@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 {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} }