Construction and validation of a risk model of proteinuria in patients with omicron COVID‐19: retrospective cohort study

Figures & data

Table 1. Demographic and clinical characteristics in derivation cohort and validation cohort.

Variables	Derivation Cohort (n = 1091)				Validation Cohort (n = 306)				p^#
	All patients	proteinuria (n = 50)	no proteinuria (n = 1041)	p*	All patients	proteinuria (n = 61)	no proteinuria (n = 245)	p*
Demographics
Age (year)	38.49 ± 16.10	41.90 ± 19.69	38.32 ± 15.89	0.125	45.93 ± 16.14	50.90 ± 17.79	44.70 ± 15.49	0.007	<0.001
Sex (male, n%)	583 (53.4)	38 (76.0)	545 (52.4)	0.001	125 (40.8)	30 (49.2)	95 (38.8)	0.148	<0.001
BMI (Kg/m^2)	24.39 ± 3.96	25.99 ± 4.66	24.31 ± 3.91	0.009	25.25 ± 4.70	26.76 ± 4.83	24.87 ± 4.60	0.005	0.002
Comorbidities
Hypertension (n, %)	128 (11.7)	14 (28.0)	114 (11.0)	0.001	80 (26.1)	31 (50.8)	49 (20.0)	<0.001	<0.001
Diabetes (n, %)	40 (3.7)	9 (18.0)	31 (3.0)	<0.001	34 (11.1)	12 (19.7)	22 (9.0)	0.023	<0.001
CVD (n, %)	38 (3.5)	9 (18.0)	29 (2.8)	<0.001	23 (7.5)	9 (14.8)	14 (5.7)	0.027	<0.001
Laboratory parameters
HGB (g/dL)	12.95 ± 1.87	13.38 ± 1.92	12.85 ± 1.86	0.053	12.88 ± 1.83	13.04 ± 1.94	12.83 ± 1.80	0.422	0.327
WBC (×10^9/L)	6.22 ± 1.85	6.95 ± 1.86	5.91 ± 1.84	0.203	6.46 ± 1.84	7.02 ± 2.43	6.32 ± 1.63	0.008	0.154
PLT (×10^9/L)	279.51 ± 57.16	294.85 ± 50.89	250.68 ± 57.20	0.062	275.89 ± 75.11	282.39 ± 72.56	274.22 ± 75.81	0.449	0.518
ALT (U/L)	28.64 [13.42-48.80]	31.37 [14.29-54.40]	28.58 [13.38-38.74]	0.311	33.13 [20.04-67.39]	39.71 [26.38-79.97]	32.38 [18.31-66.17]	0.065	0.053
BUN (mmol/L)	4.31 ± 1.33	5.49 ± 2.08	4.25 ± 1.25	<0.001	4.16 ± 1.26	4.69 ± 1.45	4.02 ± 1.17	<0.001	0.074
Cr (μmol/L)	66.89 ± 17.89	85.68 ± 34.57	65.98 ± 16.17	<0.001	60.65 ± 13.72	62.55 ± 14.12	58.92 ± 13.55	0.065	0.055
eGFR (mL/min/1.73 m^2)	110.33 ± 18.24	96.11 ± 26.59	111.02 ± 17.47	<0.001	108.90 ± 15.60	104.71 ± 17.86	109.95 ± 14.83	0.019	0.213
Na (mmol/L)	140.35 ± 2.31	140.83 ± 2.47	140.33 ± 2.30	0.331	140.82 ± 1.97	141.01 ± 1.94	140.78 ± 1.98	0.414	0.179
K (mmol/L)	4.12 ± 0.40	4.02 ± 0.45	4.12 ± 0.40	0.067	4.11 ± 0.36	4.07 ± 0.37	4.13 ± 0.36	0.304	0.836
Ca (mmol/L)	2.20 ± 0.10	2.26 ± 0.09	2.25 ± 0.10	0.374	2.19 ± 0.13	2.13 ± 0.10	2.21 ± 0.14	0.022	0.416
UA (mmol/L)	348.71 ± 95.22	398.85 ± 115.8	335.82 ± 93.20	<0.001	349.91 ± 56.91	398.48 ± 58.44	337.81 ± 49.72	<0.001	0.051
FBG (mmol/L)	5.78 ± 1.40	6.19 ± 2.09	5.34 ± 1.35	<0.001	6.13 ± 1.74	6.77 ± 2.60	5.97 ± 1.45	0.113	0.067
CRP (mg/L)	5.68 [1.53-9.69]	8.96 [4.07-19.03]	5.34 [1.47-9.34]	<0.001	6.01 [5.43-7.04 ]	7.99 [5.93-12.12]	5.86 [4.35-6.69]	<0.001	<0.001
IL-6 (pg/mL)	10.39 [7.17-15.34]	11.56 [8.42-15.68]	10.27 [7.12-15.20]	0.045	4.15 [2.98-6.28]	4.53 [3.71-6.52]	4.08 [2.78-5.70]	0.473	<0.001
LDH (U/L)	182.12 [161.31-203.39]	185.09 [169.09-210.25]	181.34 [160.85-202.50]	0.063	171.06 [154.69-195.50]	169.61 [162.40-195.22]	171.65 [153.70-196.33]	0.791	0.115
Vaccine dosage				0.008				0.002	0.001
Unvaccinated (n, %)	29 (2.7)	5 (10.0)	24 (2.3)		23 (7.5)	11 (18.0)	12 (4.9)
One dose (n, %)	68 (6.2)	5 (10.0)	63 (6.1)		16 (5.2)	5 (8.2)	11 (4.5)
Two doses (n, %)	419 (38.4)	19 (38.0)	400 (38.4)		119 (38.9)	22 (36.1)	97 (39.6)
Three doses (n, %)	575 (52.7)	21 (42.0)	554 (53.2)		148 (48.4)	23 (37.7)	125 (51.0)
Vaccine type				0.410				0.881	0.009
Sinovac (n, %)	407 (38.3)	21 (46.7)	386 (38.0)		136 (48.1)	25 (47.2)	111 (48.3)
Sinopharm (n, %)	393 (37.0)	16 (35.6)	377 (37.1)		94 (33.2)	19 (35.8)	75 (32.6)
Others (n, %)	262 (24.7)	8 (17.8)	254 (25.0)		53 (18.7)	9 (17.0)	44 (19.1)
Clinical classification				1.000
Asymptomatic cases (n, %)	973 (89.2)	46 (92.0)	927 (89.0)		114 (37.3)	21 (34.4)	93 (38.0)	0.419	<0.001
Mild type (n, %)	118 (10.8)	4 (8.0)	114 (11.0)		3 (1.0)	0 (0.0)	3 (1.2)
Ordinary type (n, %)	0 (0.0)	0 (0.0)	0 (0.0)		183 (59.8)	40 (65.6)	143 (58.4)
Severe type (n, %)	0 (0.0)	0 (0.0)	0 (0.0)		6 (2.0)	0 (0.0)	6 (2.4)

