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Background and Aims The FGF-23/Klotho ratio increases from early stages of chronic kidney disease (CKD) in parallel with kidney function declined. In some cases, serum FGF-23 levels increase is unbalanced, causing organ damage and increasing cardiovascular risk. The aim of our study was to evaluate the intact FGF-23 (iFGF-23) levels in a cohort of CKD patients and to establish its correlation with cardiovascular and bone mineral metabolism parameters. Method A prospective observational study in 59 adult normophosphatemic patients with CKD stage 2-4, was performed. Clinical and analytical variables (serum calcium, phosporus, intact parathyroid hormone (iPTH), iFGF-23, calcidiol and calcitriol) were evaluated. Basal transthoracic echocardiogram, bone densitometry (Lunar prodigy, GE iDXA), software trabecular bone score (TBS), iNsight clinical data analyzer and carotid Doppler ultrasound were performed. We excluded patients with background of primary hyperparathyroidism, hepatorenal polycystic disease, kidney transplant, tumoral nephrectomy, active neoplasm, tubulopathies or treatment with active vitamin D or calcimimetics. For statistical analysis, we use SPSS software (T Student, Xi2, Fisher test, ANOVA test, U-Mann Whitney test and correlations of Pearson and Spearman) Results Mean age was 62,7±10,5 years, 82,5% were men; 17,7% have CKD stage 2, 28,8% stage 3a, 42,3% stage 3b and 9,6% stage 4. The main CKD etiology was vascular (25%) and diabetes (22%). Previous cardiovascular disease was observed in 11% (ischemic heart disease 6,3%, cerebrovascular disease 3,2% and descompensated heart failure with hospitalization 1,6%). Mean iFGF-23 levels in CKD stage 2 were 80,4±38 ng/l (38-170, median 71 ng/l), in CKD stage 3a 95,5±39,7 ng/l (46-178,9 ng/l, median 85,5 ng/l), in CKD stage 3b 118,8±55,06 (35,5-285 ng/l, median 124,6 ng/l) and in stage 4 134,8±50,9 ng/l (65,25-216,5 ng/l, median 136,1 ng/l). We found correlation between iFGF-23 levels and glomerular filtration rate (Rho:-0,390, p: 0,003), as well as with CKD stages (ANOVA test, p: 0,057). We performed 48 carotid doppler ultrasound and observed mild carotid atheromatosis in 58,7%, mainly bilateral, and intima-media thickness >0,9 mm in 7,9%. In patients with atheromatosis, 38,9% showed iFGF-23 levels in second tertil and 36% in the third. We observed left ventricular hypertrophy (LVH) in 46% of patients, mostly mild degree. In bone densitometry, we found mean femoral neck T-Score of -1±1,1 and lumbar spine T-Score of -0,07±1,5, mean mineral bone density (DMO) in femoral neck of 0,89±0,25 g/cm2 and 1,17±0,20 g/cm2 in lumbar spine. Only 40% of patients had normal TBS score. We found correlation between serum iFGF-23 levels and phosphorus tubular reabsorption (r:-0,396, p: 0,002), calcidiol (Rho: 0,264, p:0,047), calcitriol (r: -0,412, p:0,002), iPTH (Rho: 0,296, p:0,025), lumbar T-Score (r: -0,320 p:0,022), lumbar DMO (r:-0,267, p:0,049) and TBS (r: -0,396, p:0,005). Conclusion We confirm an association between a glomerular filtration rate decline and an increase in serum iFGF-23 levels. The inverse correlation observed between iFGF-23 serum levels and lumbar T-Score, lumbar DMO and trabecular microarchitecture suggests a negative effect of iFGF-23 in bone mineralization.

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BackgroundTocilizumab (TCZ), a humanized anti-IL-6 receptor antibody, represents a new treatment strategy for RA patients.Several studies have demonstrated the association between high serum levels of TNF-inhibitors and a good clinical response in patients with RA. Little evidence exists on this relationship for other biological therapies.ObjectivesTo evaluate the association between TCZ serum through levels and disease activity in a cohort of RA patients after one year of treatment with TCZ.Methods34 RA patients treated with Tocilizumab were included. Clinical activity was assessed using the Disease Activity Score 28 (DAS28-ESR) and the Clinical and Simplified Activity Index (CDAI and SDAI), serological improvement by C-Reactive Protein- CRP- and Erythrocyte Sedimentation Rate-ESR, clinical improvement by the delta-DAS 28 and response to treatment using EULAR criteria at baseline and after one year of treatment. We stratified all patients into quartiles according to the tocilizumab levels (μg/ml) as follows: IQR1: <3,4, IQR2: 3,4–11,2, IQR3: 11,2–18,5 and IQR4 >18.5. A last observation carried forward analysis (LOCF) was performed at the first year of treatment, so patients that dropped out of the therapy before this period were included. Blood samples were collected just before intravenous (i.v) infusion. Serum drug levels were determined by a capture enzymelinked immunosorbent assay (ELISA).ResultsThe baseline demographic and clinical characteristics are shown in Table 1. When patients were categorised into quartiles, IQR1 comprised 8 (24,2%) patients; IQR2, 7 (21,2%); IQR3, 8 (24,2%) and IQR4, 10 (30,3%). Clinical activity (DAS28, CDAI and SDAI) was statistically significant higher in patients with lower serum through levels at the first year [DAS28 (IQR1: 4,46 ±1,5, IQR2: 2,58 ± 0,87, IQR 3: 3,6± 0,79; IQR4: 2,17 ± 0,74; p=0,001), CDAI (IQR1: 23±13,9, IQR2: 7,72 ± 4,44, QIR 3: 13,38± 4,35, IQR4: 6,33 ± 4,62; p=0,003) and SDAI (IQR1: 19,46 ±15,5, IQR2: 9,51± 7,4, IQR3: 12,59 ± 6,31, IQR4: 4,55 ± 3,73; p=0,005)] and also was the number of swollen joints (IQR1: 7,5 ± 6,6, IQR2: 2,29 ±2,06, IQR3: 5,63 ± 4,3, IQR4: 1,1 ± 1,6, p=0,013) and tender joints (IQR1: 5,5 ± 5,7, IQR2: 1,71 ± 2,06, IQR3: 3,13 ± 2,8, IQR4: 0,8 ± 0,9, p=0,014). In addition, the EULAR reponse was worse in those patients with lower serum drug levels [non-responders: 4 (66,7%) in IQR1 vs 1 (16,7%) in IQR2 vs 1 (16,7%) in IQ3 vs 0 (0%) in IQR4, moderate responders: 3 (37,5%) in IQR1 vs 0 (0%) in IQR2 vs 4 (50%) in IQR3 vs 1 (12,5%) in IQR4 and good responders: 1 (5,3%) in IQR1 vs 6 (31,6%) in IQR2 vs 3 (37,5%) in IQR3 vs 9 (47,4%) in IQR4, p=0,006]. In terms of acute-phase reactants, the mean ESR tended to be higher in patients with lower TCZ levels (IQR1: 22,6±14,8 vs IQR2: 5,6±1,6 vs IQR 3: 9,4 ±3,5 vs IQR4: 6,4 ± 3,5, p=0,005), and also CRP levels (RIQ1: 10,2±17,4 vs RIQ2: 2,3 ± 3,4 vs RIQ3 0,56 ± 0,4 vs RIQ 4: 0,42 ± 0,66, p=NS)].ConclusionsThe presence of low serum Tocilizumab levels correlates with a worse clinical disease activity. Consequ...

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