@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 {7915, title = {Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium.}, journal = {Am J Kidney Dis}, year = {2018}, month = {2018 Oct 19}, abstract = {

RATIONALE \& OBJECTIVE: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.

STUDY DESIGN: Cross-sectional individual participant-level analyses in a global consortium.

SETTING \& STUDY POPULATIONS: 17 CKD and 38 general population and high-risk cohorts.

SELECTION CRITERIA FOR STUDIES: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.

DATA EXTRACTION: Data were obtained and analyzed between July 2015 and January~2018.

ANALYTICAL APPROACH: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.

RESULTS: The CKD cohorts (n=254,666 participants) were 27\% women and 10\% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50\% women and 2\% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95\% CI, 2.68-3.97] to 8.91 [95\% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95\% CI, 0.60-0.99] to 1.92 [95\% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs~< 30mg/g).

LIMITATIONS: Variations in study era, health care delivery system, typical diet, and laboratory assays.

CONCLUSIONS: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2018.08.013}, author = {Inker, Lesley A and Grams, Morgan E and Levey, Andrew S and Coresh, Josef and Cirillo, Massimo and Collins, John F and Gansevoort, Ron T and Gutierrez, Orlando M and Hamano, Takayuki and Heine, Gunnar H and Ishikawa, Shizukiyo and Jee, Sun Ha and Kronenberg, Florian and Landray, Martin J and Miura, Katsuyuki and Nadkarni, Girish N and Peralta, Carmen A and Rothenbacher, Dietrich and Schaeffner, Elke and Sedaghat, Sanaz and Shlipak, Michael G and Zhang, Luxia and van Zuilen, Arjan D and Hallan, Stein I and Kovesdy, Csaba P and Woodward, Mark and Levin, Adeera} }