Cystatin C, albuminuria, and mortality among older adults with diabetes.
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ABSTRACT: Objective
Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health outcomes among individuals with diabetes. Joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population.Research design and methods
This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples.Results
Of 691 participants, 378 died over 10 years of follow-up. Cystatin C-estimated GFR <60 ml/min per 1.73 m(2), creatinine-based estimated GFR <60 ml/min per 1.73 m(2), and urine ACR > or =30 mg/g were each associated with increased mortality risk with hazard ratios of 1.73 (95% CI 1.37-2.18), 1.54 (1.21-1.97), and 1.73 (1.39-2.17), respectively, adjusting for age, sex, race, diabetes duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol, lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent heart failure. Cystatin C-estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C-estimated GFR predicted mortality more strongly than creatinine-based estimated GFR.Conclusions
Albuminuria and impaired GFR were independent, additive risk factors for mortality among older adults with diabetes. These findings support current recommendations to regularly assess both albuminuria and GFR in the clinical care of patients with diabetes; a focus on interventions to prevent or treat CVD in the presence of albuminuria, impaired GFR, or both; and further consideration of cystatin C use in clinical care.
SUBMITTER: de Boer IH
PROVIDER: S-EPMC2752913 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Compared with controls, human immunodeficiency virus (HIV)-infected persons have a greater prevalence of kidney disease, assessed according to high cystatin C level and albuminuria, but not according to creatinine level. However, the clinical importance of increased cystatin C level and albuminuria in the HIV-infected population has not been studied.We conducted an observational cohort study to determine the association of kidney disease (measured according to albuminuria, cystatin C, and serum creatinine) with mortality.922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) Study.Serum cystatin C and serum creatinine levels were used to estimate glomerular filtration rates (eGFR(SCysC) and eGFR(SCr), respectively). Albuminuria was defined as a positive urine dipstick result (? 1+) or urine albumin-creatinine ratio >30 mg/g.5-Year mortality.At baseline, decreased kidney function (eGFR(SCysC) <60 mL/min/1.73 m(2)) or albuminuria was present in 28% of participants. After 5 years of follow-up, mortality was 48% in those with both eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria, 23% in those with eGFR(SCysC) < 60 mL/min/1.73 m(2) alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory marker levels, eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria were associated with a nearly 2-fold increase in mortality, whereas eGFR(SCr) < 60 mL/min/1.73 m(2) did not appear to have a substantial association with mortality. Together, eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria accounted for 17% of the population-level attributable risk of mortality.Vital status was unknown in 261 participants from the original cohort.Kidney disease marked by albuminuria or increased cystatin C level appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice.
| S-EPMC3164880 | biostudies-literature
Project description:ObjectiveDiabetes in older age is heterogeneous, and the treatment approach varies by patient characteristics. We characterized the short-term all-cause and cardiovascular mortality risk associated with hyperglycemia in older age.Research design and methodsWe included 5,791 older adults in the Atherosclerosis Risk in Communities Study who attended visit 5 (2011-2013; ages 66-90 years). We compared prediabetes (HbA1c 5.7% to <6.5%), newly diagnosed diabetes (HbA1c ≥6.5%, prior diagnosis <1 year, or taking antihyperglycemic medications <1 year), short-duration diabetes (duration ≥1 year but <10 years [median]), and long-standing diabetes (duration ≥10 years). Outcomes were all-cause and cardiovascular mortality (median follow-up of 5.6 years).ResultsParticipants were 58% female, and 24% had prevalent cardiovascular disease. All-cause mortality rates, per 1,000 person-years, were 21.2 (95% CI 18.7, 24.1) among those without diabetes, 23.7 (95% CI 20.8, 27.1) for those with prediabetes, 33.8 (95% CI 25.2, 45.5) among those with recently diagnosed diabetes, 29.6 (95% CI 25.0, 35.1) for those with diabetes of short duration, and 48.6 (95% CI 42.4, 55.7) for those with long-standing diabetes. Cardiovascular mortality rates, per 1,000 person-years, were 5.8 (95% CI 4.6, 7.4) among those without diabetes, 6.6 (95% CI 5.2, 8.5) for those with prediabetes, 11.5 (95% CI 7.0, 19.1) among those with recently diagnosed diabetes, 8.2 (95% CI 5.9, 11.3) for those with diabetes of short duration, and 17.3 (95% CI 13.8, 21.7) for those with long-standing diabetes. After adjustment for other cardiovascular risk factors, prediabetes and newly diagnosed diabetes were not significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.03 [95% CI 0.85, 1.23] and HR 1.31 [95% CI 0.94, 1.82], respectively) or cardiovascular mortality (HR 1.00 [95% CI 0.70, 1.43] and HR 1.35 [95% CI 0.74, 2.49], respectively). Excess mortality risk was primarily concentrated among those with long-standing diabetes (all-cause: HR 1.71 [95% CI 1.40, 2.10]; cardiovascular: HR 1.72 [95% CI 1.18, 2.51]).ConclusionsIn older adults, long-standing diabetes has a substantial and independent effect on short-term mortality. Older individuals with prediabetes remained at low mortality risk over a median 5.6 years of follow-up.
