Claire Presne

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (40)260.01 Total impact

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    ABSTRACT: Background.Cardiac involvement is a major cause of mortality in thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed due to sub-clinical injuries. Cardiac troponin-I (cTnI) on admission could improve early diagnosis of cardiac involvement and have a prognostic value.Objectives.To assess the predictive value of cTnI-I in TTP for death or refractoriness.Patients/Methods.The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS13 deficiency (<10%) and included in the registry of the French reference center for thrombotic microangiopathies. Centralized cTnI measurements were performed from frozen serum on admission.Results.Between January, 2003 and December, 2011, 133 patients with TTP (mean age, 48±17 year-old) had available cTnI measurement on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI (>0.1μg/L) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. Main outcomes were death (25%) and refractoriness (17%). Age (P=0.02) and cTnI level (P=0.002) showed the greatest impact on survival. A cTnI level >0.25 μg/L was the only independent factor in predicting death (Odds-ratio [OR] 2.87; 95% confidence interval [CI]: 1.13-7.22; P=0.024) and/or refractoriness (OR 3.03; 95%CI: 1.27-7.3; P=0.01).Conclusions.CTnI >0.25 μg/L at presentation in TTP appears as an independent factor associated with a threefold increase in death risk or refractoriness. Therefore, cTnI levels should be considered as part of prognostic indicator in patients diagnosed with TTP.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 11/2014; · 6.08 Impact Factor
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    ABSTRACT: Minimal-change nephrotic syndrome (MCNS) is a common cause of steroid sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and safe alternative in childhood.
    Nephrology Dialysis Transplantation 06/2014; 29(11). · 3.49 Impact Factor
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    ABSTRACT: In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe ADAMTS13 deficiency (<10%) during remission is associated with more relapse. Preemptive (i.e., after remission) administration of rituximab in these patients to prevent relapses remains controversial. We performed a cross-sectional analysis of 12-year follow-up data to compare the relapse incidence after or not preemptive rituximab infusion. Among 48 patients who experienced at least one episode of acquired TTP followed by severe ADAMTS13 deficiency during remission, 30 received preemptive rituximab (group 1: 1 [11 patients], 2 [2 patients] or 4 [17 patients] infusions/course); the other 18 did not (group 2). After a median of 17 months (interquartile range [IQR], 11-29) following rituximab, the relapse incidence decreased from 0.57 (IQR, 0.46-0.7) to 0 (IQR, 0-0.81) episode/year (P<.01) in group 1. ADAMTS13 activity 3 months after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients required additional courses of rituximab. Five patients failed to increase durably ADAMTS13 activity. Four patients experienced manageable adverse effects. In group 2, the relapse incidence was higher (0.5 [IQR, 0.12-0.5] relapse/year, P<.01). Relapse-free survival was longer in group 1 (P=.049). A persistent severe ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses.
    Blood 05/2014; · 9.78 Impact Factor
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    ABSTRACT: Background Baclofen is a centrally acting gamma-aminobutyric acid agonist used for spasticity of brain or spinal origin. We report the case of a 60-year-old man with a chronic renal failure treated daily with 15 mg of baclofen for the treatment of a right spastic hemiplegia. Seven days after his hospitalization for an extended right nephrectomy, the patient presented an encephalopathy. The CT scan did not find any signs of stroke. A drug overdose was suspected. Materials and methods A double screening by GC/MS and HPLC/DAD was carried out on two blood samples taken before and after patient's dialysis. The concentration of baclofen was measured on the same samples by a validated method using liquid chromatography coupled to a mass spectrometer ion trap. Results The toxicology screening didn’t show the presence of baclofen. Serum concentrations of baclofen were measured at 2100 ng/mL in the sample taken before dialysis and 1150 ng/mL in the post-dialysis sampling. Conclusion Encephalopathy is most likely the result of baclofen overdose. Regression of symptoms after hemodialysis and the significant decrease in baclofen serum concentrations are in line with this hypothesis. Indeed, baclofen is mainly eliminated by glomerular filtration. So it was accumulated in this patient with impaired renal function. This observation highlights the importance of measuring baclofen trough concentrations in patients with renal impairment to avoid its accumulation by a dose adjustment.
