Quantitative determination of plasma free and total concentrations of antivitamin K drugs using a new sensitive and rapid LC-MS/MS method: Application in hemodialysis patients.

BACKGROUND AND AIMS: Vitamin K antagonists (VKAs) are the first-line anticoagulants used in end stage renal disease. This population experiences a significant variability in their International Normalized Ratio (INR) over time. There is a need for methods allowing the study of the pharmacokinetics of free and total concentrations of VKAs to explain INR variability. MATERIALS AND METHODS: We developed and validated a high-performance liquid chromatography-tandem mass spectrometry method allowing the quantification of warfarin and fluindione free and total plasma concentrations. Chromatographic separation was achieved in a raptor biphenyl column and the spectrometry acquisition was set in multiple reaction monitoring mode after negative electrospray ionization. We then applied it in describing the plasma free and total concentrations of VKAs in samples from 50 hemodialysis patients. RESULTS: The developed method is rapid, sensitive and specific. Our cohort results showed a correlation between free and total VKA concentrations. The free VKA concentrations tended to be higher in patients with higher INR. Although VKAs are highly albumin-bound drugs, albumin concentration did not totally explain the high inter-individual total VKA concentrations variability. CONCLUSION: This opens the door to further studies to understand the factors involved in their variability.

[Fanconi syndrome in a 22-year-old African patient]. / Syndrome de Fanconi chez un patient de 22 ans d'origine africaine.

Acquired Fanconi syndrome can occur in patients with monoclonal gammopathy or after exposure to heavy metals or drug agents such as ifosfamide, and some antiretroviral therapies. Fanconi syndrome is characterized by a dysfunctional of the proximal tubular responsible in its complete form for polyuria, hypokalemia, glycosuria, hypophosphatemia and low molecular weight proteinuria. We report the case of a 22-year-old patient hospitalized with an acute renal failure secondary to a tubulo-interstitial nephritis associated with a complete Fanconi syndrome in a context of a poor general condition and fever. We described and analyzed the process leading to the diagnosis.

Thrombotic thrombocytopenic purpura due to anti-ADAMTS13 antibodies in multiple myeloma.

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.

A comparison of bicarbonate kinetics and acid-base status in high flux hemodialysis and on-line post-dilution hemodiafiltration.

OBJECTIVES: To compare bicarbonate kinetics and acid base status in HD and HDF for the same patient; and to investigate the effect of patient physiologic parameters on these kinetics. METHODS: In order to monitor HCO3- kinetics during dialysis, acid-base parameters, pH, blood gases partial pressures, and HCO3- concentrations were recorded during 3 regular dialysis (HD) and 3 on-line post-dilution HDF sessions performed on 12 patients, using same dialysis fluid with a 38 mmol/l HCO3- concentration. HCO3- mass transfers through the hemodialyzers membranes and into the patients were continuously calculated during the sessions from HCO3- concentrations, together with HCO3-dialysance. The"apparent" HCO3-gain was calculated by integrating over time the instantaneous mass transfer from dialyzer and re-infusion fluid to the patient. A second method consisted in calculating the patient apparent bicarbonate space (ABS) and HCO3- mass (ABS times plasma concentration) at beginning and end of session. RESULTS: No significant differences were observed between acid base parameters at the end of HD and HDF sessions. In contrast to urea clearances, HCO3- dialysances decayed with time during sessions from 110 to 140 ml/min to about 40 ml/min after one hour. The net HCO3- gain was taken as the difference between final and initial HCO3-masses. This net gain was in average 63% of apparent gain in HD and 74% in HDF. CONCLUSIONS: Uremic acidosis was well corrected without risk of alkalosis. An unexpected result was the continuous decay of bicarbonate dialysance both in HD and HDF during runs.

Localized amyloidosis of the genitourinary tract: report of 5 new cases and review of the literature.

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.

[TREAT or not to treat: anemia in type 2 diabetes and chronic kidney disease at stages 3 and 4]. / TREAT or not to treat: anémie du patient diabétique de type 2 aux stades 3 et 4 de la maladie rénale chronique.

Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease (CKD). Although erythropoiesis-stimulating agents (ESA) can effectively increase hemoglobin (Hb) levels, their effect on clinical outcomes has not been demonstrated in CKD patients. The TREAT study is the first randomized, double-blind, placebo-controlled trial with the aim to evaluate the effect of a Hb level of 13 g/dL on the risk of death, cardiovascular events and progression to end-stage renal disease (ESRD) in type 2 diabetes with stage 3 to 4 CKD. Four thousand and thirty-eight patients were included. Death, cardiovascular events and progression to ESRD were not different between the two groups. Stroke occurred in 101 patients assigned to DA and 53 patients assigned to placebo (p<0.001), and red-cell transfusions were administered in 14.8% patients in the DA group and in 24.5% patients assigned to placebo (p<0.001). There was a modest improvement in patient-reported fatigue in the DA group. Studies performed in CKD patients who were not undergoing dialysis failed to show a benefit of the use of ESA to target a Hb level of 13 g/dl or more, on the risk of death, cardiovascular morbidity and progression to ESRD. Post hoc analysis of randomized studies suggest that the increase cardiovascular risk induced by targeting a high Hb level is more related to the resistance state of patients who failed to increase their Hb level under high ESA doses and by the rate of change in Hb concentration over time. After the release of the TREAT study, the recommendations of a Hb level of 10 to 12 g/dl in CKD patients seems adequate. This target needs to be tailored for each patient taking into account the comorbidity, age and physical activity.