Prophylaxis of chronic kidney disease after liver transplantation - experience from west China

Table 1 Clinical features between chronic kidney disease and non-chronic kidney diseas recipients n (%)

Clinical features	CKD group (n = 99)	Non-CKD group (n = 473)	P value
Age (median years)	49	42	0.001
Sex (male/female)	70/29	408/65	0.001
Donor type (DDLT/LDLT)	82/17	350/123	NS
Indications for LT
Cirrhosis	38 (38.4)	160 (33.8)	NS
Chronic active hepatitis	13 (13.1)	39 (8.2)	NS
Tumors	34 (34.3)	234 (49.5)	0.006
Others	14 (14.1)	40 (8.5)	NS
HBV infection	80 (80.8)	401 (85.0)	NS
Complications pre-LT
DM	10 (10.1)	26 (5.5)	NS
Renal dysfunction	22 (22.2)	32 (6.8)	0.001
HRS	11 (11.1)	16 (3.4)	0.003
Hemodialysis	9 (9.1)	10 (2.1)	0.002
Hypertension	5 (5.1)	8 (1.7)	NS
MELD scores	14	11	0.001
CNI type (TAC/CSA)	64/35	365/108	0.009
MMF adoption	49 (49.5)	310 (65.5)	0.003
Complications post-LT
DM	27 (27.3)	85 (18.0)	0.034
Hypertension	19 (19.2)	35 (7.4)	0.001
Hypercholesterolemia	19 (19.2)	57 (12.1)	NS
Hypertriglyceridemia	26 (26.3)	81 (17.1)	0.034
AKI	32 (32.3)	53 (11.2)	0.001
AR	18 (18.2)	56 (11.8)	NS
CR	4 (4.0)	11 (2.3)	NS
Graft failure	6 (6.1)	11 (2.3)	NS
Re-transplantation	5 (5.1)	8 (1.7)	NS

CKD: Chronic kidney disease; Age: Age at transplantation; DDLT: Deceased donor liver transplantation, LDLT: Living donor liver transplantation; NS: No significance; LT: Liver transplantation; HBV: Hepatitis B Virus; DM: Diabetes mellitus; HRS: Hepatorenal syndrome; MELD: Mayo end-stage liver disease; CNI: Calcineurin Inhibitor; TAC: Tacrolimus; CSA: Cyclosporine A; MMF: Mycophenolate mofetil; AKI: Acute kidney injury; AR: Acute rejection; CR: Chronic rejection.

Table 2 Chronic kidney disease incidence between groups 3 mo and one year after liver transplantation

Groups	Cases (CKD incidence %)	P value
Three months after LT
CSA trough concentrations
> 150 ng/mL	20/60 (32.3)	0.036
≤ 150 ng/mL	15/83 (18.1)
TAC trough concentrations
> 8 ng/mL	32/136 (23.5)	0.001
≤ 8 ng/mL	32/293 (10.9)
One year after LT
CSA trough concentrations
> 120 ng/mL	19/41 (46.3)	< 0.001
≤ 120 ng/mL	12/79 (15.2)
TAC trough concentrations
> 6 ng/mL	36/147 (24.5)	< 0.001
≤ 6 ng/mL	17/183 (9.3)

Patients were divided by the calcineurin inhibitor types and trough concentrations 3 mo post transplantation. Groups with ideal trough concentrations [cyclosporine A (CSA) trough concentrations ≤ 150 ng/mL, tacrolimus (TAC) trough concentrations ≤ 8 ng/mL] had much lower chronic kidney disease (CKD) incidence. Patients followed-up over 1-year (n = 450) were divided by the calcineurin inhibitor types and trough concentrations at one year post transplantation. Groups with ideal trough concentrations (CSA trough concentrations ≤ 120 ng/mL, TAC trough concentrations ≤ 6 ng/mL) had much lower CKD incidence. LT: Liver transplantation.

