不同肾小球滤过率估算方程在15~18岁慢性肾脏病儿童中应用比较

doi:10.12372/jcp.2022.21e1353

摘要/Abstract

摘要：

目的比较8种肾小球滤过率（GFR）估算方程在评估15~18岁慢性肾脏病（CKD）儿童肾小球滤过率中的准确性及适用性。方法收集2015年1月至2021年3月住院的CKD患儿为研究对象。应用8种肾小球滤过估算（eGFR）公式（改良Schwartz公式、CAPA公式、Counahan-Barratt公式、Filler公式、CKD-EPI-Scr2009、CKD-EPI-CysC2012、LMR18、FAS公式）估算GFR，采用^99mTc-DTPA肾动态显像Gates法为金标准GFR（sGFR）的测定方法。比较各公式的偏倚、精确性、准确性，分析各公式对于肾功能不全的诊断效能。结果纳入88例患儿，男56例、女32例，中位年龄17.0（16.0~18.0）岁；CKD 1期56例，CKD 2期18例，CKD 3期11例，CKD 4期2例，CKD 5期1例。各公式eGFR与sGFR均呈正相关（P均<0.001）。其中CKD-EPI-Scr2009公式与sGFR相关性最好（r=0.73），Filler公式相关性最差（r=0.39）。CAPA公式、CKD-EPI-Scr2009、FAS公式在整体水平上高估了患儿的GFR，其余公式均存在GFR低估现象。以sGFR为金标准，FAS公式偏倚最小，CAPA公式偏倚最大。在精确性方面，LMR18公式精确性最好，改良Schwartz公式次之，CAPA公式精确性最差。在准确性方面，LMR18公式的准确性最高（P₃₀=73.86%）。ROC曲线分析显示，CKD-EPI-Scr2009公式曲线下面积（AUC）最大（0.91），CAPA、Filler、CKD-EPI-CysC2012公式灵敏度最高（均为95.90%），LMR18、FAS公式的特异度最高（均为85.71%）。结论 8种eGFR公式中，基于CysC公式（CAPA、Filler、CKD-EPI-CysC2012公式）的准确性等方面不及基于Scr的公式（改良Schwartz、Counahan-Barratt、CKD-EPI-Scr2009、LMR18、FAS公式），其中LMR18公式精确性、准确性均最高。

关键词: 慢性肾脏病, 肾小球滤过率, 公式, 儿童

Abstract:

Objective To compare the accuracy and applicability of eight estimation formulas for glomerular filtration rate (GFR) in children aged 15-18 years with chronic kidney disease (CKD). Methods Children with CKD hospitalized from January 2015 to March 2021 wereenrolled. Eight eGFR formulas (update Schwartz formula, CAPA formula, Counahan-Barratt formula, Filler formula, CKD-EPI-Scr2009, CKD-EPI-CysC2012, LMR18, FAS formula) were applied to estimate GFR. The Gates method of 99mTc-DTPA renal dynamic imaging was used as the gold standard GFR (sGFR) determination. The bias, precision and accuracy of each formula were compared, and the diagnostic efficacy of each formula for renal insufficiency was analyzed. Results A total of 88 children were enrolled, including 56 boys and 32 girls, and the median age was 17.0 (16.0-18.0) years. There were 56 cases of CKD stage 1, 18 cases of CKD stage 2, 11 cases of CKD stage 3, 2 cases of CKD stage 4, and 1 case of CKD stage 5. The eGFR in all formulas was positively correlated with sGFR (all P<0.001). The CKD-EPI-Scr2009 formula had the best correlation with sGFR (r=0.73), and the Filler formula had the worst correlation with sGFR (r=0.39). The CAPA, CKD-EPI-Scr2009 and FAS formulas overestimated the GFR on the overall level, while the other formulas underestimated GFR. When sGFR was used as the gold standard, the FAS formula had the smallest bias and the CAPA formula had the largest bias. In terms of precision, the LMR18 formula showed the best precision, followed by the update Schwartz formula, and the CAPA formula showed the worst precision. In terms of accuracy, the LMR18 formula showed the highest accuracy (P₃₀=73.86%). ROC curve analysis showed that the area under the curve (AUC) of the CKD-EPI-Scr2009 formula was the largest (0.907), the sensitivity of CAPA, Filler, and CKD-EPI-CysC2012 formulas were the highest (95.90%), and the specificity of LMR18 and FAS formulas were the highest (85.71%). Conclusions Among the eight eGFR formulas, the accuracy of CysC-based formulas (CAPA, Filler and CKD-EPI-CysC2012 formula) is not as good as Scr-based formulas (update Schwartz, Counahan-Barratt, CKD-EPI-Scr2009, LMR18 and FAS formula), and LMR18 formula has the highest precision and accuracy.

