Leflunomide plus low-dose prednisone in patients with progressive IgA nephropathy: a multicenter, prospective, randomized, open-labeled, and controlled trial

Figures & data

Figure 1. Patient enrollment and follow-up. LEF: leflunomide.

Table 1. Baseline characteristics.

Characteristics	LEF + prednisone (n = 59)	Prednisone (alone) (n = 49)	p-Value
Male (n)	32 (54%)	23 (47%)	0.066
Female (n)	27 (46%)	26 (53%)
Age (years)	35.7 ± 11.2	35.5 ± 11.2	0.185
BMI (kg/m^2)	22.3 ± 1.3	22.5 ± 1.6	0.886
SBP (mmHg)	123.5 ± 15.6	124 ± 12.9	0.882
DBP (mmHg)	79.3 ± 12.3	79.1 ± 10.1	0.911
Duration of disease (months)	19.4 (4.1–46.8)	10.6 (6.2–40.1)	0.184
UPE (g/24 h)	1.8 (1.3–3.5)	1.9 (1.2–2.9)	0.420
sALB (g/L)	37.7 ± 5.0	37.2 ± 5.1	0.609
BUN (mmol/L)	6.6 ± 2.4	6.0 ± 1.9	0.159
Scr (μmol/L)	99.3 ± 56.8	96.4 ± 38.6	0.199
eGFR (ml/min/1.73 m^2)	83.1 ± 39.6	84.6 ± 38.5	0.947
Hb (g/L)	132.0 ± 16.6	131.1 ± 19.6	0.797
ALT (IU/L)	20.3 ± 5.8	21.5 ± 11.0	0.470
AST (IU/L)	20.7 ± 11.4	23.6 ± 20.3	0.352
FBG (mmol/L)	5.0 ± 0.4	4.9 ± 0.5	0.492

UPE: urine protein excretion; sALB: Serum albumin; BUN: blood urea nitrogen; Scr: serum creatinine, eGFR: estimated glomerular filtration rate; Hb: hemoglobin; ALT: alanine transaminase; AST: aspartate aminotransferase; LEF: leflunomide; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG: fasting blood glucose.

Note. Values for categorical variables are given as count; values for continuous variables, as mean ± standard deviation or median [IQR]. Normal reference ranges for main lab parameters in our labs are as follows: AST [10–28 U/L], ALT [0–75 U/L], ALB [34–54 g/L], and Scr [45–104 μmol/L].

Table 2. Outcomes of treatment.

Characteristics	LEF + prednisone	Prednisone (alone)	p-Value
UPE (g/24 h)
Baseline	1.8 (1.3–3.5)	1.9 (1.2–2.9)	0.318
Month 3	0.8 (0.4–1.9)**	0.9 (0.3–1.3)**
Month 6	0.8 (0.3–1.9)**	0.8 (0.2–1.6)**
Month 9	0.6 (0.3–1.8)**	0.7 (0.2–1.0)**
Month 12	0.6 (0.3–1.4)**	0.6 (0.3–1.0)**
Month 18	0.4 (0.1–0.9)**	0.5 (0.2–1.1)**
Month 24	0.5 (0.1–1.1)**	0.5 (0.3–1.0)**
sALB (g/L)
Baseline	37.7 ± 5.0	37.2 ± 5.1	0.073
Month 3	40.4 ± 3.8**	40.2 ± 3.4**
Month 6	41.5 ± 4.6**	42.9 ± 4.4**
Month 9	43.3 ± 4.2**	42.6 ± 4.0**
Month 12	44.7 ± 6.4**	43.3 ± 3.6**
Month 18	44.9 ± 2.8**	42.5 ± 5.2**
Month 24	44.3 ± 3.0**	43.3 ± 3.8**
Scr (umol/L)
Baseline	112.3 ± 56.8	96.4 ± 38.6	0.689
Month 3	107.2 ± 39.4	97.9 ± 36.1
Month 6	106.5 ± 45.2	94.4 ± 32.4
Month 9	107.6 ± 36.4	92.3 ± 32.5
Month 12	111.4 ± 43.4	97.9 ± 42.6
Month 18	101.3 ± 34.0	98.6 ± 28.4
Month 24	108.3 ± 26.4	109 ± 65.6
eGFR (ml/min/1.73 m^2)
Baseline	83.9 ± 39.6	84.6 ± 38.5	0.847
Month 3	83.4 ± 26.8	85.4 ± 25.7
Month 6	84.6 ± 28.6	85.4 ± 28.3
Month 9	84.2 ± 25.8	85.8 ± 24.6
Month 12	83.3 ± 25.4	84.8 ± 26.6
Month 18	83.4 ± 24..8	83.9 ± 25.0
Month 24	83.2 ± 20.9	83.9 ± 21.5

