[Goodpasture disease]. / La maladie de Goodpasture.

We report one case of acute renal failure with oliguria, microscopic haematuria and normocytic anemia in a 86-year old Swedish woman. A full investigation led to the diagnosis of Goodpasture disease, an isolated form of Goodpasture syndrome. Goodpasture disease is and autoimmune disorder characterized by the development of autoantibodies to the NC1 domain of the alpha3 chain of type IV collagen, found mainly in glomerular basement membranes (GBM). When the disease affects both the lung and the kidney, it is called Goodpasture syndrome but the pulmonary or renal involvement can be isolated or separated in years. Its pathogenesis is not well known. It occurs essentially in Caucasian subjects, preferentially from Nordic and Anglo-Saxon countries (higher prevalence of HLA DR B1-15 and B1-4 group). Are also mentioned, the exposure to hydrocarbons, rustproof, insecticides and greasy solvents. The annual incidence of Goodpasture syndrome is rare and has been estimated in Europe to be about 0.5 to 1 case per million inhabitants. The isolated renal form represents about 1/3 of the cases. The clinical presentation is characterized by rapidly progressive renal failure with oliguria or anuria and in case of lung involvement, pulmonary hemorrhage responsible of hemoptysis, sometimes massive. Renal biopsy and immunofluorescence analysis play a key role in the diagnosis. The presence of both linear deposits of IgG along the glomerular basement membrane (GBM) and circulating anti-GBM antibodies is of paramount importance. The treatment, which depends on the degree of renal involvement, is based on the association of corticosteroids, cyclophosphamide and plasma exchanges.

Role of complement and platelet-activating factor in the stimulation of phagocytosis and reactive oxygen species production during haemodialysis.

BACKGROUND: Neutrophil phagocytic functions have been studied extensively in haemodialysis (HD) patients; however, results are contradictory and the mechanisms that modulate phagocytosis and oxidative burst during dialysis are not completely understood. METHODS: The present study investigated neutrophil functions in a selected population of patients before and during clinical dialysis with cuprophane, and polyacrylonitrile (AN69) membranes. We measured phagocytosis of Escherichia coli and intracellular hydrogen peroxide (H2O2) production by flow cytometry in whole blood. RESULTS: Before dialysis, neutrophils from HD patients showed normal phagocytic capability and H2O2 formation. Phagocytosis of FITC-E. coli was significantly stimulated in cuprophane but not AN69-treated patients. Spontaneous and stimulated H2O2 production was enhanced with both cuprophane and AN69 membranes. We then investigated in vitro the role of complement and platelet-activating factor (PAF) in the activation of neutrophils. Incubation of whole blood with C5a increased phagocytosis but not H2O2 production. On the contrary, the addition of synthetic PAF showed a markedly stimulated H2O2 production without increase in phagocytosis. Moreover, during dialysis with formaldehyde-reused cuprophane, complement activation was abolished and phagocytosis was no longer enhanced, while the stimulation of H2O2 production persisted. In addition, we also excluded a particular role of the membrane itself in the activation of neutrophils. CONCLUSION: We demonstrated that in a selected population of HD patients, neutrophils exhibit normal phagocytic capability and normal intracellular H2O2 production. During dialysis, the stimulation of phagocytosis observed with cuprophane is complement dependent, whereas the enhanced H2O2 production observed with both cuprophane and AN69 membranes might be related to PAF production.

A previously undescribed side effect of icodextrin: overestimation of glycemia by glucose analyzer.

