Abstract Background and Aims Liver transplantation (LT) requires patients to take immunosuppression (IS). Long term IS leads to hypertension and chronic kidney disease (CKD). Calcineurin inhibitors (CNi) are known to have nephrotoxic effects. Thus, liver transplant recipients (LTRs) that are taking either long-term or high cumulative doses of CNi are at a significantly higher risk of developing CKD. This study aimed to find predictive factors for development of CKD post-LT. Furthermore, it introduced IS minimization protocol in LTRs with clinical or laboratory indications with the aim to prevent the CKD progression and decrease the burden of other comorbidities. Method 212 out of all 870 LTRs from our center were screened for eligibility and 93 were recruited in 2018 for IS minimization after obtaining informed consent. They were deemed eligible if the primary cause of LT was a non-autoimmune disease and the graft function was stable. At the time of screening, patients were on IS either triple-, dual- or monotherapy (Table 1). The IS were reduced in 3 months intervals and was minimized until monotherapy with subtherapeutic serum levels (tacrolimus <5mg/ml or cyclosporine <50mg/ml). Results The indications for IS minimization were hypertension (73.87%), CKD (35.87%), cardiovascular diseases (32%), diabetes mellitus (23.91%) or malignancies (6.52%). It was found that LTRs with CKD were older (61.8 CKD vs. 49.6 non-CKD) and predominantly male (84.85% male; 15.15% female) when compared to non-CKD patients (33.9% male; 66.1% female). Another risk factor for post-LT CKD development was higher BMI (27.57 vs. 25.35). Time from transplantation of LTR with CKD was 129.12 months while for non-CKD was 150.19 months, suggesting that longer time since transplantation is not a predictive factor for development of CKD after LT. LTRs with CKD concomitantly had hypertension (84.85% vs. 67.80%) and DM (48.48% vs. 27.12%) more often than non-CKD LTRs. It was found that CKD-LTRs at the beginning of the IS minimization were more commonly taking IS polytherapies (triple 6.06% and dual 45.45% vs. triple 0% and dual 33.9%) than monotherapy (48.48% vs. 67.80%). In the first 12 months of the study, 22 out of the 33 patients with CKD safely reached monotherapy, 11 of those reached subtherapeutic levels of CNi (50,0%). Moreover, when kidney function was compared before and after IS reduction any progression of CKD was observed. Liver function tests were elevated in 4 patients with CKD, but return to the previous dose of IS resulted in normalization of liver function. Conclusion Minimization of IS should be considered in patients after LT who suffer from IS related comorbidities, particulary CKD. Its incidence post-LT was found to be associated with male gender, BMI and IS polytherapy. Our protocol of IS minimization seems to be safe in respect to graft rejection. Table 1. Comparison of CKD and non-CKD LTRs. CKD NON- CKD n=33 % n=59 % Age 61.8 49.6 Gender Female 5 15.15 39 66.10 Male 28 84.85 20 33.90 Months from Tx 129.12 150.19 Concomitant diseases BMI at baseline 27.57 25.35 BMI after 12 mo. 27.90 25.84 Hypertension 28 84.85 40 67.80 Diabetes Mellitus 16 48.48 16 27.12 GFR At baseline 51.16 92.95 After 12 month 50.21 90.37 IS at Baseline Monotherapy 16 48,48 39 66,10 Dualtherapy 15 45.45 20 33.90 Tripletherapy 2 6.06 0 0 IS After 12 month Monotherapy 22 66.67 49 83.05 Dualtherapy 9 27.27 10 16.95 Tripletherapy 2 6.06 0 0.00 Number of LTRs taking CNi At baseline 29 87.88 54 91.53 After 12 mo. 28 84.85 55 93.22