Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors

Figures & data

Figure 1. Algorithm with the studied population, immunosuppressive (IS), and no immunosuppressive (NoIS) groups.

Table 1. Baseline data.

	Global population (n = 241)
	All (241)	No IS (124)	IS (117)	p Value
Age (years) median (pc 25–75)	32.0 (21.5–40.9)	31.7 (20.0–41.8)	32.0 (23.0–40.0)	*0.762
Sex (M) (n, %) n = 241	156 (64.7%)	73 (58.9%)	83 (70.9%)	**0.05
SBP (mmHg) median (pc 25–75) data = 232	130 (120–150)	130 (110–142)	130 (120–50)	*0.084
DBP (mmHg) median (pc 25–75) data = 232	80 (70–90)	80 (70–90)	80 (70–955)	*0.205
BP < 130/80 mmHg (n, %) data = 232	85 (37.0%)	49 (42.2%)	36 (31.6%)	**0.094
Urine protein Groups (n, %)				**0.002
<0.75 g/L or 1 g/d	90 (38.1%)	57 (47.5%)	33 (28.4%)
≥0.75 g/L or 1 g/d and ≤3 g/l or 3.5 g/d	106 (44.9%)	51 (42.5%)	55 (47.4%)
>3 g/L or 3.5 g/d	40 (16.9%)	12 (10%)	28 (24.1%)
Hematuria Groups (n, %) data = 231				**0.852
No	29 (12.6%)	15 (12.6%)	14 (12.5%)
Microhematuria	156 (67.5%)	62 (68.9%)	74 (66.1%)
Macrohematuria	46 (19.9%)	22 (18.5%)	24 (21.4%)
eGFR (mL/min/1.73 m^2) median ( pc 25–75) data = 232	77.1 (53.9-99.7)	79.3 (62.7-101.4)	73.2 (44.3-96.4)	*0.053
eGFR Groups (n, %) data = 232				**0.081
>60 mL/min/1.73 m^2	164 (71.0%)	90 (77.6%)	74 (71.0%)
30–60 mL/min/1.73 m^2	53 (22.9%)	20 (17.2%)	33 (28.7%)
<30 mL/min/1.73 m^2	14 (6.1%)	6 (5.2%)	8 (7.0%)
Histologic data (n, %)
Endocapillary hypercellularity (yes) data =222	60 (27%)	27 (24.8%)	33 (29.2%)	**0.450
Glomerulosclerosis (Yes) data =62	29 (46.8%)	9 (31%)	20 (60.6%)	**0.020
Tubulo-interstitial damage groups				**0.206
<25%	161 (73.9%)	84 (79.2%)	77 (68.6%)
25–50%	50 (22.9%)	19 (17,9%)	31 (27.7%)
>50%	7 (3.2%)	3 (2.8%)	4 (3.6%)
Crescents groups (n, %)				**0.000
None	119 (53.6%)	83 (76.1%)	36 (31.0%)
1–10%	44 (19.8%)	13 (11.9%)	31 (27.4%)
11–29%	37 (16.7%)	8 (7.3%)	29 (25.7%)
≥30%	22 (9.9%)	5 (4.6%)	17 (15.0%)
RASBs (yes) (n, %)	182 (85.4%)	85 (80.2%)	97 (90.7%)	**0.03

SBP: systolic blood pressure; DBP: diastolic blood pressure; BP: blood pressure; M: male; pc: percentile; RASBs: renin-angiotensin-aldosterone system blockers.

*Chi² test, **Mann–Whitney test p value.

Figure 2. Studied population renal survival curves. A. Kaplan–Meier renal survival curve (Event = ESKD/KRT or death). (B) Kaplan–Meier renal survival curve (Event = ESKD/KRT or death) according to immunosuppressive treatment, and the number of exposed patients at each time. (Log-rank p = 0.127). Mean survival time to combined event (CI 95%) was 28.9 (27.1–30.8) years the in global population, 30.2 (27.9–32.6) years in the No IS group, and 23.6 (21.4–25.8) years in the IS group.

