The origin and the clinical significance of urinary angiotensinogen in proteinuric IgA nephropathy patients

Figures & data

Table I. Baseline characteristics of patients.

		All	Male	Female
Number of patients (% of all )		64	41 (64.1%)	23 (35.9%)
Age (years)		36.4 ± 12.03	37.2 ± 13.18	35.1 ± 9.81
MAP (mmHg)		100.2 ± 9.59	99.8 ± 9.76	101.0 ± 9.55
Initial urinary PCR (mg/mg)		1.4 ± 0.91	1.3 ± 0.94	1.6 ± 0.83
CKD stage (eGFR) (% of all)	1 (≥90 mL/min/1.73 m^2)	19 (29.7%)	11	8
	2 (60–89 mL/min/1.73 m^2)	22 (34.4%)	14	8
	3 (30–59 mL/min/1.73 m^2)	18 (28.1%)	13	5
	4 (15–29 mL/min/1.73 m^2)	5 (7.8%)	3	2
	5 (<15 mL/min/1.73 m^2)	0	0	0
Medications (% of all)	No ARB/ACEI	25 (39.1%)	17 (41.5%)	8 (34.8%)
	ARB or ACEI	39 (60.9%)	24 (58.5%)	15 (65.2%)

Values are mean ± SD in age, MAP, and initial urinary PCR. MAP was estimated as (diastolic pressure) + ⅓(systolic pressure – diastolic pressure).

MAP = mean arterial pressure; PCR = protein-to-creatinine ratio (mg/mg); CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; ARB = angiotensin receptor blocker; ACEI = angiotensin-converting enzyme inhibitor.

Figure 1. The urinary excretion of AGT reflected renal AGT expression. A: Ln (urinary AGT/Cr) was significantly and positively correlated with AGT/β-actin measured using Western blotting (n = 63). B: Ln (urinary AGT/Cr) was significantly and positively correlated with kidney AGT density measured using immunohistochemistry (n = 35). C: There was a significant positive correlation between AGT/β-actin and kidney AGT density (n = 35). D: Representative Western blots and tissue sections showing AGT expression. Arrows indicate the AGT-stained tubules. (a) High expression of AGT; (b) intermediate expression of AGT; (c) low expression of AGT; magnification ×200 (AU = arbitrary unit).

Figure 2. Plasma AGT level was not correlated with urinary AGT excretion or renal AGT expression. A: Ln (urinary AGT/Cr) was not correlated with ln (plasma AGT) (n = 64). B: There was no correlation between ln (plasma AGT) and AGT/β-actin (n = 63). C: There was no correlation between ln (plasma AGT) and kidney AGT density (n = 35) (AU = arbitrary unit).

Figure 3. Urinary AGT excretion was positively correlated with urinary PCR and negatively correlated with eGFR. A: Ln (urinary AGT/Cr) was significantly and positively correlated with urinary PCR (n = 64). B: Ln (urinary AGT/Cr) was negatively correlated with eGFR (n = 64). C: There was no correlation between ln (plasma AGT) and urinary PCR (n = 64). D: There was no correlation between ln (plasma AGT) and eGFR (n = 64).

Figure 4. Urinary AGT excretion was positively correlated with urinary PCR 3 years later and negatively correlated with % change of eGFR for 3 years. A: Urinary PCR measured after 3 years of follow-up was positively correlated with ln (urinary AGT/Cr) (n = 52). B: Ln (urinary AGT/Cr) correlated negatively with percent change of eGFR for 3 years (n = 52).

Table II. Logistic regression analysis for patients with persistent overt proteinuria after 3 years.

Characteristics	Regression coefficient	P	Odds ratio (95% range)
Initial urinary PCR	−0.566	0.174	0.568 (0.251–1.284)
Ln (urinary AGT/Cr)	1.034	0.004	2.812 (1.379–5.731)
Average MAP	0.044	0.212	1.045 (0.975–1.121)

Average MAP was estimated from seven measurements of MAP over 3 years. MAP was estimated as (diastolic pressure) + ⅓(systolic pressure – diastolic pressure).

PCR = protein-to-creatinine ratio (mg/mg); AGT = angiotensinogen;

Cr = creatinine; MAP = mean arterial pressure.

Table III. Determinants of renal function (eGFR) after 3 years.

Characteristics	Simple linear regression		Multiple linear regression
	r	P	β coefficient ± SE	P
Age (years)	−0.680	<0.001
Initial urinary PCR	−0.394	0.004
Initial eGFR	0.948	<0.001	0.965 ± 0.074	0.000
Ln (urinary AGT/Cr)	−0.367	0.007
Average MAP	−0.556	<0.001

Average MAP was estimated from seven measurements of MAP over 3 years. MAP was estimated as (diastolic pressure) + ⅓(systolic pressure – diastolic pressure).

PCR = protein-to-creatinine ratio (mg/mg); AGT = angiotensinogen;

Cr = creatinine; MAP = mean arterial pressure.