Association of long-term aspirin use with kidney disease progression.

Background: Chronic microinflammation contributes to the progression of chronic kidney disease (CKD). Aspirin (ASA) has been used to treat inflammation for centuries. The effects of long-term low-dose ASA on CKD progression are unclear. Methods: We examined the association of long-term use of newly initiated low-dose ASA (50-200 mg/day) with all-cause mortality using Cox proportional hazard models; with cardiovascular/cerebrovascular (CV) mortality and with end stage kidney disease (ESKD) using Fine and Gray competing risk regression models; with progression of CKD defined as patients' eGFR slopes steeper than -5 mL/min/1.73m2/year using logistic regression models in a nationwide cohort of US Veterans with incident CKD. Among 831,963 patients, we identified 385,457 who either initiated ASA (N = 21,228) within 1 year of CKD diagnosis or never received ASA (N = 364,229). We used propensity score matching to account for differences in key characteristics, yielding 29,480 patients (14,740 in each group). Results: In the matched cohort, over a 4.9-year median follow-up period, 11,846 (40.2%) patients (6,017 vs. 5,829 ASA users vs. non-users) died with 25.8% CV deaths, and 934 (3.2%) patients (476 vs. 458) reached ESKD. ASA users had a higher risk of faster decline of kidney functions, i.e., steeper slopes (OR 1.30 [95%CI: 1.18, 1.44], p < 0.01), but did not have apparent benefits on mortality (HR 0.97 [95%CI: 0.94, 1.01], p = 0.17), CV mortality (Sub-Hazard Ratio [SHR]1.06 [95%CI: 0.99-1.14], p = 0.11), or ESKD (SHR1.00 [95%CI: 0.88, 1.13], p = 0.95). Conclusion: Chronic low-dose ASA use was associated with faster kidney function deterioration, and no association was observed with mortality or risk of ESKD.

Morphology, Photosynthetic Traits, and Nutritional Quality of Lettuce Plants as Affected by Green Light Substituting Proportion of Blue and Red Light.

Green light, as part of the photosynthetically active radiation, has been proven to have high photosynthetic efficiency once absorbed by plant leaves and can regulate plant physiological activities. However, few studies have investigated the appropriate and efficient way of using the green light for plant production. Thus, the objective of this study was to investigate a moderate amount of green light, partially replacing red and blue light, for plant growth and development. In this experiment, four treatments were set up by adjusting the relative amount of green light as 0 (RB), 30 (G30), 60 (G60), and 90 (G90) µmol m-2 s-1, respectively, with a total photosynthetic photon flux density of 200 µmol m-2 s-1 and a fixed red-to-blue ratio of 4:1. Lettuce (Lactuca sativa cv. 'Tiberius') plant growth and morphology, stomatal characteristics, light absorptance and transmittance, photosynthetic characteristics, and nutritional quality were investigated. The results showed that: (1) shoot dry weight increased by 16.3 and 24.5% and leaf area increased by 11.9 and 16.2% under G30 and G60, respectively, compared with those under RB. Plant stem length increased linearly with increasing green-to-blue light ratio; (2) light transmittance of lettuce leaf under treatments employing green light was higher than that under RB, especially in the green region; (3) stomatal density increased, whereas stomatal aperture area decreased with the increase in the relative amount of green light; and (4) carbohydrate accumulation increased under G60 and G90. Soluble sugar contents under G60 and G90 increased by 39.4 and 19.4%, respectively. Nitrate contents under G30, G60, and G90 decreased by 26.2, 40.3, and 43.4%, respectively. The above results indicated that 15-30% green light replacing red and blue light effectively increased the yield and nutritional quality of lettuce plants.

Constipation and risk of death and cardiovascular events.

