The association of plasma NT-proBNP level and progression of diabetic kidney disease

Figures & data

Figure 1. Flowchart of study participants.

Table 1. The clinical characteristics according to the plasma NT-proBNP concentrations.

Parameters	All (n = 122)	Group 1 (n = 54)	Group 2 (n = 34)	Group 3 (n = 34)	p
Age (years)	51.2 ± 10.6	47.9 ± 10.8	51.2 ± 8.9	56.6 ± 9.9	0.001
Body mass index (kg/m^2)	25.5 ± 3.0	25.5 ± 2.6	25.7 ± 3.3	25.3 ± 3.1	0.873
Gender (Male, %)	82 (67.2)	39 (72.2)	21 (61.8)	22 (64.7)	0.557
Duration of diabetes (months)	102 (48–168)	96 (45–159)	102 (57.5–147.0)	120 (36–180)	0.909
Hypertension (%)	74 (60.6)	28 (51.9)	20 (58.8)	26 (76.5)	0.064
SBP (mm Hg)	141.6 ± 25.1	136.2 ± 24.8	140.8 ± 23.2	150.9 ± 25.5	0.026
DBP (mm Hg)	84 (74-92)	84 (74.0-90.0)	84 (71.5-93.5)	84.5 (76.2-95.0)	0.970
24-h proteinuria (g/d)	3.3 (1.2–6.4)	1.75 (0.5–3.6)	3.3 (2.1–5.9)	6.9 (5.1–9.7)	<0.001
Serum creatinine (umol/L)	112.0 (75.0–144.0)	86.5 (65.5–125.5)	102.7 (74.2–141.7)	141.0 (114.0–164.0)	<0.001
e-GFR (mL/min/1.73 m^2)	59.0 (45.5–94.2)	83.3 (54.1–109.2)	67.0 (51.4–94.2)	43.0 (36.3–52.2)	<0.001
BUN (mg/dl)	7.4 (5.6–10.0)	6.5 (5.2–9.4)	7.3 (5.2–9.5)	9.0 (7.4–11.9)	0.002
Serum albumin (g/L)	36.9 ± 7.1	40.5 ± 5.6	36.5 ± 6.3	31.4 ± 6.3	<0.001
FBS (mmol/L)	7.9 (6.2–10.4)	8.3 (6.3–10.8)	7.5 (5.5–9.5)	7.9 (6.5–9.4)	0.359
HbA1c (%)	7.3 (6.5–8.6)	7.5 (6.7–8.2)	6.9 (6.6–9.0)	7.1 (6.4–9.4)	0.588
Triglyceride (mmol/L)	1.9 (1.4–2.5)	1.95 (1.37–2.80)	1.90 (1.40–2.50)	1.75 (1.27–2.22)	0.553
Total cholesterol (mmol/L)	4.8 (4.1–5.9)	4.60 (3.60–5.45)	5.15 (4.17–5.95)	5.2 (4.2–6.7)	0.125
Uric acid (mmol/L)	390.4 ± 80.8	397.4 ± 92.6	400.9 ± 68.5	368.7 ± 69.5	0.182
HDL cholesterol (mmol/L)	1.1 (0.9–1.4)	1.10 (0.90–1.30)	1.10 (0.90–1.50)	1.20 (1.10–1.40)	0.744
LDL cholesterol (mmol/L)	2.9 ± 1.2	2.63 ± 1.05	2.83 ± 1.10	3.32 ± 1.32	0.025
Hemoglobin (g/L)	125.3 ± 27.1	135.8 ± 27.8	122.9 ± 25.5	110.8 ± 19.9	<0.001
History of CVD	13 (10.7)	1 (1.9)	2 (5.9)	10 (29.4)	<0.001
Anti-hypertension drugs
α-blockers	24 (19.7)	4 (7.4)	8 (23.5)	12 (35.3)	0.005
β-blockers	34 (27.9)	6 (11.1)	8 (23.5)	20 (58.8)	<0.001
CCB	61 (50)	15 (27.8)	22 (64.7)	24 (70.6）	<0.001
ACEI	18 (14.8)	5 (9.3)	8 (23.5)	5 (14.7)	0.185
ARB	95 (77.9)	43 (79.6)	29 (85.3)	23 (67.6)	0.197
Diuretics	22 (18.0)	4 (7.4)	5 (14.7)	13 (38.2)	0.001
Lipid-lowering therapy
Statin	70 (57.9)	27 (50)	22 (64.7)	21 (63.6)	0.29
Baseline glucose-lowering therapies
Metformin	47 (38.8)	30 (55.6)	11 (32.4)	6 (18.2)	0.002
Sulfonylurea	7 (5.7)	6 (11.1)	0 (0)	1 (2.9)	0.073
Dipeptidyl peptidase-4 inhibitor	42 (34.4)	20 (37)	12 (35.3)	10 (29.4)	0.758
Insulin	84 (68.9)	32 (59.3)	25 (73.5)	27 (79.4)	0.109

SBP: systolic blood pressure; DBP: diastolic blood pressure; e-GFR: estimated glomerular filtration rate; FBS: fasting blood sugar; CVD: cardiovascular disease; CCB: calcium channel blockers; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker. Data are presented as the mean ± standard, the median or counts and percentages; Differences between groups were analyzed using the ANOVA, the Kruskal–Wallis H test or the chi-square test, as appropriate.

