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Biomedical subjects

C Leroux-Robert

Publications and source records attributed to C Leroux-Robert.

At least 19 recordsLinked to original sources

Factors predicting the long-term success of maintenance cyclosporine monotherapy after kidney transplantation.

BACKGROUND: The theoretical aim of maintenance cyclosporine monotherapy (mCsA) after kidney transplantation is to reduce the incidence of the metabolic complications of corticosteroids and to minimize the adverse effects of excessive long-term immunosuppression. This study was performed in low-immunological-risk cadaveric kidney transplant recipients to evaluate the risks and benefits of mCsA and the long-term graft survival, and to determine the factors predicting success of this policy. METHODS: The multicenter retrospective study was conducted in 329 Caucasian patients receiving mCsA out of 728 first cadaveric kidney transplant recipients. The inclusion criteria were: HLA antibodies < or =25%, serum creatinine <200 micromol/L, and no rejection or only one rejection episode. At the end of the study, we compared the group of patients successfully treated with mCsA (successful group) with those requiring additional immunosuppressive agents (unsuccessful mCsA group). RESULTS: Overall patient and graft survival rates for the 728 first cadaveric graft were 92% and 64%, respectively, at 8 years. Out of 329 patients enrolled in mCsA, 240 were maintained on this treatment and 89 were withdrawn (3 deaths, 18 graft losses, 68 functional grafts). The 8-year graft survival in the 329 enrolled mCsA patients was 84%, 95% in the successful mCsA group, and 70% in the unsuccessful mCsA group. Multivariate analysis showed that the factors predicting success of mCsA were: donor age <40 years (P = 0.001), serum creatinine at mCsA initiation <125 micromol/L (P = 0.02), no rejection episode before mCsA initiation (P = 0.005), and glomerulopathy as the primary renal disease (P = 0.001). CONCLUSION: Numerous kidney transplant recipients with a low immunological risk and good and stable renal function may benefit from discontinuation of prednisone and azathioprine in order to reduce the complications related to these drugs. This therapeutic approach had no adverse impact on the overall long-term graft survival for "low risk" and successful patients.

Adult↗

Whole blood production of monocytic cytokines (IL-1beta, IL-6, TNF-alpha, sIL-6R, IL-1Ra) in haemodialysed patients.

BACKGROUND: The production of monocytic cytokines by isolated mononuclear cells after stimulation by phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) is generally increased in haemodialysed (HD) patients. We performed whole blood (WB) cultures to evaluate cytokine production by blood cells inside their complex cellular and humoral network. METHODS: Diluted whole blood from HD patients (collected before dialysis) and controls was cultured alone with PHA (2.5 microg/ml) or LPS (1 and 3 microg/ml). Supernatants were collected after 24 and 48 h of culture, and concentrations of IL-1 beta, IL-6, TNF-alpha, sIL-6R and IL-1Ra were determined by ELISA. RESULTS: The low spontaneous production of IL-1beta, IL-6 and TNF-alpha in both patients and controls was not significantly modified by PHA. The lower dose of LPS (1 microg/ml) induced a significant but lower increase in production of IL-1beta, IL-6 and TNF-alpha in patients than in controls. In contrast, while it did not further increase their production in controls, the higher concentration of LPS (3 microg/ml) still increased their production in patients to the same level than in controls. The plasma concentrations of sIL-6R were higher in patients than in controls. In both groups, the sIL-6R concentration did not vary during the culture period whether the cells were stimulated or not with LPS or PHA. This suggests that the increased plasma levels of sIL-6R were not produced by blood cells. Despite a similar significant LPS and PHA induced production of IL-1Ra, the IL-1Ra/IL-1beta ratio was always higher in patients than in controls. CONCLUSION: Monocytes from HD patients in WB cultures are hyporesponsive to PHA and LPS for their IL-1beta, TNFalpha and IL-6 production in contrast to isolated monocytes that demonstrate signs of activation. If it reflects the in vivo situation it could partly explain the immune defect in uraemic and haemodialysed patients. Higher sIL-6R/IL-6 and IL-1Ra/IL-1beta ratios could also participate to the complex immune disturbances of HD patients by reducing the biological activity of two cytokines playing a major role in the immune and inflammatory network.

