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).

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.

Expanding the criteria of renal kidneys for transplantation: use of donors with acute renal failure.

BACKGROUND: Increased numbers of patients waiting for renal transplantation have led to widening selection criteria for grafts. Thus, we have evaluated the outcome of transplanted kidneys procured in the presence of acute renal failure (ARF). METHODS: Transplant patients (n = 52) with a kidney procured with ARF were studied. Clinical data from donors and recipients, serum creatinine (SCr), creatinine clearance [estimated glomerular filtration rate (eGFR)], cold ischaemia duration, time to urine flow recovery or renal function recovery, and the number of haemodialysis sessions, were collected retrospectively. RESULTS: Mean donor age was 45.7 +/- 12.7 years, and the mean SCr at the time of harvesting was 276.3 +/- 104.2 micromol/l. Recipients' mean age was 51.1 +/- 12.1 years. After transplantation, recovery of renal function was observed after 7.6 +/- 7.1 days, and required 1.9 +/- 3.0 haemodialysis sessions. SCr was 124.6 +/- 49.5 micromol/l, and eGFR was 56.2 +/- 19.8 ml/min at last follow-up. eGFR was significantly lower if the donor's death was due to stroke or cerebral haemorrhage (CH), or if the donors had previous cardiovascular disease (CVD) (P < 0.02). Patients with eGFR of <50 ml/min (n = 23) had donors who were older, and whose cause of death was more frequently related to CVD factors or to CH/stroke (P < 0.03). There were no significant differences between the two groups regarding age of recipient, gender of the donor or recipient, cold ischaemia time, occurrence of cardiac arrest, collapse or acute rejection. Linear regression analysis indicated that donor age and occurrence of acute rejection were independent factors associated with eGFR. CONCLUSIONS: ARF before organ procurement does not have a negative effect on subsequent renal function. However, old age, CVD risk factors or CH, and late renal function recovery after transplantation are correlated with subsequent lower renal function. Thus, renal grafts with ARF can be used for renal transplantations.