@article {7380, title = {Age and association of kidney measures with mortality and end-stage renal disease.}, journal = {JAMA}, volume = {308}, year = {2012}, month = {2012 Dec 12}, pages = {2349-60}, abstract = {

CONTEXT: Chronic 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.

OBJECTIVE: To 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 PARTICIPANTS: Individual-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 MEASURES: Hazard 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.

RESULTS: Mortality (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.

CONCLUSIONS: Both 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.

}, keywords = {Adolescent, Adult, Age Factors, Aged, Albuminuria, Cohort Studies, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Failure, Chronic, Male, Middle Aged, Risk, Young Adult}, issn = {1538-3598}, doi = {10.1001/jama.2012.16817}, author = {Hallan, Stein I and Matsushita, Kunihiro and Sang, Yingying and Mahmoodi, Bakhtawar K and Black, Corri and Ishani, Areef and Kleefstra, Nanne and Naimark, David and Roderick, Paul and Tonelli, Marcello and Wetzels, Jack F M and Astor, Brad C and Gansevoort, Ron T and Levin, Adeera and Wen, Chi-Pang and Coresh, Josef} } @article {1406, title = {Association of mild to moderate chronic kidney disease with venous thromboembolism: pooled analysis of five prospective general population cohorts.}, journal = {Circulation}, volume = {126}, year = {2012}, month = {2012 Oct 16}, pages = {1964-71}, abstract = {

BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted.

METHODS AND RESULTS: We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Tr{\o}ndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Troms{\o} study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95\% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria >=30 mg/g, (versus no CKD) was 1.54 (95\% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well.

CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

}, keywords = {Aged, Cohort Studies, Europe, Female, Humans, Incidence, Male, Middle Aged, Prevalence, Renal Insufficiency, Chronic, Risk Factors, Severity of Illness Index, Venous Thromboembolism}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.112.113944}, author = {Mahmoodi, Bakhtawar K and Gansevoort, Ron T and N{\ae}ss, Inger Anne and Lutsey, Pamela L and Br{\ae}kkan, Sigrid K and Veeger, Nic J G M and Brodin, Ellen E and Meijer, Karina and Sang, Yingying and Matsushita, Kunihiro and Hallan, Stein I and Hammerstr{\o}m, Jens and Cannegieter, Suzanne C and Astor, Brad C and Coresh, Josef and Folsom, Aaron R and Hansen, John-Bjarne and Cushman, Mary} } @article {6554, title = {Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.}, journal = {JAMA}, volume = {311}, year = {2014}, month = {2014 Jun 25}, pages = {2518-2531}, abstract = {

IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of -57\% or greater) is a late event.

OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.

DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.

DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.

MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.

RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95\% CI, 22.3-46.3) for changes of -57\% in estimated GFR and 5.4 (95\% CI, 4.5-6.4) for changes of -30\%. However, changes of -30\% or greater (6.9\% [95\% CI, 6.4\%-7.4\%] of the entire consortium) were more common than changes of -57\% (0.79\% [95\% CI, 0.52\%-1.06\%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99\% (95\% CI, 95\%-100\%) for estimated GFR change of -57\%, was 83\% (95\% CI, 71\%-93\%) for estimated GFR change of -40\%, and was 64\% (95\% CI, 52\%-77\%) for estimated GFR change of -30\% vs 18\% (95\% CI, 15\%-22\%) for estimated GFR change of 0\%. Corresponding mortality risks were 77\% (95\% CI, 71\%-82\%), 60\% (95\% CI, 56\%-63\%), and 50\% (95\% CI, 47\%-52\%) vs 32\% (95\% CI, 31\%-33\%), showing a similar but weaker pattern.

CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30\% reduction over 2 years) as an alternative end point for CKD progression.

}, keywords = {Adult, Aged, Aged, 80 and over, Cohort Studies, Creatinine, Disease Progression, Endpoint Determination, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Reference Values, Risk}, issn = {1538-3598}, doi = {10.1001/jama.2014.6634}, author = {Coresh, Josef and Turin, Tanvir Chowdhury and Matsushita, Kunihiro and Sang, Yingying and Ballew, Shoshana H and Appel, Lawrence J and Arima, Hisatomi and Chadban, Steven J and Cirillo, Massimo and Djurdjev, Ognjenka and Green, Jamie A and Heine, Gunnar H and Inker, Lesley A and Irie, Fujiko and Ishani, Areef and Ix, Joachim H and Kovesdy, Csaba P and Marks, Angharad and Ohkubo, Takayoshi and Shalev, Varda and Shankar, Anoop and Wen, Chi Pang and de Jong, Paul E and Iseki, Kunitoshi and Stengel, B{\'e}n{\'e}dicte and Gansevoort, Ron T and Levey, Andrew S} }