Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Carbon allotrope nanomaterials based catalytic micromotors

Carbon allotropes nanomaterials are explored here for the preparation of highly efficient tubular micromotors: 0D (C fullerene), 1D (carbon nanotubes), 2D (graphene), and 3D (carbon black, CB). The micromotors are prepared by direct electrochemical reduction or deposition of the nanomaterial into the pores of a membrane template. Subsequent electrodeposition of diverse inner catalytic layers (Pt, Pd, Ag, Au, or MnO) allows for efficient bubble-propulsion in different media (seawater, human serum, and juice samples). Atomic-force microscopy (AFM) and scanning electron microscopy characterization reveals that the micromotors exhibit a highly rough outer surface and highly microporous inner catalytic structures. A key aspect derived from the AFM characterization is the demonstration that the rough outer surface of the micromotors can greatly affect their overall speed. To date, the literature has only focused on studying the effect of the inner catalytic layer upon their speed and performance and has underestimated the effect of the outer surface layer. The speed of carbon-based micromotors is a compromise between two opposite forces: the increased catalytic activity because of improved fuel decomposition in the inner catalytic layer, which propels their advance, and the friction of the rough outer surface with the fluid, which is opposed to it. The largest outer surface area associated with the highest surface roughness of C fullerene and carbon black-Pt micromotors leads to a large friction force, which results in a reduced speed of ∼180 μm/s (1% HO). In contrast, for carbon-nanotube-Pt based micromotors, the dominant force is the high catalytic activity of the micromotor, which allows them to reach ultrafast speeds up to 440 μm/s (1% HO). The new protocol opens new avenues for the universal preparation of carbon based multifunctional micromotors for a myriad of practical applications exploiting the features of carbon allotropes

Carbon Allotrope Nanomaterials Based Catalytic Micromotors

Carbon allotropes nanomaterials are explored here for the preparation of highly efficient tubular micromotors: 0D (C₆₀ fullerene), 1D (carbon nanotubes), 2D (graphene), and 3D (carbon black, CB). The micromotors are prepared by direct electrochemical reduction or deposition of the nanomaterial into the pores of a membrane template. Subsequent electrodeposition of diverse inner catalytic layers (Pt, Pd, Ag, Au, or MnO₂) allows for efficient bubble-propulsion in different media (seawater, human serum, and juice samples). Atomic-force microscopy (AFM) and scanning electron microscopy characterization reveals that the micromotors exhibit a highly rough outer surface and highly microporous inner catalytic structures. A key aspect derived from the AFM characterization is the demonstration that the rough outer surface of the micromotors can greatly affect their overall speed. To date, the literature has only focused on studying the effect of the inner catalytic layer upon their speed and performance and has underestimated the effect of the outer surface layer. The speed of carbon-based micromotors is a compromise between two opposite forces: the increased catalytic activity because of improved fuel decomposition in the inner catalytic layer, which propels their advance, and the friction of the rough outer surface with the fluid, which is opposed to it. The largest outer surface area associated with the highest surface roughness of C₆₀ fullerene and carbon black-Pt micromotors leads to a large friction force, which results in a reduced speed of ∼180 μm/s (1% H₂O₂). In contrast, for carbon-nanotube-Pt based micromotors, the dominant force is the high catalytic activity of the micromotor, which allows them to reach ultrafast speeds up to 440 μm/s (1% H₂O₂). The new protocol opens new avenues for the universal preparation of carbon based multifunctional micromotors for a myriad of practical applications exploiting the features of carbon allotropes