Multicentre comparative study of neural epidermal growth factor-like 1 protein vs M-type phospholipase A2 receptor-associated membranous nephropathy

Table 1 Baseline characteristics of the cohort and treatment regimen followed, n (%)

Variable	Total (n = 41)	NELEL1-MN (n = 17)	PLA2R-MN (n = 24)	P value
Age (years), mean ± SD	42.6 ± 14.7	42.2 ± 16.9	42.8 ± 13.3	0.88
Male sex	15 (36.6)	4 (23.5)	11 (45.8)	0.14
Diabetes mellitus	6 (14.6)	1 (5.9)	5 (20.8)	0.18
Hypertension	14 (34.1)	6 (35.3)	8 (33.3)	0.90
TIM intake	15 (37.5)	12 (70.6)	3 (13.0)	< 0.001
Follow-up (months), median (IQR)	16 (12-24)	13 (12-19)	19.5 (12-24.5)	0.21
Disease association
Malignancy	2 (4.9)	0 (0)	2 (8.3)	0.22
Rheumatoid arthritis	2 (4.9)	2 (11.8)	0 (0)	0.08
Hypothyroidism	4 (10.5)	2 (13.3)	2 (8.7)	0.65
Psoriasis	1 (2.4)	1 (5.9)	0 (0)	0.23
HBV	0 (0)	0 (0)	0 (0)	-
HCV	0 (0)	0 (0)	0 (0)	-
HIV	0 (0)	0 (0)	0 (0)	-
SLE	0 (0)	0 (0)	0 (0)	-
Baseline laboratory parameters
Urine PCR (g/g), mean ± SD, median (IQR)	9.2 (5.2), 8.3 (4.7-12.5)	9.3 (5.9), 7.5 (6.9-11.7)	9.02 (4.8), 9.3 (4.4-13.2)	0.86, 0.91
eGFR (mL/minute/1.73 m2), mean ± SD, median (IQR)	106 (23.2), 107 (95-119)	112 (20.3), 117 (101-127)	102 (24.6), 102 (90-116)	0.17, 0.09
Serum albumin (g/dL), mean ± SD, median (IQR)	2.5 (0.7), 2.5 (1.9-3.1)	2.5 (0.9), 3 (1.7-3.4)	2.5 (0.6), 2.4 (2.1-3)	0.82, 0.67
Treatment followed
Supportive only	6 (16.6)	5 (29.4)	1 (4.1)	0.02
Cyclophosphamide + steroid	18 (43.9)	7 (41.2)	11 (45.8)	0.76
Rituximab	11 (26.3)	4 (23.5)	7 (29.2)	0.69
Calcineurin inhibitors	6 (14.7)	1 (5.9)	5 (20.3)	0.18

NELL1-MN: Neural epidermal growth factor-like 1 protein-associated membranous nephropathy; PLA2R-MN: M-type phospholipase A2 receptor-associated membranous nephropathy; IQR: Interquartile range; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; SLE: Systemic lupus erythematosus; PCR: Protein creatinine ratio; eGFR: Estimated glomerular filtration rate.

Table 2 Comparison of outcomes

Outcome	Incidence rate (Total cohort)	Incidence rate (NELL1-MN)	Incidence rate (PLA2R-MN)	P value
Remission (Complete or partial)	7.2/100-pt-months	11.7/100-pt-months	5/100-pt-months	0.01
Complete remission	5.9/100-pt-months	10.3/100-pt-months	3.8/100-pt-months	0.01
Partial remission	1.3/100-pt-months	1.3/100-pt-months	1.2/100-pt-months	0.89
No remission	1.7/100-pt-months	0/100-pt-months	2.5/100-pt-months	0.04
Spontaneous remission	1.3/100-pt-months	3.4/100-pt-months	0.3/100-pt-months	0.01

NELL1-MN: Neural epidermal growth factor-like 1 protein-associated membranous nephropathy; PLA2R-MN: M-type phospholipase A2 receptor-associated membranous nephropathy; pt: Patient.

Table 3 Univariate and multivariate association of predictors with remission

Predictor	Univariate HR1 (95%CI)	P value	Multivariate HR (95%CI)	P value
NELL1-MN2	2.98 (1.47-6.08)	0.003	2.65 (1.25-5.64)	0.01
Age	0.98 (0.96-1.01)	0.35	1.00 (0.97-1.04)	0.76
Male sex	0.54 (0.25-1.16)	0.12	0.66 (0.27-1.58)	0.35
Urine PCR	1.00 (0.94-1.08)	0.79	1.00 (0.93-1.07)	0.94
eGFR	1.01 (1.00-1.03)	0.04	1.01 (0.98-1.03)	0.39

¹Since the outcome is favourable (remission), hazard ratio (HR) > 1 indicates a beneficial association with exposure, HR < 1 indicates detrimental association and HR = 1 indicates no association.

²HR reported with M-type phospholipase A2 receptor-associated membranous nephropathy as comparator.

HR: Hazard ratio; CI: Confidence interval; NELL1-MN: Neural epidermal growth factor-like 1 protein-associated membranous nephropathy; PCR: Protein creatinine ratio; eGFR: Estimated glomerular filtration rate.