Key words: chronic kidney disease, glomerular filtration rate, formula, child

匡仟卉柠, 高春林, 朱虹, 杨晓, 彭映潮, 夏正坤. 不同肾小球滤过率估算方程在15~18岁慢性肾脏病儿童中应用比较[J]. 临床儿科杂志, 2022, 40(12): 905-911.

KUANG Qianhuining, GAO Chunlin, ZHU Hong, YANG Xiao, PENG Yingchao, XIA Zhengkun. Comparison of different estimation formulas of glomerular filtration rate in children aged 15-18 years with chronic kidney disease[J]. Journal of Clinical Pediatrics, 2022, 40(12): 905-911.

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参考文献 29

[1]	Al-Aly Z, Bowe B. Biomarkers of CKD in children[J]. J Am Soc Nephrol, 2020, 31(5): 894-896. doi: 10.1681/ASN.2020020212 pmid: 32234830
[2]	Furth SL, Pierce C, Hui WF, et al. Estimating time to ESRD in children with CKD[J]. Am J Kidney Dis, 2018, 71(6): 783-792. doi: S0272-6386(18)30101-X pmid: 29653769
[3]	王学晶. 儿童肾小球滤过率的评估方法[J]. 中华儿科杂志, 2016, 54(7): 539-542.
[4]	Mian AN, Schwartz GJ. Measurement and estimation of glomerular filtration rate in children[J]. Adv Chronic Kidney Dis, 2017, 24(6): 348-356. doi: 10.1053/j.ackd.2017.09.011
[5]	吕潇阳, 钟良宝, 王善志, 等. 肾小球滤过率评估方程在中国糖尿病合并慢性肾脏病患者中的适用性评价[J]. 临床肾脏病杂志, 2019, 19(10): 719-726.
[6]	妇幼健康研究会, 妇女儿童肥胖控制专业委员会, 中国儿童代谢健康型肥胖定义与管理专家委员会. 中国儿童代谢健康型肥胖定义与筛查专家共识[J]. 中国妇幼健康研究, 2019, 30(12): 1487-1490.
[7]	孟群, 吴冬雪, 刘小荣, 等. 儿童慢性肾脏病营养状况及其影响因素分析[J]. 中国实用儿科杂志, 2015, 30(1): 51-54.
[8]	Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults[J]. J Pediatr, 1978, 93(1): 62-66.
[9]	Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD[J]. J Am Soc Nephrol, 2009, 20(3): 629-637. doi: 10.1681/ASN.2008030287 pmid: 19158356
[10]	Grubb A, Horio M, Hansson LO, et al. Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator[J]. Clin Chem, 2014, 60(7): 974-986. doi: 10.1373/clinchem.2013.220707 pmid: 24829272
[11]	Padgett D, Ostrenga A, Lepard L. Comparison of methods of estimating creatinine clearance in pediatric patients[J]. Am J Health Syst Pharm, 2017, 74(11): 826-830. doi: 10.2146/ajhp151004
[12]	Filler G, Lepage N. Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula?[J]. Pediatr Nephrol, 2003, 18(10): 981-985. pmid: 12920638
[13]	Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate[J]. Ann Intern Med, 2009, 150(9): 604-612. doi: 10.7326/0003-4819-150-9-200905050-00006 pmid: 19414839
[14]	Terpos E, Christoulas D, Kastritis E, et al. The Chronic Kidney Disease Epidemiology Collaboration cystatin C (CKD-EPI-CysC) equation has an independent prognostic value for overall survival in newly diagnosed patients with symptomatic multiple myeloma; is it time to change from MDRD to CKD-EPI-CysC equations?[J]. Eur J Haematol, 2013, 91(4): 347-355. doi: 10.1111/ejh.12164 pmid: 23829647
[15]	Björk J, Nyman U, Delanaye P, et al. A novel method for creatinine adjustment makes the revised Lund-Malmö GFR estimating equation applicable in children[J]. Scand J Clin Lab Invest, 2020, 80(6): 456-463. doi: 10.1080/00365513.2020.1774641
