@article {1385, title = {Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.}, journal = {JAMA}, volume = {307}, year = {2012}, month = {2012 May 09}, pages = {1941-51}, abstract = {

CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking.

OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics.

DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged >= 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012.

MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years).

RESULTS: Estimated GFR was classified into 6 categories (>=90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4\% and 0.6\% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7\% to 6.3\%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7\% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95\% CI, 0.74-0.86) for all-cause mortality, 0.73 (95\% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95\% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and >=65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts.

CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

}, keywords = {African Continental Ancestry Group, Aged, Algorithms, Asian Continental Ancestry Group, Cardiovascular Diseases, Cohort Studies, Decision Support Techniques, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Models, Theoretical, Risk Assessment, Sex Factors}, issn = {1538-3598}, doi = {10.1001/jama.2012.3954}, author = {Matsushita, Kunihiro and Mahmoodi, Bakhtawar K and Woodward, Mark and Emberson, Jonathan R and Jafar, Tazeen H and Jee, Sun Ha and Polkinghorne, Kevan R and Shankar, Anoop and Smith, David H and Tonelli, Marcello and Warnock, David G and Wen, Chi-Pang and Coresh, Josef and Gansevoort, Ron T and Hemmelgarn, Brenda R and Levey, Andrew S} } @article {7364, title = {Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.}, journal = {Am J Hum Genet}, volume = {100}, year = {2017}, month = {2017 Jan 05}, pages = {51-63}, abstract = {

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in~vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2016.11.016}, author = {van Rooij, Frank J A and Qayyum, Rehan and Smith, Albert V and Zhou, Yi and Trompet, Stella and Tanaka, Toshiko and Keller, Margaux F and Chang, Li-Ching and Schmidt, Helena and Yang, Min-Lee and Chen, Ming-Huei and Hayes, James and Johnson, Andrew D and Yanek, Lisa R and Mueller, Christian and Lange, Leslie and Floyd, James S and Ghanbari, Mohsen and Zonderman, Alan B and Jukema, J Wouter and Hofman, Albert and van Duijn, Cornelia M and Desch, Karl C and Saba, Yasaman and Ozel, Ayse B and Snively, Beverly M and Wu, Jer-Yuarn and Schmidt, Reinhold and Fornage, Myriam and Klein, Robert J and Fox, Caroline S and Matsuda, Koichi and Kamatani, Naoyuki and Wild, Philipp S and Stott, David J and Ford, Ian and Slagboom, P Eline and Yang, Jaden and Chu, Audrey Y and Lambert, Amy J and Uitterlinden, Andr{\'e} G and Franco, Oscar H and Hofer, Edith and Ginsburg, David and Hu, Bella and Keating, Brendan and Schick, Ursula M and Brody, Jennifer A and Li, Jun Z and Chen, Zhao and Zeller, Tanja and Guralnik, Jack M and Chasman, Daniel I and Peters, Luanne L and Kubo, Michiaki and Becker, Diane M and Li, Jin and Eiriksdottir, Gudny and Rotter, Jerome I and Levy, Daniel and Grossmann, Vera and Patel, Kushang V and Chen, Chien-Hsiun and Ridker, Paul M and Tang, Hua and Launer, Lenore J and Rice, Kenneth M and Li-Gao, Ruifang and Ferrucci, Luigi and Evans, Michelle K and Choudhuri, Avik and Trompouki, Eirini and Abraham, Brian J and Yang, Song and Takahashi, Atsushi and Kamatani, Yoichiro and Kooperberg, Charles and Harris, Tamara B and Jee, Sun Ha and Coresh, Josef and Tsai, Fuu-Jen and Longo, Dan L and Chen, Yuan-Tsong and Felix, Janine F and Yang, Qiong and Psaty, Bruce M and Boerwinkle, Eric and Becker, Lewis C and Mook-Kanamori, Dennis O and Wilson, James G and Gudnason, Vilmundur and O{\textquoteright}Donnell, Christopher J and Dehghan, Abbas and Cupples, L Adrienne and Nalls, Michael A and Morris, Andrew P and Okada, Yukinori and Reiner, Alexander P and Zon, Leonard I and Ganesh, Santhi K} } @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} }