Blood Cells↗

[A little known cause of chronic renal insufficiency in the adult: systemic tuberous sclerosis].

BACKGROUND: Angiomyolipomas and renal cysts are commonly observed in patients with systemic tuberous sclerosis. Hemorrhagic complications related to the angiomyolipomas are well known. CASE REPORT: A 63-year old woman was hospitalized for severe chronic renal failure. Physical examination revealed skin manifestations of systemic tuberous sclerosis, which the patient had hidden to date. The radiographic work-up demonstrated complete disorganization of the renal parenchyma in both kidneys due to multiple cysts and angiomyolipomas. DISCUSSION: Chronic renal failure can be the inaugural manifestation in low-grade cases of systemic tuberous sclerosis which may go undiagnosed for years allowing progressive destruction of the kidneys.

Female↗

Decrease of serum paraoxonase activity in chronic renal failure.

Paraoxonase is an esterase that hydrolyzes organophosphate compounds. The enzyme is associated with HDL and could protect LDL against peroxidation, which suggests a possible involvement of paraoxonase in the antiatherogenic properties of HDL. Paraoxonase activity has been shown to be low in patients with myocardial infarction, diabetes mellitus, or familial hypercholesterolemia. Because cardiovascular disease is the main cause of death in chronic renal failure, serum paraoxonase activity was measured by spectrophotometry using three synthetic substrates (phenyl acetate, paraoxon, and 4-nitrophenyl acetate) in 305 patients with kidney disease, including 47 patients with non-end-stage chronic renal failure, 104 patients treated with hemodialysis, 22 patients treated with peritoneal dialysis, and 132 renal transplant patients. Patients were compared with two groups of aged-matched control subjects (total number = 195). Especially with 4-nitrophenyl acetate, paraoxonase activity was lower in patients with some degree of renal insufficiency (chronic renal failure [P < 0.05], chronic hemodialysis [P < 10(-4)], chronic peritoneal dialysis [P < 10(-4)]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure could be an essential factor of premature vascular aging, especially when dialysis is used. Renal transplantation seems to restore paraoxonase activity.

Adolescent↗

[Lymphoproliferative syndromes after renal transplantation].

UNLABELLED: Following kidney transplantation, lymphoproliferative disorders (LD) are encountered at a frequency of 1%. The onset of these LD is correlated with the degree of immunosuppression. The mortality is elevated (> 50%) especially in late forms. Since 1984 we have performed two hundred and seventeen kidney transplantations. The patients received sequential quadruple-drug immunosuppressive therapy: antilymphocyte globulin (ALG), azathioprine, corticosteroids and cyclosporine. A diagnosis of LD was established in ten patients, four were of early onset (within twelve months of transplantation) and six late (after five to nine years). Rejection occurred in two patients, one of which was steroid resistant requiring ALG. Three LD arose from the graft hilum, four had a voluminous tumor mass with extranodal sites: the graft (1), stomach (2), gingiva (1), meninges (1), and bone marrow (1). Histologically there were eight cases of large-cell B lymphoma, 1 mononucleosis-like LD, and a MALT lymphoma. A search for EBV was positive seven times. Treatment consisted of decreasing immunosuppressive therapy only (1), combined with antiviral treatment (1), or with surgical removal of the graft (3), and/or chemotherapy (5). Nine patients are still alive, in complete remission, graft loss occurred in four cases. CONCLUSION: In our series, we found a high frequency of LD. Despite 4 LD with a voluminous tumor mass and unfavorable histological prognosis requiring chemotherapy, all the LD in our series had a favorable outcome.

Adult↗

Renal infarction and thrombosis of the infrarenal aorta in a 35-year-old man with primary antiphospholipid syndrome.

Renal manifestations of the "primary" antiphospholipid syndrome are rare. We report the case of an athletic 35-year-old man with an unremarkable medical history who suddenly developed hypertension and a renal infarction. Laboratory and radiological investigations showed a complete thrombosis of the infrarenal aorta, extensive collateral circulation arising from the superior mesenteric artery, and the primary antiphospholipid syndrome. Eight cases of renal infarction have previously been reported in the primary antiphospholipid syndrome. To our knowledge, this represents the first case of an infrarenal aortic thrombosis attributable to this syndrome.

