IgA nephropathy: association of C4d with clinical and histopathological findings and possible role of IgM

Figures & data

Figure 1. C4d staining in different sites of kidney biopsy specimens of patients with primary IgAN. (A) C4d staining in a segmentally sclerotic mesangial area. (B) C4d staining in another mesangial area with no sclerosis. (C) C4d staining in renal tubular epithelium. (D) Interlobular arterial C4d staining (stained with anti-C4d monoclonal antibody; magnification ×20).

Table 1. Basic characteristics of all included patients at the time of diagnosis.

Variable	Gender	Age	eGFR (mL/min/1.73 m^2)	Proteinuria (mg/day)	Hypertension (≥140/90 mmHg)	MEST score^a	Mesangial C4d-stain	Interlobular arterial C4d stain	Tubular C4d stain	Mesangial IgM/IgG stain^b
n1	Male	36	73	700	No	0/0/1/0	Negative	Negative	Negative	Yes/yes
n2	Male	39	102	864	No	0/0/1/0	Negative	Negative	Positive	Yes/no
n3	Female	20	138	2290	No	0/0/0/0	Negative	Negative	Negative	No/no
n4	Male	34	85	2450	No	1/0/1/1	negative	Negative	Negative	No/no
n5	Male	63	54	1300	Yes	1/0/1/1	Negative	Negative	Negative	No/yes
n6	Male	32	19	4000	Yes	1/1/1/2	Negative	Positive	Negative	Yes/yes
n7	Male	31	206	540	No	1/0/0/0	Negative	Negative	Negative	No/no
n8	Male	21	90	731	No	1/0/1/0	Negative	Negative	Negative	No/no
n9	Male	25	78	1511	No	1/1/1/1	Negative	Negative	Negative	No/no
n10	Male	52	39	100	Yes	1/1/1/1	Negative	Negative	Negative	No/no
n11	Female	29	113	1990	Yes	1/1/1/1	Negative	Negative	Negative	No/yes
n12	Male	23	57	420	No	1/0/0/0	Negative	Negative	Negative	No/no
n13	Female	33	45	930	No	1/1/1/0	Negative	Negative	Negative	Yes/yes
n14	Female	39	85	290	Yes	0/0/0/0	Negative	Negative	Negative	No/no
n15	Male	67	29	540	No	1/1/1/1	Negative	Negative	Negative	No/no
n16	Male	50	78	100	No	0/0/0/0	Negative	Negative	Negative	No/yes
n17	Female	29	107	157	No	0/0/0/0	Negative	Positive	Negative	No/no
n18	Male	28	65	30	Yes	0/0/1/0	Negative	Negative	Negative	No/no
n19	Male	49	114	1340	No	1/0/1/0	Negative	Negative	Negative	No/no
n20	Female	25	82	2500	No	1/1/0/0	Negative	Negative	Negative	Yes/yes
n21	Female	34	82	134	No	0/0/0/0	Negative	Negative	Negative	No/no
n22	Male	51	9	4352	Yes	1/1/1/2	Positive	Positive	Negative	Yes/yes
n23	Male	54	40	8380	Yes	1/1/1/2	Positive	Positive	Negative	No/no
n24	Male	25	146	4400	No	1/1/1/2	Positive	Negative	Negative	Yes/yes
n25	Female	31	78	1800	No	1/1/1/1	Positive	Negative	Negative	Yes/no
n26	Male	24	81	2900	Yes	1/1/1/1	Positive	Negative	Negative	Yes/no
n27	Female	71	19	900	Yes	1/1/0/1	Positive	Positive	Positive	Yes/yes
n28	Male	55	101	2338	Yes	1/1/0/0	Positive	Negative	Negative	No/no
n29	Male	63	52	1744	No	1/1/1/1	Positive	Positive	Negative	No/no
n30	Male	53	12	5960	No	1/1/1/2	Positive	Negative	Positive	Yes/no
n31	Male	30	54	1100	Yes	1/0/1/2	Positive	Negative	Negative	Yes/no
n32	Male	50	32	5500	Yes	1/1/1/2	Positive	Positive	Negative	No/no
n33	Male	44	30	2000	Yes	0/0/1/2	Positive	Negative	Positive	Yes/yes
n34	Male	59	47	975	Yes	1/1/1/1	Positive	Positive	Negative	No/no
n35	Male	38	53	4643	Yes	1/0/1/2	Positive	Negative	Negative	Yes/no
n36	Female	34	89	2000	No	1/1/1/1	Positive	Negative	Negative	Yes/no
n37	Female	48	35	558	Yes	1/1/1/2	Positive	Negative	Negative	Yes/no

Notes: ^aMesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubular atrophy/interstitial fibrosis, respectively.

^bIgM and IgG, respectively.

Table 2. Glomerular depositions of immunoglobulins and complement molecules in glomerular C4d positive and negative groups.

C4d staining	IgG (+)^a	IgA ≥ 3(+)	IgM (+)^b	C3c ≥ 3(+)	C1q
Positive (n = 16)	4	6	11	7	0
Negative (n = 21)	7	9	5	2	0
p	0.723	1	0.006	0.024

Notes: ^aNumber of patients with positive mesangial IgG deposition in mesangial C4d positive and negative groups.

^bNumber of patients with positive mesangial IgM deposition in mesangial C4d positive and negative groups.

Table 3. Association between glomerular C4d staining and baseline histopathological analyses.

Variable	Total (n = 37)	C4d-positive (n = 16)	C4d-negative (n = 21)	p-Value
Oxford class
M0/M1	9/28	1/15	8/13	0.0565
E0/E1	20/17	3/13	17/4	<0.001^a
S0/S1	10/27	2/14	8/13	0.137
T0/T1/T2	15/12/10	1/6/9	14/6/1	<0.001/ 0.024/<0.001^a
Crescent	12	6	6	0.565^b
Cellular	7	5	2	0.202^b
Fibrotic	5	1	4	0.364
Mesangial IgM	16	11	5	0.006^c

Notes: ^aGlomerular C4d positive staining was associated with more severe endocapillary hypercellularity and interstitial fibrosis/tubular atrophy score and this was statistically significant. Severity of other Oxford classification criteria was not associated with glomerular C4d-staining.

^bCrescent formation was not associated with glomerular C4d staining even when analyzed for cellular and fibrotic crescents, separately.

^cMesangial IgM deposition was associated with glomerular C4d staining and this was statistically significant.

Table 4. Association between glomerular C4d staining and baseline clinical findings.

Variable	Total (n = 37)	C4d-positive (n = 16)	C4d-negative (n = 21)	p-Value
Presence of macroscopic hematuria	11	2	9	0.071
Presence of hypertension	17	11	6	0.022^a
eGFR (MDRD; mL/min)
Mean	70.8	54.9	82.9	0.023^b
Minimum	9	9	19
Maximum	206	146	206
Proteinuria (mg)
Mean	1847	2906	1091	0.02^c
Minimum	30	558	30
Maximum	8380	8380	4000
<1 g/day	16	3	13
>1 g/day	21	13	8

Notes: ^aAssociation of glomerular C4d staining and the presence of hypertension which was defined as blood pressure ≥140/90 mmHg or use of anti-hypertensive medicine was statistically significant.

^bGlomerular C4d positive group had a lower baseline eGFR than negative group.

^cGlomerular C4d positive group had a more severe proteinuria than negative group at the time of diagnosis.