Can Novel Biomarkers Effectively Predict Acute Kidney Injury in Liver or Kidney Transplant Recipients?

Abstract

Acute kidney injury (AKI) constitutes a common complication associated with liver or kidney transplantation, which may significantly impact the graft condition and perioperative mortality. Current AKI diagnostic criteria based on serum creatinine (sCr) and urine output alterations are widely utilized in routine clinical practice. However, the diagnostic value of sCr may be limited by various confounding factors, including age, sex, reduced or increased muscle mass, and pre-existing chronic kidney disease (CKD). Furthermore, sCr is rather a late indicator of AKI, as its concentration tends to increase only when the severity of the injury is enough to decrease the estimated glomerular filtration rate (eGFR). Recent expertise highlights the need for novel biomarkers in post-transplantation AKI diagnosis, prediction of event-associated mortality, or evaluation of indications for renal replacement treatment (RRT). Over the last decade, the diagnostic performance of various AKI biomarkers has been assessed, among which some showed the potential to outperform sCr in AKI diagnosis. Identifying susceptible individuals, early diagnosis, and prompt intervention are crucial for successful transplantation, undisturbed graft function in long-term follow-up, and decreased mortality. However, the research on AKI biomarkers in transplantation still needs to be explored. The field lacks consistent results, rigorous study designs, and external validation. Considering the rapidly growing prevalence of CKD and cirrhosis that are associated with the transplantation at their end-stage, as well as the existing knowledge gap, the aim of this article was to provide the most up-to-date review of the studies on novel biomarkers in the diagnosis of post-transplantation AKI.

Keywords: acute kidney injury; biomarkers; diagnostic performance; kidney transplantation; liver transplantation.

Figure 1

The standard classification and most common causes of acute kidney injury (AKI). Created with Biorender.com. ACEI—angiotensin converting enzyme inhibitors; ARB—angiotensin receptor blockers; ATN—acute tubular necrosis; BC—bladder cancer; CRC—colorectal cancer; HF—heart failure; MI—myocardial infarction; NSAIDs—non-steroid anti-inflammatory drugs; OC—ovarian cancer; sCr—serum creatinine; SLE—systemic lupus erythematosus.

Figure 2

The classification of selected novel acute kidney injury biomarkers by the mechanism of action and the predominant place of expression in the nephron. Created with Biorender.com. CysC—cystatin C; DKK-3—dickkopf 3; IL-18—interleukin 18; KIM-1—kidney injury molecule 1; L-FABP—liver-type fatty acid-binding protein; NGAL—neutrophil gelatinase-associated lipocalin; PENK—proenkephalin; sCr—serum creatinine; TIMP2*IGFBP7—insulin-like growth factor-binding protein 7 and tissue inhibitor metalloproteinase 2.