    Toxicologie Analytique et Clinique. 04/2014; 26(1):27–31.
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    ABSTRACT: BACKGROUND: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP.
    Transfusion 02/2014; 54(2):389-397. · 3.57 Impact Factor
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    ABSTRACT: Before kidney transplantation, recipients are routinely screened for preformed antibodies and prospective crossmatches. In this study, we compared prospective Luminex donor-specific crossmatches (LumXm) with the levels of identified, donor-specific antibodies (DSAs). LumXm was performed for 108 patient sera, 84 of which were positive for preformed antibodies and 24 of which were negative. Although LumXm can detect class I DSAs (anti-A and anti-B) with a mean fluorescence intensity (MFI) as low as 2300, the assay has a 'grey zone' for MFIs up to 4000 with a sensitivity of 54% and a specificity of 100%. LumXm can detect a class II DSA (anti-DRB1) with an MFI as low as 1300 and a sensitivity of 93% and a specificity of 99%. However, these correlations were obtained with two precautions: autocrossmatching and single-antigen bead assay with denaturing buffer were performed in discordant cases. Moreover, LumXm failed to detect anti-Cw and anti-DP in the 10 cases studied. LumXm, therefore, displays certain discrepancies with respect to single-bead assays - especially for antibodies with a low MFI. Unfortunately, LumXm has a low sensitivity for anti-A and anti-B class I antibodies.
    Tissue Antigens 04/2013; · 2.35 Impact Factor
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    ABSTRACT: Context: Thrombotic thrombocytopenic purpura (TTP) is a particularly serious form of thrombotic microangiopathy (TMA) due to the risk of multiple organ dysfunction. Several etiological factors such as infection, auto-immune disease, certain medications and cancers have been associated with TTP. Clinical cases: A 74-year-old hypertensive woman with a history of thromboembolic disease was hospitalized for acute kidney injury (AKI) associated with pneumonia. Initial investigations were suggestive of Pneumocystis jirovecii infection and myeloma cast nephropathy. Several days later, the patient presented features of TTP. Von Willebrand factor-cleaving protease activity was less than 5% with a high level of IgG antibody directed against ADAMTS13. Treatment consisted of monthly 4-day cycles of dexamethasone and melphalan in combination with plasmapheresis and resulted in a favorable outcome. Three years after ceasing treatment, the patient presented no signs of hemolysis, but required chronic hemodialysis. Conclusion: The association of TMA, especially TTP, and multiple myeloma is exceptional. The authors report such a case that induced irreversible renal damage, but with stable clinical and laboratory parameters with a follow-up of 4 years.
    Clinical nephrology 10/2012; · 1.23 Impact Factor
  • Néphrologie & Thérapeutique 09/2012; 8(5):285. · 0.55 Impact Factor
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    ABSTRACT: Acquired thrombotic thrombocytopenic purpura is still associated with a 10-20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. Non-survivors (11%) were older (P=10(-6)) and more frequently presented arterial hypertension (P=5.10(-4)) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.
    Haematologica 05/2012; 97(8):1181-6. · 5.94 Impact Factor
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    ABSTRACT: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura. Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine. Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France. Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange. Add-on rituximab therapy, four infusions over 15 days. One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred. Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.
    Critical care medicine 09/2011; 40(1):104-11. · 6.15 Impact Factor
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    ABSTRACT: Primary localized amyloidosis of the genitourinary tract is a rare entity characterized by small pseudotumors localized in the renal pelvis, ureters, or bladder. Amyloid fibrils are derived from immunoglobulin light chains, but no systemic plasma cell proliferation is detected. The clinical and radiologic features mimic urinary tract cancer, and local treatment is indicated. The prognosis is excellent in most cases, although disease recurrence is possible. We report 5 new cases of localized amyloidosis of the urinary tract, with lambda (4/5), or kappa (1/5) chain amyloid protein, involving the bladder (5/5), and the ureter and renal pelvis (1/5), with multiple, bilateral lesions in 1 case. The presenting complaint was painless hematuria in 4 cases. All cases were of primary (AL)-type amyloidosis. All patients underwent extensive investigation, and none presented any signs of generalized amyloidosis. A favorable outcome was observed in every case. We performed a comprehensive review of the literature, and summarize the data.