Adult↗

Macrophage colony stimulating factor involvement in uremic patients.

The immunodeficiency of patients with chronic renal failure (CRF) is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is recognized as a key factor in these immunological disorders. Since macrophage colony stimulating factor (M-CSF) is essential for the activation of several functions of monocytes and macrophages and their production of cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, we investigated its involvement in patients with CRF. When measured by ELISA, M-CSF serum levels were significantly higher in patients with progressive CRF and those on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate with the degree of renal insufficiency and were probably related to complex alterations in its production and/or degradation by the specific M-CSF receptors of macrophages. In HD patients the M-CSF serum concentrations inversely correlated with the number of circulating lymphocytes and were significantly higher in anemic patients requiring treatment with erythropoietin. Our results suggest that M-CSF may play a role in altering the immune system in uremic patients by maintaining in the circulation and tissues permanently primed monocytes and/or macrophages that can then be triggered to an activated state by secondary stimuli such as endotoxins, complement components, other cytokines or contact with foreign surfaces.

Adult↗

Calcium oxalate crystalluria in elderly patients and treatment with naftidrofuryl oxalate.

Crystalluria is important in the evaluation of patients with urinary stone and is more frequently encountered in elderly than in younger adults. After noting that calcium oxalate monohydrate crystalluria was higher in elderly patients, we undertook a study to determine if oral treatment with naftidrofuryl oxalate, a drug frequently prescribed for elderly patients in France, was associated with crystalluria. The presence of early morning crystalluria was assessed in non-stone-forming patients hospitalized in a geriatric department. We studied 251 patients without a history of nephrolithiasis (mean age; 81.6 +/- 8.5 years) of whom 49 had been treated orally with naftidrofuryl oxalate at a mean dosage of 485 +/- 120 mg/24h. We identified and quantified the crystals in one early morning urine sample kept at room temperature. The frequency of crystalluria in elderly patients without stones who were not taking naftidrofuryl oxalate was 31.7% compared with only 6% in the general adult population. In this group, mainly calcium phosphate crystals were found. In patients who received naftidrofuryl oxalate, the frequency of crystalluria was 51% of which the major component was calcium oxalate monohydrate and not calcium phosphate. Naftidrofuryl oxalate may enhance crystal formation in elderly patients. This should be taken into account, particularly when other predisposing factors for nephrolithiasis are present, and a preventive increase in fluid intake considered.

Administration, Oral↗

Uraemia is necessary for erythropoietin-induced hypertension in rats.

1. There is no experimental proof that renal insufficiency is a necessary condition for hypertension during erythropoietin treatment. 2. The present study compares the effect of 3 weeks treatment with r-hu EPO (50 i.u./kg) on systolic blood pressure (SBP), haematocrit and plasma cGMP in an animal model of chronic renal failure (remnant kidney model excision) and sham-operated rats. 3. Sub-total nephrectomy induced a significant fall in haematocrit and a significant increase in plasma creatinine levels. Treatment with r-hu EPO resulted in a significant haematocrit increase in uraemic as well as in non-uraemic rats. Despite this effect, r-hu EPO treatment had no effect on SBP in sham-operated rats. On the contrary, this treatment caused significant SBP elevation in uraemic rats; in these rats, SBP increase did not correlate with haematocrit increase. 4. Plasma cGMP concentrations were significantly higher in uraemic compared to sham-operated rats and were not modified by r-hu EPO treatment. 5. This study provides evidence that renal insufficiency in rats is a prerequisite for the development of hypertension during erythropoietin treatment.

Animals↗

[Peritoneal dialysis in people more than 75 years old].

Over 75 years old peritoneal dialysis patients can be treated with at least as good results as those of hemodialysis. Peritoneal dialysis is the only method used to treat old patients at home with psychological profits. Regarding the lack of references on nutritional state of uremic old patients and on early death forecast factors geriatric peritoneal dialysis knowledges are not yet well established.

Aged↗