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The link between vascular calcification (VC) and increased mortality is now well established. Over time, as clinical importance of this phenomenon has begun to be fully considered, scientists have highlighted more and more physiopathological mechanisms and signaling pathways that underlie VC. Several conditions such as diabetes, dyslipidemia and renal diseases are undoubtedly identified as predisposing factors. But even if the process is better understood, many questions still remain unanswered. This review briefly develops the various theories that attempt to explain mineralization genesis. Nonetheless, the main purpose of the article is to provide a profile of the various existing biomarkers of VC. Indeed, in the past years, a lot of inhibitors and promoters, which form a dense and interconnected network, were identified. Given importance to assess and control mineralization process, a focusing on accumulated knowledge of each marker seemed to be necessary. Therefore, we tried to define their respective role in the physiopathology and how they can contribute to calcification risk assessment. Among these, Klotho/fibroblast growth factor-23, fetuin-A, Matrix Gla protein, Bone morphogenetic protein-2, osteoprotegerin, osteopontin, osteonectin, osteocalcin, pyrophosphate and sclerostin are specifically discussed.

Among the numerous factors of bone remodelling, the local action of arachidonic acid metabolites together with cytokines, is particularly important, especially that of prostaglandin PGE2. It has been suggested that the alveolar bone destruction in periodontal disease and osteoporosis can be treated by reducing the ratio of arachidonic acid in phospholipids, which would diminish prostaglandin production. The aim of this study was to evaluate the main serum polyunsaturated fatty acids and a possible alteration in the level of arachidonic acid in patients suffering from periodontal bone loss. Of the 105 patients who participated the study, 78 were suffering from periodontal bone loss and 27 served as a control group. The fatty acids were measured in serum by gas-chromatography. The results showed that the level of fatty acids of the n-6 pathway was higher in our patients with bone loss than in the control group, whereas the reverse was observed with fatty acids of the n-3 pathway. In conclusion, our patients' bone losses are linked with an imbalance between n-6 and n-3 fatty acids, which seems to justify a diet increase in 20- and 22-carbon fatty acids.

Routine monitoring of cyclosporine and tacrolimus levels is necessary to minimize adverse side effects and to ensure effective immunosuppression. The RXL Dimension apparatus conceived for ACMIA technologies is proposed to determine C0 and C2 cyclosporine levels and also tacrolimus levels in whole blood without any dilution or pretreatment using specific calibrators and Flex reagent cartridges (reagent stability: 72 hours for Neoral C0 and C2; 48 hours for tacrolimus). The assay ranges were between 25 to 500 ng/mL for C0; 350 to 2000 ng/mL for C2; and 1.2 to 30 ng/mL for tacrolimus. Within-run and between-day imprecision were10% for cyclosporine. The coefficient of linearity was r(2) = .998 for C0, C2, and tacrolimus. Moreover, for cyclosporine and tacrolimus assays, the time for the first result was 20 minutes. Cyclosporine (C0, n = 152; C2, n = 54) and tacrolimus (n = 70) ACMIA assays were compared with enzyme-multiplied immunoassay technique (EMIT) cyclosporine and tacrolimus assays (V-Twin, Siemens ex-Dade Behring Laboratories) among 276 transplant patients: 119 kidney, 67 liver, 28 heart, and 62 bone marrow transplantations. Values obtained with the ACMIA assay were highly correlated with the EMIT assay for CsA C0 levels (ACMIA = 1.04 EMIT - 9.32; r(2) = .97); CsA C2 levels (ACMIA = 1.15 EMIT - 53.7; r(2) = .94); and tacrolimus levels (ACMIA = 0.93 EMIT - 0.16; r(2) = .93). In conclusion, the RXL Dimension analyzer is a useful tool for routine monitoring with a single method for C0 and C2 cyclosporine and tacrolimus level determinations in whole blood without any dilution or preanalytic treatment.

