Thalidomide in patients with multiple myeloma and renal failure.
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Biomedical subjects
Publications and source records attributed to Claire Presne.
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BACKGROUND: Long-term lithium administration in humans may lead to chronic tubulointerstitial nephritis, which develops very slowly. Its progression to end-stage renal disease (ESRD) has been rarely reported. The aim of this study is to document the rate of progression of lithium-induced nephropathy and its prognostic factors, and to provide an estimation of the percentage of lithium-induced ESRD in France. METHODS: Two groups have been studied: 54 patients with lithium-induced renal failure, nine of whom underwent renal biopsy; and 20 patients who were referred for systematic renal biopsy, 14 of whom were subsequently followed up. In addition, a survey of lithium-induced ESRD was conducted in French dialysis centers. RESULTS: The mean annual loss of creatinine clearance in patients with lithium-induced nephropathy was 2.29 mL/min. Among 74 patients, 12 reached ESRD at a mean age of 65 years. Creatinine clearance at referral and at last follow-up was inversely related to the duration of lithium therapy in both univariate and multivariate analyses adjusting for age, gender, hypertension, and proteinuria. The degree of interstitial fibrosis on renal biopsy was also related to the lithium duration and cumulative dose. It was predictive of the final creatinine clearance. About 35% of the patients tested had moderate hypercalcemia, due to hyperparathyroidism. The prevalence of lithium-related ESRD in France was estimated as two per 1000 dialysis patients. The average latency between onset of lithium therapy and ESRD was 20 years. CONCLUSION: Lithium-induced chronic renal disease is slowly progressive. Its rate of progression is related to the duration of lithium administration. Lithium-related ESRD represents 0.22% of all causes of ESRD in France. Regular monitoring of estimated creatinine clearance is mandatory in long-term lithium-treated patients.
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BACKGROUND: The clinical presentation, treatment, and outcome of steroid-sensitive nephrotic syndrome (SSNS) during childhood have been extensively studied. Conversely, few data regarding the outcome in adulthood of childhood SSNS have been published previously. We undertook to conduct a retrospective study of the outcome in adulthood of a large cohort of patients diagnosed with an SSNS during childhood. METHODS: We identified all children born between 1970 and 1975 who had been admitted to our institution for an SSNS. Data regarding the outcome in adulthood of these patients were obtained through mailed questionnaires or phone calls to patients and/or their parents or through attending physicians. RESULTS: One hundred seventeen patients were identified. Data regarding the outcome of SSNS in adulthood were available for 102 patients (87.2%). Forty-three patients (42.2%) experienced at least one relapse of nephrotic syndrome in adulthood. By univariate analysis, young age at onset (<6 years) and more severe disease in childhood, indicated by a greater number of relapses (12.9 for adulthood relapsers versus 5.4 for adulthood nonrelapsers; P < 0.0001) and more frequent use of immunosuppressors (74.4% versus 31.6%; P < 0.0001) or cyclosporine (42.9% versus 7.3%; P < 0.0001) were predictive of the occurrence of SSNS relapse in adulthood. Conversely, relapse rate in the first 6 months of disease was not predictive of further relapses in adulthood. By multivariate analysis, only number of relapses during childhood was predictive of adulthood relapses (P < 0.0058). Long-term side effects of steroids were found in 44.2% of adulthood relapsers; the most frequent were osteoporosis and excess weight. CONCLUSION: The incidence of childhood SSNS relapses in adulthood was relatively high in our study. Further studies are required to assess long-term complications in adults with relapses and a history of prolonged steroid and immunosuppressor use.
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As suggested by its American brand name (Sensipar), the calcimimetic cinacalcet sensitizes the parathyroid cells to the extracellular calcium signal, suppressing parathyroid hormone (PTH) release and synthesis and preventing parathyroid cell proliferation. This primary PTH suppression decreases the release of calcium and phosphate from bone without increasing intestinal absorption of calcium and phosphate. Therefore cinacalcet decreases the risk of hypercalcemia and hyperphosphatemia in contrast to 1alpha-OH vitamin D derivatives. Compared with calcium-containing oral phosphate binder (OPB), it increases the risk of hypocalcemia and may decrease the PTH-mediated phosphaturia in predialysis patients. This justifies its combined use with calcium-containing OPB in order to prevent hypocalcemia and enhance the hypophosphatemic effect of the latter, while improving PTH suppression. The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) has recommended restriction of supplemental elemental calcium to 1.5 g/day, a recommendation that we believe should be revised. No pathophysiologic or randomized trial data have yet evidenced the absolute necessity for systematically using 1alpha-OH vitamin D derivatives and noncalcium-containing OPB rather than higher doses of calcium-containing OPB alone in uremic patients without vitamin D insufficiency. In patients with hyperparathyroidism as severe as in the "Treat to Goal Study," the Durham study showed that a calcium carbonate dose more than three times the K/DOQI limit could decrease PTH into the recommended range, with the advantage of a lower calcium-phosphate product compared with the combination of calcitriol and noncalcium OPB. Besides the efficient PTH suppression associated with lower calcium-phosphate product and a good gastrointestinal tolerance, long-term data suggest that cinacalcet may decrease the risk of parathyroidectomy and fracture, while high bone turnover lesions are improved. However, no long-term data on bone mineral density and cardiovascular calcification and complications are yet available. Such studies, along with those comparing cinacalcet and 1alpha-OH vitamin D-based approaches to hyperparathyroidism, are needed.