BACKGROUND AND AIMS: Constipation is one of the most frequent symptoms encountered in daily clinical practice and is implicated in the development of atherosclerosis, potentially through altered gut microbiota. However, little is known about its association with incident cardiovascular events. METHODS: In a nationally representative cohort of 3,359,653 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 between October 1, 2004 and September 30, 2006 (baseline period), with follow-up through 2013, we examined the association of constipation status (absence or presence; defined using diagnostic codes and laxative use) and laxative use (none, one, or ≥2 types of laxatives) with all-cause mortality, incident coronary heart disease (CHD), and incident ischemic stroke. RESULTS: Among 3,359,653 patients, 237,855 (7.1%) were identified as having constipation. After multivariable adjustments for demographics, prevalent comorbidities, medications, and socioeconomic status, patients with (versus without) constipation had 12% higher all-cause mortality (hazard ratio [HR], 1.12; 95% CI, 1.11-1.13), 11% higher incidence of CHD (HR, 1.11; 95% CI, 1.08-1.14), and 19% higher incidence of ischemic stroke (HR, 1.19; 95% CI, 1.15-1.22). Patients with one and ≥2 (versus none) types of laxatives experienced a similarly higher risk of all-cause mortality (HRs [95% CI], 1.15 [1.13-1.16] and 1.14 [1.12-1.15], respectively), incident CHD (HRs [95% CI], 1.11 [1.07-1.15] and 1.10 [1.05-1.15], respectively) and incident ischemic stroke (HRs [95% CI], 1.19 [1.14-1.23] and 1.21 [1.16-1.26], respectively). CONCLUSIONS: Constipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke.

Association of Chronic Insomnia With Mortality and Adverse Renal Outcomes.

OBJECTIVE: To examine whether chronic insomnia is associated with an increased risk of adverse renal outcomes and all-cause mortality. PATIENTS AND METHODS: We examined associations of chronic insomnia (defined as the presence of both International Classification of Diseases, Ninth Revision codes 307.42, 307.49, and 780.52 and long-term use of insomnia medications) with adverse renal outcomes (end-stage renal disease, incidence of estimated glomerular filtration rate [eGFR] ≤45 mL/min per 1.73 m2, and eGFR slopes <-3.0 mL/min per 1.73 m2 per year) and all-cause mortality in a national cohort of 1,639,090 US veterans by using Cox proportional hazards and logistic regression models with multivariable adjustments. RESULTS: A total of 36,741 patients (2.24%) had chronic insomnia; 32,985 (89.8%) were male and 28,090 (76.5%) were white, with a mean baseline eGFR of 84.1±16.4 mL/min per 1.73 m2. Chronic insomnia was associated with a significantly higher risk of eGFR 45 mL/min per 1.73 m2 or less (multivariable-adjusted hazard ratio [HR], 1.39; 95% CI, 1.34-1.44; P<.001), and rapid loss of kidney function (odds ratio, 1.07; 95% CI, 1.03-1.12; P=.002), but not end-stage renal disease (HR, 1.25; 95% CI, 0.81-1.93; P=.32). Chronic insomnia was not associated with a higher risk of all-cause mortality (HR, 1.00; 95% CI, 0.97-1.03; P=.99). CONCLUSION: Chronic insomnia is associated with a higher risk of development and progression of chronic kidney disease, but not ESRD. Further studies are needed to establish the underlying mechanisms of action and to determine whether treatment of insomnia could be beneficial to prevent deteriorating kidney function.

Involvement of angiotensin-(1-7) in the neuroprotection of captopril against focal cerebral ischemia.

