Prognostic role of mesangial IgM deposition in IgA nephropathy: a long-term cohort study

Figures & data

Figure 1. Immunofluorescence findings in IgAN; A: Immunofluorescence microscopy image showing very bright (3+) granular deposits for IgA located in the mesangium of a glomerulus; B: Immunofluorescence microscopy image showing positive granular deposits (2+) for IgM predominantly located in the mesangium of a glomerulus.

Table 1. Clinical and histopathological characteristics of all patients and a comparative analysis according to the presence or absence of IgM deposition in kidney biopsy.

Variables	Total N = 93	IgM-positive n = 65	IgM-negative n = 28	p value
Age, yr	41 [33–54]	40 [33–55]	43 [37–54]	0.6
Male sex, %	68	69	64	0.6
Type 2 diabetes mellitus, %	7	8	4	0.4
Arterial hypertension, %	68	69	64	0.6
Charlson score	2 [0–3]	2 [0-3]	1 [0–3]	0.3
eGFR, mL/min	48.7 [33.6–67.5]	46.0 [33.5–62.8]	55.9 [40.3–76.7]	0.1
Urine protein, g/g	1.1 [0.4–2.2]	1.2 [0.5–2.2]	0.7 [0.1–1.8]	0.1
Hematuria, cells/HPF	190 [98–260]	190 [120–240]	205 [75–260]	0.9
Optic microscopy analysis
Oxford MEST-C score	1 [1–2]	2 [1–2]	1 [1–2]	0.4
M1, %	84	85	82	0.7
E1, %	10	9	11	0.8
S1, %	20	23	14	0.3
T1/T2, %	16/12	17/14	14/7	0.5
C1/C2, %	20/3	22/2	18/7	0.3
Severity of immune deposition in immunofluorescence
IgA (1/2/3), %	4/20/76	2/23/75	11/11/78	0.06
IgG (0/1/2/3), %	55/25/18/2	51/26/21/2	64/21/11/4	0.4
C3 (0/1/2/3), %	2/11/29/58	2/11/32/55	4/11/21/64	0.6
Transmission electron microscopy analysis
Podocyte, %
Activation	45	45	46	0.8
Effacement	87	91	79	0.1
Microvilli	46	51	36	0.1
Detachment	17	19	14	0.6
Droplets	25	28	18	0.3
Endothelial cells, %
Activation	33	34	32	0.8
Loss of fenestrations	37	39	32	0.5
Location of TEM deposits, %
Mesangial	80	83	71	0.2
Subendothelial	23	22	25	0.7
Subepithelial	20	22	18	0.6
GBM, %
Thick	13	12	14	0.7
Abnormalities	40	39	43	0.6
Duplication	18	20	14	0.5
Ischemic	12	14	7	0.3
Mesangium, %
Matrix expansion	93	92	93	0.9
Cellular proliferation	73	74	71	0.8
Lumen/Bowman space, %
Leukocytes	26	23	32	0.3
Platelets	10	8	14	0.3
Treatment and outcome
Treatment, %
ACEI/ARB	66	63	71	0.4
IS	39	39	39	0.9
Death during follow up, %	10	11	7	0.5

Group comparisons were performed with χ² test, Student’s t-test, and Mann–Whitney U test, as appropriate.

ACEI/ARB, angiotensin converting enzyme inhibitor/angiotensin receptor blocker; C1/C2, crescents; E1, endocapillary hypercellularity; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; GBM, glomerular basement membrane; IS, immunosuppression; M1, mesangial hypercellularity; S1, segmental glomerulosclerosis; TEM, transmission electron microscopy.

Figure 2. Patients with mesangial IgM positivity at immunofluorescence had a shorter mean renal survival time: 90.3 (95%CI 78.8, 101.7) versus 116.1 (95%CI 103.3, 128.8) months.

Table 2. Prediction of end stage kidney disease (ESKD) according to the IgM status on immunofluorescence and known risk factors of progression (univariate and multivariate Cox regression analysis).

Variable	Univariate		Multivariate*
	HR (95% CI)	p	HR (95% CI)	p
Age, years	1.01 (0.98, 1.04)	0.2	–
Arterial hypertension
No	Reference		Reference
Yes	2.76 (0.95, 8.00)	0.06	1.27 (0.37, 4.28)	0.6
eGFR, mL/min	0.94 (0.92, 0.96)	<0.001	0.94 (0.92, 0.97)	<0.001
Urine protein, g/g	1.19 (0.97, 1.44)	0.08	0.86 (0.66, 1.13)	0.2
Oxford MEST-C score	1.83 (1.44, 2.33)	<0.001	1.53 (1.16, 2.02)	0.002
IgM-positive
No	Reference		Reference
Yes	4.27 (1.28, 14.22)	0.01	4.75 (1.25, 17.99)	0.02
ACEI/ARB			–
No	Reference
Yes	0.94 (0.42, 2.12)	0.8
Immunosuppression treatment			–
No	Reference
Yes	1.58 (0.74, 3.38)	0.2

*Multivariate model analysis was performed only for those lesions that were significant to p < 0.1 in the univariate models.

ACEI/ARB, angiotensin converting enzyme inhibitor/angiotensin receptor blocker; CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.