Abstract: SA-PO371

Vitamin D Deficiency Impairs the Renal Expression of M2 Macrophages in Rats Submitted to 5/6 Nephrectomy

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Volpini, Rildo A., Faculty of Medicine - University of Sao Paulo, São Paulo, São PAULO, Brazil
  • Canale, Daniele, Faculty of Medicine - University of Sao Paulo, São Paulo, São PAULO, Brazil
  • Gonçalves, Janaina Garcia, Faculty of Medicine - University of Sao Paulo, São Paulo, São PAULO, Brazil
  • Shimizu, Maria HM, Faculty of Medicine - University of Sao Paulo, São Paulo, São PAULO, Brazil
  • Seguro, Antonio C., Faculty of Medicine - University of Sao Paulo, São Paulo, São PAULO, Brazil
  • de Braganca, Ana Carolina, Faculty of Medicine - University of Sao Paulo, São Paulo, São PAULO, Brazil
Background

5/6 nephrectomy (Nx) is a classical experimental model of chronic kidney disease (CKD). Many studies have shown a pivotal role of macrophages (MØ) in the progression of CKD. Broadly, two main groups of MØ are designated: M1 (proinflammatory MØ) and M2 (tissue repair MØ). Moreover, recent investigations have been linking Vitamin D Deficiency (VDD) to inflammatory process and predisposition to fibrosis formation.

Methods

For 90 days, male Wistar rats were fed a standard [Sham and Nx groups] or a vitamin D-free (VDD and VDD+Nx) diets. On day 30, Nx and VDD+Nx rats were submitted to Nx surgery. On day 90, we measured serum levels of 25(OH)D and PTH by ELISA, inulin clearance (Cin), mean arterial pressure (MAP), immunoblotted for TGF-β and performed IHC for MØ type 1 (ED1) and 2 (Mannose Receptor). Also, we estimated the interstitium enlargement by fraction interstitial area (FIA).

Results

As described in Table 1, VDD were associated with MAP elevation and decreased Cin in VDD+Nx group. Moreover, we observed higher expression of M1 macrophages and TGF-β as well as larger FIA in the renal cortex of those animals. Interestingly, we found a lower expression of M2 macrophages in VDD+Nx rats, indicating an important role of Vitamin D in the tissue repair and maintenance of inflammatory process.

Conclusion

Our study suggests that VDD is involved in tissue repair and fibrosis formation after Nx, reinforcing the role of VDD as an aggravating factor for CKD progression. (Financial Support: FAPESP 2015/05513-1)

Table 1
ParametersShamVDDNxVDD+Nx
Cin (mL/min/100g BW)0.65±0.010.58±0.030.48±0.03af0.39±0.03adi
MAP (mmHg)115.0±5.71135.9±4.20c147.6±6.04b167.1±5.2aei
25(OH)D (ng/mL)49.49±2.87<0.44 (undectable)a42.26±3.97d<0.44 (undectable)ag
PTH (pg/mL)311.2±44.20899.8±167.61,023±334.3901.7±184.3
M1 (% positive area)0.20±0.020.25±0.040.52±0.08cf0.87±0.09adh
M2 (% positive area)0.18±0.020.12±0.010.29±0.07f0.11±0.02i
TGF-β (%)100.1±8.9689.5±9.82142.5±34.53208.5±41.51cf
FIA (%)7.55±0.2614.48±0.20a19.42±1.25ad23.74±1.26adh

Data are expressed as mean±SEM. BW: Body weight. a p<0.001 vs Sham; b p<0.01 vs Sham; c p<0.05 vs Sham; d p<0.001 vs VDD; e p<0.01 vs VDD; f p<0.05 vs VDD; g p<0.001 vs Nx; h p<0.01 vs Nx; i p<0.05 vs Nx.

Funding

  • Government Support - Non-U.S.