非透析慢性肾脏病患者发生肾性贫血风险预测模型的开发与验证

杨洁; 边宇; 张蕊

doi:10.7619/jcmp.20230125

非透析慢性肾脏病患者发生肾性贫血风险预测模型的开发与验证

哈尔滨医科大学附属第二医院肾内科, 黑龙江哈尔滨, 150001

详细信息

通讯作者:
张蕊, E-mail: bronza@126.com

中图分类号: R753.9;R692.5
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出版历程
- 收稿日期: 2023-01-15
- 修回日期: 2023-04-03
- 网络出版日期: 2023-06-06

Development and validation of a risk prediction model for renal anemia in non-dialysis chronic kidney disease patients

Department of Nephrology, the Second Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang, 150001

摘要

摘要:
目的
探讨非透析慢性肾脏病(CKD)患者发生肾性贫血的影响因素，建立非透析CKD患者发生肾性贫血的风险模型，并验证预测模型的有效性。
方法
回顾性分析2017年1月—2021年12月收治的非透析CKD患者的临床资料，按7∶3比例随机分为训练集(n=388)与验证集(n=165)。利用单因素和多因素Logistic回归分析筛选影响肾性贫血的影响因素，基于赤池信息准则(AIC)最小值选取最终预测因素构建列线图，并验证模型效能。
结果
单因素Logistic回归分析显示, 17个变量[白细胞计数、中性粒细胞百分比、红细胞分布宽度(RDW)、血小板压积、碱性磷酸酶、血清白蛋白(ALB)、血胱抑素C、尿素、CKD分期、碳酸氢钠、血钾、血钙、血磷、C反应蛋白(CRP)、甘油三酯、尿白蛋白、尿隐血]与贫血的发生相关(P < 0.05)。多因素Logistic回归分析结果提示，白细胞计数、CRP、RDW、ALB、血胱抑素C、尿素、CKD分期、碳酸氢盐、血钙是贫血独立影响因素(P < 0.05)。利用危险因素构建列线图，经验证模型具有较好的区分度[训练集ROC曲线下面积(AUC)为0.915(95%CI: 0.870~0.959), 验证集为0.949(95%CI: 0.927~0.971)]。校准曲线及H-L检验均提示模型预测值与实际值差异无统计学意义(P>0.05)。临床决策曲线分析(DCA)表明该模型具有良好的临床应用价值。
结论
本研究开发的预测模型能较好地预测非透析CKD患者肾性贫血的发生风险，为临床决策提供参考。
- 非透析慢性肾脏病 /
- 贫血 /
- 危险因素 /
- 预测模型 /
- 列线图 /
- 区分度
Abstract:
Objective
To investigate the influencing factors of renal anemia in non-dialysis chronic kidney disease (CKD) patients, and to establish a risk model of renal anemia in non-dialysis CKD patients and verify its validity.
Methods
The clinical data of non-dialysis CKD patients admitted from January 2017 to December 2021 were retrospectively analyzed. The patients were randomly divided into training set (n=388) and validation set (n=165) at a ratio of 7∶3. Univariate and multivariate Logistic regression analysis was used to screen out the influencing factors for renal anemia. Based on the minimum Akaike Information Criterion (AIC) criterion, the final predictors were selected to construct the nomogram, and the efficiency of the model was verified.
Results
Multivariate Logistic regression analysis showed that 17 variables including white blood cell, percentage of neutrophil granulocyte, erythrocyte distribution width (RDW), thrombocytocrit, alkaline phosphatase, serum albumin (ALB), cystatin C, urea, CKD stage, bicarbonate, potassium, calcium, phosphorus, C-reactive protein (CRP), triglyceride, urinary albumin, occult urine were associated with anemia(P < 0.05). Multiple Logistic regression analysis showed that white blood cell count, CRP, RDW, ALB, cystatin C, urea, CKD stage, bicarbonate and blood calcium were independent influencing factors for anemia (P < 0.05). Using risk factors to construct a nomogram, the validation model had good discrimination [the area under ROC curve (AUC) of the training set was 0.915(95%CI, 0.870 to 0.959), and the validation set was 0.949(95%CI, 0.927 to 0.971)]. The calibration curve and H-L test showed that there was no significant difference between the predicted value and the actual value of the model(P>0.05). The clinical decision curve analysis (DCA) showed that the model had good clinical application value.
Conclusion
The model developed in this study can better predict the risk of renal anemia in non-dialysis CKD patients, and provide reference for clinical decision-making.
- non-dialysis chronic renal disease /
- anemia /
- risk factors /
- prediction model /
- nomogram /
- differentiation degree

