Immunofluorescence-based reclassification of idiopathic membranoproliferative glomerulonephritis: Insights from a single-center cohort

Table 1 Comparison of baseline demographic, clinical, and laboratory features by immunofluorescence classification, median (interquartile rage)/n (%)/mean ± SD

	IC-MPGN (n = 100)	C-MPGN (n = 28)	P value
Age at biopsy (years)	33.5 (22-45)	38 (28.3-53)	0.029
Gender			0.978
Male	64 (64.0)	18 (64.3)
Female	36 (36.0)	10 (35.7)
Blood pressure (mmHg)
Systolic	150 (135-160)	145 (139.2-159)	0.394
Diastolic	93.5 (80.5-100)	89 (80-100)	0.293
First clinical manifestation			0.298
Nephrotic syndrome	34 (34)	10 (35.7)
Acute GN	53 (53)	16 (57.1)
RPGN	13 (13)	2 (7.1)
Microscopic hematuria			0.018
< 2 (trace)	8 (8)	7 (25)
2-4 (+1)	17 (17)	3 (10.7)
5-10 (+2)	10 (10)	6 (21.4)
≥ 11 (+3)	65 (65)	12 (42.9)
Proteinuria (dipstick)			0.760
Trace	1 (1)	0 (0)
+1	3 (3)	0 (0)
+2	10 (10)	2 (7.1)
+3	65 (65)	18 (64.3)
+4	21 (21)	8 (28.6)
Serum creatinine (mg/dL)	2.25 (1.6-3.7)	2.55 (1.6-5.3)	0.537
eGFR (ml/minute/1.73 m2)	62.6 (40-108)	57 (20-99.8)	0.208
Total serum protein (g/dL)	5.37 ± 1.03	5.88 ± 0.99	0.020
Serum albumin (g/dL)	2.40 ± 0.60	2.68 ± 0.70	0.036
Serum C3 levels			0.084
Low (< 0.8 g/L)	65 (65)	23 (82.1)
Normal (> 0.8 g/L)	35 (35)	5 (17.9)
Serum C4 levels			0.965
Low (< 0.16 g/L)	29 (29)	8 (28.6)
Normal (> 0.16 g/L)	71 (70)	20 (71.4)
24 hours urinary protein (g/day)	3.1 (2-4.4)	3.01 (2-4.9)	0.753

Continuous variables were compared using the Mann-Whitney U test (or Student’s t-test for normally distributed data). Categorical variables were analyzed using χ² or Fisher’s exact test, as appropriate. GN: Glomerulonephritis; RPGN: Rapidly progressive glomerulonephritis; eGFR: Estimated glomerular filtration rate; IC-MPGN: Immune complex-mediated membranoproliferative glomerulonephritis; C-MPGN: Complement-mediated membranoproliferative glomerulonephritis.

Table 2 Comparison of histopathological characteristics between the two groups of membranoproliferative glomerulonephritis classified based on immunofluorescence results, median (interquartile rage)/n (%)

	IC-MPGN (n = 100)	C-MPGN (n = 28)	P value
Total glomeruli	16 (11-23)	16 (12-20)	0.924
Global sclerosis			0.725
None	54 (54)	14 (50)
25%	30 (30)	11 (39.3)
26%-50%	13 (13)	2 (7.1)
> 50%	3 (3)	1 (3.6)
Vasculopathy	28 (28)	14 (50)	0.028
Crescents			0.385
None	52 (52)	11 (39.3)
Cellular	39 (39)	15 (53.6)
Fibrocellular	9 (9)	2 (7.1)
IF/TA			0.270
None	15 (15)	2 (7.1)
Mild	63 (63)	23 (82.1)
Moderate	19 (19)	3(10.7)
Severe	3 (3)	0 (0.0)
Immunofluorescence results
IgG			0.000
Negative	11 (11)	17 (60.7)
Trace	2 (2)	3 (10.7)
+1	77 (77)	8 (28.6)
+2	9 (9)	0 (0)
+3	1 (1)	0 (0)
IgA			0.275
Negative	84 (84)	28 (100)
Trace	1 (1)	0 (0)
+1	12 (12)	0 (0)
+2	1 (1)	0 (0)
+3	2 (2)	0 (0)
IgM			0.001
Negative	56 (56)	26 (92.9)
Trace	0 (0)	0 (0)
+1	36 (36)	2 (7.1)
+2	8 (8)	0 (0)
+3	0 (0)	0 (0)
C3			0.000
Negative	10 (10)	0 (0)
Trace	4 (4)	0 (0)
+1	53 (53)	0 (0)
+2	27 (27)	9 (32.1)
+3	6 (6)	19 (67.9)
C1q			0.039
Negative	64 (64)	15 (53.6)
Trace	0 (0)	1 (3.6)
+1	24 (24)	12 (42.9)
+2	9 (9)	0 (0)
+3	3 (3)	0 (0)

Continuous variables were compared using the Mann-Whitney U test (or Student’s t-test for normally distributed data). Categorical variables were analyzed using χ² or Fisher’s exact test, as appropriate. IF: Interstitial fibrosis; TA: Tubular atrophy; IC-MPGN: Immune complex-mediated membranoproliferative glomerulonephritis; C-MPGN: Complement-mediated membranoproliferative glomerulonephritis.

