NIV Congres

Kindey injury molecule (KIM)-1 and Neutrophil gelatinase-associated lipocalin (NGAL) are promising tubular injury markers in the context of various forms of acute kidney injury, including delayed graft function (DGF) and transplantation. Both markers can be expressed by renal tubular epithelial cells and released in the urine. Here, we investigated and quantified the presence of KIM-1 and NGAL in paired samples of urine and tissue in a cohort of patients, collected 10 days after transplantation.

Regular urinary samples were collected in a prospective study of 92 patients receiving a CDD kidney. At day 10, protocol biopsies were obtained and frozen sections of 71 patients were available for analysis. Immunohistochemistry for KIM-1 and NGAL on all biopsies and a double staining on a smaller subgroup were performed. Urinary KIM-1 and NGAL were measured using specific ELISAs.

At day 10, KIM-1 concentrations in urine showed a wide distribution (range 0,1-79,8 ng/ml, mean 10,1 ng/ml), which was also observed for the values corrected for urinary creatinin (range 0,43-254 ng/mg creat). When comparing both analyses, a very strong correlation was shown (r = 0,91). A similar distribution was found for urinary NGAL concentrations (range 0,3-6269 ng/ml, mean 748 ng/ml). Importantly, KIM-1 and NGAL concentrations only showed a weak correlation (r = 0,37). Next, KIM-1 and NGAL stainings (n=71) were performed on consecutive slides. In many cases, KIM-1 was abundantly expressed on tubular epithelial cells (0,1-27,6 %, median 7,7% of surface), with a tubular expression pattern including cytoplasmic and brush border staining and a strong expression on dedifferentiated epithelial cells. NGAL staining (0,1-25,9%, median 1,9 % of surface) was more restricted to a cytoplasmic staining. Importantly, there was no relation between the quantitative scores of these stainings. Finally, a fluorescent double staining was performed and confirmed that KIM-1 and NGAL mostly showed a distinct and separate tissue distribution, and colocalization was a rare event.

Our results indicate that both KIM-1 and NGAL are interesting biomarkers in the context of DGF, but seem to represent different biological processes and might be actively involved in a protective or repair process. Our study should allow a further evaluation of the clinical importance of measuring these biomarkers, either at the tissue or urine level.