Hemoglobin A1c levels less than 7.0% and systolic blood pressure (SBP) less than 140 mmHg are each associated with lower risk of vascular complications in patients with diabetes mellitus. ...Associations between combined A1c level and SBP categories and risk of mortality and morbidity in diabetic patients are not well characterized.
We examined 891 670 US diabetic veterans with baseline estimated glomerular filtration rates more than 60 ml/min per 1.73 m (mean age 67 ± 11 years, 97% men, 17% African-Americans). The associations of mutually exclusive combined categories of A1c (<6.5, 6.5-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, and ≥10%) and SBP (<100, 100-119, 120-139, 140-159, 160-179, and ≥180 mmHg) with the risk of all-cause mortality and incident chronic kidney disease (CKD), coronary heart disease, and stroke were examined in Cox models adjusted for baseline characteristics using patients with concomitant A1c 6.5-6.9% and SBP of 120-139 mmHg as the referent group.
A total of 221 529 (25%) patients died, and 178 588 (20%), 43 373 (5%) and 36 935 (4%) developed CKD, coronary heart disease and stroke, respectively, during a median follow-up of 7.4 years. SBP displayed a J-shaped association with each outcome except CKD risk that was linearly associated with SBP across all A1c categories. A1c above 7.0% was associated with monotonically worse outcomes for all end points in all SBP categories. Patients with the combined highest A1c and SBP levels experienced the worst outcomes.
SBP greater than 120-139 mmHg and A1c greater than 7.0% are associated with higher mortality and vascular complications in diabetic patients, independent of each other. Combined efforts to improve both glycemic and blood pressure control may synergistically improve outcomes in patients with normal kidney function.
The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who ...transitioned to dialysis.
The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown.
In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA−related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event−related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities.
The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event−related hospitalizations.
In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.
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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).
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.
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.
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.
De novo statin therapy in patients receiving chronic dialysis has failed to demonstrate cardiovascular (CV) protection in randomized clinical trials and thus is not recommended by current guidelines. ...However, current guidelines recommend the continuation of statin therapy if initiated before transition to dialysis.
To investigate whether the continuation of statins from advanced chronic kidney disease into the dialysis therapy period is associated with improved survival.
Retrospective cohort study of US veterans transitioning to dialysis between October 1, 2007, and March 30, 2014. Participants were 14 298 US veterans who were receiving statins during the 12-month period before transition to dialysis and survived the first year of dialysis. Data analysis was conducted between August 2, 2017, and June 28, 2018.
Patients were characterized as statin continuers (n = 11 936) if statin therapy was continued for at least 6 months during the first year after dialysis initiation and as statin discontinuers (n = 2362) if therapy with statins was stopped or no statin therapy was received in the year posttransition.
Associations of statin continuation with 12-month all-cause mortality and CV mortality after 1 year of dialysis initiation were examined using Cox proportional hazards regression models adjusted for demographics and comorbidities.
The mean (SD) age of the cohort was 71 (10) years; the cohort was 96.7% (n = 13 828) male and 21.3% (n = 3043) African American, and 74.6% (n = 10 627) had diabetes. The 12-month all-cause mortality and CV mortality rates after 1 year of transition to dialysis were lower in statin continuers: deaths per 100 person-years were 21.9 (95% CI, 20.9-22.8) and 8.1 (95% CI, 7.5-8.6) in statin continuers vs 30.3 (95% CI, 27.8-32.8) and 9.8 (95% CI, 8.3-11.2) in statin discontinuers. Moreover, lower all-cause mortality and CV mortality risks with statin continuation persisted in adjusted analyses, with hazard ratios of 0.72 (95% CI, 0.66-0.79) and 0.82 (95% CI, 0.69-0.96), respectively. Associations were similar across subgroups, including age, race, and diabetes status.
In this study, the continuation of statin therapy after transition to dialysis was associated with reduced all-cause mortality and CV mortality. The study findings suggest that future studies are needed to examine potential CV benefits of continuing statin therapy after dialysis initiation.
Abrupt declines in kidney function often occur in patients with advanced chronic kidney disease and may exacerbate the need to initiate dialysis treatment. It is unclear how frequently such events ...occur in patients transitioning to chronic dialysis therapy, and what outcomes they are associated with.
