Fibroblast growth factor-23 is a strong predictor of insulin resistance among chronic kidney disease patients

Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3–5 CKD patients were selected beside 20 normal control subjects. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess IR in selected cases. Both groups were compared for fasting blood glucose (FBG), fasting blood insulin (FBI), HOMA-IR, estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 hydroxy vitamin D (25 OH vit D), parathormone (PTH), and uric acid (UA). Correlation study between HOMA_IR and different studied parameters was performed. HOMA-IR is significantly higher in CKD (8.87 ± 3.48 vs. 3.97 ± 0.34 in CKD vs. control, respectively, p < .001). In addition CKD patients have significantly higher FGF23 (235 ± 22.96 vs. 139 ± 12.3 pg/mL, p < .001), PTH (76.9 ± 15.27 vs. 47.9 ± 2.52 pg/mL, p < .001), P (4.3 ± 0.67 vs. 3.6 ± 0.23 mg/dL, p < .001), and UA (5 ± 1.22 vs. 4.85 ± 0.48 mg/dL, p < .001) and significantly lower Ca (8.2 ± 0.3 vs. 8.9 ± 0.33 mg/dL, p < .001), and 25 (OH) vit D (17 ± 5.63 vs. 37 ± 3.43 ng/mL, p < .001). Stepwise linear regression analysis revealed that BMI, GFR, Ca, P, and FGF23 were the only significant predictors of HOMA IR. Increased IR in CKD is a consequence of the uremic status and is intimately associated with disturbed phosphate metabolism and FGF23. Further studies are needed to look for an underlying mechanism

Validation Study Of The International Classification Criteria For The Cryoglobulinemic Vasculitis

Background/Purpose: preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been developed in 2011 by an European cooperative study, with an adequate methodology in a large number of real cases and controls (1). The aim of this study is to validate these classification criteria for CV. Methods: Centres from Europe, United States, Japan and Egypt, were involved. A dedicated chart included: l) a validated questionnaire for CV (1); 2) the pattern of organ involvement (4 items: constitutional, articular, vascular and neurologic involvement); 3) laboratory tests (3 items: rheumatoid factor, complement C4 and serum monoclonal component), according to the preliminary criteria (1). New patients with CV (Group A) and controls (Group B), i.e., subjects with cryoglobulins but lacking CV based on the golden standard clinical judgment, were studied. A sample size of at least 140 patients for each group was estimated in order to obtain a sensitivity and a specificity of at least 90.5%, based on the previous results (1). Sensitivity and specificity were calculated by comparing Group A versus Group B. Finally, not for classification purposes, but to disclose whether the Criteria may be also clinically helpful in patients lacking serum cryoglobulins, but where CV is suspected (1), Group A was also compared with Group C, including patients with diseases mimicking CV, but without serum cryoglobulins. Results: Six hundred forty-three patients were enrolled in 22 Centres (from Italy, Spain, France, Greece, Slovenia, Japan and Egypt). MajorA comprised 268 patients with CV, Group B 182 controls with serum cryoglobulins without CV, and Group C 193 controls without serum cryoglobulins. Notably, 20 patients showed type I cryoglobulinemia, 13 in Group A, and 7 in Group B. Group C included 108/193 (55.9%) systemic vasculitides, 100/108 (92.6%) were small vessel vasculitides. The classification criteria [positivity of at least 2/3 items among questionnaire (2/3 positive questions), clinical item (3/4 clinical manifestations), laboratory (2/3 tests)] showed 89.9% (95% CI 86.1–93.6) of sensitivity and 93.5% (95% CI 89.7–97.2) of specificity, replicating previous results (1). Sensitivity of 91.7% and specificity of 100% were observed in the subgroup of type I cryoglobulinemia. By the comparison of Group A vs. Group C, the Criteria showed a specificity 92.6% (88.8–96.5) and a sensitivity of 77.8% (72.6–83.0) when the laboratory item was positive (questionnairelaboratory item; or clinical laboratory item). Conclusion: the International Classification Criteria for the CV have been validated in a new real cohort. High specificity and sensitivity were confirmed. Notably, in patients where CV is suspected on clinical grounds, but where cryoglobulins are negative by initial testing, or not yet available (patients who cannot be classified as CV, as positive serum cryoglobulinemia is a conditio sine qua non for classification) (1), the Criteria appear relevant to strengthen the suspicion for CV, and to optimize the follow-up