Accumulating evidence suggests that brain angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin II type I receptor axis is activated and thus contributes to the neuronal injury during ischemic stroke. Conversely, inhibition of this axis using centrally active ACE inhibitor captopril was proven neuroprotective in rodents with focal cerebral ischemia. Interestingly, captopril was able to increase angiotensin-(1-7) [Ang-(1-7)] levels in the peripheral organs. As the main component of the alternative renin-angiotensin system axis in the brain, Ang-(1-7) was revealed to protect against focal cerebral ischemia via a MAS1 receptor-dependent manner. Based on this evidence, we hypothesized that Ang-(1-7) might contribute to the neuroprotection of captopril during ischemic stroke. In this study, we evaluated this hypothesis using a rat model of focal cerebral ischemia. We revealed that brain ACE2 activity and Ang-(1-7) levels were significantly elevated following captopril treatment in rats with focal cerebral ischemia. More importantly, we showed that the neuroprotection provided by captopril was partially reversed by A-779, an antagonist for Ang-(1-7) receptor MAS1, indicating that Ang-(1-7) was involved in the neuroprotection of captopril. These findings have uncovered new mechanisms by which captopril protects against focal cerebral ischemia and further suggest that captopril may have practical clinical use for stroke prevention and treatment in addition to its antihypertensive effect.

Changes With Lanthanum Carbonate, Calcium Acetate, and Phosphorus Restriction in CKD: A Randomized Controlled Trial.

INTRODUCTION: Abnormal phosphorus homeostasis develops early in chronic kidney disease (CKD). It is unclear if its correction results in improved clinical outcomes in non-dialysis dependent CKD. METHODS: We conducted a randomized controlled, parallel design clinical trial in 120 patients with estimated glomerular filtration rate 15 to 59 ml/min per 1.73 m2 and abnormal phosphorus homeostasis (serum phosphorus >4.6 mg/dl, parathyroid hormone [PTH] >70 pg/ml or tubular reabsorption of phosphorus [TRP] <80%). Patients were randomized to open-label lanthanum carbonate versus calcium acetate versus dietary intervention over 1 year. The co-primary outcomes were month 12 (vs. baseline) biochemical (serum phosphorus, TRP, PTH, calcium, bone-specific alkaline phosphatase [bALP], and fibroblast growth factor 23 [FGF23]) and vascular parameters (coronary artery calcium score, pulse wave velocity, and endothelial dysfunction) in all patients. Secondary outcomes were between-treatment differences in change for each parameter between month 12 and baseline. All analyses were intention to treat. RESULTS: Baseline characteristics were similar in the 3 groups. A total of 107 patients (89%) completed 12 months of follow-up. Differences were not significant at month 12 (vs. baseline) for any of the outcomes except bALP (median [25th, 75th] percentile at month 12 versus baseline: 13.8 [10.6, 17.6] vs. 15.8 [12.1, 21.1], P < .001) and FGF23 (132 [99, 216] vs. 133 [86, 189], P = .002). Changes for all outcomes were similar in the 3 arms except for PTH, which was suppressed more effectively by calcium acetate (P < .001). CONCLUSION: A 1-year intervention to limit phosphorus absorption using dietary restriction or 2 different phosphorus binders resulted in decreased bALP suggesting improved bone turnover, but no other significant changes in biochemical or vascular parameters in patients with CKD stage 3/4. (ClinicalTrials.gov: NCT01357317).

Prognostic significance of pre-end-stage renal disease serum alkaline phosphatase for post-end-stage renal disease mortality in late-stage chronic kidney disease patients transitioning to dialysis.

Background: Higher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation. Methods: Among 17 732 US veterans who transitioned to dialysis between October 2007 and September 2011, we examined the association of serum ALP levels averaged over the last 6 months of the pre-ESRD transition period ('prelude period') with all-cause, cardiovascular and infection-related mortality following dialysis initiation, using Cox (for all-cause mortality) and competing risk (for cause-specific mortality) regressions adjusted for demographics, comorbidities, medications, estimated glomerular filtration rate and serum albumin levels over the 6-month prelude period, and vascular access type at dialysis initiation. Results: During a median follow-up of 2.0 (interquartile range, 1.1-3.2) years following dialysis initiation, a total of 9196 all-cause deaths occurred. Higher ALP levels were incrementally associated with higher all-cause, cardiovascular and infection-related mortality. Compared with patients in the lowest ALP quartile (<66.0 U/L), those in the highest quartile (≥111.1 U/L) had multivariable-adjusted hazard/subhazard ratios (95% confidence interval) of 1.42 (1.34-1.51), 1.43 (1.09-1.88) and 1.39 (1.09-1.78) for all-cause, cardiovascular and infection-related mortality, respectively. The associations remained consistent in various subgroups and after further adjustment for liver enzymes, serum phosphorus and intact parathyroid hormone levels. Conclusions: Higher pre-ESRD serum ALP levels are independently associated with higher post-ESRD mortality risk. Further studies are warranted to determine if interventions that lower pre-ESRD ALP levels reduce mortality in incident dialysis patients.

