 mmol/l extracellular calcium, thrombin (2.5 units/ml) induced an increment in [Ca2+]i of 638 +/- 31 nmol/l (n = 5) and an intracellular alkalinization of 0.14 +/- 0.01 pH units (n = 8). Both responses were dependent on the concentration of thrombin, displaying a sigmoidal dose-response pattern. The intracellular alkalinization was dependent upon extracellular Na+ and was amiloride-sensitive, indicating that it was mediated by activation of the Na+/H+ exchanger. When extracellular calcium was chelated with EGTA prior to the addition of thrombin, the intracellular alkalinization was not affected (0.15 +/- 0.02 at 2.5 units/ml thrombin, n = 8). Under these circumstances, the [Ca2+]i increment represents mobilization from internal stores, reaching 157 +/- 42 nmol/l at 2.5 units/ml thrombin. When platelets were preloaded with the intracellular calcium chelator MAPTAM (1,2-bis-5-methylaminophenoxylethane-NNN'-tetraacetoxymethyl acetate) to block the increase in [Ca2+]i induced by thrombin, no increment in pHi was observed. Moreover, MAPTAM-loaded calcium-depleted platelets had a basal pHi that was more acidic than in the presence of 1 mmol/l extracellular calcium (6.93 +/- 0.09 versus 7.14 +/- 0.01, n = 26, P < 0.001). Ionomycin induced an elevation of [Ca2+]i that was accompanied by a concomitant increase in pHi, which was Na(+)-dependent and amiloride-sensitive. [Ca2+]i and pHi increases induced by ionomycin were both dependent on the concentration of ionomycin. In conclusion, an increase in [Ca2+]i is necessary for the agonist-induced activation of the Na+/H+ exchanger in platelets. Non-agonist-induced increases in [Ca2+]i seems to prompt activation of the exchanger. In addition, Ca(2+)-depleted platelets have a more acidic basal pHi, indicating that the basal level of [Ca2+]i is also important for maintaining the basal pHi.
Blood Platelets↗
Anti-neutrophil cytoplasmic autoantibodies (ANCA): antigenic specificities and clinical associations.
We have conducted a prospective study of 372 patients with well-defined forms of systemic vasculitis and connective tissue diseases to determine the prevalence, the antigenic specificities and the clinical associations of ANCA in such cases. These antibodies were detected by indirect immunofluorescence on ethanol-fixed neutrophils and also by enzyme-linked immunosorbent assay using myeloperoxidase (MPO) as a substrate. In our study, ANCA with a cytoplasmic immunostaining pattern were mainly found in patients with biopsy-proven Wegener's granulomatosis with or without renal involvement and pulmonary hemorrhage. Furthermore, MPO-ANCA strongly correlated with necrotizing glomerular and alveolar capillaritis, mostly in patients having a well-established diagnosis of polyarteritis nodosa.
Antibodies, Antineutrophil Cytoplasmic↗
Synthesis of beta 2-microglobulin in lymphocyte culture: role of hemodialysis, dialysis membranes, dialysis-amyloidosis, and lymphokines.
Dialysis-amyloidosis (A beta 2M) is a recently recognized chronic complication in long-term dialysis patients, apparently effecting 5% to 10% of all dialysis patients. In 1985, Gejyo et al (Biochem Biophys Res Commun 129:701-706, 1085) and Shirahama et al (Lab Invest 53:705-709, 1985) identified beta 2-microglobulin (beta 2-M) as the major constituent protein of this unique type of systemic amyloidosis. The specific pathogenesis of A beta 2M remains unknown, although beta 2-M has been clearly identified as playing a central role as the amyloidogenic protein. To investigate the factors responsible for in vitro beta 2-M synthesis, we studied beta 2-M production by lymphocyte cultures obtained from dialysis patients and grown under a variety of different conditions, and compared the results to a control group of subjects with normal renal function. We could not demonstrate any stimulatory influence on beta 2-M synthesis by the hemodialysis treatment, the type of dialysis membrane used, or the clinical presence of A beta 2M. Rather, dialysis membranes, sterilized with ethylene oxide or gamma rays, added to the lymphocyte cultures exerted a strong dose-dependent inhibitory effect on beta 2-M synthesis. From the results of this study, we conclude that peripheral blood lymphocytes in uremic patients synthesize beta 2-M normally and that the direct interaction between circulating lymphocytes and the dialysis membrane that occurs during hemodialysis does not seem to contribute directly to beta 2-M synthesis.
Adult↗
Penicillamine-induced rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis.
