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BackgroundSerum bicarbonate or total carbon dioxide (CO2) concentrations decline as chronic kidney disease (CKD) progresses and rise after dialysis initiation. While metabolic acidosis accelerates the progression of CKD and is associated with higher mortality among patients with end stage renal disease (ESRD), there are scarce data on the association of CO2 concentrations before ESRD transition with post-ESRD mortality.MethodsA historical cohort from the Transition of Care in CKD (TC-CKD) study includes 85,505 veterans who transitioned to ESRD from October 1, 2007, through March 31, 2014. After 1,958 patients without follow-up data, 3 patients with missing date of birth, and 50,889 patients without CO2 6 months prior to ESRD transition were excluded, the study population includes 32,655 patients. Associations between CO2 concentrations averaged over the last 6 months and its rate of decline during the 12 months prior to ESRD transition and post-ESRD all-cause, cardiovascular (CV), and non-CV mortality were examined by using hierarchical adjustment with Cox regression models.ResultsThe cohort was on average 68 ± 11 years old and included 29% Black veterans. Baseline concentrations of CO2 were 23 ± 4 mEq/L, and median (interquartile range) change in CO2 were -1.8 [-3.4, -0.2] mEq/L/year. High (≥28 mEq/L) and low (4 mEq/L/year.ConclusionBoth high and low pre-ESRD CO2 levels (≥28 and 4 mEq/L/year during 1 year before dialysis initiation were associated with greater post-ESRD all-cause, CV, and non-CV mortality. Further studies are needed to determine the optimal management of CO2 in patients with advanced CKD stages transitioning to ESRD.

BackgroundMortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) remains exceptionally high. While traditional risk factors such as obesity are paradoxically associated with better survival, nontraditional risk factors including cachexia increase the likelihood of poor outcomes. There is accumulating evidence that the endocannabinoid (ECB) system plays a major role in energy preservation and storage, factors which can prevent the deleterious effects of cachexia. Hence, in this study, we evaluated the association of circulating ECB levels with mortality in MHD patients.MethodsSerum concentrations of anandamide (AEA) and 2-arachidonoyl-sn-glycerol (2-AG), major ECB ligands, were measured in MHD patients. Their correlation with various clinical/laboratory indices and association with 12-month all-cause mortality were examined.ResultsSerum 2-AG levels positively correlated with body mass index, serum triglycerides and body anthropometric measures. Meanwhile, serum AEA levels correlated positively with serum interleukin-6, and negatively with serum very low-density lipoprotein levels. While increased serum 2-AG levels were associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.52, 95% CI 0.28-0.98), there was no clear association between serum AEA levels and mortality (HR 0.91, 95% CI 0.48-1.72).ConclusionsIn MHD patients, the circulating levels of ECB ligand, 2-AG, may play an important role in determining body mass and risk of mortality. These observations were unique to 2-AG as similar findings were not obtained with serum AEA. Future studies need to investigate the mechanisms responsible for these associations and examine the modulation of the ECB system as a potential target for therapy in ESRD.

BackgroundPopulation-based studies show there is a high prevalence of chronic kidney disease (CKD) patients suffering from chronic pain. While opiates are frequently prescribed in non-dialysis-dependent CKD (NDD-CKD) patients, there may be toxic accumulation of metabolites, particularly among those progressing to end-stage renal disease (ESRD). We examined the association of opiate versus other analgesic use during the pre-ESRD period with post-ESRD mortality among NDD-CKD patients transitioning to dialysis.MethodsWe examined a national cohort of US Veterans with NDD-CKD who transitioned to dialysis over 2007-14. Among patients who received ≥1 prescription(s) in the Veterans Affairs (VA) Healthcare System within 1 year of transitioning to dialysis, we examined associations of pre-ESRD analgesic status, defined as opiate, gabapentin/pregabalin, other non-opiate analgesic, versus no analgesic use, with post-ESRD mortality using multivariable Cox models.ResultsAmong 57,764 patients who met eligibility criteria, pre-ESRD opiate and gabapentin/pregabalin use were each associated with higher post-ESRD mortality (ref: no analgesic use), whereas non-opiate analgesic use was not associated with higher mortality in expanded case-mix analyses: HRs (95% CIs) 1.07 (1.05-1.10), 1.07 (1.01-1.13), and 1.00 (0.94-1.06), respectively. In secondary analyses, increasing frequency of opiate prescriptions exceeding 1 opiate prescription in the 1-year pre-ESRD period was associated with incrementally higher post-ESRD mortality (ref: no analgesic use).ConclusionsIn NDD-CKD patients transitioning to dialysis, pre-ESRD opiate and gabapentin/pregabalin use were associated with higher post-ESRD mortality, whereas non-opiate analgesic use was not associated with death. There was a graded association between increasing frequency of pre-ESRD opiate use and incrementally higher mortality.

