The prognostic effect of immunosuppressive therapy in IgA nephropathy with stage 3 or 4 chronic kidney disease

Figures & data

Figure 1. Flow diagram for inclusion of patients.

Table 1. Comparison of baseline clinical features between different Therapeutic Schedule.

Characteristic	supportive group (n = 41)	immunosuppression group (n = 167)	p value
Baseline (kidney biopsy)
Sex (male/female)	32/9	88/79	.004
Age, years	35.5 ± 12.2	37.7 ± 13.0	.333
Blood pressure (mmHg)
Systolic	145.7 ± 18.6	143.3 ± 23.1	.542
Diastolic	94.4 ± 15.0	90.9 ± 15.2	.188
MAP	111.5 ± 15.3	108.4 ± 16.7	.278
Serum creatinine (umol/L)	203.7 ± 84.4	187.9 ± 64.1	.188
eGFR (mL/min/1.73 m2)	39.4 ± 14.4	39.4 ± 12.0	.992
CKD stage
Stage 3	29(71)	123 (74)
Stage 4	12(29)	44 (26)
Proteinuria, g/24h	2.5 ± 1.8	2.8 ± 2.4	.339
1–3.5g	33 (80)	131 (78)	.774
≥3.5g	8 (20)	36 (22)	.774
Oxford histological score
M1	20 (49)	46 (28)	.014
E1	3 (7)	43 (26)	.011
S1	23 (56)	95 (57)	.927
T0	15 (37)	66 (40)	.858
T1	11 (26)	59 (35)	.359
T2	15 (37)	42 (25)	.171
C0	28 (68)	72 (43)	.005
C1	10 (25)	71 (43)	.048
C2	3 (7)	24 (14)	.304
Treatment
RASi under follow-up	17 (42)	100 (60)	.037

Values for categorical variables were given as count (percentage); values for continuous variables, as mean ± standard. Abbreviation: eGFR, estimated glomerular filtration rate, MAP, mean arterial pressure; RASi, renin angiotensin system inhibitor; Oxford histological score, M1 indicates mesangial score >0.5; E1, endocapillary hypercellularity (any glomeruli); S1, segmental glomerulosclerosis (any glomeruli); T0, tubular atrophy/interstitial fibrosis (<25% of cortical area); T1, tubular atrophy/interstitial fibrosis (25%–50% of cortical area); T2, tubular atrophy/interstitial fibrosis (>50% of cortical area); C0, no crescents; C1, crescents (<one-fourth of glomeruli); C2, crescents (>one-fourth of glomeruli).

Figure 2. Kaplan–Meier plots of renal survival curves for primary outcome. (a) Renal survival according to patients with immune-suppression group (IS) versus supportive care (SC) group. (b) Renal survival according to patients with IS and (or) corticosteroids (CS) versus CS group. 

Table 2. End points on the basis of the available patients at the end of the study phase.

End point	supportive group (n = 41)	immunosuppression group (n = 167)	p value
Follow-up parameters and outcomes
Mean follow-up time (month)	36.9 ± 27.0	44.0 ± 27.6	.142
eGFR (mL/min/1.73 m2)	17.2 ± 18.4	38.1 ± 29.1	<.001
Primary outcomes, No. (%)	28 (68)	64 (38)	.001
eGFR decrease ⩾50%	28 (68)	47 (28)	<.001
Onset of ESKD	27 (66)	50(30)	<.001
Kidney replacement therapy	20 (49)	48 (29)	.005
Death due to kidney disease	0 (0)	0 (0)	–
Secondary outcomes
Death due to any cause	0 (0)	1(0.9)	.803
Time-averaged proteinuria, g/d	1.9 ± 1.0	1.7 ± 1.5	.335
Rate of kidney function decline, mL/min/1.73 m2 per year	–8.4 (–18.9 to −4.1)	–2.0 (–7.3 to 4.2)	<.001

p value for primary outcome calculated using survival analysis. Other p values calculated using t-tests or Fisher exact tests. Rate of kidney function decline defined for each individual patient using the slope from least-squares linear regression of all eGFR estimates over time. Abbreviations: ESKD, end-stage kidney disease.

Table 3. Effects of immunosuppressive therapy on kidney survival IgA nephropathy patients with decreased eGFR.

Immunosuppressive therapy	HR (95% CI)	p value
Univariate	0.439 (0.280–0.687)	<.001
Multivariate model 1^a	0.375 (0.235–0.599)	<.001
Multivariate model 2^b	0.427 (0.265–0.687)	<.001
Multivariate model 3^c	0.334 (0.198–0.564)	<.001
Multivariate model 4^d	0.335 (0.209–0.601)	<.001

^aModel 1 was adjusted for age, sex, MAP, proteinuria, and eGFR.

^bModel 2 was adjusted for age, sex, MAP, proteinuria, eGFR, and RASi.

^cModel 3 was adjusted for age, sex, MAP, proteinuria, eGFR, M1, E1, S1, T1-2, and C1-2.

^dModel 4 was adjusted for age, sex, MAP, proteinuria, eGFR, M1, E1, S1, T1-2, C1-2, and RASi.

Table 4. Prespecified subgroup analysis of the primary composite outcome.

Characteristic	HR (95% CI)	p value
Baseline age
> =60y (n = 12)	0.552 (0.050–6.118)	.628
<60y (n = 196)	0.440 (0.277–0.699)	.010
Sex
Male (n = 120)	0.367 (0.209–0.646)	.001
Female (n = 88)	0.628 (0.276–1.428)	.267
Baseline eGFR
> =30 mL/min/1.73m^2 (n = 152)	0.369 (0.205–0.663)	.001
<30 mL/min/1.73m^2 (n = 56)	0.583 (0.287–1.186)	.137
Baseline proteinuria
> =3 g/d (n = 53)	0.328 (0.141–0.746)	.008
< 3 g/d (n = 155)	0.482 (0.283–0.823)	.007
Use of RASi
Yes (n = 117)	0.477(0.281–0.810)	.006
No (n = 91)	0.645(0.262–1.590)	.341

Table 5. Adverse events during the follow-up period.

	Supportive group (n = 41)	immunosuppression group (n = 167)	p value
Total AEs	11 (27)	57 (34)	.372
Pneumonia	1 (2)	10 (6)	.696
intestinal infection	0 (0)	2 (1)	1.000
Osteonecrosis of the femoral head	0 (0)	0 (0)	–
Increase of liver enzymes (ALT > 80 IU/mL)	3 (7)	20 (12)	.579
Newly diagnosed diabetes	3 (7)	17 (10)	.771
leukopenia	4 (10)	8 (5)	.258

Multiple occurrences of the same AE in one person were only counted once. AE: adverse event; ALT: alanine aminotransferase; p value for comparisons between the number of patients in the supportive group and the number of patients in the immunosuppression group.