Lipid abnormalities including increased total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) have been frequently reported in renal transplantation and could be involved in the high frequency of cardiovascular diseases in this population.Two hundred ninety-five patients were transplanted between January 1995 and October 2000 in our center. Two hundred two patients were included in this study. Seventy-six patients received tacrolimus (Tac), and 126 patients cyclosporine (CsA). Lipid parameters were assessed the day of transplantation and 1 year posttransplantation.Serum lipids were similar between the two groups at D0. At M12, TC and LDL-C were significantly higher in the CsA group (6.14 +/- 1.37 vs 5.28 +/- 1.32 mmol/L; P.05 and 3.98 +/- 1.05 vs 3.26 +/- 1.03 mmol/L; P.05 CsA vs Tac, respectively). TG were comparable in both groups (1.86 +/- 1.07 vs 1.62 +/- 0.92 mmol/L; P = .55; CsA vs Tac). Incidence of de novo hypercholesterolemia was significantly higher in the CsA group (28 vs 8%) whereas incidence of hyperTG was similar in both groups. Prevalence of LDL-C was significantly higher in the CsA group (65% vs 31%; P.001), whereas there was no difference in high density lipoprotein (HDL)-C levels.Mean serum lipid levels and incidence and prevalence of hyperTC, especially LDL-C, was significantly higher in patients receiving CsA when compared with Tac. TG and HDL-C levels were similar. Although the study was retrospective, our results confirm that CsA increases lipid levels, whereas Tac does not.Lipid disorders are frequently observed in renal transplant recipients. CsA, but not Tac, significantly increases incidence and prevalence of high TC and LDL-C.

Cyclosporine (CsA) monitoring is generally assessed by trough concentration determinations (C0). Recently, the 2-hour postdose CsA level (C2) has been proposed to be a better measurement to predict graft outcome and prevent toxicity. However, using the available methods, C2 determinations require external dilution, which impairs the precision and practicability of the assay. This study assessed the performance characteristics of a new competitive chemiluminescence immunoassay (CLIA, DiaSorin Laboratories, Anthony, France) for the determination of both C0 and C2 CsA concentrations in whole blood on a Liaison analyzer. The results were compared with the RIA method (DiaSorin) used in our laboratory as a refereence technique. Analytical performances showed that the total intra-assay variation coefficients (CVs) on the CLIA Liaison ranged from 7.6% to 11.3%, while the between-day imprecision was 11% (15.2%, 11.5%, and 6.5%). The linearity of the method was estimated over the range of 30 to 2400 ng/mL as a correlation coefficient of r = .997. Recoveries, which were checked by adding pure CsA to CsA-free blood, showed a mean value of 86%. A total of 236 whole-blood samples (31% women, 69% men of mean age 45 ± 17 years) were subjected to a comparative study of CLIA-CsA versus RIA (radioimmunoassay) values, yielding a correlation coefficient >0.90 (CLIA = 0.825RIA+21.611; r 2 > .90). In conclusion, the CLIA Liaison CsA kit represents an alternative to the radioisotopic method, which allows both C0 and C2 determinations without any preanalytical step. The chemiluminescence method demonstrated good analytical performance and practicability in routine use.

THE LIPOPROTEIN glomerulopathy (LpG) is a new glomerular disease mainly observed in Japanese families. It was first reported by Saito et al in 1989, but similar cases had been previously reported, although it had been impossible to find them a precise pathologic label.1 Two cases were reported in Japan: one in France (an Italian subject),2 and one in the United States (a chinese patient).3 We report on a new patient with LpG who received a cadaver kidney allograft and developed recurrence of LpG.

Monoclonal antibodies were proposed as an effective prophylactic immunosuppressive treatment in highly sensitized patients (HSP). In this study we compared the results obtained in HSP treated with OKT3 or antilymphocyte globulins (ALG). From January 1989 to January 1993, 38 transplantations were performed in patients with high panel reactive antibodies (PRA > 50%). The group comprised 22 women and 16 men, mean age 45 +/- 2 (23-67) years; ten were second grafts and two were third grafts. Peak PRA was > or = 80% in 24 sensitized patients and 50-80% in 14 sensitized patients. Patients were randomly assigned to either prophylactic OKT3 (n = 15) or ALG (n = 23). Oral cyclosporin A (10 mg/kg) was started at day 8 in the OKT3 group and when the serum creatinine level decreased to 200 micromol/l in the ALG group. OKT3 was systematically withdrawn on day 10 but ALG was stopped only when total blood cyclosporin A concentration reached 150-200 ng/ml. In both groups, azathioprine (150 mg/day) and prednisolone were given. During the first months, 6/15 grafts were lost in the OKT3 group (three hyperacute rejections, one renal vein thrombosis, one steroid-resistant rejection, one death); in the ALG group 4/23 grafts were lost (one hyperacute rejection, two steroid-resistant rejections, one death). Side effects were significantly more frequent in the OKT3 group than in the ALG group. After 12 months of follow up, the graft survival was 71% (27/38) and did not significantly differ (log-rank test, NS) between the OKT3 (60%, 9/15) and the ALG group (78%, 18/23). We conclude that the use of the monoclonal antibody OKT3 as a prophylactic agent in HSP does not improve the early graft survival when compared with prophylactic ALG. Polyclonal antibodies, which react with many epitopes and are much better tolerated seem to offer a good strategy for induction therapy in this population.