Dietary potassium intake, kidney function, and survival in a nationally representative cohort.

BACKGROUND: In healthy adults, higher dietary potassium intake is recommended given that potassium-rich foods are major sources of micronutrients, antioxidants, and fiber. Yet among patients with advanced kidney dysfunction, guidelines recommend dietary potassium restriction given concerns about hyperkalemia leading to malignant arrhythmias and mortality. OBJECTIVES: Given sparse data informing these recommendations, we examined associations of dietary potassium intake with mortality in a nationally representative cohort of adults from the NHANES. METHODS: We examined associations between daily dietary potassium intake scaled to energy intake (mg/1000 kcal), ascertained by 24-h dietary recall, and all-cause mortality among 37,893 continuous NHANES (1999-2014) participants stratified according to impaired and normal kidney function (estimated glomerular filtration rates <60 and ≥60 mL · min-1 · 1.73 m-2, respectively) using multivariable Cox models. We also examined the impact of the interplay between dietary potassium, source of potassium intake (animal- compared with plant-based sources), and coexisting macronutrient and mineral consumption upon mortality. RESULTS: Among participants with impaired and normal kidney function, the lowest tertile of dietary potassium scaled to energy intake was associated with higher mortality (ref: highest tertile) [adjusted HR (aHR): 1.18; 95% CI: 1.02, 1.38 and aHR: 1.17; 95% CI: 1.06, 1.28, respectively]. Compared with high potassium intake from plant-dominant sources, participants with low potassium intake from animal-dominant sources had higher mortality irrespective of kidney function. Among participants with impaired kidney function, pairings of low potassium intake with high protein, low fiber, or high phosphorus consumption were each associated with higher death risk. CONCLUSIONS: Lower dietary potassium scaled to energy intake was associated with higher mortality, irrespective of kidney function. There was also a synergistic relation of higher potassium intake, plant-based sources, and macronutrient/mineral consumption with survival. Further studies are needed to elucidate pathways linking potassium intake and coexisting dietary factors with survival in populations with and without chronic kidney disease.

The Interplay between Dietary Phosphorous, Protein Intake, and Mortality in a Prospective Hemodialysis Cohort.

(1) Background: Current dietary recommendations for dialysis patients suggest that high phosphorus diets may be associated with adverse outcomes such as hyperphosphatemia and death. However, there has been concern that excess dietary phosphorus restriction may occur at the expense of adequate dietary protein intake in this population. We hypothesized that higher dietary phosphorus intake is associated with higher mortality risk among a diverse cohort of hemodialysis patients. (2) Methods: Among 415 patients from the multi-center prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease Study, we examined the associations of absolute dietary phosphorus intake (mg/day), ascertained by food frequency questionnaires, with all-cause mortality using multivariable Cox models. In the secondary analyses, we also examined the relationship between dietary phosphorus scaled to 1000 kcal of energy intake (mg/kcal) and dietary phosphorus-to-protein ratio (mg/g) with survival. (3) Results: In expanded case-mix + laboratory + nutrition adjusted analyses, the lowest tertile of dietary phosphorus intake was associated with higher mortality risk (ref: highest tertile): adjusted HR (aHR) (95% CI) 3.33 (1.75-6.33). In the analyses of dietary phosphorus scaled to 1000 kcal of energy intake, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.74 (1.08, 2.80). Similarly, in analyses examining the association between dietary phosphorus-to-protein ratio, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.67 (1.02-2.74). (4) Conclusions: A lower intake of dietary phosphorus was associated with higher mortality risk in a prospective hemodialysis cohort. Further studies are needed to clarify the relationship between specific sources of dietary phosphorus intake and mortality in this population.

Association of thyroid status prior to transition to end-stage renal disease with early dialysis mortality.

BACKGROUND: Advanced chronic kidney disease (CKD) patients, including those receiving dialysis, have a high prevalence of thyroid dysfunction. Although hypothyroidism is associated with higher death risk in end-stage renal disease (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD period impacts mortality after dialysis initiation. METHODS: Among US veterans with CKD identified from the national Veterans Affairs database that transitioned to dialysis over the period from October 2007 to September 2011, we examined the association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year pre-dialysis ('prelude') period with all-cause mortality in the first year following dialysis initiation. RESULTS: Among 15 335 patients in the 1-year prelude cohort, TSH levels >5.0 mIU/L were associated with higher mortality in expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were observed for TSH >5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95% CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer gradations of TSH in the 1-year prelude cohort demonstrated that incrementally higher levels >5.0 mIU/L were associated with increasingly higher mortality in expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04-1.33) and 1.28 (1.03-1.59) for TSH levels >5.0-10.0 mIU/L and >10.0 mIU/L, respectively. In the 2- and 5-year cohorts, mortality associations persisted most strongly for those with TSH >10.0 mIU/L, particularly after laboratory covariate adjustment. CONCLUSIONS: Among new ESRD patients, there is a dose-dependent relationship between higher pre-ESRD TSH levels >5.0 mIU/L and post-ESRD mortality. Further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population.

Dialysis Provider and Outcomes among United States Veterans Who Transition to Dialysis.

BACKGROUND AND OBJECTIVES: Veterans with ESKD initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. It is unknown whether outcomes differ according to their dialysis provider at initiation. We sought to evaluate the association between dialysis provider and mortality and hospitalization among United States veterans initiating dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 68,727 United States veterans who initiated dialysis in 2007-2014, we examined the association of dialysis provider (VHA versus non-VHA) at initiation with mortality and hospitalization rates in the first 12 months post-initiation. Associations were examined across adjusted models, accounting for demographics and comorbidities. RESULTS: Patients were 72±11 years, 5% were women, 24% were black, and 10% (n=7584) initiated at VHA dialysis centers. VHA dialysis center patients were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower eGFR at dialysis initiation. VHA provider patients were more likely to be hospitalized in the first 12 months (adjusted incidence rate ratio, 1.10; 95% confidence interval, 1.07 to 1.14), but had lower all-cause mortality risk (adjusted hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.93) in fully adjusted models. CONCLUSIONS: Veteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units.

Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat.

The mechanisms by which n-3 polyunsaturated fatty acids (PUFAs) decrease colon tumor formation have not been fully elucidated. Examination of genes up- or down-regulated at various stages of tumor development via the monitoring of gene expression relationships will help to determine the biological processes ultimately responsible for the protective effects of n-3 PUFA. Therefore, using a 3 x 2 x 2 factorial design, we used Codelink DNA microarrays containing approximately 9000 genes to help decipher the global changes in colonocyte gene expression profiles in carcinogen-injected Sprague Dawley rats. Animals were assigned to three dietary treatments differing only in the type of fat (corn oil/n-6 PUFA, fish oil/n-3 PUFA, or olive oil/n-9 monounsaturated fatty acid), two treatments (injection with the carcinogen azoxymethane or with saline), and two time points (12 hours and 10 weeks after first injection). Only the consumption of n-3 PUFA exerted a protective effect at the initiation (DNA adduct formation) and promotional (aberrant crypt foci) stages. Importantly, microarray analysis of colonocyte gene expression profiles discerned fundamental differences among animals treated with n-3 PUFA at both the 12 hours and 10-week time points. Thus, in addition to demonstrating that dietary fat composition alters the molecular portrait of gene expression profiles in the colonic epithelium at both the initiation and promotional stages of tumor development, these findings indicate that the chemopreventive effect of fish oil is due to the direct action of n-3 PUFA and not to a reduction in the content of n-6 PUFA.