    Medicine 05/2011; 90(3):212-22. · 4.35 Impact Factor
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    ABSTRACT: The recent identification of mutations in the INF2 gene, which encodes a member of the formin family of actin-regulating proteins, in cases of familial FSGS supports the importance of an intact actin cytoskeleton in podocyte function. To determine better the prevalence of INF2 mutations in autosomal dominant FSGS, we screened 54 families (78 patients) and detected mutations in 17% of them. All mutations were missense variants localized to the N-terminal diaphanous inhibitory domain of the protein, a region that interacts with the C-terminal diaphanous autoregulatory domain, thereby competing for actin monomer binding and inhibiting depolymerization. Six of the seven distinct altered residues localized to an INF2 region that corresponded to a subdomain of the mDia1 diaphanous inhibitory domain reported to co-immunoprecipitate with IQ motif-containing GTPase-activating protein 1 (IQGAP1). In addition, we evaluated 84 sporadic cases but detected a mutation in only one patient. In conclusion, mutations in INF2 are a major cause of autosomal dominant FSGS. Because IQGAP1 interacts with crucial podocyte proteins such as nephrin and PLCε1, the identification of mutations that may alter the putative INF2-IQGAP1 interaction provides additional insight into the pathophysiologic mechanisms linking formin proteins to podocyte dysfunction and FSGS.
    Journal of the American Society of Nephrology 02/2011; 22(2):239-45. · 9.47 Impact Factor
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    ABSTRACT: Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count < 30 x 10(9)/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.2, P<.001), serum creatinine level < or =200 micromol/L (OR 23.4, 95% CI 8.8-62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0-8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.
    PLoS ONE 04/2010; 5(4):e10208. · 3.53 Impact Factor
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    ABSTRACT: Increased arterial stiffness and vascular calcification have been recognized as important predictors of cardiovascular mortality in patients with chronic kidney disease. In order to examine the precise temporal link between aortic stiffness and cardiovascular risk at the earliest stages of chronic kidney disease, we studied a cohort of 150 patients with chronic kidney disease (52 stage 2/3 patients, 51 stage 4/5 patients and 47 stage 5D patients). Each patient underwent a plain, lateral lumbar radiograph and an abdominal and thoracic multislice spiral computer tomography scan in order to identify and quantify aortic and coronary calcifications. Pulse wave velocity was used as a measure of arterial stiffness. Regardless of the disease stage, patients with chronic kidney disease had higher adjusted pulse wave velocity than controls with preserved renal function (14.6 +/- 3.8 vs. 10.7 +/- 1.7 m/s, respectively; P < 0.0001). Regarding aortic calcification, there was a gradual but significant rise in later chronic kidney disease stages. A similar trend was found for coronary calcification. In a multivariate analysis only age, mean arterial pressure, diabetes and the aortic calcification score were independent determinants of higher pulse wave velocity. We found that both vascular stiffness and vascular calcification appear early in patients with chronic kidney disease, but only vascular calcification worsens as the disease progresses. The increase of vascular stiffness in adult patients with chronic kidney disease seems to be more related to age, systolic blood pressure, diabetes and vascular calcification than to uremic toxicity.
    Journal of Hypertension 11/2009; 28(1):163-9. · 4.22 Impact Factor
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    ABSTRACT: Diuretics are pharmacological agents that increase natriuresis through inhibition of tubular re-absorption of sodium. The mechanisms and site of this inhibition differ with each drug class, accounting for their additive effects on natriuresis increase and their hydroelectrolytic side effects. The response to a given diuretic dose depends on the diuretic concentration on the urine at its action site. This concentration may be decreased by pharmacokinetic factors such as encountered in renal insufficiency or in nephrotic syndrome. These resistance mechanisms of diuretics may be corrected by dose increase, previous diuretic fixation on albumin or warfarin administration. Once these mechanisms are opposed, the diuretic concentration for maximal efficacy is reached at is action site and the natriuresis obtained as the normal maximal plateau. This is not the case when an oedematous systemic disease with effective hypovolemia is present, like in heart failure or cirrhosis, or when chronic use of loop diuretics has induced a hypertrophy of the more distant part of the tubule. In theses cases, a pharmacodynamic resistance exists, resulting in a lower maximal natriuresis plateau in spite of adequate concentration of the diuretic at its action site, even in the absence of pharmacokinetic resistance factors. The main indications of diuretics are systemic oedematous disease and hypertension. In the oedematous diseases, diuretics indication is both straightforward and sufficient only if effective hypervolemia is present. The therapeutic approach is discussed according to the various clinical conditions and pathophysiological background. In uncomplicated hypertension, diuretics are the cornerstone of the therapy. The most suitable diuretic treatment for hypertension is an association of low doses thiazide (12.5-50 mg/day) with potassium sparing diuretics. Rare indications of diuretics are also reviewed.