Figure 2. ROC curve analysis of the NT-proBNP level for prediction of progression of diabetic kidney disease.

Table 2. Baseline pathological characteristics according to the plasma NT-proBNP concentrations.

Pathological lesions	All (n = 122)	Group 1 (n = 54)	Group 2 (n = 34)	Group 3 (n = 34)		p value*	Correlation coefficient (r)	p value#
RPS classification						0.002	0.30	0.001
I	10 (8.2)	10 (18.5)	0 (0)	0 (0)	0
Iia	32 (26.2)	22 (40.7)	7 (20.6)	3 (8.8)	3
Iib	17 (13.9)	12 (22.2)	4 (11.8)	1 (2.9)	4
III	47 (38.5)	10 (18.5)	19 (55.9)	18 (52.9)	6
IV	16 (13.1)	0 (11.1)	4 (11.8)	12 (35.3)	6
IFTA						0.002	0.34	<0.001
0	6 (4.9)	6 (11.1)	0 (0)	0 (0)	0
1	58 (47.5)	29 (53.7)	18 (52.9)	11 (32.4)	7
2	48 (39.3)	18 (33.3)	11 (32.4)	19 (55.9)	9
3	10 (8.2)	1 (1.9)	5 (14.7)	4 (11.8)	11
Interstitial inflammation						0.248	0.23	0.012
0	3 (2.5)	2 (3.7)	1 (2.9)	0 (0)	0
1	93 (76.2)	44 (81.5)	26 (76.5)	23 (67.6)	3
2	26 (21.3)	8 (14.8)	7 (20.6)	11 (32.4)	4
Arteriolar hyalinosis						0.001	0.35	<0.001
0	12 (9.8)	11 (20.4)	1 (2.9)	0 (0)	0
1	77 (63.2)	33 (61.1)	24 (70.6)	20 (58.8)	0
2	33 (27.0)	10 (18.5)	9 (26.5)	14 (41.2)	3
Arteriosclerosis						0.023	0.30	0.001
0	16 (13.1)	13 (24.1)	2 (5.9)	1 (2.9)	0
1	59 (48.4)	24 (44.4)	18 (52.9)	17 (50.0)	0
2	47 (38.5)	17 (31.5)	14 (41.2)	16 (47.1)	1
D-Score						<0.001	0.42	<0.001
≤14	31 (25.4)	31 (57.4)	0 (0)	0 (0)
15–18	48 (39.3)	23 (42.6)	25 (73.5)	0 (0)
19–21	30 (24.6)	0 (0)	9 (26.5)	21 (61.8)
22–25	13 (10.7)	0 (0)	0 (0)	13 (38.2)

IFTA: interstitial fibrosis and tubular atrophy; RPS classification: Renal Pathology Society classification; D-score: diabetic renal pathological score.

Correlations between the plasma NT-proBNP level and histopathological findings.

*Kruskal–Wallis H test, ^#Spearman’s correlation analysis. A two-tailed p < 0.05 was considered statistically significance.

Table 3. Associations between NT-proBNP concentration and clinical covariates.

Parameters	Correlation coefficient (r)	p value
Age (years)	0.310	0.001
SBP (mm Hg)	0.264	0.003
24-h proteinuria (g/d)	0.552	<0.001
e-GFR (mL/min/1.73 m^2)	−0.516	<0.001
BUN (mmol/L)	0.381	<0.001

Spearman’s correlation analysis.

Figure 3. Kaplan–Meier curves of renal survival rate in patients with different plasma NT-proBNP concentrations. Log rank p = 0.001.

Table 4. Univariable and multivariable Cox proportional hazard analysis. Associations between NT-proBNP level and renal outcomes.

	Plasma NT-proBNP, median (range) (pg/ml)	Hazard ratios (95% confidence interval) & p value
		Unadjusted	Model 1	Model 2	Model 3
Per 1 SD LG (NT-proBNP)	2.29 ± 0.68	2.59 (1.57–4.29) p < 0.001	3.46 (1.97–6.06) p < 0.001	2.04 (1.09–3.83) p = 0.026	2.43 (1.9–45.29) p = 0.047
Group 1	58.1 (28.1–95.5)	Reference	Reference	Reference	Reference
Group 2	232.2 (170.7–306.8)	1.18 (0.39–3.52) p = 0.776	1.62 (0.52–5.04) p = 0.408	1.62 (0.48–5.42) p = 0.438	1.90 (0.50–7.17) p = 0.344
Group 3	1011.0 (650.9–1787.7)	5.89 (2.43–14.28) p < 0.001	10.11 (3.65–27.9) p < 0.001	4.89 (1.70–14.10) p = 0.003	6.43 (1.65–25.10) p = 0.007

Univariable and multivariable cox proportional hazard analysis. Associations between NT-proBNP level and renal outcomes. Model 1 adjusted for baseline age, gender, SBP, the history of CVD. Model 2 adjusted for covariates in model 1 plus e-GFR and proteinuria. Model 3 adjusted for covariates in model 2 plus RPS classification and IFTA. CI: confidence interval; SBP: systolic blood pressure; CVD: cardiovascular disease; e-GFR: estimated glomerular filtration rate; RPS: penal pathology society glomerular classification; IFTA: interstitial fibrosis tubular atrophy.

Data availability statement

The datasets generated during and analyzed during the current study are available from the corresponding author upon reasonable request.