Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury

Abstract

Acute kidney injury (AKI) is common in patients with cirrhosis and associated with significant mortality. The most common etiologies of AKI in this setting are pre-renal azotemia (PRA), acute tubular necrosis (ATN) and hepatorenal syndrome (HRS). Accurately distinguishing the etiology of AKI is critical as treatments differ markedly. However, establishing an accurate differential diagnosis is extremely challenging. Urinary biomarkers of kidney injury distinguish structural from functional causes of AKI and may facilitate more accurate and rapid diagnoses. We conducted a multi-center, prospective cohort study of patients with cirrhosis and AKI assessing multiple biomarkers for differential diagnosis of clinically adjudicated AKI. Patients (n=36) whose creatinine returned to within 25% of their baseline within 48 hours were diagnosed with PRA. 76 patients with progressive AKI were diagnosed via blinded retrospective adjudication. Of these progressors, thirty-nine (53%) patients were diagnosed with ATN, 19 (26%) with PRA and 16 (22%) with HRS. Median values for neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP) and albumin differed between etiologies and were significantly higher in patients adjudicated with ATN. The fractional excretion of sodium (FENa) was lowest in patients with HRS, 0.10%, but did not differ between those with PRA, 0.27%, or ATN, 0.31%, p=0.54. The likelihood of being diagnosed with ATN increased step-wise with number of biomarkers above optimal diagnostic cutoffs. Conclusion Urinary biomarkers of kidney injury are elevated in patients with cirrhosis and AKI due to ATN. Incorporating biomarkers into clinical decision making has the potential to more accurately guide treatment by establishing which patients have structural injury underlying their AKI. Further research is required to document biomarkers specific to HRS.

Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome

“…Diagnostic mainstays such as the fractional excretion of sodium and urea have been shown to be suboptimal in a variety of clinical settings (13)(14)(15)(16)(17). Assessment of biomarkers for renal tubular injury (e.g., neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1] and IL-18) at the time of creatinine-based diagnosis of AKI offers prognostic information in multiple clinical settings such as cardiac surgery, ICU, transplantation, and cirrhosis (18)(19)(20)(21)(22)(23). However, their utility has not been tested in ADHF.…”

Renal dysfunctions in cirrhosis

“…Serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), interleukin -18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP) were found to be significantly higher in patients with ATN. The increases in the serum concentrations of these markers were specific for structural kidney damage and may aid in the differential diagnosis from other clinic conditions associated with functional renal impairment (37).…”

Cirrhosis and Renal Dysfunction

“…Hastanede takip edilen siroz hastalarının yaklaşık %20' sinde AKI gelişmektedir (6 (10). AKI gelişen 83 sirozlu hastanın değerlendirildiği bir çalışmada %53 ATN, %6 prerenal böbrek hasarı ve %22 HRS tespit edilmiştir (11).…”

“…Her ikisinde de granüler silendirler bulunur. ATN'de HRS'den farklı olarak renal tübüler epitel hücreler görülür ve fraksiyonel sodyum atılımı (FENa) >%2'dir (11).…”