Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation

Abstract

Background: To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). Methods: Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) <60 mL/min provided urine/blood samples at baseline and serially until LT for biomarkers in serum (pg/mL) and urine (pg/mg creatinine). Results: Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD <16. Thirty-seven people died over 1 year from the time of listing, with twofold increased odds with AKI. Among 67 patients with MDRD <60, only urinary epidermal growth factor was different comparing AKI (increase in serum creatinine ≥0.3 mg/dL from baseline within past 3 months) vs. no AKI (2,254 vs. 4,253, p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 <30 prior to LT, biomarkers were not different comparing 5 patients recovering renal function (MDRD-6 >50 mL/min) at 6 months vs. 10 without recovery. Conclusions: AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.

Incidence, Mortality and Predictors of Acute Kidney Injury in Patients with Cirrhosis: A Systematic Review and Meta-analysis

“…47 It has been shown in prospective studies that the index episode of AKI is a risk factor for subsequent episodes of AKI. 48 With each episode of AKI, the renal reserve declines due to the inability of kidneys to recover function completely to original baseline level and resulting in risk for development of chronic kidney disease and impacting the outcomes negatively. 31,33 While patients with cirrhosis constitute a heterogeneous cohort, the subpopulations at an increased risk of developing AKI have not been sufficiently studied.…”

“…Also, association of AKI with model for end-stage liver disease score and Child-Pugh class found in our study are in line with the prior studies. 48 – 50 Model for end-stage liver disease score is the most frequently used score all over the world to estimate patient outcomes and survival among patients with cirrhosis. Renal function apart from serum bilirubin and coagulation status is an important component of the model for end-stage liver disease score.…”

Simultaneous liver kidney transplantation

“…Data on association of these biomarkers with post‐LT recovery of renal function are limited and scanty. In a prospective study at our centre, none of these biomarkers was associated with renal function recovery after LT alone . Biomarkers levels were measured in this study within a month prior to LT and were examined for association with renal function recovery at 6 months after LT. As renal function is dynamic and potentially confounded by variables in the pretransplant and post‐transplant period, true association of cross‐sectional measurement of biomarkers may not reflect renal function after LT. Studies using other biomarkers of renal injury or exploring markers based on metabolomics or exosome analysis of urine samples may be designed to examine novel biomarkers for accurate prediction of renal recovery after LT alone.…”

“…Furthermore, renal function is dynamic and changes over time while patients are awaiting LT. For example, about 37% of SLK recipients in one study never required dialysis prior to LT, 22% were on dialysis for <2 months, 9% for 2–6 months and only 23% received dialysis for >6 months . It should also be recognized that these patients frequently develop second or multiple episodes of AKI, with risk for the development of residual renal injury with each AKI episode and subsequent CKD . AKI may also develop on underlying CKD secondary to diabetes and/or hypertension, especially in patients with fatty liver disease .…”

Management of Hepatorenal Syndrome: A Review

“…However, none of the biomarkers tested within 30 days prior to LT among patients with cirrhosis and AKI were useful in predicting recovery of renal function after LT alone. 53 There remains unmet need of accurate biomarkers for differentiation of HRS from ATN and predictors using clinical variables or biomarkers or combination of both for recovery of renal function after LT alone, as basis for optimal SLK allocation and use of already scarce donor kidney pool.…”