We examined a national cohort of 23,349 US veterans with incident end-stage renal disease (ESRD) and with available pre-ESRD estimated glomerular filtration rate (eGFR) to identify abrupt declines in kidney function, defined as an unexpected >50% decrease in eGFR at the time of chronic dialysis transition. Associations with all-cause mortality and with renal recovery were examined in Cox proportional hazard and competing risk regression models.
A total of 4804 (21%) patients experienced an abrupt decline in kidney function at dialysis transition. Renal recovery occurred in 586 (12.2%) and 297 (1.6%) patients with and without an abrupt decline, respectively (adjusted subhazard ratio: 4.42; 95% confidence interval CI: 3.72–5.27; P < 0.001). In the first 6 months after dialysis transition 1178 patients (24.5%) with abrupt decline died (annualized mortality rate 574/1000 patient-years), compared with 2354 deaths (12.7%) in patients without abrupt decline (274 deaths/1000 patient-years). An abrupt decline was associated with 45% higher mortality after multivariable adjustments (hazard ratio: 1.45; 95% CI: 1.33–1.57).
Abrupt declines in kidney function are common in patients transitioning to chronic dialysis, and are associated with higher mortality. Patients with abrupt declines also experience a higher rate of renal recovery; hence, careful attention to residual kidney function is warranted in these patients.
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.
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.
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.
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.
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.
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.
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.
Pre-ESRD dementia is associated with increased risk of early post-ESRD mortality in veterans transitioning to dialysis.
An achiral Non-Symmetric Bent Liquid Crystal (BLC) with a Oxadiazole based hetero cyclic central moiety, abbreviated as C12C10 viz., ...dodecyl4-{5-(4′-decyloxy)biphenyl-4-yl}-1,2,4-oxadiazol-3-ylbenzoate, exhibiting FerroElectric (FE) response is reported. Product is confirmed by 1H NMR, 13C NMR and elemental analysis. Characterization of BLC phases is carried out by Polarized Optical Microscopy (POM), Differential Scanning Calorimetry (DSC), Spontaneous Polarization (PS) and Low Frequency (10Hz–10MHz) Dielectric Relaxation studies. C12C10 exhibits enantiotropic LC SmA, FE B2, SmG, SmE phase variance. I–SmA, B2–SmG and SmG–SmE transitions are of first order nature. FE B2 phases exhibits a moderate PS of ~80nCcm−2. B2 phase exhibits Curie–Weiss behavior to confirm FE nature. Off-centered low frequency (KHz) dispersion infers a scissor mode and a high frequency (MHz) mode to reflect the distinct time-scale response. Dielectric Dispersion is relatively susceptible in lower frequency KHz region. Arrhenius shift in Relaxation Frequency (fR) infers higher activation energy (Ea) in non-FE phases for HF mode and lower value for KHz mode. Trends of fR, dielectric strength Δε, α-parameter and Ea are discussed in view of the data reported in other LC compounds.
The current social and legal landscape is likely to foster the medicinal and recreational use of cannabis. Synthetic cannabinoid use is associated with acute kidney injury (AKI) in case reports; ...however, the association between natural cannabis use and AKI risk in patients with advanced chronic kidney disease (CKD) is unknown.
From a nationally representative cohort of 102,477 U.S. veterans transitioning to dialysis between 2007 and 2015, we identified 2215 patients with advanced CKD who had undergone urine toxicology (UTOX) tests within a year before dialysis initiation and had inpatient serial serum creatinine levels measured within 7 days after their UTOX test. The exposure of interest was cannabis use compared with no use as ascertained by the UTOX test. We examined the association of this exposure with AKI using logistic regression and inverse probability of treatment weighting with extensive adjustment for potential confounders.
The mean age of the overall cohort was 61 years; 97% were males, 51% were African Americans, 97% had hypertension, 76% had hyperlipidemia, and 75% were diabetic. AKI occurred in 56% of the cohort, and in multivariable-adjusted analysis, cannabis use (when compared with no substance use) was not associated with significantly higher odds of AKI (odds ratio 0.85, 95% confidence interval 0.38-1.87;
=0.7). These results were robust to various sensitivity analyses.
In this observational study examining patients with advanced CKD, cannabis use was not associated with AKI risk. Additional studies are needed to characterize the impact of cannabis use on risk of kidney disease and injury.
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