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

Atributos químicos, mineralógicos e micromorfológicos de horizontes coesos de latossolos e argissolos dos tabuleiros costeiros do estado de Alagoas Mineralogy and micromorphology of cohesive horizons in oxisols and ultisols of the coastal tablelands of Alagoas, Brazil

O caráter coeso é um atributo característico de horizontes subsuperficiais que, quando secos, apresentam consistência muito dura e extremamente dura, passando a friável ou firme quando úmidos. A formação desses horizontes, entretanto, ainda é um assunto polêmico, não estando completamente esclarecida. O objetivo deste trabalho foi realizar uma caracterização química, mineralógica e micromorfológica de solos coesos, visando entender a sua gênese e definir características que possam complementar a definição do caráter coeso no Sistema Brasileiro de Classificação de Solos. Quatro perfis de solos foram coletados na região dos tabuleiros costeiros de Alagoas, envolvendo um Argissolo Amarelo, um Argissolo Acinzentado e dois Latossolos Amarelos. Os solos foram descritos morfologicamente, e as amostras dos horizontes coesos e não coesos foram coletadas para execução de análises químicas de Fe, Al e Si por extração com DCB, oxalato, CaCl2 e água quente, análises mineralógicas por DRX e caracterização micromorfológica. Os solos apresentaram baixos teores de Fe, com domínio das formas de baixa cristalinidade e predominância de caulinitas com moderado a alto grau de desordem estrutural em todos os horizontes. Não foi observada, nos horizontes coesos, tendência de aumento dos teores de Al e Si extraídos com DCB e oxalato, indicando que a sua gênese não se deve à presença de agentes cimentantes. Os resultados das análises mineralógicas e micromorfológicas sugerem que a gênese do caráter coeso apresenta duas fases distintas, sendo formado inicialmente pelo entupimento dos poros decorrente da iluviação de argila fina, havendo posteriormente uma perda de Fe na parte superior, que colapsa a estrutura e provoca um ajuste face a face da caulinita.<br>The cohesive character is a property of subsurface soil horizons with hard to extremely hard consistency when dry, and friable or firm when wet. Despite the agricultural importance, the formation of these horizons has not been fully explained. The objective of this study was a chemical, mineralogical and micromorphological characterization of cohesive soils of the Coastal Tablelands in Northeast Brazil, to understand their pedogenesis and identify properties for the definition of the cohesive character by the Brazilian System of Soil Classification. The following four soil profiles were morphologically characterized: a Yellow Argisol (Ultisol), a Gray Argisol (Ultisol) and two Yellow Latosols (Oxisols). Samples from cohesive and non cohesive horizons were taken for chemical analysis of Fe, Al and Si extracted by DCD, oxalate, CaCl2 and hot water, mineralogy by X ray diffraction, and micromorphological characterization. The Fe contents in the soils were low and kaolinite with a moderate to high degree of structural disorder predominated in all studied soil horizons. No increase in Al and Si extracted by DCB and oxalate was observed in the cohesive horizons, indicating the absence of cementation in its genesis. Results of the mineralogical and micromorphological characterization suggest two distinct phases in the genesis of the cohesive character. The first step was determined by clay illuviation, clogging the soil pores, and later iron loss, destroying the soil structure and resulting in a direct adjustment with kaolinite particles