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图 1 非CKD患者肾性贫血预测列线图

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图 2 训练集及验证集ROC曲线

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图 3 建模人群校准图

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图 4 验证人群校准图

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图 5 训练集及验证集临床决策曲线

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表 1 训练集及验证集基本资料比较[n(%)]

变量	分类	训练集			验证集
变量	分类	贫血组(n=286)	非贫血组(n=102)	合计(n=388)	贫血组(n=129)	非贫血组(n=36)	合计(n=165)
年龄	18~44岁	59	29	88(22.7)	30	12	42(25.5)
	45~60岁	120	36	156(40.2)	42	18	60(36.4)
	> 60岁	107	37	144(37.1)	57	6	63(38.2)
性别	男	159	57	216(55.7)	82	16	98(59.4)
	女	127	45	172(44.3)	47	20	67(40.6)
高血压	有	220	69	289(74.5)	102	27	129(78.2)
	无	66	33	99(25.5)	27	9	36(21.8)
糖尿病	有	82	33	115(29.6)	44	9	53(32.1)
	无	204	69	273(70.4)	85	27	112(67.9)
白细胞计数	< 4×10⁹/L	18	1	19(4.9)	11	0	11(6.7)
	(4~10)×10⁹/L	242	86	328(84.5)	107	29	136(82.4)
	> 10×10⁹/L	26	15	41(10.6)	11	7	18(10.9)
中性粒细胞百分比	< 70%	108	56	164(42.3)	54	26	80(48.5)
	≥70%	78	46	124(57.7)	75	10	85(51.5)
淋巴细胞百分比	< 40%	280	99	379(97.7)	127	36	163(98.8)
	≥40%	6	3	9(2.3)	2	0	2(1.2)
红细胞分布宽度	< 15%	224	101	325(83.8)	110	36	146(88.5)
	≥15%	62	1	63(16.2)	19	0	19(11.5)
血小板计数	< 300×10⁹/L	237	86	323(83.2)	115	30	145(87.9)
	≥300×10⁹/L	49	16	65(16.8)	14	6	20(12.1)
平均血小板容积	< 9 fl	19	2	21(5.4)	6	0	6(3.6)
	≥9 fl	267	100	367(94.6)	123	36	159(96.4)
血小板分布宽度	< 17%	277	94	371(95.6)	126	31	157(95.2)
	≥17%	9	8	17(4.4)	3	5	8(4.8)
血小板压积	< 0.23%	147	32	179(46.1)	73	7	80(48.5)
	≥0.23%	139	70	209(53.9)	56	29	85(51.5)
碱性磷酸酶	< 125 U/L	252	98	350(90.2)	119	34	153(92.7)
	≥125 U/L	34	4	38(9.8)	10	2	12(7.3)
白蛋白	< 35 g/L	127	15	142(36.6)	47	9	56(33.9)
	≥35 g/L	159	87	246(63.4)	82	27	109(66.1)