[Dynamic Changes of Nitrogen-Transforming and Phosphorus-Accumulating Bacteria Along with the Formation of Cyanobacterial Blooms].

In order to reveal the dynamic changes of nitrogen-transforming and phosphorus-accumulating bacteria in the process of cyanobacterial bloom formation, bacterial community structure and functional genes associated with nitrogen cycling were analyzed using high-throughput sequencing and real-time quantitative PCR (qPCR). The high-throughput sequencing results showed that the diversity of bacterial communities decreased during cyanobacterial blooms, and the lacustrine free-living and bloom-attached bacterial communities varied with increased bloom density. With increasing density of cyanobacteria, the relative abundance of Actinobacteria and Bacteroidetes decreased, whereas that of Firmicutes increased. Moreover, the growth of phosphate-accumulating organisms was increased in the phycosphere of cyanobacterial blooms, while that of nitrifiers was inhibited. Denitrifiers increased significantly under moderate blooms. The qPCR data also revealed that the abundance of nitrification and denitrification genes decreased or disappeared with the development of cyanobacterial blooms, indicating that the nitrogen transformation process might be inhibited, which showed a positive feedback of bacterial community to the development of Microcystis blooms by satisfying the needs of the nutrients budget.

[Characterization of a Newly Isolated Strain Pseudomonas sp. N3 for Denitrification at Low Temperature].

Based on traditional microbiological methods, a novel denitrifier Pseudomonas sp. N3 with excellent denitrification capacity at low temperature was isolated and identified using phenotypic and phylogenetic analysis. Complete nitrate removal was achieved at C/N=8, that is, 70 mg·L-1 nitrate. In addition, the isolate exhibited a great adaptability for low temperature and can reach 100% removal of 15 mg·L-1 nitrate at a temperature as low as 4℃ within 36 h. The denitrification genes of narG and nirS were highly expressed; they were at the same order of magnitude as those at 30℃. Semicontinuous experiments were conducted to test the stability of N3 immobilized with polyvinyl alcohol and sodium alginate at 10℃. The results show that immobilized N3 can remove 15 mg·L-1 nitrate completely within three days and maintains a strong mechanical performance and stability during the whole 54 days. The cold resistance and high denitrification ability of the strain N3 make it applicable to nitrogen wastewater treatment in winter.

Association of the frequency of pre-end-stage renal disease medical care with post-end-stage renal disease mortality and hospitalization.

Background: Previous studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients. Methods: In all, 23 089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52 172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models. Results: When entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3) years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9) mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24 months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15 303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24 months compared with 2-≤4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively. Conclusions: More frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

Pre-End-Stage Renal Disease Hemoglobin Variability Predicts Post-End-Stage Renal Disease Mortality in Patients Transitioning to Dialysis.