[16]	Pottel H, Hoste L, Dubourg L, et al. An estimated glomerular filtration rate equation for the full age spectrum[J]. Nephrol Dial Transplant, 2016, 31(5): 798-806. doi: 10.1093/ndt/gfv454
[17]	National Kidney Foundation. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease [S]. Kidney International Supplements, 2013, 3: 1-150.
[18]	石鑫淼, 刘贝妮, 钟旭辉, 等. 儿童慢性肾脏病流行病学研究进展[J]. 中华儿科杂志, 2019, 57(9): 721-724.
[19]	Weingart C, Wirnsberger GH. Clinical implications of the estimated glomerular filtration rate[J]. Z Gerontol Geriatr, 2021, 54(3): 205-210. doi: 10.1007/s00391-021-01839-1
[20]	Selistre L, De Souza V, Cochat P, et al. GFR estimation in adolescents and young adults[J]. J Am Soc Nephrol, 2012, 23(6): 989-996. doi: 10.1681/ASN.2011070705 pmid: 22499586
[21]	Selistre L, Rabilloud M, Cochat P, et al. Comparison of the Schwartz and CKD-EPI equations for estimating glomerular filtration rate in children, adolescents, and adults: a retrospective cross-sectional study[J]. PloS Med, 2016, 13(3): e1001979. doi: 10.1371/journal.pmed.1001979
[22]	Webster-Clark M, Jaeger B, Zhong Y, et al. Low agreement between modified-Schwartz and CKD-EPI eGFR in young adults: a retrospective longitudinal cohort study[J]. BMC Nephrol, 2018, 19(1): 194. doi: 10.1186/s12882-018-0995-1 pmid: 30081844
[23]	Björk J, Grubb A, Sterner G, et al. Revised equations for estimating glomerular filtration rate based on the Lund-Malmö Study cohort[J]. Scan J Clin Lab Invest, 2011, 71(3): 232-239. doi: 10.3109/00365513.2011.557086
[24]	Nyman U, Berg U, Grubb A, et al. GFR estimation in children-age-adjusted creatinine makes the adult Lund-Malmö equation applicable in children and facilitates automatic GFR reporting from the clinical laboratory[J]. Lakartidningen, 2021, 118: 20134.
[25]	Gowrishankar M, VanderPluym C, Robert C, et al. Value of serum cystatin C in estimating renal function in children with non-renal solid organ transplantation[J]. Pediatr Transplant, 2015, 19(1): 27-34. doi: 10.1111/petr.12381 pmid: 25377124
[26]	Podracka L, Feber J, Lepage N, et al. Intra-individual variation of cystatin C and creatinine in pediatric solid organ transplant recipients[J]. Pediatr Transplant, 2010, 9(1): 28-32. doi: 10.1111/j.1399-3046.2005.00235.x
[27]	Huidobro E JP, Guzmán AM, Tagle R. Use of cystatin C to estimate glomerular filtration rate[J]. Rev Med Chil, 2021, 149(1): 98-102. doi: 10.4067/S0034-98872021000100098
[28]	Zheng K, Gong M, Qin Y, et al. Validation of glomerular filtration rate-estimating equations in Chinese children[J]. PloS One, 2017, 12(7): e0180565.
[29]	Feldman HI, Briggs JP. Race and the estimation of GFR: getting it right[J]. J Am Soc Nephrol, 2021, 32(6): 1269-1270. doi: 10.1681/ASN.2021020206 pmid: 33837121

