Clotilde Muller

Role of Plasma Exchange in the Thyroid Storm

Inadequately treated thyroid storm can lead to death. Therapeutic plasma exchange (TPE) is a suggested treatment when conventional treatments fail, but its indication is not well codified. We report our experience through three explicit cases. Three elderly patients were admitted to our hospital for cardiac or neurologic symptoms due to thyroid storm. After initiation of conventional therapy, TPE was performed with clinical and biological improvement. The speed of symptom resolution varies depending on the severity. This technique must be carried out by experienced medical staff as many complications can occur; nevertheless, in our patients with severe comorbidities, no complications occurred. The action of TPE mainly results from plasma removal of cytokines, putative antibodies, and thyroid hormones and their bound proteins. TPE has a transitory effect and thus should be associated with other thyroid blockers. When there are threatening symptoms, TPE should be done early, without waiting for the efficiency of conventional treatment, since it is the fastest method known for the improvement of the clinical condition. We also suggest starting TPE in case of neurologic symptoms because of very slow and incomplete regression. The Burch and Wartofsky score seems to be a helpful tool in establishing the diagnosis of thyroid storm and for deciding on when to initiate TPE.

Association of Estimated GFR With Platelet Inhibition in Patients Treated With Clopidogrel

BACKGROUND The reasons that decreased glomerular filtration rate (GFR) might alter the clinical efficacy of clopidogrel are poorly understood. STUDY DESIGN In this study, we sought to evaluate whether decreased GFR alters platelet response to clopidogrel in patients receiving a maintenance dose of clopidogrel (75 mg/d for at least 8 days). SETTINGS & PARTICIPANTS 126 consecutive patients categorized by estimated GFR: stages 1-2 (>60 mL/min/1.73 m(2); n = 29), stage 3a (45-59 mL/min/1.73 m(2); n = 21); stage 3b (30-44 mL/min/1.73 m(2); n = 26), stage 4 (15-29 mL/min/1.73 m(2); n = 14), and stage 5 (<15 mL/min/1.73 m(2); n = 36) were prospectively enrolled. PREDICTOR Residual platelet reactivity, defined in the VASP (Vasodilator Stimulated Phosphoprotein) flow cytometry test as platelet reactivity index (PRI) ≥61% and in the VerifyNow turbidimetric-based assay as a value >235 PRU (adenosine diphosphate receptor reaction units) or percentage of platelet inhibition <15%. OUTCOMES We examined factors associated with low response to clopidogrel using logistic regression. RESULTS A significant relationship between estimated GFR, PRI, PRU, and percentage of inhibition was found. The prevalence of residual platelet reactivity was highest in patients with GFR stage 5. PRI ≥61% occurred in 52.8% of patients with stage 5 versus 30.8% of stage 3b and 24.1% of stages 1-2 (P = 0.1). PRU >235 was found in 63.6% of patients with stage 5 versus 36.8% of stage 3b and 17.2% of stages 1-2 (P = 0.005). Inhibition <15% affected 66.7% of patients with stage 5 versus 21.1% of stage 3b and 17.2% of stages 1-2 (P < 0.001). In the multivariable model, GFR stage 5 (adjusted prevalence ratio [PR], 3.10; 95% CI, 1.23-9.43; P = 0.02), and obesity (adjusted PR, 1.92; 95% CI, 1.34-2.23; P = 0.004) were the sole predictors of residual platelet reactivity. LIMITATIONS Interference of hemodialysis with the pharmacokinetics of clopidogrel could not be excluded. CONCLUSION GFR stage 5 is associated with substantial impairment of platelet inhibition independently of diabetes mellitus.