球蛋白	< 35 g/L	214	81	295(76)	90	29	119(72.1)
	≥35 g/L	72	21	93(24)	39	7	46(27.9)
血胱抑素C	< 2.5 mg/L	60	88	148(38.1)	28	30	58(35.2)
	≥2.5 mg/L	226	14	240(61.9)	101	6	107(67.8)
尿素	< 7.5 mmol/L	11	44	55(14.2)	5	7	12(7.3)
	≥7.5 mmol/L	275	58	333(85.8)	124	29	153(92.7)
慢性肾脏病分期	CKD1期	12	45	57(14.7)	9	12	21(12.7)
	CKD2期	23	26	49(12.6)	9	12	21(12.7)
	CKD3期	97	28	125(32.2)	38	10	48(29.1)
	CKD4期	81	3	84(21.6)	33	1	34(20.6)
	CKD5期	73	0	73(18.8)	40	1	41(24.8)
尿酸	< 420 μmol/L	115	50	165(42.5)	50	17	67(40.6)
	≥420 μmol/L	171	52	223(57.5)	79	19	98(59.4)
碳酸氢盐	< 22 mmol/L	150	19	169(43.6)	57	5	62(37.6)
	≥22 mmol/L	136	83	219(56.4)	72	31	103(62.4)
钾	< 5.5 mmol/L	231	96	327(84.3)	110	35	145(87.9)
	≥5.5 mmol/L	55	6	61(15.7)	19	1	20(12.1)
钠	< 145 mmol/L	265	96	361(93)	119	34	153(92.7)
	≥145 mmol/L	21	6	27(7)	10	2	12(7.3)
钙	< 2.25 mmol/L	227	46	273(70.4)	102	14	116(70.3)
	≥2.25 mmol/L	59	56	115(29.6)	27	22	49(29.7)
磷	< 1.61 mmol/L	165	99	264(68)	70	33	103(62.4)
	≥1.61 mmol/L	121	3	124(32)	59	3	62(37.6)
C反应蛋白	< 10 mmol/L	204	94	298(76.8)	90	32	122(73.9)
	≥10 mmol/L	82	8	90(23.2)	39	4	43(26.1)
总胆固醇	< 5.72 mmol/L	235	76	311(80.2)	114	22	136(82.4)
	≥5.72 mmol/L	51	26	77(19.8)	15	14	29(17.6)
甘油三酯	< 1.7 mmol/L	158	40	198(51)	62	12	74(44.8)
	≥1.7 mmol/L	128	62	190(49)	67	24	91(55.2)
高密度脂蛋白	< 0.9 mmol/L	92	26	118(30.4)	48	10	58(35.2)
	≥0.9 mmol/L	194	76	270(69.6)	81	26	107(67.8)
低密度脂蛋白	< 4.1 mmol/L	266	95	361(93)	126	30	156(94.5)
	≥4.1 mmol/L	20	7	27(7)	3	6	9(5.5)
尿白蛋白	0	30	29	59(15.2)	14	10	24(14.5)
	+	37	21	58(14.9)	22	4	26(15.8)
		85	26	111(28.6)	39	7	46(27.9)
		118	20	138(35.6)	46	13	59(35.8)
		16	6	22(5.7)	8	2	10(6.1)
尿隐血	0	99	60	159(41)	55	11	66(40.0)
	+	95	19	114(29.4)	37	9	46(27.9)
		68	14	82(21.1)	27	88	35(21.2)
		24	9	33(8.5)	10	8	18(10.9)