A 67-year-old woman with rheumatoid arthritis presented rapidly progressive glomerulonephritis (RPGN) after 5 months of D-penicillamine (250 mg/day) treatment. Light microscopy study showed severe glomerulonephritis with crescent formation in 60% of the glomeruli and infiltration of inflammatory cells in the wall of an arteriole. Immunofluorescence revealed scanty granular IgG, IgA and C3 deposits along the capillary walls and mesangium. The patient was treated with steroid pulse, plasmapheresis, cyclophosphamide and antiplatelet agents. A complete recovery of renal function was achieved in a few weeks. This new case of RPGN in the course of D-penicillamine treatment emphasizes the need for frequent monitoring of renal function and evaluation of urinary sediment and proteinuria in these patients. The prompt discontinuation of D-penicillamine and vigorous treatment measures could allow for a good prognosis as in this case.
Aged↗
Blood and graft eosinophilia as a rejection index in kidney transplant.
The relevance of eosinophilia in the physiopathology of transplant rejection has yet to be established. The appearance of eosinophilia has been occasionally associated with an adverse prognosis on graft rejection episodes. The aim of the present study was to evaluate the role and prognostic implications of blood and graft eosinophilia in kidney transplant rejection. We have examined the intrarenal infiltrate in 173 fine-needle aspiration biopsies from 36 consecutively transplant patients, and blood samples obtained simultaneously with fine-needle aspirations. Two different immunosuppressive regimens were administered: triple therapy (azathioprine + prednisone + antilymphocytic globulin) in patients with posttransplant acute tubular necrosis and cyclosporine A monotherapy in the rest of the patients. Comparing the two immunosuppressive groups, more elevated eosinophil values were observed in the monotherapy group during stable graft and also at the rejection episode. In the monotherapy group, a significant increase in the eosinophil values, in peripheral blood samples and in the intragraft infiltrates were noted at the rejection episode with respect to the stable situation. Following pulsed-steroid treatment an immediate disappearance of the eosinophils was evident. In contrast, no differences could be demonstrated between these two clinical situations in the TT group. Higher rates of eosinophils in the intrarenal infiltrate with respect to peripheral blood samples were observed during rejection episodes, suggesting some role of the eosinophils in the physiopathology of graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
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.
Adult↗
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.
Aged↗
Central pontine myelinolysis secondary to frequent and rapid shifts in plasma glucose in a diabetic haemodialysis patient.
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Adult↗
[Nephropathy in human immunodeficiency virus infection].
BACKGROUND: Patients with the human immunodeficiency virus (HIV) infection may present different types of nephropathy with focal segmentary glomerulosclerosis (FSGS) being the most specific lesion associated to HIV (HIVN). The prevalence of this entity varies between 1 to 23%. These differences have been attributed to ethnic factors and/or intravenous drug addiction (IVDA). The renal alterations presented in these patients with HIV infection were analyzed. METHODS: Two groups of patients were studied: Group I with 300 consecutive patients with advanced HIV infection (complex related with AIDS) treated with zidovudine without initial kidney infection followed for a mean of 19 +/- 11 months (99% caucasian, 65% IVDA, 66% AIDS); and group II with 11 patients with HIV infection remitted for kidney involvement (4 on hemodialysis). RESULTS: Group I: 26 cases (9%) presented acute reversible kidney failure (12 prerenal, 9 nephrotoxicity and 5 mixed). No patient presented HIVN criteria. Group II: one black patient developed HIVN and had no known risk factors. The remaining patients presented glomerular changes different from those of HIVN. CONCLUSIONS: The scarce prevalence of human immunodeficiency virus nephropathy in the present series is of note despite the high number of intravenous drug addicts included suggesting that ethnic factors determine the differences observed in different series. The most frequent kidney disturbances seen are those related with infectious complications associated to the acquired immunodeficiency syndrome and the treatment of the same.
Acquired Immunodeficiency Syndrome↗
Anti-myeloperoxidase autoantibodies in patients with necrotizing glomerular and alveolar capillaritis.