| S-EPMC6971785 | biostudies-literature
Project description:OBJECTIVE:Cystatin C (CysC) is a marker of kidney function that is relevant for the health and cognition of older adults. Little is known about the link between psychological factors and CysC. Therefore, the present study examined whether subjective age is related to CysC level and changes in CysC over time. METHOD:Participants were 5,066 individuals drawn from the Health and Retirement Study aged from 50 to 107 years (60% women, mean age = 69.36 years, SD = 9.54). They provided data on subjective age, demographic covariates, and CysC at baseline. CysC was assessed again 4 years later. RESULTS:Analysis revealed that an older subjective age was related to higher level of CysC at baseline and to an increase in CysC over 4 years, controlling for demographic factors. An older subjective age was also related to higher risk of exceeding the clinical threshold of CysC at baseline and 4 years later. Additional analysis revealed that disease burden, depressive symptoms, physical inactivity, and BMI partly mediated these associations. CONCLUSION:The present study provides new evidence on the role of subjective age as a psychological factor associated with individuals' risk of kidney dysfunction, an association beyond chronological age.
| S-EPMC6377033 | biostudies-literature
Project description:OBJECTIVE:Improved blood pressure control and use of renin-angiotensin-aldosterone system blockers have altered the clinical presentation or phenotype of chronic kidney disease (CKD) in U.S. adults with diabetes. These changes may influence mortality. RESEARCH DESIGN AND METHODS:Data from the National Health and Nutrition Examination Surveys (NHANES) 1988-2006 were used to examine mortality trends in adults with diabetes, defined as physician diagnosis, fasting glucose ≥126 mg/dL, HbA1c >6.5% (48 mmol/mol), or use of glucose-lowering medications. Mortality trends by CKD phenotype (estimated glomerular filtration rate [eGFR] and urine albumin-to-creatinine ratio [ACR] level) were obtained via linkage with the National Death Index through 31 December 2011 while accounting for the complex survey design. RESULTS:From 1988 to 2006, adults with an eGFR <60 mL/min/1.73 m2 and an ACR <30 mg/g increased from ∼0.9 million (95% CI 0.7, 1.1) or 6.6% of the total population with diabetes during years 1988-1994 to 2.4 million (95% CI 1.9, 2.9) or 10.1% of the total population with diabetes during years 2007-2010. Mortality rates generally trended downward for adults with diabetes and an ACR ≥30 mg/g but increased in those with eGFR <60 mL/min/1.73 m2 and an ACR <30 mg/g from 35 deaths per 1,000 person-years (95% CI 22, 55) during years 1988-1994 to 51 deaths per 1,000 person-years (95% CI 33, 83) during years 2003-2006. CONCLUSIONS:ACR values are decreasing in U.S. adults with diabetes, but optimal management strategies are needed to reduce mortality in those with a low eGFR and an ACR <30 mg/g.