Abbreviations: BMI, body mass index; CVD, cardiovascular and cerebrovascular diseases; HGB, hemoglobin; WBC, white blood cell; PLT, platelets; ALT, alanine transaminase; BUN, blood urea nitrogen; Cr, creatinine; eGFR, estimated glomerular filtration rate; Na, sodium; K, potassium; Ca, calcium; UA, uric acid; FBG, fasting blood glucose; CRP, C reactive protein; IL-6, interleukin 6; LDH, lactic dehydrogenase.

* Independent sample T test, Mann–Whitney U test, chi squared test or Fisher’s exact test as appropriate between patients with or without proteinuria.

^# Independent sample T test, Mann–Whitney U test, chi squared test or Fisher’s exact test as appropriate between derivation cohort and validation cohort.

Table 2. Logistic regression analysis of variables assessing proteinuria in derivation cohort.

Variables	Univariate		Multivariate
	OR (95% CI)	p	OR (95% CI)	p
Age >60.5 years	2.939 (1.488-5.805)	0.002	0.592 (0.151-2.328)	0.453
Sex (male)	2.882 (1.489-5.578)	0.002	0.363 (0.115-1.144)	0.084
BMI >27.2 Kg/m^2	2.834 (1.478-5.434)	0.002	1.455 (0.648-3.268)	0.363
Hypertension (Yes)	3.162 (1.655-6.041)	<0.001	0.960 (0.321-2.878)	0.943
Diabetes (Yes)	7.152 (3.197-15.999)	<0.001	7.974 (1.835-34.665)	0.006
CVD (Yes)	7.660 (3.406-17.227)	<0.001	6.092 (1.290-28.758)	0.022
HGB >15.1 g/L	2.091 (1.172-3,731)	0.013	0.858 (0.334-2.203)	0.751
WBC >5.4 × 10^9/L	2.414 (1.244-4.683)	0.009	1.897 (0.736-4.889)	0.185
BUN >4.62 mmol/L	3.688 (2.019-6.736)	<0.001	3.340 (1.430-7.801)	0.005
Cr >73.2 μmol/L	5.189 (2.754-9.777)	<0.001	3.406 (1.206-9.622)	0.021
Na >141.4 mmol/L	1.772 (0.996-3.152)	0.052	2.502 (1.066-5.869)	0.035
Ca <2.23 mmol/L	1.858 (0.987-3.496)	0.055	1.982 (0.810-4.849)	0.134
UA >395.9 mmol/L	3.548 (1.988-6.330)	<0.001	3.244 (1.366-7.702)	0.008
FBS >5.4 mmol/L	3.251 (1.811-5.835)	<0.001	1.524 (0.674-3.444)	0.312
CRP >9.83 mg/L	4.075 (2.279-7.289)	<0.001	5.270 (2.308-12.036)	<0.001
IL-6 > 10.1 pg/mL	2.111 (1.132-3.934)	0.019	2.162 (0.909-5.140)	0.081
Vaccine dosage
Unvaccinated	reference		reference
One dose compared unvaccinated	0.383 (0.101-1.449)	0.158	0.408 (0.068-2.447)	0.327
Two doses compared unvaccinated	0.226 (0.078-0.661)	0.007	0.192 (0.041-0.901)	0.036
Three doses compared unvaccinated	0.172 (0.059-0.499)	0.001	0.092 (0.019-0.448)	0.003

