Kidney Week

Abstract: FR-PO1062

The Renal Damage Induced by an Experimental Model of Early CKD Is Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) Dependent

Session Information

• CKD Mechanisms: Progression, Fibrosis, and Beyond
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Figueroa, Stefanny M., Institute of Biomedical Sciences, Universidad Autónoma de Chile, Santiago, Chile

Stefanny M. Figueroa,

• Reyes Osorio, Javier Ignacio, Laboratory of Renal Physiopathology, Faculty of Medicine and Sciences Health, Universidad San Sebastián, Santiago, Chile

Javier Ignacio Reyes Osorio,

• Araos, Patricio A., Institute of Biomedical Sciences, Universidad Autónoma de Chile, Santiago, Chile

Patricio A. Araos,

• Fuenzalida, Maria Jose, Laboratory of Neuroimmunology, Fundación Ciencia & Vida, Santiago, Chile

Maria Jose Fuenzalida,

• Pacheco, Rodrigo, Laboratory of Neuroimmunology, Fundación Ciencia & Vida, Santiago, Chile

Rodrigo Pacheco,

• Amador, Cristián A., Laboratory of Renal Physiopathology, Faculty of Medicine and Sciences Health, Universidad San Sebastián, Santiago, Chile

Cristián A. Amador,

Background

In chronic kidney disease (CKD), the progressive decline in renal function is accompanied by inflammatory and fibrotic processes. These processes can contribute to the increasing levels of proteinuria, which is recognized as a risk factor in patients and associated to the CKD progression. Neutrophil gelatinase-associated lipocalin (NGAL) is an accepted biomarker for assessing renal damage in CKD patients and experimental animals. However, it is still uncertain whether NGAL actively promotes proteinuria in the context of early CKD, and whether this phenomenon is related to the renal pro-inflammatory/fibrotic status.
Objective: To determine whether the 5/6 nephrectomy (Nx_5/6) at 5 days in mice is associated to renal dysfunction and to the pro-inflammatory/fibrotic damage, and whether this is NGAL-dependent.

Methods

Male C57BL/6 Wild type (WT) and knock-out for NGAL (NGAL-KO) mice (8-12 weeks), underwent a model of Nx_5/6for 5-days (n=4-6), to evaluate function and kidney damage.

Results

The Nx_5/6 model at 5 days in WT and NGAL-KO mice resulted in a significant reduction in glomerular filtration rate, with 56.1% and 58.2%, respectively. Notably, the increase in blood urea levels was significantly higher in WT mice compared to NGAL-KO (43.07±2.15 vs. 29.58±13.08mg/dl). Also, the ratio protein/creatinine in urine exhibited NGAL-dependency (10.29±3.90 vs. 2.09±0.62 arbitrary units in NGAL-KO). Concerning the renal damage, the early CKD model induced tubular lumen dilation in WT mice (13.6±0.9 vs. 8.0±0.3mm in Sham), which was prevented by the NGAL absence (P<0.01). Additionally, the normalized fibrosis area in remanent kidney was significantly 2.3 times lower in the NGAL-KO mice with respect to WT animals, which correlated with the mRNA abundance of interleukin-6 (P<0.01). Finally, we found an increased protein production of macrophage (Mf) monocyte chemoattractant (CCL2) in kidneys of WT mice due to Nx_5/6 model, which was not observed NGAL-KO mice (P<0.05).

Conclusion

Our results show that renal overexpression of IL-6 and CCL2 after 5-days of Nx_5/6 are NGAL-dependent. This pro-inflammatory phenotype correlates with the tubular remodeling, fibrosis, and the proteinuria, suggesting a possible role of NGAL for the CKD progression from the early stages.

Funding

• Government Support – Non-U.S.