    Néphrologie & Thérapeutique 11/2007; 3(6):392-426. · 0.55 Impact Factor
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    ABSTRACT: Ischaemia-reperfusion and hyperglycaemia are two main sources of oxidative stress that plays an important role in the pathophysiology of tissue injury in transplant recipients. We hypothesized that controlling hyperglycaemia with insulin during the first hours following kidney transplantation could improve antioxidant defences and therefore decrease ischaemia-reperfusion-induced injury. We performed a prospective randomized study in non-diabetic dialysed patients receiving a first cadaveric renal allograft, and assigned them to receive either 200 g/day of glucose infusion (control group, n=23) or the same glucose infusion and intravenous insulin to maintain blood glucose<10 mmol/l (insulin group, n=20). Antioxidant defences were assessed by the plasma total radical-trapping antioxidant parameter (TRAP). TRAP values remained stable throughout the study in the Insulin group, whereas they decreased from admission to day 1 (-2.70+/-0.16 vs -2.98+/-0.26, P<0.0001), and tended to retrieve the basal values at day 15 in the control group. TRAP values were significantly higher in the insulin group compared with the control group at days 1 (-2.80+/-0.19 vs -2.98+/-0.16, P<0.05) and 4 (-2.80+/-0.19 vs -2.95+/-0.20, P<0.05). No differences were found between the two groups on urinary malondialdehyde determination, two markers of oxidative damage, nor in graft function or patient outcome. This is the first clinical trial to demonstrate improvement in insulin-induced antioxidant defences at the early stage of kidney transplantation. More extensive studies will tell if this strategy has beneficial impact in long-term graft outcome.
    Nephrology Dialysis Transplantation 07/2007; 22(7):1979-85. · 3.49 Impact Factor
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    ABSTRACT: We report a case of a retroperitoneal hematoma occurring in a patient under anticoagulation therapy for deep-venous thrombosis and presenting as an anuric acute renal failure. A coexisting polycythemia vera led to misdiagnosis that could have been life-threatening. A woman, known for polycythemia vera and a single functioning right kidney, was admitted with mild abdominal pain in a context of recent deep venous thrombosis under low-molecular weight heparin. Clinical examination revealed hepatomegaly associated with polycythemia vera. Biochemical evaluation disclosed an acute renal failure, and renal ultrasonography showed no dilation of the renal pelvis. Retroperitoneal hematoma resulted in shock, progressive anemia and obstructive renal failure, related to renal pelvic compression. A right renal indwelling catheter was introduced to restore urine flow after one hemodialysis session, and an inferior vena cava filter was placed because of anti-coagulation contra-indication. However, pulmonary embolism occurred, so that oral anticoagulants were introduced. The hematoma resorbed spontaneously, and a year after this episode, the patient is still alive and well. Retroperitoneal hematoma is a rare cause of obstructive acute renal failure and a life-threatening complication of anti-coagulation therapy.
