Mortality caused by sepsis in patients with end-stage renal disease compared with the general population

Mortality caused by sepsis in patients with end-stage renal disease compared with the general population.BackgroundIn the United States, infection is second to cardiovascular disease as the leading cause of death in patients with end-stage renal disease (ESRD), and septicemia accounts for more than 75% of this category. This increased susceptibility to infections is partly due to uremia, old age, and comorbid conditions. Although it is intuitive to believe that mortality caused by sepsis may be higher in patients with ESRD compared with the general population (GP), no such data are currently available.MethodsWe compared annual mortality rates caused by sepsis in patients with ESRD (U.S. Health Care Financing Administration 2746 death notification form) with those in the GP (death certificate). Data were abstracted from the U.S. Renal Data System (1994 through 1996 Special Data request) and the National Center for Health Statistics. Data were stratified by age, gender, race, and diabetes mellitus (DM). Sensitivity analyses were performed to account for potential limitations of the data sources.ResultsOverall, the annual percentage mortality secondary to sepsis was approximately 100- to 300-fold higher in dialysis patients and 20-fold higher in renal transplant recipients (RTRs) compared with the GP. Mortality caused by sepsis was higher among diabetic patients across all populations. After stratification for age, differences between groups decreased but retained their magnitude. These findings remained robust despite a wide range of sensitivity analyses. Indeed, mortality secondary to sepsis remained approximately 50-fold higher in dialysis patients compared with the GP, using multiple cause-of-death analyses; was approximately 50-fold higher in diabetic patients with ESRD compared with diabetic patients in the GP, when accounting for underreporting of DM on death certificates in the GP; and was approximately 30-fold higher in RTRs compared with the GP, when accounting for the incomplete ascertainment of cause of death among RTRs. Furthermore, despite assignment of primary cause-of-death to major organ infections in the GP, annual mortality secondary to sepsis remained 30- to 45-fold higher in the dialysis population.ConclusionsPatients with ESRD treated by dialysis have higher annual mortality rates caused by sepsis compared with the GP, even after stratification for age, race, and DM. Consequently, this patient population should be considered at high-risk for the development of lethal sepsis

Effect of Blood Pressure Control on Long-Term Risk of End-Stage Renal Disease and Death Among Subgroups of Patients With Chronic Kidney Disease.

Background Our objective was to explore the effect of intensive blood pressure (BP) control on kidney and death outcomes among subgroups of patients with chronic kidney disease divided by baseline proteinuria, glomerular filtration rate, age, and body mass index. Methods and Results We included 840 MDRD (Modification of Diet in Renal Disease) trial and 1067 AASK (African American Study of Kidney Disease and Hypertension) participants. We used Cox models to examine whether the association between intensive BP control and risk of end-stage renal disease (ESRD) or death is modified by baseline proteinuria (≥0.44 versus <0.44 g/g), glomerular filtration rate (≥30 versus <30 mL/min per 1.73 m2), age (≥40 versus <40 years), or body mass index (≥30 versus <30 kg/m2). The median follow-up was 14.9 years. Strict (versus usual) BP control was protective against ESRD (hazard ratio [HR]ESRD, 0.77; 95% CI, 0.64-0.92) among those with proteinuria ≥0.44 g/g but not proteinuria <0.44 g/g. Strict (versus usual) BP control was protective against death (HRdeath, 0.73; 95% CI, 0.59-0.92) among those with glomerular filtration rate <30 mL/min per 1.73 m2 but not glomerular filtration rate ≥30 mL/min per 1.73 m2 (HRdeath, 0.98; 95% CI, 0.84-1.15). Strict (versus usual) BP control was protective against ESRD among those ≥40 years (HRESRD, 0.82; 95% CI, 0.71-0.94) but not <40 years. Strict (versus usual) BP control was also protective against ESRD among those with body mass index ≥30 kg/m2 (HRESRD, 0.75; 95% CI, 0.61-0.92) but not body mass index <30 kg/m2. Conclusions The ESRD and all-cause mortality benefits of intensive BP lowering may not be uniform across all subgroups of patients with chronic kidney disease. But intensive BP lowering was not associated with increased risk of ESRD or death among any subgroups that we examined

Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study.

IntroductionUrinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1) are established markers of subclinical acute kidney injury. In persons with reduced estimated glomerular filtration rate (eGFR) and albuminuria who are at high risk for end-stage renal disease (ESRD) and death, the associations of these urinary markers with incident ESRD or death is an area of active investigation.MethodsAmong 1472 black and white participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study with eGFR ≤60 ml/min per 1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] cystatin, 2012) and albumin-to-creatinine ratio (ACR) ≥30 mg/g, we evaluated the associations of baseline uNGAL and uKIM-1 with progression to ESRD and all-cause death. Cox models were sequentially adjusted for urinary creatinine, traditional risk factors, C-reactive protein, ACR, and eGFR.ResultsThere were 257 ESRD events and 819 deaths over a median follow-up of 5.7 and 6.5 years, respectively. In demographic adjusted models, higher levels of uNGAL were associated with increased risk of ESRD and death, but these associations were attenuated in fully adjusted models including baseline eGFR for both ESRD (hazard ratio [HR] = 1.06 per doubling, 95% confidence interval [CI] 0.98-1.14) and death (HR = 1.04, 95% CI = 1.00-1.08). Higher levels of uKIM-1 were associated with increased risk of ESRD and death in demographic-adjusted models, and although attenuated in fully adjusted models, remained statistically significant for both ESRD (HR = 1.24 per doubling, 95% CI = 1.08-1.42) and death (HR = 1.10, 95% CI =1.03-1.19).ConclusionIn this cohort of high-risk patients with baseline eGFR ≤60 ml/min per 1.73 m2 and albuminuria, renal tubular injury is associated with higher mortality and progression to ESRD. Further studies are necessary to investigate the mechanism underlying this increased risk

Association of urinary uromodulin with kidney function decline and mortality: the health ABC study .

BackgroundUrine uromodulin (uUMOD) is a protein secreted by the kidney tubule. Recent studies have suggested that higher uUMOD may be associated with improved kidney and mortality outcomes.MethodsUsing a case-cohort design, we evaluated the association between baseline uUMOD levels and ≥ 30% estimated glomerular filtration rate (eGFR) decline, incident chronic kidney disease (CKD), rapid kidney function decline, and mortality using standard and modified Cox proportional hazards regression.ResultsThe median value of uUMOD was 25.8 µg/mL, mean age of participants was 74 years, 48% were women, and 39% were black. Persons with higher uUMOD had lower prevalence of diabetes and coronary artery disease (CAD), and had lower systolic blood pressure. Persons with higher uUMOD also had higher eGFR, lower urinary albumin to creatinine ratio (ACR), and lower C-reactive protein (CRP). There was no association of uUMOD with > 30% eGFR decline. In comparison to those in the lowest quartile of uUMOD, those in the highest quartile had a significantly (53%) lower risk of incident CKD (CI 73%, 18%) and a 51% lower risk of rapid kidney function decline (CI 76%, 1%) after multivariable adjustment. Higher uUMOD was associated with lower risk of mortality in demographic adjusted models, but not after multivariable adjustment.ConclusionHigher levels of uUMOD are associated with lower risk of incident CKD and rapid kidney function decline. Additional studies are needed in the general population and in persons with advanced CKD to confirm these findings.


Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community

AbstractObjectivesThe goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of subjects aged 45 to 64 years.BackgroundThe level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD, but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community.MethodsCox proportional-hazards regression was used to evaluate the association of glomerular filtration rate (GFR) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects. We searched for nonlinear relationships between GFR and ASCVD.ResultsDuring a mean follow-up time of 6.2 years, 965 (6.3%) of subjects had ASCVD events. Subjects with GFR of 15 to 59 ml/min/1.73 m2(n = 444, hazard ratio 1.38 [1.02, 1.87]) and 60 to 89 ml/min/1.73 m2(n = 7,665, hazard ratio 1.16 [1.00, 1.34]) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m2. Each 10 ml/min/1.73 m2lower GFR was associated with an adjusted hazard ratio of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), and 1.06 (0.99, 1.13) for ASCVD, de novo ASCVD, and recurrent ASCVD, respectively. A nonlinear model did not fit the data better than a linear model.ConclusionsThe level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study