BACKGROUND: Hemoglobin variability (Hb-var) has been associated with increased mortality both in non-dialysis dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD) patients. However, the impact of Hb-var in advanced NDD-CKD on outcomes after dialysis initiation remains unknown. METHODS: Among 11,872 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 through September 2011, we assessed Hb-var calculated from the residual SD of at least 3 Hb values during the last 6 months before dialysis initiation (prelude period) using within-subject linear regression models, and stratified into quartiles. Outcomes included post-transition all-cause, cardiovascular, and infection-related mortality, assessed in Cox proportional hazards models and adjusted for demographics, comorbidities, length of hospitalization, medications, estimated glomerular filtration rate (eGFR), type of vascular access, Hb parameters (baseline Hb [i.e., intercept] and change in Hb [i.e., slope]), and number of Hb measurements. RESULTS: Higher prelude Hb-var was associated with use of iron and antiplatelet agents, tunneled dialysis catheter use, higher levels of baseline Hb, change in Hb, eGFR, and serum ferritin. After multivariable adjustment, higher prelude Hb-var was associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality (adjusted hazard ratios [95% CI] for the highest [vs. lowest] quartile of Hb-var, 1.10 [1.02-1.19], 1.28 [0.93-1.75], and 0.93 [0.79-1.10], respectively). CONCLUSIONS: High pre-ESRD Hb-var is associated with higher mortality, particularly from infectious causes rather than cardiovascular causes. Further research is required to clarify the underlying mechanisms and true causal nature of the observed association.

Changes in Albuminuria and Subsequent Risk of Incident Kidney Disease.

BACKGROUND AND OBJECTIVES: Albuminuria is a robust predictor of CKD progression. However, little is known about the associations of changes in albuminuria with the risk of kidney events outside the settings of clinical trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a nationwide cohort of 56,946 United States veterans with an eGFR≥60 ml/min per 1.73 m2, we examined the associations of 1-year fold changes in albuminuria with subsequent incident CKD (>25% decrease in eGFR reaching <60 ml/min per 1.73 m2) and rapid eGFR decline (eGFR slope <-5 ml/min per 1.73 m2 per year) assessed using Cox models and logistic regression, respectively, with adjustment for confounders. RESULTS: The mean age was 64 (SD, 10) years old; 97% were men, and 91% were diabetic. There was a nearly linear association between 1-year fold changes in albuminuria and incident CKD. The multivariable-adjusted hazard ratios (95% confidence intervals) of incident CKD associated with more than twofold decrease, 1.25- to twofold decrease, 1.25- to twofold increase, and more than twofold increase (versus <1.25-fold decrease to <1.25-fold increase) in albuminuria were 0.82 (95% confidence interval, 0.77 to 0.89), 0.93 (95% confidence interval, 0.86 to 1.00), 1.12 (95% confidence interval, 1.05 to 1.20), and 1.29 (95% confidence interval, 1.21 to 1.38), respectively. Qualitatively similar associations were present for rapid eGFR decline (adjusted odds ratios; 95% confidence intervals for corresponding albuminuria changes: adjusted odds ratio, 0.86; 95% confidence interval, 0.78 to 0.94; adjusted odds ratio, 0.98; 95% confidence interval, 0.89 to 1.07; adjusted odds ratio, 1.18; 95% confidence interval, 1.08 to 1.29; and adjusted odds ratio, 1.67; 95% confidence interval, 1.54 and 1.81, respectively). CONCLUSIONS: Relative changes in albuminuria over a 1-year interval were linearly associated with subsequent risk of kidney outcomes. Additional studies are warranted to elucidate the underlying mechanisms of the observed associations and test whether active interventions to lower elevated albuminuria can improve kidney outcomes.

Pre-ESRD Depression and Post-ESRD Mortality in Patients with Advanced CKD Transitioning to Dialysis.