Impaired platelet P2Y12 inhibition by thienopyridines in chronic kidney disease: mechanisms, clinical relevance and pharmacological options

Patients with chronic kidney disease (CKD) represent an increasing proportion of the population undergoing percutaneous coronary intervention (PCI) and up to 40% of the patients treated for acute coronary syndrome (ACS). Several studies and registries in the setting of ACS and elective PCI have reported a negative association between CKD and mortality, stent thrombosis, post-procedural ischaemic events and bleeding events. Pharmacological inhibition of the adenosine diphosphate receptor by thienopyridines or ticagrelor and disruption of the cyclooxygenase pathway by aspirin constitute the current standards of care to prevent thrombotic complications following stent-based PCI. In CKD patients, the avoidance of anti-platelet therapy may be driven by the lack of clinical trial data to support its efficacy, by errors or omissions, or by a reluctance to use this therapy in a population characterized by its enhanced bleeding risk. However, there is growing evidence to suggest that a severely decreased glomerular filtration rate per se, independent of the presence of diabetes mellitus, is an important determinant of high residual platelet reactivity under a clopidogrel maintenance dose. Recent reports have emphasized that the impact of impaired platelet inhibition by thienopyridines is of paramount importance in CKD patients, with an enhanced mortality rate in low-responder patients. Pharmacodynamic studies indicate the phosphodiesterase 3 inhibitor, cilostazol, the third generation thienopyridine prasugrel and the reversible P2Y12 antagonist ticagrelor to be potent strategies to overcome this biological resistance. In clinical practice, platelet function testing should be considered in CKD patients undergoing PCI, especially in those who experience thrombotic events despite dual therapy. Newer agents should be contemplated in patients who display higher residual platelet aggregability after standard treatment. Among these, the non-thienopyridine P2Y12 receptor antagonist ticagrelor, which does not require biotransformation, could be the drug of choice in CKD patients with ACS. In this population, ticagrelor has been found to reduce mortality and ischaemic events with an acceptable bleeding risk.

A confusional state associated with use of lanthanum carbonate in a dialysis patient: a case report

A 75-year-old woman was admitted with febrile confusion and abdominal pain. She was taking medications that included lanthanum carbonate. Examination, biology, a cerebral scan, and a review of her medications could not explain the confusion. The plain film of the abdomen revealed multiple diffuse calcium-like deposits throughout the digestive tract. The plasma levels of lanthanum were higher than normal. The confusion resolved after discontinuation of the lanthanum carbonate. This case raises the problem of the potential role played by lanthanum tablet residue in the genesis or aggravation of diverticular flare-up and the problem of the potential permeability of the blood-brain barrier with lanthanum use in case of its digestive accumulation, leading to increased serum concentrations.

Recent changes in chronic kidney disease-mineral and bone disorders (CKD-MBD) and associated fractures after kidney transplantation.

Background The management of chronic kidney disease–mineral and bone disorders has recently changed. We investigated the modifications of chronic kidney disease–mineral and bone disorder with a special focus on the incidence of fractures in the first year after kidney transplantation (KT). Methods We retrospectively compared 2 groups of patients who consecutively underwent transplantation at our center 5 years from each other. Group 1 consisted of patients (n = 152) transplanted between 2004 and 2006, whereas patients in group 2 (n = 137) underwent KT between 2009 and 2011. Results During the end-stage renal disease phase at the time of transplant, cinacalcet, and native vitamin D were used significantly more frequently in group 2. Median intact parathyroid hormone levels were lower and severe hyperparathyroidism decreased significantly. Vitamin D deficiency dropped from 64% to 20%. After transplantation, persistent hyperparathyroidism (parathyroid hormone > 130 ng/L) and bone turnover markers were significantly reduced in group 2. Native vitamin D supplementation increased over time, whereas the use of active vitamin D was unchanged. The 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were significantly higher. The fracture incidence at 1 year decreased significantly (3.1% vs 9.1%; P = 0.047). No steroid sparing was observed in group 2. Bisphosphonates after KT were more frequently used in group 2. Conclusions Recent changes in clinical practice are associated with reductions in pretransplant and posttransplant hyperparathyroidism, vitamin D deficiency, and fracture risk after KT.