UPE: urine protein excretion; sALB: Serum albumin; Scr: serum creatinine, eGFR: estimated glomerular filtration rate; LEF: leflunomide.

**p < 0.01 vs. baseline value.

Table 3. The complete, partial, and overall response between LEF + prednisone group and prednisone (alone) group.

	LEF + prednisone		Prednisone (alone)		p-Value
	n/N	Rate (%)	n/N	Rate (%)
Month 12
CR	17/52	33	18/45	40	0.592
PR	19/52	37	12/45	27	0.411
Overall response	36/52	69	30/45	67	0.959

CR: complete remission; PR: partial remission; n/N: event number/total number.

Table 4. The relapsing rate between LEF + prednisone group and prednisone (alone) group.

	LEF + prednisone		Prednisone (alone)		p-Value
	n/N	Rate (%)	n/N	Rate (%)
Month 24
Relapsing	2/59	3	5/49	10	0.299

n/N: event number/total number.

Figure 2. The dosage of prednisone in the LEF + prednisone group was much lower than that in the prednisone (alone) group. ***p < 0.001 vs. prednisone (alone) group.

Table 5. The daily prednisone dose in LEF + prednisone group and prednisone (alone) group.

Treatment time	LEF + prednisone (mg/day)	Prednisone (alone) (mg/day)	p-Value
Baseline	40.4 ± 5.5	55.7 ± 9.5	<0.001
Month 3	30.4 ± 9.2	43.5 ± 9.2	<0.001
Month 6	15.9 ± 8.3	21.9 ± 7.8	<0.001
Month 9	12.0 ± 5.6	13.5 ± 5.9	0.181
Month 12	8.8 ± 5.0	9.5 ± 6.0	0.493
Total	21.5 ± 13.4	28.8 ± 20.0	0.031

Table 6. Adverse events during the treatment period.

	LEF + prednisone (n = 59) (n, %)	Prednisone (alone) (n = 49) (n, %)	p-Value
Respiratory and pulmonary infection	4 (7)	9 (18)	0.122
Urinary tract infection	0 (0)	1 (2)	0.926
Diarrhea	2 (3)	0 (0)	0.559
Slightly elevated liver enzyme	4 (7)	4 (8)	0.924
Rash	1 (2)	4 (8)	0.257
Elevated blood pressure	1 (2)	1 (2)	0.559
Fever	2 (3)	1 (2)	0.870
Sepsis	0 (0)	1 (2)	0.926
Itching	2 (3)	0 (0)	0.559
Nausea	1 (2)	0 (0)	0.926
Agrypnia	1 (2)	0 (0)	0.926
Paraesthesia	1 (2)	0 (0)	0.926
Insanity	1 (2)	0 (0)	0.926
Lipsotrichia	1 (2)	0 (0)	0.926
Herpes zoster	0 (0)	2 (4)	0.396
Toothache	0 (0)	1 (2)	0.926
Fatigue	0 (0)	1 (2)	0.926
Menstrual disorder	0 (0)	1 (2)	0.926
Insomnia	0 (0)	1 (2)	0.926
Obesity or weight gain	0 (0)	0 (0)	1.000
Impaired glucose tolerance or diabetes	0 (0)	0 (0)	1.000
Cataract	0 (0)	0 (0)	1.000
Acne	0 (0)	0 (0)	1.000
Avascular necrosis of hips	0 (0)	0 (0)	1.000
Total (n)	21 (36)	27 (55)	0.066

Data availability statement

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.