Serum Levels of Lipocalin-2/NGAL, Kidney Injury Molecule 1 (KIM-1), and Interleukin-18 Are Not Related to Risk Predictions for Cardiovascular and Renal Events in Type 2 Diabetes

Type 2 diabetes is currently one of the leading causes of cardiovascular and renal morbidity and mortality. The quest for reliable biologic markers for future cardiovascular and renal events is still ongoing.

Objective. This study was designed to explore serum levels of Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Interleukin-18 (IL-18) in type 2 diabetes patients and to describe their relationship with computer-based predictions for future cardiovascular (CV) and renal events.

Materials and methods. This was a cross-sectional observational study. One hundred sixty-five patients with type 2 diabetes participated: 1) group A – non-insulin hypoglycemic treatment (84 patients); 2) group B on insulin treatment (with or without added oral agents, 81 patients). The glycemic and metabolic parameters were assessed by routine methods: glycated hemoglobin A1c in % and mmol/mol, lipid profiles (mmol/l), serum creatinine in μmol/l urinary albumin/creatinine ratio (ACR in ma/mmol/l and μa/mg). and estimated glomerular filtration rate (eGFR in ml/min/1.72 m²) using the MDRD formula, Interieukin-18 and Lipocalin-2/NGAL were measured by ELISA (BioVendor), while Human KIM-1 was measured using the FineTest Kit (Wuhan Fine Biotech Co.). Cardiovascular risks were calculated using the UKPDS version 2.0 and the ADVANCE risk engines. In addition, the ADVANCE risk engine allowed predictions about future renal events. All statistical analyses were performed on an IBM SPSS 19.0 for Windows platform (SPSS Corp., Chicago, IL).

Results. The three markers did not differ between patients treated with insulin or non-insulin drugs. We found minor differences in levels of NGAL and IL-18 in patients with CKD grade 4 only, as well as of KIM-1 in CKD grade 1. No intergroup differences based on the presence/grade of albuminuria were detected. No differences in the three kidney markers were detected among the three risk groups for coronary artery disease based on the ADVANCE and UKPDS formulas. No differences were found in the three ADVANCE-based risk groups for renal events or new-onset albuminuria except for the levels of KIM. The correlation analyses were unable to find a relationship between the renal markers and the calculated risk for CV or renal events.

Conclusion. Our results show an almost complete lack of relationship between the three markers for kidney damage (IL-18, NGAL, and KIM- 1) and the calculations of long-term CV- and renal risks. The presence/absence of CKD and/or albuminuria did not affect the mean levels of the three markers. Therefore, those markers should be regarded as indicators for acute kidney damage only without any direct relationship to the actual renal or CV-conditions or calculated future risks.