OBJECTIVE: Serious discrepancies between glycemia measurements obtained with an Accutrend Sensor (Boehringer Mannheim GmbH, Mannheim, Germany) type analyzer (based on a glucose dehydrogenase enzymatic reaction) and measurements obtained in the laboratory by a reference method (hexokinase) have been found in an insulin-requiring, diabetic, continuous ambulatory peritoneal dialysis (CAPD) patient treated with icodextrin 7.5% (Extraneal; Baxter Healthcare SA, Castlebar, Ireland), a new osmotic agent for peritoneal dialysis. We therefore investigated the respective role of the Analyzer and of the glucose polymer in this hitherto undescribed problem. DESIGN: Glycemia was measured simultaneously on venous blood using a reference laboratory technique, and on capillary blood using the Accutrend Sensor glucose analyzer in three groups of CAPD patients: 6 patients on Extraneal for at least 1 week, 6 patients receiving their first Extraneal exchange, and 8 patients never exposed to Extraneal. In the first group of patients, glycemia was also measured with another analyzer (Glucocard; Menarini Diagnostics, Firenze, Italy) using a different enzymatic reaction (glucose oxidase). In a separate study, whole blood of a normal subject was spiked with concentrated solutions of glucose and icodextrin and some of its metabolites (maltose, maltotriose, maltopentaose). Once again, comparative measurements of glycemia were performed with the Accutrend Sensor, with two other kits using a glucose dehydrogenase enzyme reaction, and with the hexokinase reference method. RESULTS: In 6 CAPD patients treated with once-daily exchanges with Extraneal for a minimum of 7 consecutive days, we confirmed overestimation of glycemia by the Accutrend Sensor of 65 +/- 26 mg/dL compared to reference values (p < 0.01), and of 69 +/- 25 mg/dL (p < 0.001) compared to measurements obtained with the Glucocard monitor. In 6 other CAPD patients studied at the end of one single icodextrin exchange, overestimation of 61 +/- 11 mg/dL was already present (p < 0.001). On the other hand, in 8 CAPD patients never treated with icodextrin, there was no discrepancy between the Accutrend Sensor readings and reference values. The measurements in spiked blood confirmed that only the Accutrend Sensor overestimates glycemia in the presence of maltose and glucose polymers. The overestimation decreased as the molecular size of the saccharides added to blood increased. There was no overestimation when other kits using a dehydrogenase enzyme were tested. CONCLUSION: The overestimation observed is probably related to the presence of oligosaccharides (mainly maltose), derivatives of glucose polymers present in Extraneal and absorbed via the peritoneal route, in the blood of patients treated with icodextrin. The glucose dehydrogenase characterizing the Accutrend Sensor, an enzyme of the pyrroloquinolinequinone class, very likely reacts with the free reducing group of the glucose molecule located at the end of each saccharide chain. This would not be the case for the Glucocard monitor using glucose oxidase, for other kits using glucose dehydrogenase, and for the reference method based on hexokinase. The Accutrend Sensor type of analyzers are therefore not suitable for regular monitoring of glycemia in diabetic PD patients treated with icodextrin.

[Regional anticoagulation with sodium citrate: chronic utilization in the hemodialysis patient]. / Anticoagulation régionale au citrate de sodium: utilisation chronique chez le patient hémodialysé. A propos de trois cas.

We used an alternative technique for regional citrate anticoagulation (citrate 0.48 Mol; bicarbonate containing dialysate with Ca 1.75 Mmol) in three patients at chronic risk of bleeding and for a mean follow-up period of ten months. No bleeding recurrence was observed nor any complication related to citrate. Hemoglobin and hematocrit rose without transfusions. Serum bicarbonate increased during the first four months of treatment. No significant change was observed in serum calcium nor serum sodium concentration.

Effects of recombinant human erythropoietin on T lymphocyte subsets in hemodialysis patients.

Lymphocyte subpopulations were studied by immunofluorescence staining with monoclonal antibodies and laser flow cytometry in the blood of 23 hemodialysis patients before and after 3 months of treatment with recombinant human erythropoietin (rhEPO). Correction of anemia was accompanied by an increase in natural killer cells and a decrease in B lymphocytes. In the 11 patients (Group 1) with a baseline helper/suppressor (T4/T8) ratio greater than or equal to 2, the latter significantly decreased from 3.0 +/- 0.3 to 2.1 +/- 0.3 through both an increase in T8 cells and a decrease in T4 cells (p less than 0.005). Among the 12 patients with a pre-EPO T4/T8 ratio less than 2 (Group 2), no difference in T cell subsets was observed. The decrease in ferritin levels observed over the study period was not significant. In addition, the mean increase in hemoglobin levels during the first month of rhEPO therapy was greater in Group 2 than in Group 1 (1.1 +/- 0.3 vs. 0.6 +/- 0.3 g/dl, p less than 0.025). No change in any parameter was observed in eight control patients not receiving rhEPO. These results suggest that rhEPO can induce changes in lymphocyte subpopulations of hemodialysis patients through mechanism(s) yet to be clarified; conversely, the T4/T8 ratio might be a predictive factor for the erythropoietic response to rhEPO.

