Nader Bassilios

L-Carnitine Treatment in Incident Hemodialysis Patients: The Multicenter, Randomized, Double-Blinded, Placebo-Controlled CARNIDIAL trial

BACKGROUND L-carnitine levels decrease rapidly and steadily with duration of hemodialysis, and carnitine depletion can impair response to recombinant human erythropoietin (rHuEPO). The study hypothesis was that L-carnitine supplementation during the first year of hemodialysis would improve this response. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS From October 2006 through March 2010, this multicenter, randomized, double-blinded study assigned 92 incident hemodialysis patients to receive placebo or 1 g of intravenous L-carnitine after each dialysis session for 1 year. The primary outcome measure compared the groups for rHuEPO resistance index (EPO-RI), defined as weekly rHuEPO doses (IU/kg body weight divided by hemoglobin level) (g/dl). RESULTS In the L-carnitine group, carnitine concentration increased from a mean ± SD of 79 ± 51 µmol/L to 258 ± 137 µmol/L; in the placebo group, it declined from 68 ± 25 µmol/L to 53 ± 24 µmol/L (interaction group × time, P<0.001). Carnitine deficiency affected about 30% of the patients in the placebo group during the study period. EPO-RI varied from 15.8 ± 11.3 to 9.5 ± 5.8 IU/kg per g/dl in the placebo group and from 20.6 ± 12.8 to 15.6 ± 15.9 IU/kg per g/dl in the L-carnitine group, for a mean variation of -3.94 ± 12.5 IU/kg per g/dl and -2.98 ± 15.5 IU/kg per g/dl, respectively (P=0.7). After adjustment for baseline characteristics, the EPO-RI course was similar in each group (difference between groups, P=0.10; interaction group × time, P=0.9). CONCLUSIONS Carnitine levels decrease by about 11% ± 33% during the first year of hemodialysis. Treatment of incident hemodialysis patients with L-carnitine does not improve their response to rHuEPO.

Pharmacokinetics of Tramadol in a Hemodialysis Patient

Accessible online at: www.karger.com/journals/nef Dear Sir, Tramadol is a centrally acting analgesic agent which is extensively metabolized in the liver. However, 30% of a dose is excreted unchanged in urine [1] and renal impairment may alter the pharmacokinetics of tramadol. However, there are no data for patients with end-stage renal disease undergoing hemodialysis. We thus report a pharmacokinetic study of tramadol in a patient requiring chronic hemodialysis. The patient was a 70-year-old male (65 kg, 170 cm) with a long history of multiple myeloma. He suffered from renal failure with the following laboratory values within the last 6 months: serum creatinine 180 Imol/l, urea 25 mmol/l, and normal liver enzymes. He was treated with ibuprofen for acute pain secondary to pathologic thigh bone fracture and developed end-stage renal disease. On admission, the patient complained of pain and leg cramps. Analgesic treatment with tramadol was instituted (50 mg twice daily) with a good analgesic efficacy. Because of persistent anuric renal insufficiency, hemodialysis was started. The study of tramadol pharmacokinetics was performed 1 week after starting hemodialysis, after oral administration of a 50-mg dose in the pattern of a long-term twice-daily treatment. Blood samples were collected just before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 8 h after oral administration. The study was conducted on a hemodialysis-free day. Paired arterial and venous blood samples were also obtained simultaneously 2 h after starting a hemodialysis session, on a hemodialysis day. On that day, the patient was administered tramadol 1 h before the session was started. Hemodialysis was performed for 4 h using a F60 polysulfone dialyzer (surface area 1.6 m2) with a double-needle access to a double lumen catheter with a constant dialysate flow rate of 500 ml/min and blood flow rate between 250 and 300 ml/min. Pharmacokinetic parameters were compared to those of subjects with normal renal function [2], FHD, which represents the participation of hemodialysis clearance in total body clearance of the drug during the session was calculated using the formula: FHD = CLHD/(CLHD + CLER) [3], where CLHD is hemodialysis clearance and CLER is ‘extrarenal’ clearance, equal to interdialytic total body clearance of the drug. Neither clinical side effects, nor overdosage symptoms, such as obnibulation, respiratory system depression, nor constipation, were observed. Our results (table 1) showed that Tmax and T1/2 were the same in our patient and in healthy subjects. However, total body clearance was decreased in our patient as compared to healthy subjects. Since the apparent total body clearance of a drug CL/F is linked to its volume of distribution Vd/F with the relation CL/F = (0.693/T1/2) ! Vd/F, the decrease in CL/F in our patient was due to an Table 1. Pharmacokinetic parameters of tramadol in an hemodialysis patient

Detection of Vascular Access Stenosis by Measurement of Access Blood Flow from Ionic Dialysance

Background/Aim: The measurement of the vascular access blood flow rate (Qa) in chronic hemodialyzed patients was proposed to predict access thrombosis. We have recently presented a new method based on the measurements of ionic dialysance at normal and reversed positions of the blood lines. We evaluate the reliability of the measurement of Qa by this method in detecting significant access stenoses. Methods: Twenty-five patients on chronic hemodialysis and having a vascular access cannulated with two needles were studied. The Qa was evaluated by the Diascan® ionic dialysance (Qa-id) method and by the ultrasound dilution technique (Qa-us; Transonic®) during the same dialysis session. The measurements were available for 23 patients. In addition, the patients had ultrasonography of their fistula followed by angiography, if a stenosis was detected. Results: Qa-id and Qa-us were not significantly different, showing a difference in Qa at 32 ± 469 ml/min. Qa-id was significantly different between patients with or without stenosis (508 ± 241 vs. 1,125 ± 652 ml/min, p < 0.05). Among patients with a Qa <500 ml/min by Qa-id, 5 had a stenosis detected by ultrasonography (sensitivity 83%), and 3 had no stenosis (false-positive rate 18%). Of these 3 patients, 2 had a thrombotic event at 1 and 3 months, suggesting that a more sensitive detection of stenosis for this range of Qa is needed and that a Qa <500 ml/min has a higher power to predict thromboses than a stenosis by ultrasonography. Conclusions: The measurement of the access flow rate by the Qa-id method has a clinical relevance to the detection of vascular access stenosis. An intervention program based on the Qa-id has to be evaluated.

USE OF GADOLINIUM-BASED CONTRAST AGENT FOR RENAL ANGIOGRAPHY: CASE REPORT AND REVIEW OF THE LITERATURE

A 67-year-old woman suffering from chronic renal failure (Creatinine 480 μmol/L) underwent a gadolinium renal angiography, which visualized a stenosis of the right renal artery. There was no deterioration of renal function after the arteriography. A review of the literature is presented which show the efficiency of this technique to visualize the renal arteries, and the absence of nephrotoxicity after the use of gadolinium as a based contrast agent in high risk patients.