BACKGROUND AND OBJECTIVES: Depression in patients with nondialysis-dependent CKD is often undiagnosed, empirically overlooked, and associated with higher risk of death, progression to ESRD, and hospitalization. However, there is a paucity of evidence on the association between the presence of depression in patients with advanced nondialysis-dependent CKD and post-ESRD mortality, particularly among those in the transition period from late-stage nondialysis-dependent CKD to maintenance dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From a nation-wide cohort of 45,076 United States veterans who transitioned to ESRD over 4 contemporary years (November of 2007 to September of 2011), we identified 10,454 (23%) patients with a depression diagnosis during the predialysis period. We examined the association of pre-ESRD depression with all-cause mortality after transition to dialysis using Cox proportional hazards models adjusted for sociodemographics, comorbidities, and medications. RESULTS: Patients were 72±11 years old (mean±SD) and included 95% men, 66% patients with diabetes, and 23% blacks. The crude mortality rate was similar in patients with depression (289/1000 patient-years; 95% confidence interval, 282 to 297) versus patients without depression (286/1000 patient-years; 95% confidence interval, 282 to 290). Compared with patients without depression, patients with depression had a 6% higher all-cause mortality risk in the adjusted model (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.09). Similar results were found across all selected subgroups as well as in sensitivity analyses using alternate definitions of depression. CONCLUSION: Pre-ESRD depression has a weak association with post-ESRD mortality in veterans transitioning to dialysis.

Effect of Age on the Association of Vascular Access Type with Mortality in a Cohort of Incident End-Stage Renal Disease Patients.

BACKGROUND/AIMS: All hemodialysis (HD) patients are generally recommended to create a fistula first; but to create a mature arteriovenous fistula (AVF) can be challenging in elderly individuals. It is unclear if elderly incident HD patients derive a survival benefit from an AVF over an arteriovenous graft (AVG) or a tunneled central venous catheter (TDC). METHODS: We examined the association of vascular access type (AVF, AVG, and TDC with and without a maturing AVF/AVG at dialysis transition) at HD initiation with all-cause, cardiovascular (CV), and infection-related mortality in 46,786 US veterans using Cox models with adjustment for confounders. Effect modification by age was examined by examining associations in pre-specified age subgroups (<60, 60-<70, 70-<80, and ≥80 years old), and by including interaction terms. RESULTS: Patients numbering 8,940 (19%) started HD with an AVF, 1,090 (3%) with an AVG, 8,262 (18%) with a TDC and a maturing AVF/AVG and 28,494 (61%) with a TDC without a maturing AVF/AVG. A total of 13,303 all-cause, 4,392 CV, and 1,058 infection-related deaths were observed in the first year after HD transition. Compared to patients with AVF, those with AVG and TDC with and without maturing AVF/AVG had incrementally higher overall risk of all-cause mortality and CV mortality. Only TDC use was associated with higher infection-associated mortality. These associations were not modified by age. CONCLUSION: Although most of our patients consisted of male veterans and the results may not be generalized to the general population, the use of TDCs is associated with poor outcomes even in the most elderly incident HD patients.

Pre-ESRD Dementia and Post-ESRD Mortality in a Large Cohort of Incident Dialysis Patients.

BACKGROUND: Conservative management may be a desirable option for elderly, fragile, or demented patients who reach end-stage renal disease (ESRD), yet some patients with dementia are placed on renal replacement therapy nonetheless. METHODS: From a nationwide cohort of 45,076 US veterans who transitioned to ESRD over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified 1,336 (3.0%) patients with International Classification of Diseases, Ninth Revision, Clinical Modification code-based dementia diagnosis during the prelude (predialysis) period. We examined the association of prelude dementia with all-cause mortality within the first 6 months following transition to dialysis, using a propensity-matched cohort and Cox proportional hazards models. RESULTS: In the entire cohort, the overall mean ± standard deviation age at baseline was 72 ± 11 years, 95% were male, 23% were African-American, and 66% were diabetic. There were 8,080 (18.5%) deaths (mortality rate, 412; 95% confidence interval [CI], 403-421/1,000 patient-years) in the dementia-negative group, and 396 (29.6%) deaths (mortality rate, 708; 95% CI, 642-782/1,000 patient-years) in the dementia-positive group in the entire cohort in the first 6 months after dialysis initiation. Presence of dementia was associated with higher risk of all-cause mortality (adjusted hazard ratio, 1.25; 95% CI, 1.12-1.38) compared to dementia-free patients in the first 6 months after dialysis initiation. CONCLUSION: Pre-ESRD dementia is associated with increased risk of early post-ESRD mortality in veterans transitioning to dialysis.

