Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial.

BACKGROUND: The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. METHODS: CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. RESULTS: Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. CONCLUSION: L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).

Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly.

Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and ß2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.

Sirolimus therapy may cause cardiac tamponade.

The side-effects associated with the immunosuppressive drug sirolimus are numerous and constitute a major limitation for its use in renal transplantation. In this study, we describe two cases of renal transplant recipients treated with sirolimus who developed pericardial tamponade associated with interstitial pneumonia, proteinuria, microcytic anemia and, in one case, lymphocytic meningitidis. An extensive search for infectious agents was negative, and all symptoms disappeared after sirolimus interruption. Therefore, this case demonstrates for the first time that sirolimus can cause pericardial tamponade as well as lymphocytic meningitidis.

[Intravascular large B-cell lymphoma revealed by proteinuria: a case report]. / Lymphome intravasculaire de type B révélé par une protéinurie: à propos d'une observation.

We report the case of an intravascular large B-cell lymphoma in a 49-year-old woman, which was revealed by proteinuria. This type of lymphoma is very rare and corresponds to the proliferation of malignant lymphoid cells within the lumina of small vessels, resulting in ischemic lesions involving mainly brain and skin. Renal involvement is quite rare and remains asymptomatic, being discovered at autopsy. In this case, the renal biopsy demonstrated the presence of large malignant B cells in the glomerular lumina, associated with minimal glomerular damage. The mechanisms of the proteinuria occurring during intravascular lymphoma remain to elucidate.

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.

Renal failure and occupational exposure to organic solvents: what work-up should be performed?

The etiological work-up of a disease with an occupational component, such as renal failure associated with exposure to organic solvents, may include several complementary investigations. The authors discussed certain elements of the etiological work-up in the light of a clinical case, particularly the individual and collective advantages and disadvantages of this work-up. Further investigations would not have provided the patient with any individual or collective benefit and were therefore not performed, whereas other investigations (environmental studies, screening of fellow workers) may provide collective rather than individual benefits, but must be decided by a multidisciplinary approach. A multidisciplinary study (general practitioner, nephrologist, occupational health physician, and specialist in toxicology) is necessary to discuss the appropriate etiological work-up, taking into account the individual and collective benefit-risk balance.