Relative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar.
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ABSTRACT:
SUBMITTER: Wen CP
PROVIDER: S-EPMC4048178 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease.To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease.A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008.All-cause mortality and end-stage renal disease.At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2).Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.
| S-EPMC3124770 | biostudies-other
Project description:Hypokalemia and hyperkalemia are often noted in chronic kidney disease (CKD) patients, but their impact on mortality and end-stage renal disease (ESRD) is less well understood. We aimed at studying the associations between potassium disorders, and mortality and progression to ESRD in a CKD population.Using our electronic health record-based CKD registry, 36,359 patients with eGFR <60 ml/min/1.73 m(2) and potassium levels measured from January 1, 2005 to September 15, 2009 were identified. We examined factors associated with hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) using logistic regression models and associations between serum potassium levels (both as continuous and categorical variables) and all-cause mortality or ESRD using Cox-proportional hazards models.Serum potassium <3.5 mmol/l was noted among 3% and >5.0 mmol/l among 11% of the study population. In the multivariable logistic regression analysis, lower eGFR, diabetes and use of ACE inhibitors or Angiotensin-Receptor Blockers were associated with higher odds of having hyperkalemia. Heart failure and African American race were factors associated with higher odds of hypokalemia. After adjustment for covariates including kidney function, serum potassium <4.0 and >5.0 mmol/l were significantly associated with increased mortality risk, but there was no increased risk for progression to ESRD. Time-dependent repeated measures analysis confirmed these findings. When potassium was examined as a continuous variable, there was a U-shaped association between serum potassium levels and mortality.In patients with stage 3-4 CKD, serum potassium levels <4.0 and >5.0 mmol/l are associated with higher mortality but not with ESRD.
| S-EPMC4686260 | biostudies-literature
Project description:ContextChronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial.ObjectiveTo evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks.Design, setting, and participantsIndividual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years).Main outcome measuresHazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates.ResultsMortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories.ConclusionsBoth low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.
| S-EPMC3936348 | biostudies-literature
Project description: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.
| S-EPMC5837395 | biostudies-literature
Project description: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.
| S-EPMC5707124 | biostudies-literature
Project description:IntroductionHyperuricemia and diabetes mellitus (DM) are associated with increased mortality risk in patients with chronic kidney disease (CKD). Here we aimed to evaluate the independent and joint risks of these two conditions on mortality and end stage kidney disease (ESKD) in CKD-patients.MethodsThis retrospective cohort study enrolled 4380 outpatients (with CKD stage 3-5) with mortality and ESKD linkage during a 7-year period (from 2007 to 2013). All-causes mortality and ESKD risks were analyzed by multivariable-adjusted Cox proportional hazards models (adjusted for age, sex, smoke, previous coronary arterial disease, blood pressure, and medications for hyperlipidemia, hyperuricemia and renin-angiotensin system inhibitors).ResultsOverall, 40.5% of participants had DM and 66.4% had hyperuricemia. In total, 356 deaths and 932 ESKD events occurred during the 7 years follow-up. With the multivariate analysis, increased risks for all-cause mortality were: hyperuricemia alone, HR = 1.48 (1-2.19); DM alone, and HR = 1.52 (1.02-2.46); DM and hyperuricemia together, HR = 2.12 (1.41-3.19). Similar risks for ESKD were: hyperuricemia alone, HR = 1.34 (1.03-1.73); DM alone, HR = 1.59 (1.15-2.2); DM and hyperuricemia together, HR = 2.46 (1.87-3.22).ConclusionsDM and hyperuricemia are strongly associated with higher all-cause mortality and ESKD risk in patients with CKD stage 3-5. Hyperuricemia is similar to DM in terms of risk for all-cause mortality and ESKD. DM and hyperuricemia when occurred together further increase both risks of all-cause mortality and ESKD.
| S-EPMC9034537 | biostudies-literature
Project description:BackgroundAnemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.Methods249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003-2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models.ResultsPatients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05).ConclusionsWe found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define "high risk" populations in CKD.
| S-EPMC4404250 | biostudies-literature
Project description:BackgroundPrevious 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.MethodsIn 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.ResultsWhen 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.ConclusionsMore 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.