BackgroundIncident hemodialysis patients have a high mortality risk within the first months after dialysis initiation. Pre-end-stage renal disease (ESRD) factors like anemia management may impact early post-ESRD outcomes. Therefore, we evaluated the impact of pre-ESRD hemoglobin (Hgb) and pre-ESRD Hgb slope on post-ESRD mortality and hospitalization outcomes.MethodsThe study included 31,472 veterans transitioning to ESRD. Using Cox and negative binomial regression models, we evaluated the association of pre-ESRD Hgb and Hgb slope with 12-month post-ESRD all-cause and cardiovascular mortality and hospitalization rates using 4 levels of hierarchical multivariable adjustment, including erythropoietin use and kidney decline in slope models.ResultsThe cohort was 2% female, 30% African-American, and on average 68 ± 11 years old. Compared to Hgb 10-< 11 g/dL, both low (< 10 g/dL) and high (≥12 g/dL) levels were associated with higher all-cause mortality after full adjustment (HR 1.25 [95% CI 1.15-1.35] and 1.09 [95% CI 1.02-1.18], respectively). Similarly, Hgb exhibited a U-shaped association with CV mortality, while only lower Hgb was associated with a higher hospitalization rate. Neither an annual pre-ESRD decline in Hgb nor increase was associated with higher post-ESRD mortality risk after adjustment for kidney decline. However, we observed a modest J-shaped association between pre-ESRD Hgb slope and post-ESRD hospitalization rate.ConclusionsLower and higher pre-ESRD Hgb levels are associated with a higher risk of early post-ESRD mortality, while there was no association between the pre-ESRD slope and mortality. An increase in pre-ESRD Hgb slope was associated with higher risk of post-ESRD hospitalization. Additional studies aimed at anemia management prior to ESRD transition are warranted.

BackgroundNeutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been previously suggested as oncologic prognostication markers. These are associated with malnutrition and inflammation, and hence, may provide benefit in predicting mortality among hemodialysis patients.MethodsAmong 108,548 incident hemodialysis patients in a large U.S. dialysis organization (2007-2011), we compared the mortality predictability of NLR and PLR with baseline and time-varying covariate Cox models using the receiver operating characteristic curve (AUROC), net reclassification index (NRI), and adjusted R2.ResultsDuring the median follow-up period of 1.4 years, 28,618 patients died. Median (IQR) NLR and PLR at baseline were 3.64 (2.68-5.00) and 179 (136-248) respectively. NLR was associated with higher mortality, which appeared stronger in the time-varying versus baseline model. PLR exhibited a J-shaped association with mortality in both models. NLR provided better mortality prediction in addition to demographics, comorbidities, and serum albumin; ΔAUROC and NRI for 1-year mortality (95% CI) were 0.010 (0.009-0.012) and 6.4% (5.5-7.3%) respectively. Additionally, adjusted R2 (95% CI) for the Cox model increased from 0.269 (0.262-0.276) to 0.283 (0.276-0.290) in the non-time-varying model and from 0.467 (0.461-0.472) to 0.505 (0.500-0.512) in the time-varying model. There was little to no benefit of adding PLR to predict mortality.ConclusionsHigh NLR in incident hemodialysis patients predicted mortality, especially in the short-term period. NLR, but not PLR, added modest benefit in predicting mortality along with demographics, comorbidities, and serum albumin, and should be included in prognostication approaches.