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表 2 单因素及多因素Logistic回归分析

变量	分类	单因素分析		多因素分析
变量	分类	OR(95%CI)	P	OR(95%CI)	P
年龄	18~44岁	1
	45~60岁	1.64(0.92~2.93)	0.095	—	—
	> 60岁	1.42(0.80~2.54)	0.235	—	—
性别	女	1
	男	0.99(0.63~1.56)	0.96	—	—
高血压	无	1
	有	1.59(0.97~2.62)	0.066	—	—
糖尿病	无	1
	有	0.84(0.52~1.37)	0.485	—	—
白细胞计数	< 4×10⁹/L	1
	(4~10)×10⁹/L	0.16(0.02~1.19)	0.073	0.13(0.01~2.10)	0.150
	>10×10⁹/L	0.10(0.01~0.80)	0.03	0.01(0~0.33)	0.008
中性粒细胞百分比	< 70%	1		—	—
	≥70%	2.01(1.27~3.17)	0.003	—	—
淋巴细胞百分比	< 40%	1
	≥40%	0.71(0.17~2.88)	0.629	—	—
红细胞分布宽度	< 15%	1
	≥15%	27.96(3.82~204.39)	0.001	18.03(1.97~164.85)	0.010
血小板计数	< 300×10⁹/L	1
	≥300×10⁹/L	1.11(0.60~2.06)	0.737	—	—
平均血小板体积	< 9 fl	1
	≥9 fl	0.28(0.06~1.23)	0.092	—	—
血小板分布宽度	< 17%	1
	≥17%	0.38(0.14~1.02)	0.054	—	—
血小板压积	< 0.23 fl	1
	≥0.23 fl	0.43(0.27~0.70)	0.001	—	—
碱性磷酸酶	< 125 U/L	1
	≥125 U/L	3.31(1.14~9.56)	0.027	3.72(0.68~20.39)	0.130
白蛋白	< 35 g/L	1
	≥35 g/L	0.22(0.12~0.39)	0	0.27(0.11~0.70)	0.007
球蛋白	< 35 g/L	1
	≥35 g/L	1.30(0.75~2.25)	0.352	—	—
血胱抑素C	< 2.5 mg/L	1
	≥2.5 mg/L	23.68(12.60~44.50)	0	2.85(1.06~7.71)	0.039
尿素	< 7.5 mmol/L	1
	≥7.5 mmol/L	18.97(9.24~38.94)	0	5.90(2.04~17.08)	0.001
慢性肾脏病分期	CKD1期	1
	CKD2期	3.32(1.42~7.75)	0.006	2.06(0.69~6.15)	0.193
	CKD3期	12.99(6.06~27.85)	0	3.30(1.06~10.28)	0.040
	CKD4期	101.25(27.13~377.93)	0	10.19(1.70~61.09)	0.011
	CKD5期	433682 972.79(0~Inf)	0.979	86 627 793.63(0~Inf)	0.987
尿酸	< 420 mmol/L	1
	≥420 mmol/L	1.43(0.91~2.25)	0.123	—	—
碳酸氢钠	< 22 mmol/L	1
	≥22 mmol/L	0.21(0.12~0.36)	0	0.36(0.15~0.82)	0.016
钾	< 5.5 mmol/L	1
	≥5.5 mmol/L	3.81(1.59~9.15)	0.003	—	—
钠	< 145 mmol/L	1
	≥145 mmol/L	1.27(0.50~3.24)	0.619	—	—
钙	< 2.25 mmol/L	1
	≥2.25 mmol/L	0.21(0.13~0.35)	0.000	0.35(0.16~0.75)	0.007
磷	< 1.61 mmol/L	1
	≥1.61 mmol/L	24.20(7.50~78.13)	0.000	—	—
C反应蛋白	< 10 mmol/L	1
	≥10 mmol/L	4.72(2.19~10.16)	0.000	4.26(1.19~15.20)	0.025
总胆固醇	< 5.72 mmol/L	1
	≥5.72 mmol/L	0.63(0.37~1.09)	0.098	—	—
甘油三酯	< 1.7 mmol/L	1
	≥1.7 mmol/L	0.52(0.33~0.83)	0.006	—	—
高密度脂蛋白	< 0.9 mmol/L	1
	≥0.9 mmol/L	0.72(0.43~1.20)	0.209	—	—
低密度脂蛋白	< 4.1 mmol/L	1
	≥4.1 mmol/L	1.02(0.42~2.49)	0.965	—	—
尿白蛋白	0	1
	+	1.70(0.81~3.57)	0.158	—	—
		3.16(1.61~6.20)	0.001	—	—
		5.70(2.84~11.44)	0.000	—	—
		2.58(0.89~7.50)	0.082	—	—
尿隐血	0	1
	+	3.03(1.68~5.46)	0.000	—	—
		2.94(1.52~5.69)	0.001	—	—
		1.62(0.70~3.71)	0.257	—	—

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