| S-EPMC6065479 | biostudies-literature
Project description:Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, high-risk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation.To compare the risk of ESRD in kidney donors with that of a healthy cohort of nondonors who are at equally low risk of renal disease and free of contraindications to live donation and to stratify these comparisons by patient demographics.A cohort of 96,217 kidney donors in the United States between April 1994 and November 2011 and a cohort of 20,024 participants of the Third National Health and Nutrition Examination Survey (NHANES III) were linked to Centers for Medicare & Medicaid Services data to ascertain development of ESRD, which was defined as the initiation of maintenance dialysis, placement on the waiting list, or receipt of a living or deceased donor kidney transplant, whichever was identified first. Maximum follow-up was 15.0 years; median follow-up was 7.6 years (interquartile range [IQR], 3.9-11.5 years) for kidney donors and 15.0 years (IQR, 13.7-15.0 years) for matched healthy nondonors.Cumulative incidence and lifetime risk of ESRD.Among live donors, with median follow-up of 7.6 years (maximum, 15.0), ESRD developed in 99 individuals in a mean (SD) of 8.6 (3.6) years after donation. Among matched healthy nondonors, with median follow-up of 15.0 years (maximum, 15.0), ESRD developed in 36 nondonors in 10.7 (3.2) years, drawn from 17 ESRD events in the unmatched healthy nondonor pool of 9364. Estimated risk of ESRD at 15 years after donation was 30.8 per 10,000 (95% CI, 24.3-38.5) in kidney donors and 3.9 per 10,000 (95% CI, 0.8-8.9) in their matched healthy nondonor counterparts (P?<?.001). This difference was observed in both black and white individuals, with an estimated risk of 74.7 per 10,000 black donors (95% CI, 47.8-105.8) vs 23.9 per 10,000 black nondonors (95% CI, 1.6-62.4; P?<?.001) and an estimated risk of 22.7 per 10,000 white donors (95% CI, 15.6-30.1) vs 0.0 white nondonors (P?<?.001). Estimated lifetime risk of ESRD was 90 per 10,000 donors, 326 per 10,000 unscreened nondonors (general population), and 14 per 10,000 healthy nondonors.Compared with matched healthy nondonors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small. These findings may help inform discussions with persons considering live kidney donation.
| S-EPMC4411956 | biostudies-literature
Project description:Controversy exists regarding the benefits and risks of warfarin therapy in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In this study, we assessed mortality and cardiovascular outcomes associated with warfarin treatment in patients with stages 3-5 CKD and ESRD admitted to the University of California-Irvine Medical Center.In a retrospective matched cohort study, we identified 59 adult patients with stages 3-6 CKD initiated on warfarin during the period 2011-2013, and 144 patients with stages 3-6 CKD who had indications for anticoagulation therapy but were not initiated on warfarin. All-cause mortality risk associated with warfarin treatment was estimated using Cox proportional hazard regression analysis, and the risk of significant bleeding and major adverse cardiovascular events were analyzed with Poisson regression analysis. Adjustment models were used to account for age, gender, diabetes mellitus, use of antiplatelet agents, and preexisting cardiovascular disease, and stratified by pre-dialysis CKD stages 3-5 vs. ESRD.During 5.8 years of follow-up, unadjusted mortality risk was higher in CKD patients on warfarin therapy (hazard ratio [HR] 2.34 with 95% CI 1.25-4.39; p < 0.01). After multivariate adjustment and stratification by CKD stage, the mortality risk remained significant in ESRD patients receiving warfarin (HR 6.62 with 95% CI 2.56-17.16; p < 0.001). Furthermore, adjusted rates of significant bleeding (incident rate ratio, IRR 3.57 with 95% CI 1.51-8.45; p < 0.01) and myocardial infarction (IRR 4.20 with 95% CI 1.78-9.91; p < 0.01) were higher among warfarin users. No differences in rates of ischemic or hemorrhagic strokes were found between the 2 groups.Warfarin use was associated with several-fold higher risk of death, bleeding, and myocardial infarction in dialysis patients. If additional studies suggest similar associations, the use of warfarin in dialysis patients warrants immediate reconsideration.
| S-EPMC5657430 | biostudies-literature