Background: A high proportion of patients develop chronic kidney disease (CKD) after liver transplantation (LT). However, the ability to better select patients for nephroprotective interventions early after LT, prior to the onset of CKD, is impeded by the lack of markers of subclinical renal injury.

Aim: To characterize a proteomic signature of subclinical renal injury early after LT that predicts the development of late CKD.

Methods: We compared multi-analyte panels (Myriad DiscoveryMAP®; 171 proteins) on sera collected at 3 months post-LT in 105 patients with preserved measured iothalamate GFR (mGFR>60 ml/min) that either progressed to CKD (cases; mGFR<45 ml/min) or maintained mGFR>60 ml/min (controls) within 5 years. We performed analyses to determine significant protein differences between cases and controls (Benjamini-Hochberg method for multiple comparisons).

Results: 35 cases [age 56 (34-70); 46% male; 89% Caucasian; 23% HCV; 25% diabetes; 54% hypertension] and 70 controls [age 48 (28-64); 68% male; 70% Caucasian; 41% HCV; 25% diabetes, 61% hypertension] had sera collected at 3 months post-LT when mGFR>60. All but one control was on CNI therapy and all had normal liver tests. Unadjusted analysis revealed seven proteins different between cases and controls. After adjustment for variables known to affect renal function (age, sex, race, hypertension, diabetes, hepatitis C), levels of six proteins at 3 months (when mGFR>60) were statistically higher in cases who developed CKD vs. controls over five years (Table 1).

Conclusion: We have identified a signature of six serum proteins that early after LT can distinguish patients who will or will not eventually develop CKD. Interestingly, of the 171 proteins spanning multiple pathways, these six are well-known renal injury markers. These findings validate the notion that a novel proteomic biomarker panel can be used to reliably predict CKD in LT recipients and stratify patients into less nephrotoxic immunosuppressive regimens.