Background Aggregation of solid-phase calcium–phosphate and fetuin-A form nanoparticles called calciprotein particles (CPP). Serum CPP levels are increased in CKD patients and correlated with vascular stiffness and calcification. In this study, we evaluated effects of lanthanum carbonate (LC) and calcium carbonate (CC) on serum CPP levels in hemodialysis (HD) patients. Methods Twenty-four (24) HD patients (50% men, age; 68 ± 12 years, dialysis period; 6.2 ± 4.8 years, Kt/v; 1.74 ± 0.34) were treated with CC during 0–8 weeks and then switched to LC during 9–16 weeks. Blood samples were obtained at 0, 8, 16 weeks. Serum CPP levels (TCPP) were measured by the gel-filtration method. Low-density CPP (LCPP) levels were determined by centrifuging the serum samples at 16,000 g for 2 h and measuring CPP levels in the supernatant. The difference between TCPP and LCPP was defined as the high-density CPP (HCPP) level. We evaluated association of TCPP, LCPP, and HCPP with serum calcium (Ca), phosphorus (P), intact PTH, FGF23, Klotho, fetuin-A, aortic calcification index (ACI), LDL cholesterol, and hs-CRP. Results TCPP and LCPP levels were significantly decreased after switching CC to LC, whereas Ca and P levels were not changed. HCPP levels were below the lower limit quantification in all patients. The changes in P, Ca × P, LDL cholesterol, but not ACI and the changes in hs-CRP, were correlated with the change in TCPP levels. Conclusion The TCPP levels were significantly decreased after switching CC to LC. Non-calcium-containing phosphate binders may be preferable for lowering CPP levels.
Calciprotein particles (CPPs) are circulating colloidal mineral-protein complexes containing crystalline and/or non-crystalline (amorphous) calcium-phosphate (CaPi). Serum CPP levels correlate with vascular stiffness and calcification in patients with chronic kidney disease (CKD). In vitro studies showed that CPPs containing crystalline CaPi were more arteriosclerogenic and inflammogenic than CPPs without containing crystalline CaPi. Thus, we hypothesized that not only the quantity but also the quality of CPPs (the phase of CaPi) might affect clinical outcomes. To test this hypothesis, we quantified amorphous CaPi ratio defined as the ratio of the amorphous CaPi amount to the total CaPi amount in serum CPPs from 183 hemodialysis patients and explored its possible correlation with serum parameters associated with prognosis of hemodialysis patients. Multivariate analysis revealed that the amorphous CaPi ratio correlated positively with hemoglobin and negatively with fibroblast growth factor-21 (FGF21), which remained significant after adjusting for the total CaPi amount. Because low hemoglobin and high FGF21 are associated with increased mortality, the present study warrants further studies to determine whether low amorphous CaPi ratio in circulating CPPs may be associated with poor prognosis in hemodialysis patients.
Background and Aims Serum calciprotein particles (CPP) are increased in CKD patients and correlated with vascular stiffness and calcification. CPPs are can be distinguished amorphous and crystal CPPs. Crystal CPPs are non-incubated CPPs and amorphous CPPs are the difference(Δ) incubated CPPs and non-incubated CPPs. In this study, we evaluated amorphous CPPs and crystal CPPs in hemodialysis (HD) patients. Method 183 end stage renal disease patients undergoing HD (57.6% men, median age 71, dialysis period; 98.4 ± 87 months) were treated in single hospital. Serum CPP levels were measured by the gel filtration method. Incubated CPPs were incubated in 24°C, 24hous then were measured similarly. We assessed the association of serum calcium (Ca), phosphorus (P), intact-PTH, FGF21, LDL-cholesterol, CRP with CPP. Results In multivariate analysis, P remained significant independent factors for the non-incubated CPP levels. Ca, P remained significant independent factors for the incubated CPP levels. P remained significant independent factors for the Δ CPP levels. The association of ΔCPP levels / the incubated CPP levels with clinical variables are examined. In multivariate analysis, hemoglobin remained significant independent factors. Conclusion Amorphous CPPs and crystal CPPs could each be a prognostic factors. Figure: Association of ΔCPP levels / incubated CPP levels with clinical variables. Univariate Multivariate
Background and Aims Renal ischemia-reperfusion injury (IRI) is a clinically significant condition that leads to acute kidney injury (AKI). AKI is followed by tissue repair characterized by collagen deposition and fibrosis which ultimately results in progression to chronic kidney disease (CKD). Especially in renal transplantation, the degree of IRI has directly led to poor long-term graft survival. Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine, has been linked with progression of CKD. Linaclotide, a guanylate cyclase C agonist, has been reported decrease the plasma levels of TMAO. We investigated whether the reduction of TMAO by linaclotide protect renal function after IRI using an experimental mouse model. Method Linaclotide (100μg/kg) was administered for 2weeks before IRI and continued for 2weeks after IRI. After 2weeks since IRI, the renal function was evaluated by serum creatinine level and removed kidneys sections were performed Azan stain to evaluate the level of fibrosis. Results The administration of linaclotide before IRI significantly improved renal function. (Fig.1) Histological examination of kidneys showed linaclotide limits to expand fibrosis area after I/R injury. (Fig.2) Conclusion The reduction of TMAO by linaclotide before renal IRI could prevent renal fibrosis and improve renal function. Linaclotide may be useful for the patient expected to suffer renal IRI for example renal transplantation and partial nephrectomy. Fig2
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