Supplementary Material for: Cystatin C-Creatinine Based Glomerular Filtration Rate Equation in Obese Chronic Kidney Disease Patients: Impact of Deindexation and Gender

Background: Cystatin C is considered an alternative to creatinine to estimate glomerular filtration rate (GFR). However, studies have reported that increased adiposity is associated with a higher level of circulating cystatin C questioning the performance of estimation of GFR using cystatin C in obese subjects. Methods: We prospectively included 166 obese stages 1-5 chronic kidney disease (CKD) patients between 2013 and 2015. GFR was measured with a reference method without (measured GFR [mGFR]) and with adjustment to body surface area (mGFRr) and estimated (eGFR) or de-indexed eGFR using the Chronic Kidney Disease and Epidemiology (CKD-EPI) equation using creatinine (CKD-EPIcreat), cystatin (CKD-EPIcyst) and the combination of cystatin and creatinine (CKD-EPIcyst-creat). Results: The biases between mGFR and de-indexed CKD-EPIcyst-creat were significantly lower than de-indexed CKD-EPIcreat (p = 0.001). Accuracies were significantly better with de-indexed CKD-EPIcyst-creat compared to CKD-EPIcreat and CKD-EPIcyst, respectively (p = 0.04 and 0.03). Bland and Altman plot showed a great dispersion of all formulae when patients had a GFR >60 ml/min. Interestingly, there is a gender difference; biases, precisions and accuracies of de-indexed CKD-EPIcyst-creat were significantly lower in obese women. These results may be related to a difference in the change of body composition during obesity in men versus women and in fact only waist circumference (WC) was positively and significantly correlated with cystatin C (p < 0.0001) whereas body mass index (BMI; p = 0.3) was not; bias for CKD-EPIcyst-creat was related with WC. Conclusion: Cystatin C-creatinine-based GFR equations outperform creatinine-based formula in obese CKD patients especially those with BMI ≥35 and in obese women.

背景：半胱氨酸蛋白酶抑制剂C（Cystatin C）被认为是估算肾小球滤过率（glomerular filtration rate, GFR）的肌酐替代标志物。然而已有研究表明，体脂升高与循环半胱氨酸蛋白酶抑制剂C水平升高相关，这对肥胖人群中使用半胱氨酸蛋白酶抑制剂C估算GFR的效能提出了质疑。
方法：本研究于2013至2015年间前瞻性纳入166例处于1至5期慢性肾脏病（chronic kidney disease, CKD）的肥胖患者。采用参考方法测定肾小球滤过率（measured GFR, mGFR），并针对体表面积进行校正得到校正后实测肾小球滤过率（mGFRr）；同时采用慢性肾脏病流行病学合作（Chronic Kidney Disease and Epidemiology, CKD-EPI）公式，分别基于肌酐（CKD-EPIcreat）、半胱氨酸蛋白酶抑制剂C（CKD-EPIcyst）以及二者联合（CKD-EPIcyst-creat）估算肾小球滤过率（estimated GFR, eGFR）或去指数化估算肾小球滤过率。
结果：实测肾小球滤过率与去指数化CKD-EPIcyst-creat之间的偏差显著低于去指数化CKD-EPIcreat（p=0.001）。去指数化CKD-EPIcyst-creat的准确率显著优于CKD-EPIcreat与CKD-EPIcyst（分别对应p=0.04与0.03）。Bland-Altman图显示，当患者GFR>60ml/min时，所有公式的预测结果均存在较大离散度。值得注意的是，本研究存在性别差异：肥胖女性的去指数化CKD-EPIcyst-creat的偏差、精密度与准确率均显著更低。上述结果可能与男女肥胖患者体成分变化的差异相关；事实上，仅腰围（waist circumference, WC）与半胱氨酸蛋白酶抑制剂C水平呈显著正相关（p<0.0001），而体质量指数（body mass index, BMI, p=0.3）则无此关联；CKD-EPIcyst-creat的偏差与腰围相关。
结论：基于半胱氨酸蛋白酶抑制剂C-肌酐联合公式的GFR估算效果优于单纯基于肌酐的公式，尤其适用于BMI≥35的肥胖慢性肾脏病患者以及肥胖女性。