Table 3 Renal function comparison between immune complex-mediated membranoproliferative glomerulonephritis and complement-mediated membranoproliferative glomerulonephritis at baseline and 36 months, including outcomes, median (interquartile rage)/n (%)/mean ± SD

	IC-MPGN (n = 100)	C-MPGN (n = 28)	P value
At presentation
Serum creatinine (mg/dL)	2.25 (1.6-3.7)	2.55 (1.6-5.3)	0.537
eGFR (mL/minute/1.73 m2)	62.6 (40-108)	57 (20-99.8)	0.208
Serum albumin (g/dL)	2.40 ± 0.60	2.68 ± 0.70	0.036
Patients followed for 36 months	88 (88)	24 (85.7)
Serum creatinine (mg/dL)	1.5 (0.80-7.0)	1.8 (1.0-7.7)	0.507
eGFR (mL/minute/1.73 m2)	72.2 (14-118)	68 (22-95.2)	0.62
Serum albumin (g/dL)	3.17 ± 0.76	3.32 ± 0.79	0.385
Final outcomes			0.555
CR	27 (27)	5 (17.85)
PR	35 (35)	12 (42.85)
ESKD	26 (26)	7 (25)
Lost to FU	8 (8)	4 (14.2)	0.32
Overall mortality	4 (4)	0 (0)	0.24
Renal survival	62 (62)	17(60.7)	0.62

Continuous variables were compared using the Mann-Whitney U test (or Student’s t-test for normally distributed data). Categorical variables were analyzed using χ² or Fisher’s exact test, as appropriate. eGFR: Estimated glomerular filtration rate; CR: Complete remission; PR: Partial remission; ESKD: End-stage kidney disease; FU: Follow-up; IC-MPGN: Immune complex-mediated membranoproliferative glomerulonephritis; C-MPGN: Complement-mediated membranoproliferative glomerulonephritis.

Table 4 Therapeutic strategies, treatment response, and renal outcomes in immune complex-mediated membranoproliferative glomerulonephritis vs complement-mediated membranoproliferative glomerulonephritis by immunosuppressive regimen, n (%)

	IC-MPGN (n = 100)	C-MPGN (n = 28)	P value
Immunosuppressives	51 (51)	19 (67.8)
Steroids alone	35 (35)	8 (28.57)
CR	8 (22.9)	0 (0)	0.134
PR	13 (37.1)	4 (50)	0.692
ESKD	12 (34.2)	4 (50)	0.68
Mortality	2 (5.7)	0 (0)	0.99
Cyclophosphamide + steroids	16 (16)	11 (39.28)
CR	2 (12.5)	3 (27.3)	0.37
PR	6 (37.5)	4 (36.4)	0.99
ESKD	6 (37.5)	4 (36.4)	0.89
Mortality	2 (12.5)	0 (0)	0.49

Continuous variables were compared using the Mann-Whitney U test (or Student’s t-test for normally distributed data). Categorical variables were analyzed using χ² or Fisher’s exact test, as appropriate. CR: Complete remission; PR: Partial remission; ESKD: End-stage kidney disease; IC-MPGN: Immune complex-mediated membranoproliferative glomerulonephritis; C-MPGN: Complement-mediated membranoproliferative glomerulonephritis.

Table 5 Cox regression analysis for factors associated with disease remission and end-stage kidney disease among the two groups of membranoproliferative glomerulonephritis

Variables	Remission		ESKD		Remission		ESKD
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Blood pressure on admission	1.01 (0.34-1.46)	0.72	1.12 (0.71-1.8)	0.79	0.39 (0.11-1.16)	0.07	0.45 (0.22-1.8)	0.63
Proteinuria on admission (g/day)	1.25 (0.75-2.48)	0.29	0.84 (0.32-1.96)	0.89	0.38 (0.14-1.10)	0.06	0.53 (0.29-1.1)	0.54
Vasculopathy	0.97 (0.67-1.8)	0.07	1.58 (0.6-1.89)	0.62	0.43 (0.26-1.17)	0.24	1.2 (0.50-3.10)	0.04
Presence of crescents	0.27 (0.16-0.8)	0.07	0.49 (0.3-0.81)	0.32	1.02 (0.22-1.8)	0.08	1.3 (0.23-3.2)	0.02
IF/TA	1.1 (0.58-1.6)	0.24	1.45 (1.1-3.2)	0.02	1.9 (0.62-5.1)	0.19	1.5 (0.82-6.01)	0.07
Steroids alone	0.67 (0.54-2.1)	0.42	0.28 (0.16-1.27)	0.08	0.29 (0.16-1.15)	0.07	1.39 (0.16-4.01)	0.71
Cyclophosphamide	1.21 (0.48-2.75)	0.49	0.78 (0.2-1.8)	0.71	0.9 (0.30-2.0)	0.87	0.22 (0.23-1.96)	0.26

IF: Interstitial fibrosis; TA: Tubular atrophy; HR: Hazard ratio; CI: Confidence interval; ESKD: End-stage kidney disease.