    Clinical nephrology 06/2007; 67(5):318-20. · 1.23 Impact Factor
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    ABSTRACT: Post-allogeneic haematopoietic stem cell transplantation (HSCT) membranous nephropathy (MN), a rare complication of HSCT, remains an ill-defined entity. We describe the clinical and biological characteristics and outcome of five patients with post-HSCT MN, review the previously reported cases and discuss the pathogenic aspects of this nephropathy. Cases were identified by using a questionnaire sent to nephrologists and pathologists in French university and general hospitals. Medical records and kidney biopsy specimens were reviewed and relevant data were collected. Moreover, the IgG subclasses in glomerular deposits and the presence of chimeric renal cells were studied. Five patients were identified. All had a history of chronic graft-vs-host disease (cGVHD) and all had active manifestations of cGVHD at MN diagnosis. Mean time between HSCT and diagnosis of MN was 24.4 months. Renal insufficiency was present in four patients. Renal biopsy examination showed typical features of MN in all patients. IgG1 and IgG4 were the predominant IgG subclasses in the glomerular deposits. No chimeric glomerular cell was detected. Initial treatment for MN consisted in corticosteroids and immunosuppressors (ciclosporin, mycophenolate mofetil, rituximab, chlorambucil) in all patients. Complete remission of nephrotic syndrome (NS) occurred in two patients, partial remission in one patient, while treatment was inefficacious in one (data not available for one patient). Most interestingly, the evolution of NS paralleled the evolution of cGVHD in all patients. Our data suggest an association between cGVHD and post-HSCT MN. Treatment, mainly steroids and ciclosporin, should be aimed at the control of acute manifestations of cGVHD.
    Nephrology Dialysis Transplantation 06/2007; 22(5):1369-76. · 3.49 Impact Factor
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    ABSTRACT: Molecular biology has recently evidenced that activation of parathyroid calcium receptor was preponderant on that of vitamin D receptor in suppressing parathyroid hormone (PTH) secretion and synthesis and preventing parathyroid hyperplasia. Furthermore, whereas calcium receptor gene deletion is lethal, the hyperparathyroidism and mineralization disorders induced in mice by vitamin D receptor gene deletion can be controlled simply by increasing the calcium/phosphate ratio in the diet to 2. Thus there is no more dogmatic justification for increasing serum calcitriol to supraphysiological levels in spite of the induction by uremia of a resistance to vitamin D. This is all the more less justified that parathyroid cell may produce in situ calcitriol, provided serum calcidiol is sufficient, so that synthesis of PTH may be decreased at its transcriptional step. These new physiopathological mechanisms justify to prevent early hyperparathyroidism (as soon as creatinine clearance decreases below 60 ml/min) by very simple means: supplementation of vitamin D2 or D3 or of their 25 hydroxylated metabolites in order to have a sufficient serum concentration of 25 OH vitamin D (≥30 ng/dl) and oral calcium supplement given with the meals for both, compensating the calcium deficiency induced by the dairy product restriction (prescribed for limiting phosphate intake), and for complexing phosphates. The only limitation for this calcium supplement is the increase of albumin corrected serum calcium above 2.37 mmol/l. It is only when this rational basic treatment fails to maintain serum concentrations of Ca, PO4 and PTH below the upper limit of their optimal ranges recommended by the NKF-K/DOQI that 2 additional alternative therapeutical strategies may be considered: 1) Use of non-calcium-based oral phosphate binder (or nicotinamide which decreases sodium dependent phosphate absorption)+1α-hydroxylated vitamin D derivatives; 2) Use of calcimimetics (cinacalcet)+increase of calcium load by the Ca-based- oral phosphate binder (and/or the dialysate if the patients is on dialysis). These 2 alternatives are justified by the facts that: 1) 1α-OH vitamin D can be used without hypercalcemic and hyperphosphatemic hazards only when combined with non-calcium-based oral phosphate binder; 2) Calcimimetics suppress PTH by sensitizing the parathyroid calcium receptor to extracellular calcium and induce an hypocalcemia which should be corrected by oral calcium and not by 1α-OH vitamin D in order to better control the hyperphosphatemia. This is particularly important in predialysis patients because in these patients the cinacalcet-induced PTH decrease is associated with an increase in serum phosphate because of increased phosphate tubular reabsorption.
    Immuno-analyse & Biologie Spécialisée 02/2006; 21(1):9-32. · 0.11 Impact Factor
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    ABSTRACT: 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.
    Seminars in Dialysis 05/2005; 18(3):226-38. · 2.07 Impact Factor

Publication Stats

365 Citations
260.01 Total Impact Points


  • 2014
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Centre Hospitalier Universitaire Rouen
      • Service de Médecine Interne
      Rouen, Haute-Normandie, France
  • 2011
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 2005
    • Université de Picardie Jules Verne
      Amiens, Picardie, France