Number 2
For the second best paper of 2012 I have selected is the paper by Inker et al published in the NEJM on a new GFR prediction equation. You may have expected me to recommend a juicy RCT, but I chose this paper because it was very well done, beautifully written and has broad impact in it's effect on clinical practice.
For the second best paper of 2012 I have selected is the paper by Inker et al published in the NEJM on a new GFR prediction equation. You may have expected me to recommend a juicy RCT, but I chose this paper because it was very well done, beautifully written and has broad impact in it's effect on clinical practice.
The MDRD and the CKD-Epi equations are routinely used (MDRD more so than the CKD-Epi equation), but they are [relatively] imprecise, potentially leading to the overdiagnosis of chronic kidney disease. The cross-sectional study from Tufts proposes a formula that combines measurement of creatinine and cystatin C to come upwith a more precise estimate of GFR.
The investigators utillized diverse populations totaling 5352 participants from 13 studies. They developed equations which were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials.
They report (excerpt from the paper):
- Mean measured GFRs were 68 and 70 ml per minute per 1.73 m2 of body-surface area in the development and validation data sets, respectively.
- In the validation data set, the creatinine–cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m2 with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m2 with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively.
- Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m2, respectively [P=0.001 and P less than 0.001]), and the results were more accurate (percentage of estimates that were greater than 30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P less than 0.001 for both comparisons]).
- In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m2, the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m2 or greater than or equal to 60 ml per minute per 1.73 m2 (net reclassification index, 19.4% [P less than 0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 as having a GFR of 60 ml or higher per minute per 1.73 m2.
The bottom-line - the combined creatinine–cystatin C equation performed better than equations based on either of these markers alone. For patients with borderline eGFR where classifiying someone as "CKD" versus "low GFR" makes a difference the use of this new equation will be important. In the long-run, if cystatin C measurements become widespread, replacing the MDRD or CKD-epi equation would also seem reasonable.