Left atrial myxoma associated with systemic AA amyloidosis.

A 76-year-old woman presenting with generalized amyloidosis of the AA-type protein was found to have a left atrial myxoma. Retrospective estimation of the concentration of SAA protein, a serum precursor of AA amyloid, before and after surgical removal of the myxoma, showed that the SAA protein had disappeared after the operation. A common manifestation of myxoma is the development of a severe inflammatory syndrome that sometimes simulates rheumatic fever or bacterial endocarditis. However, to our knowledge, it has never been described in association with amyloidosis. We suggest that atrial myxoma should be added the list of neoplastic and inflammatory diseases predisposing to AA amyloidosis.

Critical role of iron overload in the increased susceptibility of haemodialysis patients to bacterial infections. Beneficial effects of desferrioxamine.

Iron overload, which is a common complication in haemodialysis patients, is known to enhance bacterial growth and virulence, and to alter phagocytosis. We reviewed the data of 61 haemodialysed patients to clarify the clinical relevance of iron status to the risk of bacterial infection. Increased concentrations of serum ferritin were associated with a greater infection rate (P less than 0.0025), which was already true for ferritin values between 500 and 1000 micrograms/l (P less than 0.025). Furthermore, in 21 iron-overloaded patients treated with an iron-chelator (desferrioxamine), the infection rate decreased from 1/19 patient-months to 1/112 (P less than 0.005), and returned to previous values when desferrioxamine was stopped. Our results demonstrate the importance of haemosiderosis in the increased susceptibility of haemodialysed patients to infections; this susceptibility is decreased by desferrioxamine therapy, which probably acts by restoring phagocytosis and reducing the bioavailability of iron for pathogens.

[Bone and joint complications in patients treated with continuous ambulatory peritoneal dialysis (CAPD) for more than 3 years]. / Complications osseuses et articulaires des patients traités par dialyse péritonéale continue ambulatoire (DPCA) pendant plus de trois ans.

The clinical, biochemical, radiological and scintigraphical data related to renal osteodystrophy were followed in 18 patients on CAPD for 3 to 5 years. The majority maintained normal serum calcium, bicarbonate and alkaline phosphatase concentrations; serum phosphate concentration decreased after starting CAPD but remained somewhat elevated. Only half of the patients needed phosphate binders. Serum PTH concentrations fell in those with high values at the start and remained stable in most others. Serum aluminum concentrations never exceeded 50 micrograms/l while serum 25(OH)D3 levels remained low. Bone radiology and scintigraphy were characterized by their stability over time. We think that CAPD, with the addition of calcium carbonate, phosphate binders and vitamin D analogs can achieve good control of renal osteodystrophy. In addition, joint problems are not common in CAPD patients but we present evidence that they too are at risk of dialysis amyloidosis.

Continuous ambulatory peritoneal dialysis vs haemodialysis: a lesser risk of amyloidosis?