Figure 3. (A) Baseline and Last available proteinuria data (n = 177). Levels: Mild <0.75 g/L o 1 g/d, Moderate between 0.75 g/L or 1 g/d and 3 g/L or 3.5 g/d and Severe > 3 g/L or 3.5 g/d. (B) Baseline and (C). Last proteinuria, in No Immunosuppressive (No IS, n = 88) and Immunosuppressive (IS, n = 89) Groups. Baseline vs Last proteinuria was significantly different in the No IS group (Chi² p = 0.04) and in the IS group (Chi² p = 0.007). The time between baseline and last data (median, IQR): Studied population 65 (82) months, IS group 64 (74) months, no IS group 65 (93) months.

Table 2A. Risk to ESKD/KRT or death in the Global studied population, in the NoIS and IS groups. Bivariate Cox regression analysis.

	All (241)			No IS group (124)			IS group (117)
	HR	CI 95%	p	HR	CI 95%	p	HR	CI 95%	p
Age (years) (continuous)	1.018	0.999–1.037	0.068	1.017	0.989–1.046	0.229	1.018	0.991–1.045	0.190
Sex (Ref. male)	1.156	0.678–1.971	0.594	0.515	0.215–1.233	0.136	2.460	1.227–4.933	0.011
BP initial (Ref < 130/80 mmHg)	1.365	0.770–2.418	0.287	1.671	0.721–3.873	0.231	1.032	0.471–2.262	0.937
eGFR initial (Ref > 60 mL/min/1.73 m^2)			0.000			0.000			0.000
30–60 mL/min/1.73 m^2	2.898	1.584–5.301	0.001	2.189	0.839–5.713	0.109	3.405	1.491–7.775	0.004
<30 mL/min/1.73 m^2	20.123	9.831–41.188	0.000	15.069	5.254–43.223	0.000	24.508	8.798–68.267	0.000
Proteinuria initial groups (Ref. mild)			0.006			0.000			0.559
Moderate	2.244	1.144–4.399	0.019	2.826	0.995–8.025	0.051	1.575	0.653–3.798	0.312
Severe	3.375	1.578–7.218	0.002	13.463	4.300–42.149	0.000	1.172	0.410–3.349	0.767
Endocapillary hypercellularity (Ref. NO)	2.085	1.207–3.604	0.008	2.277	1.009–5.138	0.048	1.899	0.906–3.980	0.089
Glomerulosclerosis (Ref. NO)	1.955	0.639–5.980	0.240	0.747	0.078–7.182	0.800	2.512	0.523–12.154	0.249
Tubule-interstitial damage groups (Ref. <25%)			0.000			0.000			0.000
25–50%	4.403	2.463–7.873	0.000	3.286	1.359–7.941	0.008	5.243	2.312–11.887	0.000
>50%	26.115	10.617–64.236	0.000	16.027	4.353–59.001	0.000	41.067	10.816–155.929	0.000
Crescents group (Ref. none)			0.000			0.048			0.000
≤10%	0.834	0.336–2.070	0.695	2.008	0.665–6.067	0.217	0.389	0.078–1.933	0.248
11 a 29%	1.957	0.961–3.985	0.064	1.388	0.317–6.081	0.663	2.114	0.767–5.823	0.148
≥30%	6.664	3.329–13.342	0.000	5.680	1.623–19.876	0.007	6.697	2.414–18.582	0.000

BP: blood pressure; eGFR: estimated glomerular filtration rate; Ref: reference

Table 2B. Risk to ESKD/KRT or death in the studied population (all), no immunosuppressive (NoIS) and immunosuppressive (IS) groups by multivariate Cox regression analysis.

