Renal L-Type Fatty Acid–Binding Protein in Acute Ischemic Injury

Abstract

Fatty acid-binding proteins (FABPs) bind unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia. We evaluated the potential role of L-type FABP (L-FABP) as a biomarker of renal ischemia in both human kidney transplant patients and animal models. Urinary L-FABP levels were measured in the first urine produced from 12 living-related kidney transplant patients immediately after reperfusion of their transplanted organs, and intravital video analysis of peritubular capillary blood flow was performed simultaneously. A significant direct correlation was found between urinary L-FABP level and both peritubular capillary blood flow and the ischemic time of the transplanted kidney (both P Ͻ 0.0001), as well as hospital stay (P Ͻ 0.05). In human-L-FABP transgenic mice subjected to ischemiareperfusion injury, immunohistological analyses demonstrated the transition of L-FABP from the cytoplasm of proximal tubular cells to the tubular lumen. In addition, after injury, these transgenic mice demonstrated lower blood urea nitrogen levels and less histological injury than injured wild-type mice, likely due to a reduction of tissue hypoxia. In vitro experiments using a stable cell line of mouse proximal tubule cells transfected with h-L-FABP cDNA showed reduction of oxidative stress during hypoxia compared to untransfected cells. Taken together, these data show that increased urinary L-FABP after ischemic-reperfusion injury may find future use as a biomarker of acute ischemic injury.

Tolerance of the Human Kidney to Isolated Controlled Ischemia

“…Other explanations for the absence of progressive functional changes are the use of mannitol or protective factors present in the human kidney that are absent in rodents, such as tubule cell production of LFABP. 40 Previously reported information on monkey kidneys suggests similar or even greater resistance with lack of consistent functional impairment at clamp durations of ,90 minutes. 41 Also relevant is a human study in which minimal functional changes developed after aortic cross-clamping averaging 65 minutes.…”

Rationale and design of the Eplerenone combination Versus conventional Agents to Lower blood pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effects of an aldosterone blocker in hypertensive patients with albuminuria

“…The primary trial objective is to compare the antialbuminuric effects of a 1-year treatment with eplerenone or placebo. Key secondary objectives are: (1) to compare eplerenone-and placebo-treated patients in terms of changes in serum Cr levels, estimated glomerular filtration rate (eGFR) and urinary liver-type free fatty acid-binding protein levels (L-FABP; an early marker of tubulointerstitial stress) 26,27 and (2) to determine the effect of high salt intake on the putative renoprotective effects of eplerenone.…”

Urine Liver-Type Fatty Acid-Binding Protein and Kidney Injury Molecule-1 in HIV-Infected Patients Receiving Combined Antiretroviral Treatment Based on Tenofovir

“…8 An increased excretion of this protein in patients with acute renal failure was observed. 9 The prognostic significance of its evaluation in patients with chronic kidney disease was also confirmed. 10 Kidney injury molecule-1 (KIM-1) is a sensitive and specific biomarker for acute kidney injury.…”