We compared plasma beta-2-microglobulin (beta 2M) at a 1-year interval in 25 CAPD patients and 25 patients haemodialysed with cuprophane membranes and matched for residual renal function and duration of renal replacement therapy. Plasma beta 2M remained lower in CAPD patients throughout the study, and increased significantly with time both in CAPD and haemodialysis patients, as renal function decreased. In both groups, plasma beta 2M was negatively correlated with residual creatinine clearance, the influence of the latter being much greater in haemodialysis, as demonstrated by comparison of the regression lines. In haemodialysis, but not in CAPD, plasma beta 2M also correlated with time on dialysis. In CAPD patients, the daily peritoneal output averaged 38 mg (range 16-59 mg), and was directly correlated with plasma beta 2M. CAPD thus allows a significant peritoneal removal of beta 2M, which progressively takes over from the declining renal function, resulting in lower plasma beta 2M than in matched haemodialysis patients. However, the peritoneal removal of beta 2M remains insufficient and values increase with time as renal function declines. Thus, if beta 2M amyloidosis is related to raised plasma levels, the risk of beta 2M amyloidosis in CAPD should simply be delayed as compared to haemodialysis.

Effect of aluminum on porphyrin metabolism in hemodialyzed patients.

In patients with renal failure and on chronic hemodialysis, serum aluminum, serum delta-aminolevulinic acid, serum porphobilinogen and erythrocyte zinc protoporphyrin (ZPP) are significantly elevated, whereas erythrocyte delta-aminolevulinic acid dehydratase activity (ALAD, values in percent) is significantly reduced. The last two parameters (ZPP and ALAD) are statistically related to serum aluminum concentration (Al-S), but only the correlation between Al-S and ALAD remains statistically significant after standardization for the degree of renal insufficiency (expressed in terms of urea level). This study does not support the hypothesis that the retention of aluminum is responsible for the increase of ZPP in uremic patients on dialysis. The disturbances of porphyrin metabolism found in patients with renal failure and on chronic dialysis are not similar to those observed in porphyria cutanea tarda.

Improvement of anemia with deferoxamine in hemodialysis patients with aluminum-induced bone disease.

As microcytic anemia is a feature of aluminium intoxication, we prospectively studied the hematologic effects of deferoxamine in 10 hemodialysis patients with aluminum-induced bone disease. Comparing the mean monthly results of a 4 month period before and during deferoxamine therapy, we observed an important decrease of the transfusion needs (alpha less than 0.025) and an increase of hematocrit (p less than 0.02), hemoglobin (p less than 0.02), MCV (p less than 0.02) and MCH (p less than 0.05); the number of red blood cells remained unchanged. Our results show that deferoxamine treatment of dialysis patients with aluminum bone disease can markedly improve their anemia, even in the absence of recent aggravation, microcytosis and hypochromia. They also suggest that aluminum could participate in the anemia of dialysis patients even if it is normocytic.

Campylobacter fetus peritonitis followed by septicaemia in a patient on continuous ambulatory peritoneal dialysis.

A 62-year-old man being treated by continuous ambulatory peritoneal dialysis (CAPD) developed peritonitis due to Campylobacter fetus subspecies fetus (intestinalis), an organism seldom isolated in such circumstances. After appropriate and apparently effective antibiotic therapy, the patient relapsed 6 weeks later with septicaemia. Blood cultures yielded a similar organism, thereby suggesting a clinically silent metastatic infection during the episode of peritonitis, probably at an old arteriovenous fistula. Parenteral tobramycin followed by oral erythromycin achieved a complete cure of this unusual complication.

Red blood cells indices and aluminium toxicity in haemodialysis patients.

Microcytic, hypochromic anaemia is a feature of aluminium toxicity. To detect the possible influence of aluminium on erythropoiesis in a general haemodialysis population we studied the evolution of red blood cell parameters and aluminium status in 30 patients (27 without aluminium toxicity symptoms). Aluminium status was assessed by serum aluminium measurements before (BAl) and after (PAl) a desferrioxamine infusion. The evolution with time (delta) of PAl and DAl (= PAl - BAl) during the prospective study inversely correlated with delta mean corpuscular volume (2 alpha less than 0.01) and delta mean corpuscular haemoglobin (2 alpha less than 0.001). Patients with DAl greater than 180 micrograms/L had lower mean corpuscular haemoglobin values (p less than 0.05). These findings suggest that aluminium inhibits haemoglobin synthesis even in haemodialysis patients free of aluminium toxicity symptoms.