| S-EPMC5860846 | biostudies-other
Project description:The mortality prediction models for the general diabetic population have been well established, but the corresponding elderly-specific model is still lacking. This study aims to develop a mortality prediction model for the elderly with diabetes. The data used for model establishment were derived from the nationwide adult health screening program in Taiwan in 2007-2010, from which we applied a 10-fold cross-validation method for model construction and internal validation. The external validation was tested on the MJ health screening database collected in 2004-2007. Multivariable Cox proportional hazards models were used to predict five-year mortality for diabetic patients ?65 years. A total of 220,832 older subjects with diabetes were selected for model construction, of whom 23,241 (10.5%) died by the end of follow-up (December 31, 2011). The significant predictors retained in the final model included age, gender, smoking status, body mass index (BMI), fasting glucose, systolic and diastolic blood pressure, leukocyte count, liver and renal function, total cholesterol, hemoglobin, albumin, and uric acid. The Harrell's C in the development, internal-, and external-validation datasets were 0.737, 0.746, and 0.685, respectively. We established an easy-to-use point-based model that could accurately predict five-year mortality risk in older adults with diabetes.
| S-EPMC5627261 | biostudies-literature
Project description:BACKGROUND:The prevailing diagnostic criteria for CKD are age-independent, but have been challenged in light of the eGFR decline associated with normal aging. The stages of CKD communicate magnitude of risk of ESRD, cardiovascular morbidity, and mortality. AIMS:This study aims to provide more insight into the morbidity and mortality associated with eGFR levels corresponding to the current CKD stages in older adults. METHODS:The 2931 older adults in the Good Aging in Skåne study were randomized from the general population. The exposure variable used was eGFR level (CKD-EPI based on creatinine and cystatin C) with eGFR 60-89 mL/min/1.73 m2 as a reference; the outcomes were mortality, acute cardiovascular disease, congestive heart failure, and rapid kidney function decline (RKFD; defined as a decline in eGFR by 3 mL/min/1.73 m2 per year or more). RESULTS:The mean age at baseline was 73 (SD 11) and mean follow-up time 11 (SD 5) years. Mortality was higher at lower eGFR levels with adjusted HR (95% CI) being 1.58 (1.34-1.88), 1.22 (1.05-1.41), 1 (reference), and 0.90 (0.67-1.21) for eGFR?<?45, 45-59, 60-89 and ??90 mL/min/1.73 m2, respectively. For acute CVD the adjusted HR (95% CI) were 1.23 (0.81-1.87), 1.21 (0.87-1.69), 1 (reference), and 0.53 (0.28-1.00) for the same eGFR levels. CONCLUSIONS:This study confirms that mortality in older adults increases with decreasing eGFR at eGFR levels below today's threshold for CKD. The correlation was less certain for lower eGFR and incident cardiovascular disease.
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Project description:BackgroundAlbuminuria is highly prevalent among older adults, especially those with diabetes. It is associated with several chronic diseases, but its overall impact on the health of older adults, as measured by hospitalization, has not been quantified.MethodWe followed up 3,110 adults, mean age 78 years, for a median 9.75 years, of whom 654 (21%) had albuminuria (≥30 mg albumin/gram creatinine) at baseline. Poisson regression models, adjusted for cardiovascular, renal, and demographic factors, were used to evaluate the association of albuminuria with all-cause and cause-specific hospitalizations, as defined by ICD, version 9, categories.ResultsThe rates of hospitalization per 100 patient-years were 65.85 for participants with albuminuria and 37.55 for participants without albuminuria. After adjustment for covariates, participants with albuminuria were more likely to be hospitalized for any cause than participants without albuminuria (incident rate ratio, 1.39 [95% confidence intervals, 1.27. 1.53]) and to experience more days in hospital (incident rate ratio 1.56 [1.37, 1.76]). The association of albuminuria with hospitalization was similar among participants with and without diabetes (adjusted incident rate ratio for albuminuria versus no albuminuria: diabetes 1.37 [1.11, 1.70], no diabetes 1.40 [1.26, 1.55]; p interaction nonsignificant). Albuminuria was significantly associated with hospitalization for circulatory, endocrine, genitourinary, respiratory, and injury categories.ConclusionsAlbuminuria in older adults is associated with an increased risk of hospitalization for a broad range of illnesses. Albuminuria in the presence or absence of diabetes appears to mark a generalized vulnerability to diseases of aging among older adults.
