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).

Crystalline light chain proximal tubulopathy with chronic renal failure and silicone gel breast implants: 1 case report.

A 39-year-old female patient was admitted to explore chronic renal failure. Clinical history included silicone breast implants. Clinical examination was normal. Urinalysis revealed tubular proteinuria with Bence-Jones κ protein. Monoclonal immunoglobulin G κ and free monoclonal κ-light chains (LCs) were revealed by serum protein immunoelectrophoresis. Bone marrow aspiration with karyotype analysis and skeletal radiologic survey were normal. Kidney biopsy revealed a peculiar pattern of proximal tubular cells with hypertrophy and clarification initially diagnosed as an osmotic nephrosis. Immunofluorescence study, including immunoglobulin LCs conjugates was normal. Immunoelectron microscopy finally revealed a crystalline LC proximal tubulopathy κ. Our case presents some peculiarities: the absence of hematologic malignancy sign and the young patient's age. The silicone breast implants have been reported to be involved in the generation of monoclonal gammopathy.

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.

Monitoring of glomerular filtration rate in lithium-treated outpatients--an ambulatory laboratory database surveillance.

BACKGROUND: The long-term risk of chronic kidney disease (CKD) in lithium (Li)-treated patients has been well established in the recent years. METHODS: We have evaluated GFR and serum calcium monitoring in 1179 Li-treated outpatients from an ambulatory laboratory database study. This has been performed in a single private laboratory in Paris from February 1997 to December 2004. Estimated GFR (eGFR) has been calculated using the abbreviated MDRD equation. RESULTS: During an 8-year period, 695 patients (59%) had at least one serum creatinine measurement, whereas 484 had no creatinine measurement. The former group had also more frequent serum Li measurements. Mean serum lithium levels, were similar in both groups, 0.65 mmol/l vs 0.62 mmol/l. The percentage of patients with CKD stage 3 (eGFR 30-59 ml/min/1.73 m(2)) were 36%, 53%, 73% and 77%, and with CKD stage 4, 3%, 5%, 5%, 8% in patients aged 20-39, 40-59, 60-69, and > or = 70 years respectively. There was no significant rise in creatinine measurements (from 35% of the patients with at least one serum creatinine in 2003 to 39% in 2004; P = 0.66) despite intervention to intensify GFR monitoring by physicians. Serum calcium was tested at least once in 212 patients (18%) of whom 15 (7%) were found with hypercalcaemia. CONCLUSION: A very high percentage of Li-treated outpatients have low eGFR. GFR monitoring is neglected in these patients, the majority of whom are no longer attending specialized clinics. Hypercalcaemia is less common but serum calcium monitoring is even more neglected. Ambulatory laboratory database surveillance provides a powerful means to contribute to CKD screening and monitoring.

[Continued late referral of patients with chronic kidney disease. Causes, consequences, and approaches to improvement]. / Retard persistant au suivi néphrologique de l'insuffisance rénale chronique. Causes, conséquences et moyens d'amélioration.

OBJECTIVES: Efforts in recent years have aimed at increasing physicians' awareness of the frequent and harmful consequences of late referral to nephrologists of patients with chronic kidney disease (CKD), shown in repeated concordant studies. We sought to determine whether these efforts have led to improved predialysis care of these patients. METHODS: This study included all 1391 consecutive patients who began maintenance dialysis at Necker Hospital between January 1989 and December 2000. We examined baseline data and outcomes and determined for four three-year periods the percentage of patients who received early specialized care (at least 6 months before onset of dialysis). RESULTS: Late referral (<6 months before dialysis) did not change significantly over the four periods, remaining around 30%, even during the most recent period (1998-2000). Clinical condition and laboratory indicators of patients referred early but not those referred late improved in the latest period, compared with the initial period (1989-1991). Overall, prevalence of major cardiovascular events (myocardial or cerebral infarction, peripheral arteriopathy, or heart failure) was more than twice as high in patients who received nephrologic care for less than 6 months and nearly twice as high even in those followed 6-35 months than in patients followed for at least 36 months before beginning dialysis. Subsequent mortality after maintenance dialysis was also significantly higher in patients with late referral than in those followed at least 3 years before dialysis. Multivariate Cox proportional model analysis identified graded duration of predialysis nephrologic care as a significant independent factor predictive of risk of mortality while on dialysis. CONCLUSION: Late referral of CKD patients for specialist care remains frequent, around 30%, although it is most often unjustified. Late referral deprives the patient of early implementation of a reno- and cardioprotective therapeutic strategy that reduces cardiovascular comorbidity and mortality. Better coordinated cooperation between family doctors and nephrologists, through the implementation of regional healthcare networks, now appears as the most effective way to improve the care of CKD patients.

Mesenteric ischaemia in haemodialysis patients: a case/control study.

BACKGROUND: Mesenteric ischaemia is not uncommon in dialysis patients and seems to have been increasing in the last decade. However, the risk factors for mesenteric ischaemia are unclear and prognosis of patients after this type of ischaemic accident is not well defined. METHODS: From January 1988 to June 1999, 15 haemodialysis patients (0.3% per patient-year) from a single institution presented with mesenteric ischaemia and the clinical, biological and radiological aspects of the ischaemia were described. To identify risk factors for mesenteric ischaemia, each ischaemic patient (case) was matched with two other haemodialysis patients not having ischaemia (controls). Survival curves were then established for the two groups. RESULTS: A marked hypotensive episode was present in seven out of 15 case patients (47%) during dialysis sessions that preceded mesenteric ischaemia. Abdominal pain, guarding, fever and hyperleucocytosis were all present in 13 out of 15 patients (87%). An abdominal computerized tomography scan with opaque enema enabled a rapid diagnosis for six patients. The caecum was the most frequently (47%) affected segment. Twelve patients were surgically treated and the remaining three were given medical support. The two groups (case and control) were not different in cardiovascular risk factors, comorbidity, administered drugs or main haemodialysis characteristics. The median survival of the case group was 600 days, whereas 80% of the control group survived beyond this period (P=0.0132). Eleven case patients survived >3 months after mesenteric ischaemia and had a median survival of 1500 days, which was identical to their matched control patients. CONCLUSIONS: Mesenteric ischaemia should be systematically suspected in patients experiencing abdominal pain during or after dialysis sessions. Prompt diagnosis and treatment usually allow for a favourable prognosis.

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 (Q(a)) 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 Q(a) 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 Q(a) was evaluated by the Diascan ionic dialysance (Q(a-id)) method and by the ultrasound dilution technique (Q(a-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: Q(a-id) and Q(a-us) were not significantly different, showing a difference in Q(a) at 32 +/- 469 ml/min. Q(a-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 Q(a) <500 ml/min by Q(a-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 Q(a) is needed and that a Q(a) <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 Q(a-id) method has a clinical relevance to the detection of vascular access stenosis. An intervention program based on the Q(a-id) has to be evaluated.