Predictive value of sub classification of focal segmental glomerular sclerosis in Oxford classification of IgA nephropathy

Figures & data

Figure 1. Enrolment and Follow-up. 1,436 patients were assessed for eligibility, of whom 419 were deemed eligible for enrolment and all enrolled in group 1 to 3 (Research group, 348; Control group, 71), including cases that suffered a combined event within 1 year during follow-up. And this study specifies the longest follow-up period is 5 years. *M0E0S0T0C0 according to the Oxford classification of IgAN. S, segmental glomerular sclerosis. S < 25%, the proportion of segmental glomerular sclerosis <25％. S ≥ 25%, the proportion of segmental glomerular sclerosis ≥25％. MN: membranousnephropathy. DKD: diabetic kidney disease.

Table 1. Baseline and follow-up characteristics of IgAN patients enrolled.

			S1 group(N = 348)
Characteristics	S0 group (control group) n = 71	Total N = 348	S1a group (S < 25%) n = 287	S1b group (S ≥ 25%) n = 61
At renal biopsy
Men, n (%)	30 (42)	135 (39)	110 (38)	25 (41)
Age, yr (median, IQR)	26 (20, 32)	32 (25, 41)^a	32 (26, 41)^a	29 (23, 42)
BMI, kg/m^2 (mean ± SD)	22.69 ± 2.84	22.82 ± 3.37	23.06 ± 3.42	21.08 ± 2.73
Hypertension, n (%)	9 (13)	100 (29)^a	79 (28)^a	21 (34)^a
Hemoglobin, g/L (mean ± SD)	136.1 ± 17.9	131.2 ± 17.1^a	131.5 ± 17.1	130.1 ± 17.1
ALB, g/L (median, IQR)	38.6 (31.3, 43.1)	37.8(33.7, 40.9)	38.3 (34.4, 41.0)	35.8 (30.8, 40.4)^b
24-h urine protein, g/d (median, IQR)	0.25 (0.11, 0.90)	0.56 (0.31, 1.52)^a	0.50 (0.28, 1.23)^a	1.05 (0.58, 2.01)^ab
Microscopic hematuria, n (%)	55 (78)	295 (84)	237 (83)	56 (92)
initial eGFR, mL/min per 1.73 m^2 (median, IQR)	123 (106, 130)	101 (79, 120)^a	105 (83, 122)^a	85 (64, 105)^ab
UA, µmol/L (median, IQR)	312.4 (241.9, 367.5)	322.0 (263.2, 391.3)	318.9 (260.4, 387.0)	364.4 (272.3, 441.0)^ab
TG, mmol/L (median, IQR)	1.01 (0.70, 1.75)	1.33 (0.90, 2.17)^a	1.32 (0.90, 2.00)	1.46 (0.97, 2.71)^a
Pathological parameters (Oxford-MESTC score)
M1, n (%)	—	229 (66)	191 (67)	38 (62)
E1, n (%)	—	9 (3)	7 (2)	2 (3)
T0, T1, T2, n (%)	—	274 (79), 68 (19), 6 (2)	235 (82), 47 (16), 5 (2)	39 (64), 21 (34)^b, 1 (2)
C0, C1, C2, n (%)	—	223 (64), 114 (33), 11 (3)	196 (68), 86 (30), 5 (2)	27 (44), 28 (46)^b, 6 (10)^b
Proportions of global sclerosis, % (median, IQR)	0 (0, 6)	12 (5, 25)	11 (4, 24)^a	18 (9, 27)^ab
Follow-up parameters
Length of follow-up, yr (median, IQR)	2.09 (1.28, 3.27)	2.36 (1.60, 3.41)	2.35 (1.54, 3.38)	2.36 (1.67, 3.75)
Any immunosuppressive agents, n (%)	43 (61)	300 (86)^a	242 (84)^a	58 (95)^ab
Glucocorticoids, n (%)	18 (25)	62 (18)	42 (15)	20 (33)^b
Tripterygium wilfordii, n (%)	16 (23)	262 (75)^a	212 (74)^a	50 (82)^a
RASB, n (%)	33 (47)	295 (85)^a	235 (82)^a	60 (98)^ab
25% decrease in eGFR,%	2	16	14	28 ^ab
eGFR < 30 mL/min per 1.73 m^2,%	0	6	6	7
ESRD,%	0	2	2	2
Combined event,%	2	17^a	14	28^ab
Complete remission of proteinuria,%	70	58	63	34^ab

^aCompared with S0 group, p < 0.05; ^bCompared with S1a group, p < .05. —, not applicable. Values were presented as mean ± SD, median (IQR), or number (percentage). IQR, interquartile range. IgAN, IgA nephropathy. S0, absence of segmental glomerular sclerosis/adhesion. S1, segmental glomerular sclerosis/adhesion. S < 25%, the proportion of segmental glomerular sclerosis < 25%. S ≥ 25%, the proportion of segmental glomerular sclerosis ≥25％. ALB, serum albumin. eGFR was calculated with CKD-EPI equation. UA, serum uric acid. BUN, blood urea nitrogen. TG, blood triglyceride. M, mesangial hyper cellularity. E, presence of end capillary proliferation. T, severity of tubular atrophy/interstitial fibrosis. C, presence of crescent. Immunosuppressive agents contained glucocorticoids. ESRD, end stage renal disease. Complete remission, urine sediment test negative or 24-hour urine protein <0.3 g/d.