| S-EPMC7662181 | biostudies-literature
Project description:BackgroundThis study examines the association between cystatin C (cysC) levels and risks of progression of frailty status or death in older men.MethodsProspective study of 2,613 men without overt frailty aged 67 years and older enrolled in the MrOS ancillary sleep study. Baseline measurements included serum cysC, serum creatinine, and frailty status. Repeat frailty status, performed an average of 3.4 years later, was assessed as an ordinal outcome of robust, intermediate stage (prefrail), frail or dead.ResultsMean age was 75.7 years. Men with higher cysC were older and had a higher comorbidity burden. After adjusting for age, clinical site, and race, higher cysC was associated with nearly twofold greater odds of being classified as intermediate stage versus robust (OR quartile 4 vs 1; 1.82, 95% confidence interval [CI] 1.35-2.45), a threefold greater odds of frailty versus robust (OR quartile 4 vs 1; 3.13, 95% CI 2.03-4.82), and a more than fivefold greater odds of death versus robust (OR quartile 4 vs 1; 5.48, 95% CI 2.98-10.08). Results were similar for cysC-based estimated glomerular filtration rate (eGFR). This relationship was attenuated but persisted after adjusting for additional potential confounders including baseline frailty status, body mass index, smoking status, comorbidity burden, self-reported disability, and serum albumin. In contrast, neither serum creatinine nor creatinine-based eGFR was associated in a graded manner with higher risks of development of frailty or death.ConclusionsIn this cohort of older men without overt frailty, higher cysC and cysC-based eGFR, but not creatinine or creatinine-based estimates of GFR, were associated with increased risks of frailty or death. These findings suggest that higher cysC level may be a promising biomarker for unsuccessful aging as manifested by increased risks of frailty and death.
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Project description:Falls are common and associated with adverse outcomes in patients on dialysis. Limited data are available in earlier stages of CKD.We analyzed data from 8744 Reasons for Geographic and Racial Differences in Stroke Study participants ?65 years old with Medicare fee for service coverage. Serious fall injuries were defined as a fall-related fracture, brain injury, or joint dislocation using Medicare claims. Hazard ratios (HRs) for serious fall injuries were calculated by eGFR and albumin-to-creatinine ratio (ACR). Among 2590 participants with CKD (eGFR<60 ml/min per 1.73 m(2) or ACR?30 mg/g), cumulative mortality after a serious fall injury compared with age-matched controls without a fall injury was calculated.Overall, 1103 (12.6%) participants had a serious fall injury over 9.9 years of follow-up. The incidence rates per 1000 person-years of serious fall injuries were 21.7 (95% confidence interval [95% CI], 20.3 to 23.2), 26.6 (95% CI, 22.6 to 31.3), and 38.3 (95% CI, 31.2 to 47.0) at eGFR levels ?60, 45-59, and <45 ml/min per 1.73 m(2), respectively, and 21.3 (95% CI, 20.0 to 22.8), 31.7 (95% CI, 27.5 to 36.5), and 42.2 (95% CI, 31.3 to 56.9) at ACR levels <30, 30-299, and ?300 mg/g, respectively. Multivariable adjusted HRs for serious fall injuries were 0.91 (95% CI, 0.76 to 1.09) and 1.09 (95% CI, 0.86 to 1.37) for eGFR=45-59 and <45 ml/min per 1.73 m(2), respectively, versus eGFR?60 ml/min per 1.73 m(2) and 1.31 (95% CI, 1.11 to 1.54) and 1.81 (95% CI, 1.30 to 2.50) for ACR=30-299 and ?300 mg/g, respectively, versus ACR<30 mg/g. Among participants with CKD, cumulative 1-year mortality rates among patients with a serious fall and age-matched controls were 21.0% and 5.5%, respectively.Elevated ACR but not lower eGFR was associated with serious fall injuries. Evaluation for fall risk factors and fall prevention strategies should be considered for older adults with elevated ACR.
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