Glomerulosclerosis is a prognostic risk factor in patients with membranous nephropathy and non-nephrotic proteinuria

Figures & data

Figure 1. Flowchart of the study.

Table 1. Demographic and clinical characteristics.

	ALL (n = 112)	Low (n = 64)	Middle (n = 24)	High (n = 24)	p Value
Gender [male (%)]	48 (42.86)	24 (37.50)	11 (45.8)	13 (54.2)	0.373
Age (year)	47.45 ± 12.10	46.53 ± 12.00	46.75 ± 10.26	50.58 ± 13.90	0.360
Systolic pressure (mmHg)	128.49 ± 15.62	126.25 ± 14.85	122.92 ± 12.67	140.04 ± 15.08^a,b	p < 0.001
Diastolic pressure (mmHg)	82 (76–90)	80 (73.5–86.75)	81 (80–88.5)	88.5 (80–100)^a,b	0.012
Edema [n (%)]	95 (84.82)	56 (87.5)	19 (79.2)	20 (83.3)	0.595
24-h urinary protein (g/d)	2.21 ± 0.81	2.18 ± 0.82	2.05 ± 0.86	2.45 ± 0.69	0.424
Serum globulin (g/L)	25.95 (24.1–28.6)	25.7 (23.95–28.60)	26.05 (24.63–28.33)	26.2 (23–32.3)	0.789
A/G ratio	1.20 ± 0.33	1.18 ± 0.32	1.3 ± 0.28	1.16 ± 0.41	0.1885
Serum albumin (g/L)	31.06 ± 7.35	30.48 ± 7.19	34.14 ± 6.70	29.53 ± 7.78	0.058
Serum creatinine (μmol/L)	61 (53.25–75.75)	59 (51.5–69.25)	62 (56–81.5)	70 (57.5–90)	0.100
CKD staging [n (%)]					0.230
CKD1	94 (83.93)	55 (85.94)	22 (91.7)	17 (70.8)
CKD2	15 (13.39)	8 (12.5)	2 (8.3)	5 (20.8)
CKD3	3 (2.68)	1 (1.56)		2（8.3）
eGFR (ml/min/1.73 m^2)	102.78 ± 18.48	105.27 ± 18.66	104.27 ± 12.78	94.68 ± 21.04	0.0502
Serum uric acid (umol/L)	340.30 (284.95–397.25)	324.6 (275.78–375.13)	342.3 (284.95–415.15)	381.95 (303.53–422)	0.093
Diabetes [n (%)]	4 (3.57)	2 (3.12)		2 (8.3)	0.389
Hypertension [n (%)]	25 (22.32)	12 (18.75)	2 (8.3)	11 (45.8)^a,b	0.004
Hyperlipidemia [n (%)]	79 (70.54)	47 (73.44)	17 (70.8)	15 (62.5)	0.688
Coronary heart disease [n (%)]	2 (1.79)	1 (1.56)		1 (4.2)	0.676
ACEI/ARB [n (%)]	43 (39.39)	20 (31.25)	9 (37.5)	14 (58.3)	0.065
Glucocorticoid [n (%)]	59 (52.68)	38 (59.37)	10（41.7）	11 (45.8)	0.287
Immunosuppressant [n (%)]	77 (68.75)	45 (70.31)	16 (66.7)	16 (66.7)	0.924

^a p < 0.05 Low vs high; ^bp < 0.05 Middle vs high; ^cp < 0.05 Low vs Middle. A/G ratio: Serum albumin/Serum Globulin; CKD staging:Clinical kidney diease staging; eGFR: The estimated glomerular filtration rate; ACEI/ARB: Treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blocker.

Table 2. Pathological characteristics.

	All (n = 112)	Low (n = 64)	Middle (n = 24)	High (n = 24)	p Value
IgG					0.362
–	5 (4.46)	4 (6.25)	1 (4.17)	0
+-∼++	20 (17.86)	8 (12.5)	3 (12.5)	6 (25)
+++	87 (77.68)	52 (81.25)	20 (83.33)	18 (75)
IgA					0.879
–	105 (93.75)	60 (93.75)	22 (91.7)	23 (95.8)
+∼++	7 (6.25)	4 (6.25)	2 (8.3)	1 (4.2)
C3					1.000
–	13 (11.61)	7 (10.94)	3 (12.5)	3 (12.5)
+-∼+++	99 (88.39)	57 (89.06)	21 (87.5)	21 (87.5)
C1Q					0.371
–	101 (94.39)	58 (93.55)	19 (90.48)	24 (100)
+	6 (5.61)	4 (6.45)	2 (9.52)
IgM					0.438
–	75 (66.96)	46 (71.88)	14 (58.3)	15 (62.5)
+∼++	37 (33.04)	18 (28.12)	10 (41.7)	9 (37.5)
PLA2R ab					1.000
–	8 (12.5)	5 (13.16)	1 (11.11)	2 (11.76)
+∼++	56 (87.5)	33 (86.84)	8 (88.89)	15 (88.24)
The pathological stage of MN [n (%)]					0.085
I	40 (35.7)	26 (40.6)	9 (37.5)	5 (20.8)
II	55 (49.1)	31 (48.4)	10 (41.7)	14 (58.3)
III	13 (11.6)	7 (10.9)	2 (8.3)	4 (16.7)
IV	4 (3.6)		3 (12.5)	1 (4.2)
Renal interstitial lesion score					<0.0001
0	86 (76.78)	56 (87.5)	20 (83.3)	10 (41.7)
1	24 (21.43)	8 (12.5)	4 (16.7)	12 (50)
2	2 (1.79)			2 (8.3)
Renal tubular atrophy lesion score					0.117
0	83 (74.11)	52 (81.2)	15 (62.5)	16 (66.7)
1	26 (23.21)	9 (14.1)	9 (37.5)	8 (33.8)
2	3 (2.68)	3 (4.7)
Number of glomeruli	14 (10–20)	13 (9–19)	21.5 (17–31)^b, c	11.5 (10–12)	<0.001
Percent of renal glomerular sclerosis (%)	0 (0–6.78)^a, c	0 (0–0)	5.49 (435–6.67)^b	15.84 (9.32–24.31)	<0.001

