내과 R1 문정락 / prof. 정경환 N Engl J Med 369;10 nejm.org 932 september 5, 2013

baBackground The estimated glomerular filtration rate (eGFR) is the clinical standard for the assessment of kidney function. But, measurement of creatinine to determine the eGFR has limitations in risk prediction, particularly in patients with reduced muscle mass Addition of Cystatin C measurements to creatinine measurements in calculating the eGFR significantly improves the risk classification for death, cardiovascular disease, and end-stage renal disease As compared with the use of Cr based eGFR, the use of the recently developed cystatin C equations would strengthen the relationships between various categories and adjusted risks of death from any cause, death from CVD and ESRD ??

Study Design and Participants Meta-analysis include 11 general population studies (with participants) And 5 studies of patients with Chronic kidney disease (with 2960 participants) Using latest equations from the chronic kidney disease Epidemiology collaboration 1. serum Creatinine 2. Cystatin C 3. Both Creatinine and Cystatin C Age, sex, race (except for Cystatin C) Method

Study Outcomes 1. Death from any causes 2. Death from cardiovascular disease (MI, HF) 3. End-stage renal disease (need for renal replacement therapy) Age >18years old Primary analysis : general population cohort Secondary analysis : performed in cohort with CKD

Method Study Analysis 1. Evaluate the distribution for each eGFR equation 2. Constructed Cox proportional hazard models fitted with eGFR linear splines - with adjustment for age, sex, race, smoking status, Hx of CVD, SBP, diabetes, Total Chol level, BMI, Albuminuria level 3. Computed & pooled Hazard ratios for each increment in the eGFR Of 1ml per minute per 1.73m2 of BSA (eGFR ) 4. Multivariable Cox proportional hazard models to assess risk of adverse outcomes for whom eGFR reclassified to higher of lower value 5. Assessed the overall improvement in reclassfication Net reclassification improvement approach

Result

Study outcomes 9.7% 13.7% 10.0% 13.7% vs. 9.7%

Result Death from any cause 59 ml/min/1.73m2 83 ml/min/1.73m2 88 ml/min/1.73m2 Reference Point : 95 ml/min/1.73m2 11 general population cohort (13.6% ) / 90,750 for 7.7 yr

Result Death from Cardiovascular causes Reference Point : 95 ml/min/1.73m2 69 ml/min/1.73m2 83 ml/min/1.73m2 86 ml/min/1.73m2 10 general population cohort 3193 / for 8.8 yr

Result End-stage Renal disease Reference Point : 61 ml/min/1.73m2 2 general population cohort 357 / for 8.8 yr 5 CKD cohort 1297/2955 for 9.3 yr

Result Risk of clinical Outcomes

Result Net classification Improvement

In conclusion, the use of cystatin C to calculate the eGFR strengthened the associations between eGFR categories and the risks of death and end-stage renal disease across diverse populations. We also found that the risk of death was increased when values for both cystatin C–based eGFR and eGFR based on combined creatinine and cystatin C measurements Were below a threshold of approximately 85 ml per minute per 1.73 m2 Conclusion

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