Early Mortality Associated with Inpatient versus Outpatient Hemodialysis Initiation in a Large Cohort of US Veterans with Incident End-Stage Renal Disease.

BACKGROUND: Mortality in the immediate post-hemodialysis transition period is extremely high. Many end-stage renal disease (ESRD) patients in the US start dialysis in an inpatient setting, but the characteristics of patients starting dialysis as inpatients, and the association of inpatient hemodialysis transition with mortality remain unclear. METHODS: We examined 48,261 US veterans who transitioned to hemodialysis between October 2007 and September 2011. Associations of inpatient hemodialysis starting with all-cause mortality were examined in Cox proportional hazard models, with adjustments for demographics, comorbidities, vascular access type, pre-dialysis nephrology care and medication use, and last pre-ESRD estimated glomerular filtration rate and hemoglobin. RESULTS: A total of 22,338 (46.3%) patients received the first hemodialysis treatment in an inpatient setting. Inpatient hemodialysis transition was associated with older age, presence of a tunneled catheter, higher comorbidity burden, and lack of pre-dialysis nephrology care. A total of 8,674 patients died (mortality rate 405/1,000 patient-years, 95% CI 397-413) during the first 6 months after transition to hemodialysis. The starting of inpatient vs. outpatient hemodialysis was associated with significantly higher crude all-cause mortality, but this association was attenuated after multivariable adjustments. CONCLUSIONS: Transition to hemodialysis in an inpatient setting is more common in older and sicker individuals, and in patients without pre-dialysis nephrology care and those who used a catheter for vascular access. Future studies are needed to determine if a higher proportion of patients could start hemodialysis treatment in outpatient clinics, through interventions targeting modifiable risk factors such as timely vascular access placement or earlier nephrology referrals.

Pre-end-stage renal disease visit-to-visit systolic blood pressure variability and post-end-stage renal disease mortality in incident dialysis patients.

OBJECTIVES: Higher SBP visit-to-visit variability (SBPV) has been associated with increased risk of adverse events in patients with chronic kidney disease, but the association of SBPV in advanced nondialysis-dependent chronic kidney disease with mortality after the transition to end-stage renal disease (ESRD) remains unknown. METHODS: Among 17 729 US veterans transitioning to dialysis between October 2007 and September 2011, we assessed SBPV calculated from the SD of at least three intraindividual outpatient SBP values during the last year prior to dialysis transition (prelude period). Outcomes included factors associated with higher prelude SBPV and post-transition all-cause, cardiovascular, and infection-related mortality, assessed using multivariable linear regression and Cox and competing risk regressions, respectively, adjusted for demographics, comorbidities, medications, cardiovascular medication adherence, SBP, BMI, estimated glomerular filtration rate, and type of vascular access. RESULTS: Modifiable clinical factors associated with higher prelude SBPV included higher SBP, use of antihypertensive medications and erythropoiesis-stimulating agents, inadequate cardiovascular medication adherence, and catheter use. After multivariable adjustment, higher prelude SBPV was significantly associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality [hazard/subhazard ratios (95% confidence interval) for the highest (vs. lowest) quartile of SBPV, 1.08 (1.01-1.16), 1.02 (0.89-1.15), and 1.41 (1.10-1.80) for all-cause, cardiovascular, and infection-related mortality, respectively]. CONCLUSION: High pre-ESRD SBPV is potentially modifiable and associated with higher all-cause and infection-related mortality following dialysis initiation. Further studies are needed to test whether modification of pre-ESRD SBPV can improve clinical outcomes in incident ESRD patients. VIDEO ABSTRACT:.

Blood Pressure Before Initiation of Maintenance Dialysis and Subsequent Mortality.