估算公式	表达式/mL·(min·1.73 m²)^-1
改良Schwartz	0.413×身高/cm·Scr(mg·dL ^-1)^-1
CAPA	130×CysC^-1.069×年龄^0.117-7
Counahan-Barratt	0.43×身高cm·Scr(mg·dL^-1)^-1
Filler	91.62×CysC^-1.123/mg·L ^-1
CKD-EPI-Scr 2009 男性 Scr≤0.9/mg·dL^-1 Scr >0.9/mg·dL ^-1 女性 Scr≤0.7/mg·dL^-1 Scr >0.7/mg·dL^-1	141×(Scr/0.9)^-0.411×0.993^年龄 141×(Scr/0.9)^-1.209×0.993^年龄 141×(Scr/0.7)^-0.329×0.993^年龄 141×(Scr/0.7)^-1.209×0.993^年龄
CKD-EPI-CysC 2012 CysC≤0.8/mg·dL^-1 CysC >0.8/mg·dL^-1	133×(CysC/0.8)^-0.499×0.996^年龄×0.932^女性 133×(CysC/0.8)^-1.328×0.996^年龄×0.932^女性
LMR18	LMR18=e^{X-0.0158×max（年龄；18）+0.438×ln[max（年龄；18）]}
男性 ln（$(\widehat{C r})$）=ln（Cr）+0.259×(18-年龄)-0.543× ln(18/年龄)-0.00763×(18²-年龄²)+0.0000790×(18³-年龄³)
$(\widehat{C r})$<180 /μmol·L^-1 $(\widehat{C r})$≥180 /μmol·L^-1	X=2.56+0.00968×(180-$(\widehat{C r})$) X=2.56-0.926×ln($(\widehat{C r})$/180)
女性 ln（$(\widehat{C r})$）=ln（Cr）+0.177×(18-年龄)-0.223× ln(18/年龄)-0.00596×(18²-年龄²)+0.0000686×(18³-年龄³)
$(\widehat{C r})$<150μmol·L^-1 $(\widehat{C r})$≥150 /μmol·L^-1	X=2.50+0.0121×(150-$(\widehat{C r})$) X=2.50-0.926×ln（$(\widehat{C r})$/150）
FAS	FAS-eGFR=107.3·(Scr/Q^#)^-1

性别	例数	年龄/岁	Scr/μmol·L^-1	CysC/mg·L^-1	身高/cm	体重/kg
男性	56	17.0(16.0~17.0)	78.2(65.0~91.9)	1.1(0.9~1.3)	172.9±5.7	68.6±15.7
女性	32	16.0(16.0~18.0)	62.0(51.8~88.5)	1.1(0.8~1.9)	165.2±5.6	56.5±8.5
统计量		Z=0.35	Z=0.55	Z=1.32	t=6.15	t=4.01
P		0.730	0.582	0.191	<0.001	<0.001

估算公式	偏倚	精确性/%	准确性/%
改良Schwartz	-10.05	25.61	63.64
CAPA	66.75	65.83	30.68
Counahan-Barratt	-6.62	26.16	62.50
Filler	-8.54	38.43	45.45
CKD-EPI-Scr2009	17.29	25.73	53.41
CKD-EPI-CysC2012	-12.87	36.14	45.45
LMR18	-10.63	22.94	73.86
FAS	1.69	26.41	61.36

估算公式	最佳截断值	AUC	95%CI	约登指数	灵敏度/%	特异度/%
改良Schwartz	57.91	0.89	0.77~1.00	0.72	93.20	78.57
CAPA	76.90	0.82	0.67~0.97	0.60	95.90	64.29
Counahan-Barratt	60.30	0.89	0.77~1.00	0.72	93.20	78.57
Filler	41.30	0.82	0.67~0.97	0.60	95.90	64.29
CKD-EPI-Scr2009	87.06	0.91	0.82~1.00	0.71	91.90	78.57
CKD-EPI-CysC2012	36.23	0.82	0.67~0.97	0.60	95.90	64.29
LMR18	76.71	0.89	0.78~1.00	0.68	82.40	85.71
FAS	81.77	0.89	0.77~1.00	0.71	85.10	85.71