Table 3 Chronic complications and graft function between different groups of calcineurin inhibitor trough concentrations

Complications	Cases (CKD incidence %)	Group 1 (%)	Group 2 (%)	P value
DM	112 (19.6)	17.6	23.5	NS
Hypertriglyceridemia	107 (18.7)	18.1	19.9	NS
Hypercholesterolemia	76 (13.3)	12.8	14.3	NS
Hypertension	54 (9.4)	8.2	11.7	NS
AR	74 (12.9)	11.7	15.3	NS
CR	15 (2.6)	2.1	3.8	NS
Graft failure	17 (3.0)	2.7	3.6	NS
Re-transplantation	13 (2.3)	2.1	2.6	NS

Patients were divided according to the trough concentrations 3 mo after liver transplantation. Group 1: 376 cases, tacrolimus (TAC) ≤ 8 ng/mL or cyclosporine A (CSA) ≤ 150 ng/mL; Group 2: 196 cases, TAC > 8 ng/mL or CSA > 150 ng/mL. No statistical significance was found between groups. DM: Diabetes mellitus; AR: Acute rejection; CR: Chronic rejection; CKD: Chronic kidney disease.

Table 4 The risk factors of chronic kidney disease by univariate logistic regression

Clinical factors	P value	OR	95% CI
Factors before LT
Gender (female = 0, male = 1)	0.001	0.385	0.232-0.638
Ages at LT	0.001	1.048	1.025-1.072
Liver cirrhosis	0.303	1.590	0.658-3.840
End stage liver disease	0.014	1.740	1.120-2.703
HBV infection	0.327	0.756	0.432-1.323
DM	0.091	1.932	0.900-4.147
Hypertension	0.052	3.092	0.990-9.659
Renal dysfunction	0.001	3.937	2.173-7.134
HRS	0.002	3.570	1.603-7.953
Hemodialysis	0.001	4.630	1.830-11.716
TB	0.014	1.001	1.000-1.003
MELD	0.000	1.049	1.023-1.075
Factors after LT
Re-operation	0.454	1.324	0.635-2.761
Use of TAC	0.010	0.541	0.340-0.861
Use of MMF	0.003	0.520	0.336-0.805
CNI trough concentrations	0.001	2.528	1.627-3.927
AKI	0.001	3.785	2.275-6.296
Hypertension	0.001	2.972	1.619-5.455
DM	0.035	1.712	1.037-2.824
AR	0.509	1.107	0.820-1.494
CR	0.338	0.565	0.176-1.814
Graft failure	0.055	2.710	0.978-7.510
Re-transplantation	0.052	3.092	0.990-9.659
Hypertriglyceridemia	0.036	1.724	1.038-2.863
Hypercholesterolemia	0.059	1.733	0.979-3.070

OR: Odds ratios; CI: Confidence intervals; LT: Liver transplantation; HBV: Hepatitis B virus; DM: Diabetes mellitus; HRS: Hepatorenal syndrome; TB: Total serum bilirubin at baseline; TAC: Tacrolimus; MMF: Mycophenolate mofetil; AKI: Acute kidney injury; AR: Acute rejection; CR: Chronic rejection.

Table 5 The risk factors of chronic kidney disease by multivariate logistic regression

Clinical factors	P value	OR	95% CI
Age at LT	0.001	1.048	1.020-1.076
Pre-operative renal dysfunction	0.049	2.300	1.005-5.260
AKI	0.001	4.435	2.404-8.182
CNI trough concentration	0.001	3.233	1.923-5.438
Post-operative hypertension	0.035	2.230	1.059-4.696
Female	0.018	0.464	0.245-0.877
Use of MMF	0.002	0.435	0.255-0.741

OR: Odds ratios; CI: Confidence intervals; LT: Liver transplantation; AKI: Acute kidney injury; CNI: Calcineurin inhibitor; MMF: Mycophenolate mofetil.