	All (241)*			No IS group (124)*			IS group (117)**
	HR	CI 95%	p	HR	CI 95%	p	HR	CI 95%	p
Proteinuria initial groups (Ref. mild)			0.145			0.000
Moderate	1.580	0.757–3.299	0.223	2.211	0.747–6.542	0.152
Severe	2.254	1.001–5.076	0.050	13.724	3.835–49.118	0.000
Endocapillary hypercellularity (Ref. NO)	1.394	0.750–2.591	0.293	1.652	0.585–4.665	0.343
Tubule-interstitial damage groups (Ref. <25%)			0.000			0.048			0.000
25–50%	3.529	1.869–6.661	0.000	3.077	1.162–8.147	0.024	3.089	1.273–7.498	0.012
>50%	13.429	4.971–36.280	0.000	3.326	0.626–17.681	0.159	28.559	7.218–112.999	0.000
Crescents group (Ref. none)			0.223			0.193			0.013
≤10%	0.878	0.345–2.234	0.785	2.874	0.792–10.424	0.108	0.522	0.103–2.650	0.590
11 a 29%	1.331	0.630–2.811	0.454	0.912	0.193–4.302	0.907	1.849	0.669–5.108	0.232
≥30%	2.185	0.984–4.848	0.055	4.086	0.836–19.977	0.082	4.233	1.461–12.269	0.005

*Adjusted to proteinuria, endocapillary hypercellularity, tubule-interstitial damage, and crescents percentage.

**Adjusted to sex, tubule-interstitial damage and crescents percentage as proteinuria and endocapillary hypercellularity were not significant in bivariate Cox analysis and the glomerular filtration rate was associated with tubule-interstitial damage (Cramer’s V = 0.438).

ESKD/KRT: end-tage kidney disease/kidney replacement therapy; HR: Hazard ratio; CI: confidence interval: Ref: reference

Figure 4. Survival to KRT or death according to crescent’s percentage in KB. Global Mean survival (CI 95%) was 28.7 (26.7–30.7) years, No-crescents group was 30.8 (28.4–33.2) years and for the ≥30% crescents was 9.4 (5.9–12.9) years. Survival at 20 years was 78.8% (group without crescents), 86.4% (group with 1–10% crescents), 72.6% (group with 11–29% crescents), and 36.4% (group ≥30% crescents). Log-rank p = 0.000.

Table 3. Immunosuppressive treatment (IS) and crescents percentage group. A Treatment according to crescents percentage groups. (B) Risk to ESKD/KRT or death. Bivariate Cox regression analysis according to IS (reference NoIS).

	0	1–10%	11–29%	≥30%	Total	p (Chi^2 test)
A. Crescents percentage groups and IS.
Number	119	44	37	22	222
Immunosuppressive treatment (data = 222)	36 (30.3%)	31 (70.5%)	29 (78.4%)	17 (77.3%)	113(50.9%)	0.000
Prednisone (data = 210)	36 (32.1%)	30 (69.8%)	27 (75.0%)	16 (84.2%)	109 (51.9%)	0.000
Methylprednisolone (bolus iv)	6 (6.2%)	11 (30.6%)	15 (42.9%)	10 (52.6%)	42 (22.5%)	0.000
Cyclophosphamide (data = 196)	2 (1.9%)	6 (14.6%)	7 (21.9%)	9 (50%)	24 (12.2%)	0.000
Azathioprine (data = 202)	17 (15.6%)	19 (47.5%)	21 (61.8%)	12 (63.2%)	69 (34.2%)	0.000
MMF (data = 206)	5 (4.6%)	1 (2.4%)	1 (2.7%)	2 (10.5%)	9 (4.4%)	0.665
B. Bivariate Cox regression analysis Risk to ESKD/KRT or death, in each group, according to IS (Reference No IS).
HR	0.977	0.179	1.614	1.082
CI 95%	0.379–2.521	0.033–0.980	0.344–7.587	0.300–3.903
p Value	0.962	0.047	0.544	0.905

ESKD/KRT: end-stage kidney disease/kidney replacement therapy; MMF: Mofetil mycophenolate; HR: Hazard ratio; CI: confidence interval

Data availability statement

Upon request, Dataset could be available as a Supplemental online archive.