BACKGROUND: Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after dialysis therapy initiation remains unknown. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years. PREDICTOR: Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (<120 to ≥160mmHg in 10-mmHg increments) and 5 (<60 to ≥90mmHg in 10-mmHg increments) categories, respectively, and as continuous measures. OUTCOMES & MEASUREMENTS: Postdialysis all-cause mortality, assessed over different follow-up periods (ie, <3, 3-<6, 6-<12, and ≥12 months after dialysis therapy initiation) using Cox regressions adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access. RESULTS: Mean predialysis SBP and DBP were 141.2±16.1 (SD) and 73.7±10.6mmHg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP<140mmHg. Mortality risks associated with lower SBP were greatest in the first 3 months after dialysis therapy initiation, with multivariable-adjusted HRs of 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), 1.35 (95% CI, 1.13-1.62), 0.98 (95% CI, 0.78-1.22), and 0.76 (95% CI, 0.57-1.00) for SBP <120, 120 to <130, 130 to <140, 150 to <160, and ≥160 (vs 140-<150) mmHg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality. LIMITATIONS: Results cannot be inferred to show causality and may not be generalizable to women or the general US population. CONCLUSIONS: Lower predialysis SBP is associated with higher all-cause mortality in the immediate postdialysis period. Predialysis DBP showed no consistent association with postdialysis mortality. Further studies are needed to clarify ideal predialysis SBP levels among incident dialysis patients as a potential means to improve the excessively high early dialysis mortality.

Constipation and Incident CKD.

Constipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m2, we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope <-10, -10 to <-5, and -5 to <-1 versus -1 to <0 ml/min per 1.73 m2 per year, 1.17; 95% CI, 1.14 to 1.20; 1.07; 95% CI, 1.04 to 1.09; and 1.01; 95% CI, 1.00 to 1.03, respectively). More severe constipation associated with an incrementally higher risk for each renal outcome. In conclusion, constipation status and severity associate with higher risk of incident CKD and ESRD and with progressive eGFR decline, independent of known risk factors. Further studies should elucidate the underlying mechanisms.

Association between vascular access creation and deceleration of estimated glomerular filtration rate decline in late-stage chronic kidney disease patients transitioning to end-stage renal disease.

BACKGROUND: Prior studies have suggested that arteriovenous fistula (AVF) or graft (AVG) creation may be associated with slowing of estimated glomerular filtration rate (eGFR) decline. It is unclear if this is attributable to the physiological benefits of a mature access on systemic circulation versus confounding factors. METHODS: We examined a nationwide cohort of 3026 US veterans with advanced chronic kidney disease (CKD) transitioning to dialysis between 2007 and 2011 who had a pre-dialysis AVF/AVG and had at least three outpatient eGFR measurements both before and after AVF/AVG creation. Slopes of eGFR were estimated using mixed-effects models adjusted for fixed and time-dependent confounders, and compared separately for the pre- and post-AVF/AVG period overall and in patients stratified by AVF/AVG maturation. In all, 3514 patients without AVF/AVG who started dialysis with a catheter served as comparators, using an arbitrary 6-month index date before dialysis initiation to assess change in eGFR slopes. RESULTS: Of the 3026 patients with AVF/AVG (mean age 67 years, 98% male, 75% diabetic), 71% had a mature AVF/AVG at dialysis initiation. eGFR decline accelerated in the last 6 months prior to dialysis in patients with a catheter (median, from -6.0 to -16.3 mL/min/1.73 m2/year, P < 0.001), while a significant deceleration of eGFR decline was seen after vascular access creation in those with AVF/AVG (median, from -5.6 to -4.1 mL/min/1.73 m2/year, P < 0.001). Findings were independent of AVF/AVG maturation status and were robust in adjusted models. CONCLUSIONS: The creation of pre-dialysis AVF/AVG appears to be associated with eGFR slope deceleration and, consequently, may delay the onset of dialysis initiation in advanced CKD patients.