Characteristics of IgA and macromolecular IgA in sera from IgA nephropathy transplanted patients with and without IgAN recurrence.
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Biomedical subjects
Publications and source records attributed to F Berthoux.
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Continuous renal replacement therapies have been used increasingly in critically ill patients in nephrologic and intensive care units. These techniques are nevertheless time consuming and lack an easy control of ultrafiltration. We conducted continuous venovenous hemodialysis (CVVHD) on a dialysate delivery machine which ensures a volumetric control of ultrafiltration, and which produces both dialysate and infusate with the on-line technique. This new mode of CVVHD was firstly assessed in a feasibility study and was secondly used in a randomized prospective study whose goal was to establish the usefulness of convection. On-line continuous venovenous hemodiafiltration (OL-CVVHDF) appeared safe and time saving, and allowed the fine control of fluid management in critically ill patients. Convective transfers were achieved by a 2 L/h predilutional infusion and increased urea and creatinine clearances twofold. OL-CVVHDF revealed itself to be a valuable method for the control of ultrafiltration and for efficient convective transfers during CVVHD.
34 patients had 37 Quinton Permcath (PKT), surgically implanted in jugular vein (internal: 29, or external: 8). The first 20 were used for a temporary vascular access (mean: 21 weeks). Then, the next 17 were used for permanent vascular access. 8 could be used for more than 1 year and 2 for more than two years. Anti-aggregant (29 cases) or anticoagulant treatment (8 cases) were systematically prescribed. 6 patients died for unrelated causes (mean delay: 35 weeks). 3 catheters were mispositioned. 2 catheters had to be removed because they were damaged (mean 53 and 69 weeks). Complications were: vein thrombosis (internal jugular vein): 2 cases, vein stenosis (inominate vein): 1 case, heparin overdoses: 3 cases. A partial thrombosis of a single lumen was common but always easily cured by local thrombolysis. Nurses were strongly motivated and followed rigorous educations with help of video-movie. This could be why no infectious (local or generalised) complication was observed. Long-term Permcath dialysis is a precious tool for patient without any peripheral vascular access or in elderly and short-live expectancy.
In transplant recipients, immunosuppressive regimens are deleterious on natural killer (NK) and lymphokine-activated killer (LAK) cells, which beyond their well-known antitumoral activity display many important biological functions. In order to find which regimens could preserve NK and LAK functions we tested the influence of CsA, FK506, 6-mercaptopurine and prednisolone on HLA-unrestricted cytotoxicity during an in-vitro IL-2 activation. For each drug we obtained peripheral blood samples from 11 healthy volunteers. Non-adherent PBMC were incubated 2 days with either CsA, FK506, 6-mercaptopurine or prednisolone, whose concentrations ranged from 0 to 10 micrograms/ml, in order to screen infratherapeutic, therapeutic, and supratherapeutic doses. Thereafter, 100 IU of IL-2 were added for a further 3-day culture. Before and after the culture, we analysed (1) the cell subsets by direct immunofluorescence staining with anti-CD3/CD16/CD56 antibodies, (2) the LAK activity with the lysis of Daudi cells, (3) the cell proliferation with a 24-h incorporation of thymidine. Cyclosporin and FK506 did not impair the LAK cytotoxicity nor the number of LAK cells, whereas both prednisolone and 6-mercaptopurine decreased the LAK cytotoxicity, the number of CD3- CD16+ CD56+ cells, and the thymidine uptake. As a whole, the LAK cytotoxicity was correlated with the number of CD3- CD16+ CD56+ cells but not with the number of CD3+ CD16- CD56- cells, and it also increased with the incorporation of thymidine. This latter was correlated with the number of CD3- CD16+ CD56+ cells, but not with the number of CD3+ CD16- CD56- cells.(ABSTRACT TRUNCATED AT 250 WORDS)
