Elevated Serum Osteoprotegerin is Associated with Reduced Risks of Albuminuria and CKD Progression in Patients with Type 2 Diabetes

Figures & data

Figure 1 Population groupings by albuminuria, eGFR and the KDIGO risk categories.

Notes: I: low risk; II: moderate risk; III: high risk and very high risk.

Abbreviations: UACR, urinary albumin/urinary creatinine ratio; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes.

Table 1 Characteristics of Subjects

Variables	Values
Male (n, %)	261 (53.9%)
Age (years)	62 ± 12
BMI (kg/m^2)	24.9 ± 3.5
Duration of diabetes (years)	7 (3–11)
HbA1c (%)	8.7 (7.0–10.7)
Hypertension (n, %)	265 (54.8%)
SBP (mmHg)	134 (124–145)
DBP (mmHg)	80 (74–85)
Current smoking (n, %)	150 (31.0%)
Drinking behavior (n, %)	49 (10.1%)
eGFR (mL/min/1.73m^2)	117.26 ± 42.84
UACR (mg/g)	22.75 (11.30–90.80)
OPG (pg/mL)	941.30 (547.53–1332.62)

Abbreviations: BMI, body mass index; HbA1c, hemoglobin A1c; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; eGFR, estimated glomerular filtration rate; UACR, urinary albumin/urinary creatinine ratio; OPG, osteoprotegerin.

Table 2 Comparison of OPG Levels by Persistent Albuminuria Categories

	Persistent Albuminuria Categories
	A1	A2	A3	P
Numbers (%)	286 (59.1%)	127 (26.2%)	71 (14.7%)	–
Age (years)	60.51 ± 11.59	65.25 ± 11.66*	63.00 ± 11.83	<0.001
BMI (kg/m^2)	24.67 ± 3.11	25.29 ± 4.20	25.21 ± 3.75	0.19
Duration of diabetes (years)	5 (2–10)	10 (5–15)*	10 (5–20)*^#	<0.001
HbA1c (%)	8.56 (6.9–10.7)	9 (7.4–10.7)	8.7 (7–10.6)	0.54
Hypertension (n, %)	131 (49.4%)	78 (29. 3%)	56 (21.3%)	–
SBP (mmHg)	130 (120–140)	134 (130–148)*	140 (130–160)*	<0.001
DBP (mmHg)	80 (70–85)	80 (78–86)	80 (78–86)	0.28
Current smoking (n, %)	87 (58%)	30 (20%)	33 (22%)	–
Drinking behavior (n, %)	32 (65.3%)	11 (22.5%)	6 (12.2%)	–
OPG (pg/mL)	974.82 (617.99–1343.78)	964.43 (546.02–1305.53)	815.40 (325.55–1243.53)*^#	0.007

Notes: A1, A2 and A3 defined as UACR<30, 30–300 and >300 mg/g. *P < 0.05, compared with A1; ^#P < 0.05, compared with A2.

Abbreviations: BMI, body mass index; HbA1c, hemoglobin A1c; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; OPG, osteoprotegerin.

Table 3 Comparison of OPG Levels by eGFR Categories

	eGFR Categories
	G1	G2	G3–5	P
Numbers (%)	356 (73.6%)	80 (16.5%)	48 (9.9%)	–
Age (years)	60.13 ± 11.50	68.93 ± 10.19*	65.45 ± 11.83*	<0.001
BMI (kg/m^2)	24.84 ± 3.27	25.23 ± 4.56	24.87 ± 3.58	0.68
Duration of diabetes (years)	6 (2–10)	10 (5–16.5)*	13.5 (9–20)*	<0.001
HbA1c (%)	8.75 (7.1–10.7)	9.15 (7.3–10.95)	7.65 (6.4–9.2)	0.051
Hypertension (n, %)	173 (65.28%)	55 (20.76%)	37 (13.96%)	–
SBP (mmHg)	130 (122–140)	139 (126–150)	141 (129–160)*	0.004
DBP (mmHg)	80 (74–86)	80 (70–82)	80 (77–83)	0.35
Current smoking (n, %)	111 (74%)	21 (14%)	18 (12%)	–
Drinking behavior (n, %)	40 (81.63%)	5 (10.20%)	4 (8.17%)	–
OPG (pg/mL)	964.51 (536.15–1333.02)	937.83 (636.98–1332.09)	795.01 (380.55–1211.72)	0.31

Notes: G1, G2 and G3–5 defined as eGFR≥90, 60–89 and <60 mL/min/1.73m². *P < 0.05, compared with G1.

