Microproteinuria for detecting calcineurin inhibitor-related nephrotoxicity after liver transplantation

Table 1 Demographic data of patients at the point of entry into this study (mean ± SD)

Variable (n = 143)	Group 1 (n = 102)	Group 2 (n = 35)	Group 3 (n = 6)	Group 4 (n = 0)
Age (yr), median(range)	48.6 (28-66)	49.2 (33-67)	48.5 (21-68)	0
Body mass index (BMI) (kg/m2)	22.0 ± 2.8	20.5 ± 2.4	21.8 ± 2.9	0
Pre-transplant MELD score	17.8 ± 7.6	16.2 ± 8.4	15.7 ± 9.7	0
BUN (mmol/L)	5.6 ± 2.3	6.0 ± 2.5	5.9 ± 2.8	0
SCr (&mgr;mol/L)	54.7 ± 15.8	60.5 ± 20.1	68.7 ± 17.4	0
GFR (mL/min per 1.73 m2)	105.4 ± 20.5	99.6 ± 15.2	103.3 ± 23.1	0
Dosage (mg/kg per day)
Cyclosporine A	4.0 ± 1.1	4.6 ± 1.5	5.1 ± 1.2	0
Tacrolimus	0.055 ± 0.03	0.061 ± 0.07	0.057 ± 0.05a	0
Trough levels (ng/mL)
Cyclosporine A	212.4 ± 45.8	243.7 ± 56.2	251.3 ± 61.6	0
Tacrolimus	6.3 ± 0.6	6.7 ± 0.7	7.5 ± 0.9a	0
Duration of previous treatment (mo)
Cyclosporine A	5.8 ± 3.4	6.7 ± 4.6	6.9 ± 3.9	0
Tacrolimus	5.3 ± 2.8	6.2 ± 3.5	6.7 ± 2.5	0
Time post-transplant	7.5 ± 2.2	8.8 ± 2.6	8.2 ± 3.1	0
Microproteinuria (mg/L)
β2m	0.2 ± 0.1	0.3 ± 0.1	0.5 ± 0.3a	0
α1m	14.2 ± 10.6	18.5 ± 17.3	24.8 ± 20.1a	0
Microalbumin	28.6 ± 19.3	37.7 ± 28.1	40.1 ± 30.5	0
Immunoglobulin	27.4 ± 8.3	25.1 ± 11.4	29.3 ± 15.6	0
Transferrin	2.8 ± 0.7	2.4 ± 1.6	3.1 ± 1.4a	0

^aP < 0.05, vs group 1. Group 1: GFR declined from baseline by 0%-10%; Group 2: GFR declined from baseline by 11%-20%; Group 3: GFR declined from baseline by 21%-40%; Group 4: GFR declined from baseline by > 40% and/or SCr was increasing.

Table 2 Mean values of every follow-up time point in the study groups (mean ± SD)

Variable (n = 143)	Group 1 (n = 73)	Group 2 (n = 40)	Group 3 (n = 30)	Group 4 (n = 5)
GFR (mL/min per 1.73 m2)	97.4 ± 12.7	85.6 ± 17.9	62.3 ± 20.5	49.6 ± 20.2
The declining percentage of GFR from baseline (%)	7.3 ± 2.6	16.7 ± 10.1ac	32.5 ± 12.9ac	52.4 ± 20.8ac
SCr (&mgr;mol/L)	76.3 ± 16.2	83.7 ± 15.4	90.3 ± 19.8	173.7 ± 28.5ac
BUN (mmol/L)	5.8 ± 1.7	6.3 ± 1.2	6.9 ± 1.5	11.2 ± 2.6ac
Dosage (mg/kg per day)
Cyclosporine A	2.5 ± 0.8	3.0 ± 1.0	3.3 ± 0.9	3.8 ± 1.1a
Tacrolimus	0.049 ± 0.03	0.052 ± 0.07	0.054 ± 0.05	0.058 ± 0.03a
Trough levels
Cyclosporine A (ng/mL)	145.2 ± 30.5	154.8 ± 25.6	165.3 ± 39.4	183.2 ± 31.2a
Tacrolimus (ng/mL)	5.1 ± 0.8	5.5 ± 1.2	6.2 ± 1.0a	6.8 ± 1.3ac
Diabetes (%)	9.2	10.5	9.3	11.1
Hypertension (%)	38.5	34.2	37.2	33.3
Follow-up time, mean (range, mo)	35.6 (23-36)	33.7 (24-36)	30.4 (19-36)	27.8 (16-36)
Microproteinuria
β2m (mg/L)	0.2 ± 0.1	0.4 ± 0.2a	1.0 ± 1.3ac	4.2 ± 2.5ac
α1m (mg/L)	22.6 ± 21.1	38.9 ± 25.4a	42.3 ± 35.9ac	65.1 ± 30.4ac
Microalbumin (mg/L)	46.9 ± 26.2	83.6 ± 55.5a	70.9 ± 33.8	45.4 ± 32.9
Immunoglobulin (mg/L)	23.9 ± 14.6	21.5 ± 29.1	37.3 ± 26.4	33.5 ± 29.1
Transferrin (mg/L)	3.2 ± 10.2	10.8 ± 27.8	8.2 ± 15.9	8.1 ± 12.4

^aP < 0.05, vs group 1;

^cP < 0.05, vs group 2. Group 1: GFR declined from baseline by 0%-10%; Group 2: GFR declined from baseline by 11%-20%; Group 3: GFR declined from baseline by 21%-40%; Group 4: GFR declined from baseline by > 40% and/or SCr was increasing.