@article {7377, title = {Cystatin C versus creatinine in determining risk based on kidney function.}, journal = {N Engl J Med}, volume = {369}, year = {2013}, month = {2013 Sep 05}, pages = {932-43}, abstract = {

BACKGROUND: Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined.

METHODS: We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C.

RESULTS: In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7\% vs. 9.7\%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95\% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95\% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR.

CONCLUSIONS: The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. (Funded by the National Kidney Foundation and others.).

}, keywords = {Creatinine, Cystatin C, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Kidney Function Tests, Reference Standards, Renal Insufficiency, Chronic, Risk, Risk Assessment}, issn = {1533-4406}, doi = {10.1056/NEJMoa1214234}, author = {Shlipak, Michael G and Matsushita, Kunihiro and Arnl{\"o}v, Johan and Inker, Lesley A and Katz, Ronit and Polkinghorne, Kevan R and Rothenbacher, Dietrich and Sarnak, Mark J and Astor, Brad C and Coresh, Josef and Levey, Andrew S and Gansevoort, Ron T} } @article {6797, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {591-601}, abstract = {

BACKGROUND: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).

STUDY DESIGN: Collaborative meta-analysis.

SETTING \& POPULATION: 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).

SELECTION CRITERIA FOR STUDIES: Available eGFR, ACR, and 50 or more AKI events.

PREDICTORS: Age, sex, race, eGFR, urine ACR, and interactions.

OUTCOME: Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

RESULTS: 16,480 (1.3\%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6\%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95\% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95\% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.

LIMITATIONS: Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.

CONCLUSIONS: Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.

}, keywords = {Acute Kidney Injury, Adolescent, Adult, African Americans, Age Distribution, Aged, Albuminuria, Continental Population Groups, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Young Adult}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.337}, author = {Grams, Morgan E and Sang, Yingying and Ballew, Shoshana H and Gansevoort, Ron T and Kimm, Heejin and Kovesdy, Csaba P and Naimark, David and Oien, Cecilia and Smith, David H and Coresh, Josef and Sarnak, Mark J and Stengel, B{\'e}n{\'e}dicte and Tonelli, Marcello} } @article {6796, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {602-12}, abstract = {

BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.

STUDY DESIGN: Meta-analysis of cohort studies.

SETTING \& POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.

SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.

PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.

OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.

LIMITATIONS: AKI identified by diagnostic code.

CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

}, keywords = {Acute Kidney Injury, Adult, Aged, Comorbidity, Diabetes Mellitus, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Incidence, Kidney Failure, Chronic, Male, Middle Aged, Prognosis, Renal Insufficiency, Chronic}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.338}, author = {James, Matthew T and Grams, Morgan E and Woodward, Mark and Elley, C Raina and Green, Jamie A and Wheeler, David C and de Jong, Paul and Gansevoort, Ron T and Levey, Andrew S and Warnock, David G and Sarnak, Mark J} } @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} }