Abbreviations: BMI, body mass index; CVD, cardiovascular and cerebrovascular diseases; HGB, hemoglobin; WBC, white blood cell; BUN, blood urea nitrogen; Cr, creatinine; Na, sodium; Ca, calcium; UA, uric acid; FBG, fasting blood glucose; CRP, C reactive protein; IL-6, interleukin 6.

Figure 1. ROC curve of the risk model for the derivation and validation cohort.

Area under the ROC curve to determine the assessing ability of the model in two cohorts, respectively, representing the sensitivity on the ordinate axis and specificity in the abscissa. Blue represents ROC curve of the Derivation cohort. Red represents ROC curve of the Validation cohort.

Table 3. The point assignment for assessing variables in the derivation cohort.

Variables	β regression coefficients (95% CI)	score
Diabetes (Yes)	2.076	5
CVD (Yes)	1.807	4
BUN >4.6 mmol/L	1.206	3
Na >141.4 mmol/L	0.917	2
UA >395.9 mmol/L	1.177	3
CRP >9.8 mg/L	1.662	4
Vaccine dosage
Unvaccinated	reference	0
One dose	−0.895	0
Two doses	−1.651	−4
Three doses	−2.383	−5

Abbreviations: CVD, cardiovascular and cerebrovascular diseases; BUN, blood urea nitrogen; Na, sodium; UA, uric acid; CRP, C reactive protein.

Table 4. Diagnostic accuracy of the assessing score for after omicron proteinuria in derivation cohort and validation cohort.

Score	Sensitivity (95% CI)	Specificity (95% CI)
>−4.5
Derivation Cohort	100.0 (94.1 to 100.0)	23.2 (18.3 to 29.0)
Validation Cohort	100.0 (92.6 to 100.0)	11.5 (9.61 to 13.6)
>−1.5
Derivation Cohort	88.5 (78.2 to 94.3)	60.34 (54.0 to 66.4)
Validation Cohort	93.8 (83.2 to 97.9)	37.93 (35.0 to 41.0)
>1.5
Derivation Cohort	65.6 (53.1 to 76.3)	83.1 (77.8 to 87.4)
Validation Cohort	85.4 (72.8 to 92.8)	62.9 (59.8 to 65.9)
>4.5
Derivation Cohort	44.3 (32.5 to 56.7)	92.4 (88.3 to 95.1)
Validation Cohort	72.9 (59.0 to 83.4)	83.0 (80.6 to 85.3)
>7.5
Derivation Cohort	23.0 (14.2 to 34.9)	97.1 (94.0 to 98.6)
Validation Cohort	41.7 (28.9 to 55.7)	94.7 (93.1 to 95.9)
>10.5
Derivation Cohort	8.20 (3.55 to 17.8)	98.3 (95.7 to 99.3)
Validation Cohort	16.7 (8.70 to 29.6)	99.3 (98.5 to 99.7)
>13.5
Derivation Cohort	4.92 (1.34 to 13.5)	99.2 (97.0 to 99.9)
Validation Cohort	12.5 (5.86 to 24.7)	99.6 (99.0 to 99.8)
>16.5
Derivation Cohort	3.28 (0.583 to 11.2)	100.0 (98.4 to 100.0)
Validation Cohort	6.25 (2.148 to 16.8)	100.0 (99.6 to 100.0)

Abbreviations: CI, confidence interval.