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

Evaluation of a therapeutic vaccine for the prevention of recurrent urinary tract infections versus prophylactic treatment with antibiotics

INTRODUCTION AND HYPOTHESIS: Urinary tract infections (UTIs) are considered the most common bacterial infections, especially in women. The objective of this study was to evaluate the use of the sublingual bacterial vaccine Uromune® in order to prevent recurrent UTIs (RUTIs). METHODS: This study was conceived as a multicenter observational study. The clinical history of 319 women who presented at least 2 episodes of UTI in the last 6 months or 3 in 12 months was reviewed. Data related to treatment and clinical evolution were recorded and analyzed. A total of 159 patients received prophylactic treatment with Uromune® for a period of 3 months (group A) and 160 with sulfamethoxazole/trimethoprim 200/40 mg/day for a period of 6 months (group B). Uromune® contained an inactivated bacterial cell suspension of selected strains of Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis. RESULTS: Patients in group A experienced a highly significant reduction in the number of infections compared to patients in group B. In the first 3 months, the mean number of infections was 0.36 versus 1.60 (P < 0.0001), respectively. A significant reduction was also observed after 9 and 15 months (P < 0.0001). The numbers of patients who did not have any UTI at 3, 9, and 15 months were 101, 90, and 55 in group A versus 9, 4, and 0 in group B (P < 0.0001). CONCLUSIONS: The results obtained in this study favor the use of this bacterial-based therapeutic vaccine as an effective strategy to reduce frequency, duration, severity, and costs of RUTIs

Delay in diagnosis of influenza A (H1N1)pdm09 virus infection in critically ill patients and impact on clinical outcome

Background: Patients infected with influenza A (H1N1)pdm09 virus requiring admission to the ICU remain an important source of mortality during the influenza season. The objective of the study was to assess the impact of a delay in diagnosis of community-acquired influenza A (H1N1)pdm09 virus infection on clinical outcome in critically ill patients admitted to the ICU. Methods: A prospective multicenter observational cohort study was based on data from the GETGAG/SEMICYUC registry (2009–2015) collected by 148 Spanish ICUs. All patients admitted to the ICU in which diagnosis of influenza A (H1N1)pdm09 virus infection had been established within the first week of hospitalization were included. Patients were classified into two groups according to the time at which the diagnosis was made: early (within the first 2 days of hospital admission) and late (between the 3rd and 7th day of hospital admission). Factors associated with a delay in diagnosis were assessed by logistic regression analysis. Results: In 2059 ICU patients diagnosed with influenza A (H1N1)pdm09 virus infection within the first 7 days of hospitalization, the diagnosis was established early in 1314 (63.8 %) patients and late in the remaining 745 (36.2 %). Independent variables related to a late diagnosis were: age (odds ratio (OR) = 1.02, 95 % confidence interval (CI) 1.01–1.03, P < 0.001); first seasonal period (2009–2012) (OR = 2.08, 95 % CI 1.64–2.63, P < 0.001); days of hospital stay before ICU admission (OR = 1.26, 95 % CI 1.17–1.35, P < 0.001); mechanical ventilation (OR = 1.58, 95 % CI 1.17–2.13, P = 0.002); and continuous venovenous hemofiltration (OR = 1.54, 95 % CI 1.08–2.18, P = 0.016). The intra-ICU mortality was significantly higher among patients with late diagnosis as compared with early diagnosis (26.9 % vs 17.1 %, P < 0.001). Diagnostic delay was one independent risk factor for mortality (OR = 1.36, 95 % CI 1.03–1.81, P < 0.001). Conclusions: Late diagnosis of community-acquired influenza A (H1N1)pdm09 virus infection is associated with a delay in ICU admission, greater possibilities of respiratory and renal failure, and higher mortality rate. Delay in diagnosis of flu is an independent variable related to death