Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients

Figures & data

Table 1 Baseline Characteristics of Enrolled Subjects

Items	Total (n=182)
Age (years)	46 (32–56)
Male (n, %)	116 (63.7%)
BMI (kg/m^2)	26.2 (23.7–28.7)
Baseline eGFR (mL/min/1.73 m^2)	98.68±20.55
eGFR<60 (n, %)	8 (4.4%)
Blood creatinine (μmol/L)	75.67±20.75
Proteinuria (g/24 h)	4.67 (3.22–6.55)
Serum albumin (g/L)	25.89±5.76
PLA2R (Ru/mL)	27.86 (5.30–96.85)
Plasma tacrolimus concentration (ng/mL)	5.10 (3.90–7.65)
Nephrotic syndrome (n, %)	114 (62.6%)
Initial dose of tacrolimus (mg/kg/d)	0.045±0.014
Concomitant RAS blockers (n, %)	121 (66.5%)
Concomitant corticosteroids (n, %)	70 (38.5%)
Prior use of corticosteroids and/or immunosuppressants (n, %)	37 (20.3%)
Pathological stage (n, %)
I	90 (49.5%)
II	85 (46.7%)
III	7 (3.8%)
IV	0
With intrarenal arteriosclerosis (n, %)	26 (14.3%)
With chronic tubulointerstitial injury (n, %)	6 (3.3%)

Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; PLA2R, anti-phospholipase A2 receptor antibody.

Table 2 Characteristics of Responders and Non-Responders

Items	Responders (n=154)	Non-Responders (n=28)	p-value
Age (years)	46 (32–56)	43 (32–57)	0.964
Male (n, %)	95 (61.7%)	21 (75.0%)	0.178
BMI (kg/m^2)	26.1 (23.3–28.4)	28.4 (24.8–33.6)	0.008
eGFR (mL/min/1.73 m^2)	98.73±20.90	98.41±18.79	0.940
Blood creatinine (μmol/L)	75.36±20.42	77.41±22.79	0.631
Proteinuria (g/24 h)	4.58 (3.15–6.44)	5.37 (3.32–6.99)	0.204
Serum albumin (g/L)	26.36±5.73	23.26±5.28	0.008
PLA2R (Ru/mL)	24.90 (4.73–88.29)	42.43 (23.76–261.48)	0.023
Nephrotic syndrome (n, %)	94 (61.0%)	20 (71.4%)	0.296
Initial dose of tacrolimus (mg/kg/d)	0.046±0.013	0.040±0.015	0.056
Concomitant RAS blockers (n, %)	102 (66.2%)	19 (67.9%)	0.867
Concomitant corticosteroids (n, %)	59 (38.3%)	11 (39.3%)	0.922
Prior use of corticosteroids and/or immunosuppressants (n, %)	30 (19.5%)	7 (25%)	0.504
Period of full-dose tacrolimus (months)	9.4 (4.5–15.4)	7.2 (2.8–12.0)	0.144

Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; PLA2R, anti-phospholipase A2 receptor antibody.

Table 3 Factors Predicting Remission of Tacrolimus Treatment in Univariate and Multivariate Analysis

Items	Univariate			Multivariate
	HR	95% CI	p-value	HR	95% CI	p-value
Age (years)	0.991	0.979–1.003	0.126
Gender (M vs F)	0.721	0.518–1.003	0.052	0.633	0.406–0.989	0.045
BMI (kg/m^2)	0.948	0.915–0.982	0.003	0.941	0.893–0.993	0.026
eGFR (mL/min/1.73 m^2)	1.004	0.996–1.013	0.304
Proteinuria (g/24h)	0.927	0.868–0.990	0.024
Serum albumin (g/L)	1.047	1.017–1.078	0.002	1.053	1.003–1.106	0.037
PLA2R (Ru/mL)	0.998	0.996–1.000	0.015
Nephrotic syndrome (n, %)	0.760	0.548–1.055	0.101
Concomitant RAS blockers (n, %)	1.192	0.851–1.670	0.307
Concomitant corticosteroids (n, %)	1.229	0.885–1.706	0.218
Prior use of corticosteroids and/or immunosuppressants (n, %)	0.988	0.662–1.475	0.953
Period of full-dose tacrolimus (months)	0.972	0.955–0.990	0.002

Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; PLA2R, anti-phospholipase A2 receptor antibody.

Figure 1 Cumulative remission rate during tacrolimus treatment.

Table 4 Factors Predicting Relapse of Tacrolimus Treatment in Univariate and Multivariate Analysis

Items	Univariate			Multivariate
	HR	95% CI	p-value	HR	95% CI	p-value
Age (years)	0.996	0.977–1.015	0.675
Gender (M vs F)	1.387	0.796–2.418	0.248
BMI (kg/m^2)	1.038	0.970–1.111	0.276
eGFR (mL/min/1.73 m^2)	0.997	0.984–1.010	0.667
Proteinuria (g/24 h)	1.042	0.939–1.156	0.443
Serum albumin (g/L)	1.017	0.970–1.065	0.489
PLA2R (Ru/mL)	0.999	0.996–1.003	0.736
Concomitant RAS blockers (n, %)	0.954	0.549–1.657	0.866
Concomitant corticosteroids (n, %)	1.278	0.747–2.186	0.370
Prior use of corticosteroids and/or immunosuppressants (n, %)	1.493	0.811–2.748	0.198
Nephrotic syndrome (n, %)	0.946	0.549–1.629	0.840
Course of full-dose tacrolimus (months)	0.964	0.932–0.997	0.034	0.816	0.674–0.988	0.037
Duration of tacrolimus tapering (months)	0.984	0.959–1.009	0.197
Blood creatinine upon tacrolimus taper (n=103)	1.003	0.987–1.019	0.725
Proteinuria upon tacrolimus tapering (n=103)	1.300	1.082–1.561	0.005
Serum creatinine upon discontinuation of tacrolimus (n=64)	1.032	1.012–1.053	0.002	1.084	1.005–1.168	0.036
Proteinuria upon discontinuation of tacrolimus (n=64)	1.623	1.383–1.903	0.000	1.832	1.216–2.759	0.004

Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; PLA2R, anti-phospholipase A2 receptor antibody.

Figure 2 Cumulative incidence of relapse after complete remission.

Figure 3 Cumulative incidence of relapse after partial remission.