Uremic CPPs and EVs are important players in the mechanisms of widespread calcification in CKD. We propose a major role for cGRP as inhibitory factor to prevent calcification at systemic and tissue levels.

Mineralization of soft tissues is an abnormal process that occurs in any body tissue and can greatly increase morbidity and mortality. Vitamin K-dependent (VKD) proteins play a crucial role in these processes; matrix Gla protein is considered one of the most relevant physiological inhibitors of soft tissue calcification know to date. Several studies have suggested that other , still unknown , VKD proteins might also be involved in soft tissue calcification pathologies. We have recently identified in sturgeon a new VKD protein , Gla-rich protein (GRP) , which contains the highest ratio between number of Gla residues and size of the mature protein so far identified. Although mainly expressed in cartilaginous tissues of sturgeon , in rat GRP is present in both cartilage and bone. We now show that GRP is a circulating protein that is also expressed and accumulated in soft tissues of rats and humans , including the skin and vascular system in which, when affected by pathological calcifications , GRP accumulates at high levels at sites of mineral deposition , indicating an association with calcification processes. The high number of Gla residues and consequent mineral binding affinity properties strongly suggest that GRP may directly influence mineral formation , thereby playing a role in processes involving connective tissue mineralization. (Am J Pathol

Background: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. Methods: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2–3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. Results: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (p = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (p = 0.050); concentric hypertrophy (p = 0.041), and serum phosphate ≥ 3.6 mg/dL (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044). Conclusions: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.

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Aims. To evaluate the association of different apelin levels with cardiovascular mortality, hospitalization, renal function, and cardiovascular risk factors in type 2 diabetic patients with mild to moderate CKD. Methods. An observational, prospective study involving 150 patients divided into groups according to baseline apelin levels: 1 ≤ 98 pg/mL, 2 = 98–328 pg/mL, and 3 ≥ 329 pg/mL. Baseline characteristics were analyzed and compared. Multivariate Cox regression was used to find out predictors of cardiovascular mortality, and multivariate logistic regression was used to find out predictors of hospitalization and disease progression. Simple linear regressions and Pearson correlations were used to investigate correlations between apelin and renal disease and cardiovascular risk factors. Results. Patients' survival at 83 months in groups 1, 2, and 3 was 39%, 40%, and 71.2%, respectively (P = 0.046). Apelin, age, and eGFR were independent predictors of mortality, and apelin, creatinine, eGFR, resistin, and visfatin were independent predictors of hospitalization. Apelin levels were negatively correlated with cardiovascular risk factors and positively correlated with eGFR. Patients with lower apelin levels were more likely to start a depurative technique. Conclusions. Apelin levels might have a significant clinical use as a marker/predictor of cardiovascular mortality and hospitalization or even as a therapeutic agent for CKD patients with cardiovascular disease.

Our results showed that Klotho levels are influenced by FGF23, vitamin D and insulin resistance. This suggests that Klotho levels might be affected by renal function as well as having a relevant role on insulin metabolism and ACR homeostasis.

BackgroundThe aim of our study was to evaluate the relevance of magnesium and FGF-23 in terms of cardiovascular disease in a population of type 2 diabetic patients with nephropathy.MethodsIn a cross-sectional study, we included 80 type 2 diabetic patients with chronic kidney disease (CKD) stages 2, 3 and 4. We analysed mineral metabolism, inflammation, oxidative stress and insulin resistance. Our population was divided into two groups according to their pulse pressure (PP) as follows: G-1 with PP < 50 mmHg (n = 34) and G-2 with PP ≥ 50 mmHg (n = 46).ResultsWe found that G-2 patients showed lower calcium (P = 0.004), eGFR (P = 0.001), magnesium (P = 0.0001), osteocalcin (P = 0.0001) and 25(OH)D3 (P = 0.001), and higher iPTH (P = 0.001), FGF-23 (P = 0.0001), malonaldehyde (P = 0.0001), interleukin 6 (P = 0.001) and HOMA-IR (P = 0.033). No differences were found between the two groups regarding age, duration of disease, haemoglobin, HgA1c and phosphorus. In a multivariate analysis, we found that FGF-23 and magnesium independently influenced the PP [OR = 1.239 (1.001–2.082), P = 0.039 and OR = 0.550 (0.305–0.727), P = 0.016, respectively].ConclusionsIn our diabetic population with early stages of CKD, FGF-23 as well as lower magnesium levels were significantly and independently associated with higher PP levels, an established marker of cardiovascular morbidity and mortality.

In patients on chronic hemodialysis (CHD), hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). In the last few years, calcitriol intravenously (IV) has been used with success in the treatment of the HPTH, secondary to chronic renal failure. However, the effects of calcitriol on the hematological parameters of these patients have never been well evaluated. This study included 11 elderly CHD patients (f = 6, m = 5; mean age = 73.6 years, mean time on CHD = 42.8 months) with HPTH under EPO therapy (IV). They were treated for 12 months with calcitriol IV (mean dose = 2.33 mcg/pt/week). Patients with iron deficiency anemia (ferritin < 200 ng/ml) were excluded. The patients were compared before and after 12 months of calcitriol treatment, with respect to several laboratory parameters and with respect to EPO dose. A paired t-test was used. After treatment, we found a decrease of PTH (634 vs. 418 pg/ml, P = 0.029); the serum calcium increased (8.8 vs. 9.9 mg/dl, P = 0.002); no differences were noted in the plasma levels of alkaline phosphatase, phosphorous, BUN, creatinine, Na and K. Mean levels of Hb (10.2 vs. 11.4 g/dl, P = 0.004) and the Hct (30 vs. 34.3, P = 0.004) increased after 12 months of calcitriol; the levels of serum iron (70 vs. 78 microg/dl, P = ns) and ferritin (531 vs. 785 ng/ml, P = ns) and the EPO dose (105 vs. 100 U/kg/week, P = ns) were similar before and after treatment. Our data show that the treatment of HPTH in CHD elderly patients with calcitriol can increase Hb level without increasing EPO dose.