Abbreviations: BMI, body mass index; HbA1c, hemoglobin A1c; SBP, systolic blood pressure; DBP, Diastolic blood pressure; eGFR, estimated glomerular filtration rate.

Table 4 Comparison of OPG Levels by KDIGO Categories

	KDIGO Categories
	I	II	III	P
Numbers (%)	282 (58.3%)	114 (23.6%)	88 (18.2%)	–
Age (years)	62.80 ± 11.54	61.21 ± 12.76	60.95 ± 11.45	0.30
BMI (kg/m^2)	25.17 ± 3.74	24.89 ± 3.32	24.01 ± 2.84*	0.03
Duration of diabetes (years)	7 (3–11)	7 (2–10)	8 (3–11.5)	0.50
HbA1c (%)	9 (7.3–10.9)	8.5 (6.8–10.1)	8.1 (6.8–10.6)	0.10
Hypertension (n, %)	156 (58.87%)	61 (23.02%)	48 (18.11%)	–
SBP (mmHg)	132 (124–144)	134 (120–145)	130 (125–146)	0.90
DBP (mmHg)	80 (74–85)	80 (74–80.5)	80 (77–90)	0.29
Current smoking (n, %)	79 (52.67%)	40 (26.67%)	31 (20.66%)	–
Drinking behavior (n, %)	22 (44.90%)	12 (24.49%)	15 (30.61%)	–
OPG (pg/mL)	978.29 (616.44–1348.51)	979.57 (560.15–1326.32)	804.65 (329.08–1211.72)*^#	0.001

Notes: I, II and III defined as low, moderately increased, and high or very high risk of CKD progression. *P < 0.05, compared with I; ^#P < 0.05, compared with II.

Abbreviations: BMI, body mass index; HbA1c, hemoglobin A1c; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; KDIGO, Kidney Disease, Improving Global Outcomes.

Table 5 Effects of Each 100 Pg/Ml Increase in OPG Levels on Albuminuria

Persistent Albuminuria Categories	Model 1		Model 2		Model 3
	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
A1	1	–	1	–	1	–
A2	0.98 (0.95–1.02)	0.31	0.99 (0.95–1.03)	0.62	1.00 (0.96–1.04)	0.88
A3	0.94 (0.90–0.99)	0.02	0.94 (0.89–0.99)	0.02	0.92 (0.86–0.99)	0.02

Notes: Model 1, no adjustment; Model 2, adjustment for sex, age, BMI; Model 3, adjustment for sex, age, BMI, duration of diabetes, HbA1c, FPG, 2hPG, history of hypertension (yes or no), systolic and diastolic blood pressure, current smoking and drinking behavior (yes or no), and eGFR.

Table 6 Effects of Each 100 Pg/mL Increase in OPG Levels on eGFR

eGFR Categories	Model 1		Model 2		Model 3
	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
G1	1	–	1	–	1	–
G2	1.00 (0.96–1.04)	0.86	1.00 (0.96–1.05)	0.95	1.02 (0.97–1.07)	0.42
G3–5	0.97 (0.91–1.02)	0.19	0.97 (0.91–1.02)	0.25	1.00 (0.93–1.09)	0.91

Notes: Model 1, no adjustment; Model 2, adjustment for sex, age, and BMI; Model 3, adjustment for sex, age, BMI, duration of diabetes, HbA1c, FPG, 2hPG, history of hypertension (yes or no), systolic and diastolic blood pressure, current smoking and drinking behavior (yes or no), and UACR.

Table 7 Effects of Each 100 Pg/mL Increase in OPG Levels on KDIGO Categories

KDIGO Categories	Model 1		Model 2		Model 3
	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
I	1	–	1	–	1	–
II	0.99 (0.95–1.02)	0.44	0.99 (0.96–1.03)	0.77	1.01 (0.96–1.05)	0.80
III	0.94 (0.90–0.98)	0.006	0.94 (0.89–0.98)	0.01	0.94 (0.89–0.99)	0.04

Notes: Model 1, no adjustment; Model 2, adjustment for sex, age, and BMI; Model 3, adjustment for sex, age, BMI, duration of diabetes, HbA1c, FPG, 2hPG, history of hypertension (yes or no), systolic and diastolic blood pressure, and current smoking and drinking behavior (yes or no).