03326nas a2200409 4500008004100000022001400041245007900055210006900134260001600203300001100219490000800230520214100238653001502379653001502394653003102409653001102440653002802451653002602479653002402505653003302529653000902562653002002571100002402591700002502615700001902640700002102659700001602680700002702696700002702723700002002750700001902770700001802789700002102807700002302828710002902851856003602880 2013 eng d a1533-440600aCystatin C versus creatinine in determining risk based on kidney function.0 aCystatin C versus creatinine in determining risk based on kidney c2013 Sep 05 a932-430 v3693 a

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.).

10aCreatinine10aCystatin C10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aKidney Function Tests10aReference Standards10aRenal Insufficiency, Chronic10aRisk10aRisk Assessment1 aShlipak, Michael, G1 aMatsushita, Kunihiro1 aArnlöv, Johan1 aInker, Lesley, A1 aKatz, Ronit1 aPolkinghorne, Kevan, R1 aRothenbacher, Dietrich1 aSarnak, Mark, J1 aAstor, Brad, C1 aCoresh, Josef1 aLevey, Andrew, S1 aGansevoort, Ron, T1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/737703720nas a2200445 4500008004100000022001400041245015900055210006900214260001600283520232600299100002102625700002102646700002102667700001802688700002102706700002102727700002302748700002602771700002102797700002102818700002402839700001702863700002402880700002302904700002102927700002402948700002302972700002702995700002103022700002003043700002403063700001703087700002503104700002103129700002203150700001903172700001803191710002903209856003603238 2018 eng d a1523-683800aRelationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium.0 aRelationship of Estimated GFR and Albuminuria to Concurrent Labo c2018 Oct 193 a

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.

1 aInker, Lesley, A1 aGrams, Morgan, E1 aLevey, Andrew, S1 aCoresh, Josef1 aCirillo, Massimo1 aCollins, John, F1 aGansevoort, Ron, T1 aGutierrez, Orlando, M1 aHamano, Takayuki1 aHeine, Gunnar, H1 aIshikawa, Shizukiyo1 aJee, Sun, Ha1 aKronenberg, Florian1 aLandray, Martin, J1 aMiura, Katsuyuki1 aNadkarni, Girish, N1 aPeralta, Carmen, A1 aRothenbacher, Dietrich1 aSchaeffner, Elke1 aSedaghat, Sanaz1 aShlipak, Michael, G1 aZhang, Luxia1 avan Zuilen, Arjan, D1 aHallan, Stein, I1 aKovesdy, Csaba, P1 aWoodward, Mark1 aLevin, Adeera1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/7915