Objectives Gastrointestinal symptoms can significantly impact patients' nutritional status. Effective management using antiemetics is crucial for maintaining adequate nutrition. However, the effect of antiemetics on long-term renal function remains unclear. This study aimed to examine the association of antiemetics with the incident chronic kidney disease (CKD) in patients with normal renal function. Methods In a historical cohort study involving 323,970 US Veterans with normal estimated glomerular filtration rate, we identified 13,154 Veterans initiating antiemetics. The Cox proportional hazards model adjusted for demographics, major comorbidities, and laboratory measurements was used to estimate the relationship between antiemetics and the incident CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 on two occasions, separated by ≥ 90 days. Propensity score (PS) matching and PS overlap weighting were also performed. Results The mean age of nonusers and users of antiemetics was 64.1 ± 14.2 and 62.1 ± 12.9 years. Antiemetic users were more likely to be female, smokers, and had a higher prevalence of comorbidities. Antiemetic use was associated with an increased risk of incident CKD across various models: unmatched adjusted (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.22-1.31), PS matched (HR 1.22; 95% CI 1.17-1.28), and PS overlap weighting (HR 1.28; 95% CI 1.18-1.46). Conclusions Antiemetic use is associated with a higher risk of incident CKD in individuals without preexisting kidney disease. This association appears robust across different analytical models. While antiemetics are essential for managing gastrointestinal symptoms—potentially improving nutritional status—the results underscore the necessity for careful monitoring of renal function in patients prescribed antiemetics.

BackgroundChronic 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.MethodsWe 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).ResultsIn 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).ConclusionChronic low-dose ASA use was associated with faster kidney function deterioration, and no association was observed with mortality or risk of ESKD.

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.

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 m(2) 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.

BackgroundHigher 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.MethodsAmong 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.ResultsDuring 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.ConclusionsHigher 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.

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 m(2) 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)

Background/Aims—Fistula first is the general recommendation for all hemodialysis (HD) patients, but creating 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 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 hemodialysis initiation with all-cause, cardiovascular 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—8,940 (19%) patients 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 cardiovascular, and 1,058 infection-related deaths were observed in the first year after hemodialysis transition. Compared to patients with AVF, those with AVG and TDC with and without maturing AVF/AVG had incrementally higher overall risk of allcause mortality and cardiovascular mortality. Only TDC use was associated with higher infectionassociated mortality. These associations were not modified by age. Address for correspondence: Csaba P. Kovesdy, MD, Nephrology Section, Memphis VA Medical Center, 1030 Jefferson Ave., Memphis, TN 38104, Phone: 901-523-8990, Fax: 901-577-7539, ckovesdy@uthsc.edu. DISCLOSURES None. HHS Public Access Author manuscript Nephron. Author manuscript; available in PMC 2018 May 18. Published in final edited form as: Nephron. 2017 ; 137(1): 57–63. doi:10.1159/000477271. A uhor M anscript

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.

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.

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.

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.

Objectives—Higher systolic blood pressure (SBP) visit-to-visit variability (SBPV) has been associated with increased risk of adverse events in patients with chronic kidney disease (CKD), but the association of SBPV in advanced non-dialysis dependent CKD (NDD-CKD) with mortality after the transition to end-stage renal disease (ESRD) remains unknown. Methods—Among 17,729 US veterans transitioning to dialysis between 10/2007–9/2011, we assessed SBPV calculated from the standard deviation of at least three intra-individual 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, body mass index, 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 Address for correspondence: Csaba P. Kovesdy, MD, Nephrology Section, Memphis VA Medical Center, 1030 Jefferson Ave., Memphis, TN 38104, Phone: 901-523-8990, Fax: 901-577-7539, ckovesdy@uthsc.edu. Disclosures: None of the authors have relevant conflicts of interest. HHS Public Access Author manuscript J Hypertens. Author manuscript; available in PMC 2018 September 01. Published in final edited form as: J Hypertens. 2017 September ; 35(9): 1816–1824. doi:10.1097/HJH.0000000000001376. A uhor M anscript