Utility of urinary tubular markers for monitoring chronic tubulointerstitial injury after ischemia–reperfusion

• Published in: Nephrology (Carlton, Vic.) Vic.), 2018-04, Vol.23 (4), p.308-316
• Main Authors: Ichikawa, Daisuke, Kamijo‐Ikemori, Atsuko, Sugaya, Takeshi, Ohata, Keiichi, Hisamichi, Mikako, Hoshino, Seiko, Kimura, Kenjiro, Shibagaki, Yugo
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - pathology; Acute Kidney Injury - urine; Albumin; Albuminuria - pathology; Albuminuria - urine; Animals; Biomarkers - blood; Biomarkers - urine; Creatinine; Creatinine - blood; Disease Models, Animal; Fatty acid-binding protein; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - urine; Fibrosis; Gelatinase; Hepatitis A Virus Cellular Receptor 1 - metabolism; ischaemia–reperfusion; Ischemia; kidney injury molecule‐1; Kidney Tubules - metabolism; Kidney Tubules - pathology; Kidneys; Lipocalin; L‐type fatty acid binding protein; Male; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Transgenic; Nephrectomy; Predictive Value of Tests; Reperfusion; Reperfusion Injury - pathology; Reperfusion Injury - urine; Rodents; Severity of Illness Index; Time Factors; Transgenic mice; Urinalysis; urinary marker
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/nep.12998

Aim The aim of this study was to elucidate whether urinary tubular markers during the chronic phase of acute kidney injury (AKI) are associated with chronic tubulointerstitial damage. Methods Male human L‐type fatty acid binding protein (L‐FABP) chromosomal transgenic (Tg) mice underwent ischaemic reperfusion (I/R) injury via renal pedicle clamping for either 10 min or 20 min. Contralateral nephrectomy was performed at the time of tissue reperfusion. The kidneys were analyzed 20 days after the last I/R. Results Serum creatinine levels 20 days post‐I/R were significantly higher in the 20 min I/R than in the 10 min I/R and control groups and were similar between the 10 min I/R and control groups. The degree of tubulointerstitial damage 20 days post‐I/R was significantly more severe in the 20 min I/R than in the 10 min I/R and control groups, as well as in the 10 min I/R than in the control group. Urinary levels of human L‐FABP, albumin, and kidney injury molecule‐1 (KIM‐1) 20 days post‐I/R were significantly higher in the 20 min I/R than in the control group, whereas urinary L‐FABP was significantly higher in the 10 min I/R than in the control group. Conversely, urinary neutrophil gelatinase‐associated lipocalin levels did not significantly differ between the three groups. Finally, the urinary levels of human L‐FABP, albumin, and KIM‐1 levels 20 days post‐I/R were significantly correlated with the degree of renal damage. Conclusions Urinary levels of human L‐FABP, albumin and, KIM‐1 may be useful for monitoring AKI‐to‐CKD transition in clinical practice. Summary at a Glance L‐FABP is a promising biomarker of several kidney diseases. However, experimental modelling has been problematic due to its lack of expression in the mouse kidney. In this study, Ichikawa et al. use a transgenic model of L‐FABP expression to compare L‐FABP and other biomarkers in murine ischaemia‐reperfusion injury.