Oral antidiabetics use among diabetic type 2 patients with chronic kidney disease. Do nephrologists take account of recommendations

BACKGROUND There is an increasing prevalence of diabetes type 2 and chronic kidney disease, challenging appropriate prescribing of oral anti-diabetic drugs (OADs). METHODS We have described the practice patterns of 13 nephrologists in 4 centers, in a cohort of 301 consecutive adult type 2 diabetic patients. Among oral anti-diabetic prescriptions, we have detailed drugs dosage for each subject, with 3 different formulae for estimating glomerular filtration rate (GFR) and its adequation according to the latest ERBP recommendations (2015). As individuals were mostly obese in this work, we also compare adequacy rates using both standard indexed CKD-EPI formula and CKD-EPI formula de-indexed from body surface area. RESULTS Using the CKD-EPI formula as the reference method for estimating GFR, 53.5% of patients were outside the recommendations, mostly for metformin (30% of the whole cohort) and for sitagliptin (17.9% of the whole cohort). With Cockcroft and Gault formula, 38.2% of persons were outside recommendations and 45.9% (p<0.001) with CKD-EPI de-indexed. Among individuals consulting a nephrologist for the first time (n=90), 61.1% were outside recommendations (p=0.1). Among those persons under diabetologist supervision (n=103), 63.1% were outside recommendations (p=0.09), and were taking significantly more often metformin and insulin. CONCLUSION We have found a substantial number of inadequate OAD prescriptions in type 2 diabetic patients with chronic kidney disease. The proportion of individuals outside guidelines was strongly affected by the method used for estimating GFR and by the type of practice, i.e., specialists versus general practitioners.

Pre-existing donor-specific antibodies are detrimental to kidney allograft only when persistent after transplantation

Donor‐specific antibodies (DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty‐seven patients (15.5%) had pre‐existing DSA detected the day of transplantation. After 5 years, the pre‐existing DSA disappeared in 22 patients whereas they persisted in 12. Variables associated with DSA persistence were age <50 years (P = 0.009), a history of previous transplantation (P = 0.039), the presence of class II DSA (P = 0.009), an MFI of preformed DSA >3500 (P < 0.001), and the presence of two or more DSA (P < 0.001). DSA persistence was associated with a higher risk of graft loss and antibody‐mediated rejection. Previously undetected preformed DSA are deleterious to graft survival only when they persist after transplantation.

Radio-opaque fecal impaction and pseudo-occlusion in a dialyzed patient taking lanthanum carbonate

Lanthanum therapy is an efficient therapy of hyperphosphoremia by chelating phosphore in the digestive tract. Lanthanum is a silvery white metallic element that belongs to group 3 of the periodic table. This drug is lightly absorbed and has low water solubility. It should be borne in mind that abdominal X‐rays of patients taking lanthanum carbonate may have a radio‐opaque appearance typical of imaging agents. This characteristic is suggested to confirm adherence of the patient by doing an abdominal X‐ray. We describe in our case a particular good compliant patient with slow digestive transit, which ends by pseudo‐occlusion.

Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study

BackgroundCardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation.MethodsThe study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared.ResultsThe mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03–6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status.ConclusionsKT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.

0361: Impaired P2Y12 inhibition by clopidogrel in patients with kidney transplantation

Introduction Several studies have indicated that impaired GFR is an important predictor factor associated with impaired platelet inhibition by clopidogrel. In chronic kidney disease, the presence of low platelet inhibition by clopidogrel is associated with adverse outcome following PCI and stenting. In the present study, we sought to determine if renal transplantation per se alters clopidogrel pharmacodynamics. Patients and methods 36 patients with kidney transplantation were enrolled in one single center (Nephrology Department, Hopitaux Universitaires de Strasbourg). Control patients were 126 patients with different degrees of chronic renal failure, tested in the same conditions. Inclusion criteria were patients under clopidogrel treatment of 75mg per day for at least 8 days. Unstable patients or those presenting with any conditions that could account for reduced platelet inhibition by clopidogrel (heart failure, shock) were excluded. Treatment and medical history were collected at inclusion. Clopidogrel pharmacodynamics was studied using the VASP assay. Results Patients with kidney transplantation were younger (58.3 vs 72.6 years, p Conclusion In kidney transplantation patients treated by clopidogrel, impaired platelet inhibition exist, even after adjustment on estimated glomerular filtration rate. The mechanisms by which immunosuppressive treatments may alter clopidogrel pharmacodynamics requires further investigation