Dialysate Potassium and Mortality in a Prospective Hemodialysis Cohort.

BackgroundStudies examining the association of dialysate potassium concentration and mortality in hemodialysis patients show conflicting findings. We hypothesized that low dialysate potassium concentrations are associated with higher mortality, particularly in patients with high pre-dialysis serum potassium concentrations.MethodsWe evaluated 624 hemodialysis patients from the prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease study recruited from 16 outpatient dialysis facilities over 2011-2015 who underwent protocolized collection of dialysis treatment characteristics every 6 months. We examined the association of dialysate potassium concentration, categorized as 1, 2, and 3 mEq/L, with all-cause mortality risk in the -overall cohort, and stratified by pre-dialysis serum potassium (< 5 vs. ≥5 mEq/L) using case-mix adjusted Cox models.ResultsIn baseline analyses, dialysate potassium concentrations of 1 mEq/L were associated with higher mortality, whereas concentrations of 3 mEq/L were associated with similar mortality in the overall cohort (reference: 2 mEq/L): adjusted hazard ratios (aHRs; 95% CI) 1.70 (1.01-2.88) and 0.95 (0.64-1.39), respectively. In analyses stratified by serum potassium, baseline dialysate potassium concentrations of 1 mEq/L were associated with higher mortality in patients with serum potassium ≥5 mEq/L but not in those with serum potassium < 5 mEq/L: aHRs (95% CI) 2.87 (1.51-5.46) and 0.74 (0.27-2.07), respectively (p interaction = 0.04). These findings were robust with incremental adjustment for serum potassium, potassium-binding resins, and potassium-modifying medications.ConclusionLow (1 mEq/L) dialysate potassium -concentrations were associated with higher mortality, particularly in hemodialysis patients with high pre-dialysis serum potassium. Further studies are needed to identify therapeutic strategies that mitigate inter-dialytic serum potassium accumulation and subsequent high dialysate serum potassium gradients in this population

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Estudio de la hidrólisis del ion Niquel(II) y de la formación de los complejos de Niquel(II) con los ácidos Picolínico y Dipicolínico en NaCl 1,0 mol.dm-3 a 25°C

Estudio de la hidrólisis del ion Niquel(II) y de la formación de los complejos de Niquel(II) con los ácidos Picolínico y Dipicolínico en NaCl 1,0 mol.dm-3 a 25°[email protected] productos de hidrólisis (formación de compuestos hidroxilados) del ion Níquel(II) y de las especies complejas formadas entre el Ni(II) y los ligandos ácido picolínico (Hpic) y ácido dipicolínico (H2dipic), se han estudiado potenciométricamente en solución acuosa (a 25ºC, en medio iónico de NaCl I = 1,0 mol.dm-3). En la aplicación del programa informático de mínimos cuadrados generalizados, LETAGROP, a la data experimental de fem(H), se observó la formación de los productos de hidrólisis [Ni(OH)]+, [Ni(OH)2] y [Ni4(OH)4]4-. Adicionalmente, se ha detectado la formación de los complejos [Ni(pic)]+, [Ni(pic)2] y [Ni(pic)3]- con ácido picolínico y de las especies [Ni(dipic)] y [Ni(dipic)2]2- con ácido dipicolínico. Las constantes de estabilidad de los complejos formados fueron determinadas por mediciones potenciométricas

Association of the Novel Cachexia Marker “Growth Differentiation Factor 15” (GDF15) With Mortality in a Prospective Hemodialysis Cohort

Cachexia and protein-energy wasting are potent predictors of higher mortality risk in dialysis-dependent chronic kidney disease (CKD) patients. The novel cachexia marker, GDF15, is a protein associated with inflammation, cardiovascular disease, and decreased survival in patients with underlying malignancy. However, the impact of GDF15 on the survival of CKD patients is unknown. Among 203 prevalent hemodialysis patients enrolled in the prospective MADRAD study over the period of 10/2011-8/2014, we examined the association of GDF15 levels with all-cause mortality risk. Associations between GDF15 categorized into tertiles with mortality were estimated using unadjusted and case-mix adjusted Cox models. Compared with the lowest GDF15 tertile, the highest GDF15 tertile was associated with higher mortality risk in unadjusted and case-mix adjusted models: HR (95%CI) 3.19 (1.35-7.55) and 2.45 (1.00-6.00), respectively, p-for-trend 0.03 (Figure 1A). Higher circulating GDF15 levels in hemodialysis patients are associated with higher all-cause mortality. Future studies are needed to determine whether modulation of GDF15 levels and subsequent correction of cachexia improves survival in this population

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort.

Background/aimsCardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients.MethodsAmong prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage.ResultsThe mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models.ConclusionHigher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort.

Background/aimsCardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients.MethodsAmong prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage.ResultsThe mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models.ConclusionHigher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population