TNF is clearly involved in allograft rejection but measurement of serum cytokine levels do not reflect reliably the rejection crisis. TNF induces release of soluble receptor parts that are more stable, are catabolized by kidneys and have inhibitory activity. Thus it is crucial to analyse their kinetics during renal function recovery after transplantation to forecast their potential clinical use in rejection monitoring or treatment. A sequential study was performed in 61 patients undergoing kidney graft, compared to 60 graft patients with long follow-up and 15 healthy controls. Soluble TNF and Il2 receptors were measured by ELISA and TNF was measured by RIA. The sTNF-Rs were markedly increased in renal failure, much more than another soluble cytokine receptor, the sIl2-R. Levels progressively decreased with the recovery of renal function and became directly correlated to the renal function. Normal levels were only reached after some weeks. No significant changes were observed during graft rejection at that stage of renal function but p75 were higher after antilympocyte antiserum and tubular necrosis. High sTNF-R did not seem to minimize rejection risk or gravity. In long-standing recipients, sTNF-R rose in some patients, particularly with glomerulonephritis, and may help in monitoring chronic rejection activity. sTNF-R but not sIl2-R markedly accumulate in ESRF and mask any changes that could be helpful in the monitoring of early graft events. However, increased levels above renal impairment (sTNF-R/SCr) may be clinically relevant in late rejection or glomerulonephritides.
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A retrospective analysis of 565 cases of IgA nephropathy, defined by the presence of predominant and diffuse IgA deposits in the glomerular mesangium, led to the classification of 510 primary forms or Berger's focal glomerulonephritis and 55 cases secondary to Henoch-Schönlein syndrome. Crescent proliferation was observed in 9.4% of the renal biopsies taken from patients with Berger's disease; they were generally contained and do not seem to be correlated with disease prognosis. On the other hand, the presence of glomerular crescents seems to represent a major prognostic factor in Henoch-Schönlein purpura-associated glomerulonephritis, because all the patients who developed chronic renal failure (5%) had extracapillary proliferation affecting more than 25% of the glomeruli. The detection of glomerular crescents in Henoch-Schönlein syndrome justifies the initiation of aggressive therapy.
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We conducted a dual study of phenotype and function of natural killer cells (NK) using flow cytometry, this study being applied to renal transplantation. The CD 16 and CD 56 clusters correlated well with NK cytotoxicity, especially for CD 3 lymphocytes, whereas CD 57 should no longer be considered a NK marker. NK activity was determined on K 562 or Daudi cells, either spontaneously or after in vitro activation with r-interleukin 2 (LAK). Cytotoxicity was analyzed after labeling of target cells by carboxyfluoro-diacetate and measured by flow cytometry. We found that in renal transplant recipients NK cells were deficient in numbers and functions and showed that LAK activity was also diminished. Azathioprine appeared to be the main immunosuppressant impairing NK cells. Viral infections increased the numbers and functions of NK cells, whereas during malignancies they remain as low as in uncomplicated recipients. NK cells deficiency might be involved in the high incidence of de novo malignancies in renal transplant recipients.
Between November 1980 and July 1989, 29 ex vivo reconstructions were performed in 12 women and five men (mean age: 42 years) for dysplastic lesions of renal artery branches. Fifteen patients had hypertension, associated with advanced renal failure in one case. The internal iliac artery was used routinely for reconstruction. The saphenous vein was used on one side where bilateral repairs were necessary. A total of 52 distal anastomoses were performed, an average of 2.6 per revascularized kidney. Mean follow-up was four years and 10 months. No patients were lost to follow-up. There were no early or late deaths. At least one follow-up arteriogram and technetium99 diethylene triamine pentacetic acid scintiscan was obtained for all patients. Forty-five (86%) of 52 anastomoses remained patent. Eleven of 15 hypertensive patients completely recovered while four were improved. Systolic arterial blood pressure decreased by an average of 42 mmHg (p less than 0.001), and results remained stable with time. For fibromuscular dysplasia occurring in young patients whose life expectancy is usually long, this type of surgery provides excellent long-term clinical and anatomical results.
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