BACKGROUND Chronic kidney disease (CKD) has been increasingly shown to be a negative prognostic factor after liver transplantation (Ltx). Creatinine-based glomerular filtration rate (GFR) formulas are notoriously insensitive. In children, non-invasive determination of GFR by measurement of serum cystatin C is feasible and repeatedly correlated to the gold standards of GFR measurements. The aim of our study was to determine GFR using cystatin C (GFR(cys)) in comparison with conventional calculated creatinine clearance (GFR(crea)) in the long-term follow-up after paediatric liver transplantation (pLtx) in a large number of patients. METHODS GFR of 168 children following liver transplantation was determined using cystatin C (GFR(cys)) and the Schwartz formula (GFR(crea)). In order to evaluate risk factors for CKD, a logistic regression analysis was performed. A multivariate model was applied to assess the impact of immunosuppressive treatment. RESULTS The mean follow-up after transplantation was 7.8 (0.44-15.72) years. Due to a high overestimation of GFR as demonstrated in a Bland-Altman plot, only three patients with CKD stages 2-3 were detected with GFR(crea) compared with 34 with GFR(cys) (P < 0.001). Thus, prevalence of CKD with GFR((cys)) < 90 mL/min/1.73 m2; was 30.4%, 7.6% and 27% in patients with 5, 10 and > 10 years of follow-up, respectively. Patients on cyclosporine had a significantly lower GFR than patients on tacrolimus. Logistic regression analysis did not show any significant risk factor for the development of CKD. CONCLUSIONS The cystatin C equation is a non-invasive and sensitive diagnostic tool to detect renal dysfunction in children after Ltx at an early stage. The choice of first-line calcineurin inhibitor has an important impact on the development of CKD.