^a p < 0.05 Low vs high; ^bp < 0.05 Middle vs high; ^cp < 0.05 Low vs Middle; PLA2R ab: Phospholipase A2 receptor antibody; The pathological stage of MN: The pathological stage of Membranous nephropathy under light microscope.

Table 3. Prognosis.

	All (n = 112)	Low (n = 64)	Middle (n = 21)	High (n = 21)	p Value
Primary endpoint					0.005
CR	29 (25.89)	21 (32.8)	7 (29.2)	1 (4.2)
NS	66 (58.93)	32 (50)	12 (50)	22 (91.7)^a, b
Non-nephrotic range proteinuria	17 (15.18)	11 (17.2)	5 (20.8)	1 (4.2)
eGFR decreased by more than 20% [n (%)]	9 (8.04)	3 (4.7)	1 (4.2)	5 (20.8)^a, b	0.048
ESRD [n (%)]	1 (0.89)			1 (4.2)	0.429
Death [n (%)]	2 (1.79)			2 (8.3)	0.089
NS [n (%)]	12 (12)	5 (8.2)	3 (13.04)	4 (25)	0.161
Non-nephrotic range proteinuria [n (%)]	47 (47)	27 (44.26)	11 (47.83)	9 (56.25)	0.719
CR [n (%)]	41 (41)	29 (47.54)	9 (39.13)	3 (18.75)	0.124

^a p < 0.05 Low vs high; ^bp < 0.05 Middle vs high; ^cp < 0.05 Low vs Middle. CR: complete remission; NS: nephrotic syndrome; ESRD: end-stage renal disease.

Figure 2. Relationship between glomerulosclerosis and primary and secondary endpoints.

Table 4. Correlation between glomerulosclerosis and clinical pathological indices.

	Rho	p Value
Gender	−0.109	0.251
Age	0.107	0.262
SBP	0.162	0.089
DBP	0.215	0.023
Edema	−0.036	0.707
Pathological stage	0.190	0.045
24-h urinary protein	0.062	0.517
Serum globulin	0.052	0.588
A/G	0.018	0.854
Serum albumin	0.004	0.967
Serum creatinine	0.177	0.062
CKD stage	0.100	0.295
eGFR	−0.186	0.049
Serum uric acid	0.150	0.116
PLA2R ab	0.023	0.855
IgG	−0.041	0.665
IgA	0.005	0.957
C3	−0.019	0.839
C1Q	−0.068	0.486
IgM	0.139	0.145
Renal interstitial lesion score	0.399	0.00001
Renal tubular atrophy lesion score	0.198	0.036

SBP: Systolic pressure; DBP: Diastolic pressure; A/G: Serum albumin/Serum Globulin; PLA2R ab: Phospholipase A2 receptor antibody; C3: Complement C3; C1Q: Complement C1q; Edema: Edema of the eyelids or the lower limbs.

Figure 3. Kaplan–Meier curve survival analysis of patients in the three groups.

Table 5. Cox regression analysis of the glomerulosclerosis ratio and renal prognosis.

Group	Model 0		Model 1
	P	HR 95% CI	p Value	HR 95% CI
	0.010	1.031 (1.007–1.054)	0.021	1.056 (1.008–1.105)
High	Ref		Ref
Low	0.002	0.111 (0.027–0.452)	0.022	0.127 (0.022–0.742)
Middle	0.014	0.057 (0.006–0.562)	0.028	0.043 (0.003–0.708)
	Model 2		Model 3
	P	HR 95% CI	p Value	HR 95% CI
	0.019	1.085 (1.104–1.161)	0.107	1.024 (0.995–1.053)
Group
High	Ref		Ref
Low	0.017	0.088 (0.012–0.652)	0.009	0.076 (0.011–0.532)
Middle	0.007	0.006 (0.0001–0.024)	0.007	0.004 (0.00008–0.226)

Model 0: Unadjusted; Model 1: Adjusted for age, gender, systolic blood pressure, 24-h urinary protein, serum creatinine; Model 2: Adjusted for model 1 plus treatment plan; Model 3: Adjusted for mode 2 plus renal interstitial lesion score and renal tubular atrophy lesion score; CI: confidence interval; HR: hazard ratio; Ref: Reference.