CKD classification based on estimated GFR over three years and subsequent cardiac and mortality outcomes: a cohort study

<p>Abstract</p> <p>Background</p> <p>It is unknown whether defining chronic kidney disease (CKD) based on one versus two estimated glomerular filtration rate (eGFR) assessments changes the prognostic importance of reduced eGFR in a community-based population.</p> <p>Methods</p> <p>Participants in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study were classified into 4 groups based on two eGFR assessments separated by 35.3 ± 2.5 months: sustained eGFR < 60 mL/min per 1.73 m²(1 mL/sec per 1.73 m²); eGFR increase (change from below to above 60); eGFR decline (change from above to below 60); and eGFR persistently ≥60. Outcomes assessed in stratified multivariable Cox models included cardiac events and a composite of cardiac events, stroke, and mortality.</p> <p>Results</p> <p>There were 891 (4.9%) participants with sustained eGFR < 60, 278 (1.5%) with eGFR increase, 972 (5.4%) with eGFR decline, and 15,925 (88.2%) with sustained eGFR > 60. Participants with eGFR sustained < 60 were at highest risk of cardiac and composite events [HR = 1.38 (1.15, 1.65) and 1.58 (1.41, 1.77)], respectively, followed by eGFR decline [HR = 1.20 (1.00, 1.45) and 1.32 (1.17, 1.49)]. Individuals with eGFR increase trended toward increased cardiac risk [HR = 1.25 (0.88, 1.77)] and did not significantly differ from eGFR decline for any outcome. Results were similar when estimating GFR with the CKD-EPI equation.</p> <p>Conclusion</p> <p>Individuals with persistently reduced eGFR are at highest risk of cardiovascular outcomes and mortality, while individuals with an eGFR < 60 mL/min per 1.73 m²at any time are at intermediate risk. Use of even a single measurement of eGFR to classify CKD in a community population appears to have prognostic value.</p

Kidney Function and Cognitive Health in Older Adults: The Cardiovascular Health Study

Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study, recruited from 4 U.S. communities, and studied from 1992 - 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFR[subscript cys]). Cognitive function was assessed using the Modified Mini-Mental State Exam and the Digit Symbol Substitution Test administered up to 7 times during annual visits. There was an association between eGFR[subscript cys] and change in cognitive function after adjustment for confounders; persons with eGFR[subscript cys] < 60 ml/min/1.73m² had a 0.64 (95% confidence interval: 0.51, 0.77) point/year faster decline in Modified Mini-Mental State Exam score and a 0.42 (95% confidence interval: 0.28, 0.56) point/year faster decline in Digit Symbol Substitution Test score compared with persons with eGFR[subscript cys] ≥ 90 ml/min/1.73m². Additional adjustment for intermediate cardiovascular events modestly impacted these associations. Participants with eGFR[subscript cys] < 60 ml/min/1.73m² had fewer cognitive impairment-free life-years on average compared with those with eGFR[subscript cys] ≥ 90 ml/min/1.73m², independent of confounders and mediating cardiovascular events (-0.44, 95% confidence interval: -0.62, -0.26). Older adults with reduced kidney function are at increased risk of worsening cognitive function.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the author(s) and published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. It can be found at: http://aje.oxfordjournals.org/Keywords: stroke, aging, myocardial infarction, successful aging, chronic kidney disease, cognitive function, prospective study, congestive heart failur

Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

<p>Abstract</p> <p>Background</p> <p>In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease.</p> <p>Methods</p> <p>Platelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP). Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined.</p> <p>Results</p> <p>We studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease) and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8) vs. 11.4 (9.2-12.2), P = 0.032), ADP (1.6 (1.2-2.1) vs. 2.6 (1.9-3.5), P = 0.002) and CRP (9.2 (8.5-10.8) vs. 11.5 (9.5-12.9), P = 0.004). Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups.</p> <p>Conclusion</p> <p>In this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.</p