Figure 2. ROC curves of the optimal cut-off of proportion of S lesion in IgAN. AUC: area under curve. CI: confidence interval.

Table 2. Correlations between S lesion ≥ 25% and clinic pathological features in IgAN patients: univariate and multivariate Logistic regression analysis.

	Univariate		Multivariate
	OR(95%CI)	P value	OR(95%CI)	p value
Female^a	0.90 (0.51–1.57)	0.70
Age	0.99 (0.96–1.01)	0.29
Hypertension	1.40 (0.77–2.52)	0.27
Haemoglobin	1.00 (0.98–1.01)	0.57
ALB	0.96 (0.92–0.99)	0.03^b	0.98 (0.94–1.03)	.42
24-h urine protein	1.00 (1.00–1.00)	0.19
Microscopichematuria	2.36 (0.90–6.20)	0.08	2.91 (0.93–9.14)	.07
initial eGFR	0.98 (0.97–0.99)	0.001^b	0.99 (0.98–1.00)	.04^c
UA	1.00 (1.00–1.01)	0.02^b	1.00 (1.00–1.01)	.34
TG	1.12 (0.95–1.32)	0.17
M1	0.83 (0.47–1.47)	0.53
E1	1.36 (0.28–6.69)	0.71
T		0.01		.03
T1	2.69 (1.45–4.99)	0.002	2.50 (1.29–4.85)	.01
T2	1.21 (0.14–10.59)	0.87	1.27 (0.11–14.86)	.85
C		<0.001		.001
C1	2.36 (1.32–4.25)	0.004	2.18 (1.17–4.03)	.01
C2	8.71 (2.49–30.50)	0.001^b	9.34 (2.46–35.46）	.001^c

OR: odds ratio; CI: confidential interval. ^aCompared to men. ^bBy univariate analysis, p < .05. ^cBymultivariate analysis, p < .05.

Figure 3. Associations between the subclassification of S lesion and endpoint events (survival from a combined event and complete remission of proteinuria) in IgAN patients. (1) Kaplan-Meier Curve for the survival of a combined event (a) and complete remission rate of proteinuria (b). a. S0, S1a > S1b: The survival from a combined event for S1b group was significantly lower than S0 group (p = .005) and S1a group (p = .03). b. S0, S1a > S1b: The complete remission rate of proteinuria for S0 group (p < .001) and S1a group (p = .01) were significantly higher than S1b group. (2) Cox regression model for survival of a combined event (c) and complete remission rate of proteinuria (d). c. S0, S1a > S1b: The survival from a combined event for S1b group was significantly lower than S0 group (HR = 0.08, p = .03) and S1a group (HR = 0.37, p = .02) (Adjusted for M scores and the proportions of global sclerosis). d. S0, S1a > S1b: The complete remission rate of proteinuria for S0 group (HR = 2.85, p = .001) and S1a group (HR = 1.94, p = .02) were significantly higher than S1b group (Adjusted for initial eGFR and blood triglyceride).

Table 3. Differences in renal outcomes between patients with S lesion given immunosuppression or not given immunosuppression.

	Any immunosuppression, n (%)		No immunosuppression, n (%)		Total, n	OR (95%CI)	p Value^a
	Achieve endpoint	Not achieve endpoint	Achieve endpoint	Not achieve endpoint
Primary end point	33 (15)	165 (76)	4 (2)	14 (7)	216	2.59 (1.21–5.54)	.01
S1a group	19 (12)	126 (78)	3 (2)	14 (8)	162
S1b group	14 (26)	39 (72)	0 (0)	1 (2)	54
Secondary end point	180 (52)	120 (34)	35 (10)	13 (4)	348	2.71 (1.53–4.79)	.001
S1a group	157 (55)	85 (30)	33 (11)	12 (4)	287
S1b group	23 (38)	35 (57)	2 (3)	1 (2)	61

^ap value showed results of S1b group compared to S1a group. OR: odds ratio; CI: confidential interval.

Table 4. Differences in renal outcomes between patients with S lesion in varying degrees of global sclerosis.

	Proportions of global sclerosis in glomeruli, n (%)					Total, n	OR (95%CI)	p Value^a
	0–10%	11–20%	21–30%	31–40%	41–50%
Primary end point	79 (37)	44 (20)	44 (20)	32 (15)	17 (8)	216	2.45 (1.16–5.16)	.02
S1a group	67 (41)	26 (16)	31 (19)	26 (16)	12 (7)	162
S1b group	12 (22)	18 (33)	13 (24)	6 (11)	5 (10)	54
Secondary end point	159 (46)	78 (22)	57 (16)	37 (11)	17 (5)	348	2.92 (1.64–5.20)	<.001
S1a group	141 (49)	60 (21)	41 (14)	31 (11)	14 (5)	287
S1b group	18 (30)	18 (29)	16 (26)	6 (10)	3 (5)	61

^ap value showed results of S1b group compared to S1a group. OR: odds ratio; CI: confidential interval.

Data availability statement

The data underlying this article were provided by the Second Xiangya Hospital by permission. Data will be shared on request to the corresponding author with permission of the Second Xiangya Hospital.