We conducted a prospective study of 651 Mediterranean patients from Catalonia (Spain) with well-defined forms of systemic vasculitis, connective tissue diseases, and renal and pulmonary disorders to determine the prevalence and clinical value of antineutrophil cytoplasmic autoantibodies (ANCA) with myeloperoxidase (MPO) specificity (MPO-ANCA). ANCA were first tested by indirect immunofluorescence on ethanol-fixed neutrophils. When a positive result was obtained, then MPO-ANCA were identified by performing the immunofluorescence assay again on neutrophils from a voluntary donor known to have a complete and selective deficiency of MPO. This disorder was detected by automated flow cytochemistry with the Technicon system and was further verified by cytochemical and biochemical studies. We detected MPO-ANCA in 61 of 70 (87%) patients with a perinuclear pattern (p-ANCA), but in none of 25 with a cytoplasmic pattern (c-ANCA). These results were corroborated by enzyme-linked immunosorbent assay (ELISA) using human purified MPO as a substrate. On immunofluorescence microscopy, all patients with MPO-ANCA were found to have a typical and restrictive immunostaining pattern. In our study, while c-ANCA were mainly found in patients with biopsy-proven Wegener's granulomatosis, MPO-ANCA identified those with idiopathic and polyarteritis nodosa-associated necrotizing and crescentic glomerulonephritis. In addition, pulmonary hemorrhage with necrotizing alveolar capillaritis as the main morphologic substrate occurred frequently among patients with MPO-ANCA, including three affected by polyarteritis nodosa and three who had pulmonary hemorrhage as the only clinical finding. On the other hand, these antibodies could be also detected in 30% of patients with a proven diagnosis of anti-glomerular basement membrane (GBM) disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Antineutrophil Cytoplasmic↗
Calciphylaxis in a hemodialysis patient: appearance after parathyroidectomy during a psoriatic flare.
Chronic renal failure patients are prone to soft tissue calcifications. A phenomenon of acute ischemic skin necrosis and dermohypodermic arteriolar medial calcification has been described recently in patients with chronic renal failure and secondary hyperparathyroidism (HPT). This phenomenon, termed calciphylaxis, occurs in response to certain factors, the most important of which appears to be an elevated blood calcium-phosphate product. Accordingly, parathyroidectomy in addition to normalization of calcium-phosphate product has been proposed as the only effective therapeutic approach for this condition. We describe a case of chronic renal failure with severe secondary HPT in which the patient developed calciphylaxis 4 days after the appearance of a psoriatic flare. Four months before, a subtotal parathyroidectomy was performed for severe HPT and at the time the ulcerations appeared, blood calcium-phosphate product was correct. Etiological and physiopathological aspects of calciphylaxis are discussed.
Calciphylaxis↗
Recombinant human erythropoietin treatment improves platelet function in uremic patients.
The effect of recombinant human erythropoietin (rHuEPO) on primary hemostasis was tested in 19 hemodialyzed patients. Bleeding time, platelet aggregation and platelet interaction with vessel subendothelium (SE) under flow conditions were determined before treatment and after patients reached hematocrits greater than or equal to 30%. Two thrombotic events (an acute myocardial infarction and an AV fistula clotting) were recorded during the early stages of treatment. A shortening of average bleeding times (P less than 0.01), an increase in platelet count (P less than 0.01) and an improvement of platelet aggregation (P less than 0.01) and of platelet-SE interaction (P less than 0.01) were observed. A low correlation index was found between hematocrit and bleeding time (r = -0.351, P less than 0.05). To assess a possible effect of rHuEPO on platelet function, the same parameters were evaluated before and after receiving three doses of rHuEPO (40 U/kg i.v. post-hemodialysis) in 14 of the patients. No changes in platelet or erythrocyte counts were observed, the mean bleeding time remained unchanged, but platelet aggregation induced by arachidonic acid (P less than 0.05), ADP (P less than 0.01) and ristocetin (P less than 0.05) improved. Perfusion studies confirmed moderate but significant increases in the parameters that quantify platelet-SE interaction (P less than 0.05). Improvement of ADP-induced aggregation correlated with the increase of platelet adhesion to SE (r = 0.675, P less than 0.05). We conclude that rHuEPO treatment improves primary hemostasis in uremia through an increase of red cell mass but also through a beneficial effect on platelet function, which is independent of the hematocrit rise.
Adult↗
Arginine vasopressin infusion increases plasma levels of atrial natriuretic factor in humans.
Seven normal subjects underwent sequential 20-min infusion of arginine vasopressin (AVP) at 0.5 and 2 ng/(kg.min) and a complete right-side heart hemodynamic evaluation during the study to analyze the effect of this hormone on atrial natriuretic factor (ANF) secretion in humans and to elucidate whether this effect was primary or secondary to the hemodynamic or hormonal changes induced by AVP. Plasma ANF levels increased at the end of the first (P less than 0.05) and second (P less than 0.01) infusion periods. No significant changes in mean arterial, pulmonary artery, right and left atrial pressures were recorded during the study. Cardiac output (P less than 0.05) and heart rate (P less than 0.05) decreased, while total vascular resistances (P less than 0.05) increased with respect to basal values in both infusion periods. Plasma renin activity decreased (P less than 0.01) at the end of the infusion, while plasma aldosterone, epinephrine and norepinephrine showed no significant changes. We conclude that arginine vasopressin increases plasma ANF levels in humans and that this effect cannot be ascribed to hemodynamic or hormonal changes induced by this hormone, suggesting a direct effect of vasopressin on the atrial myocyte.
Adult↗