Abstract: TH-PO604

Effects of Smoking on Pkd1-Deficient Cystic Mice: An Extended Study on the Renal and Cardiac Phenotypes

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Sousa, Marciana V., University of Sao Paulo, Sao Paulo, Brazil
  • Amaral, Andressa G., University of Sao Paulo, Sao Paulo, Brazil
  • Balbo, Bruno E., University of Sao Paulo, Sao Paulo, Brazil
  • Messias, Fernanda S., University of Sao Paulo, Sao Paulo, Brazil
  • Melo, Marcelo D., University of Sao Paulo, Sao Paulo, SP, Brazil
  • Hortegal, Renato A., University of Sao Paulo, Sao Paulo, SP, Brazil
  • Castro, Isac De, University of Sao Paulo, Sao Paulo, Brazil
  • Salemi, Vera Mc, University of Sao Paulo, Sao Paulo, SP, Brazil
  • Onuchic, Luiz F., University of Sao Paulo, Sao Paulo, Brazil
Background

Previous studies have shown that heavy smoking increases the risk of advanced chronic kidney disease and that smoking raises the risk of progression to ESKD in men with ADPKD.

Methods

Cystic Pkd1flox/flox:Nestincre and noncystic Pkd1flox/flox mice were exposed to cigarette smoking (CYS and NCS, respectively) from conception to 18 weeks of life, twice a day, 30-min periods. Control groups also included cystic and noncystic mice not submitted to smoking (CY and NC, respectively). Renal function, cystic index and cell proliferation; cardiac function, including deformation (strain); body weight (BW); and kidney and heart apoptosis, fibrosis and weight were analyzed at 16-18 weeks.

Results

We showed in a 2016 ASN abstract that BUN was higher in CYS mice than CY and NC, and in NCS than NC, while no difference was detected between CYS and NCS. CYS kidneys developed increased cystic index, cell proliferation in cyst epithelium and fibrosis compared to CY. Higher tubular cell proliferation and fibrosis were found in NCS kidneys than NC. CYS animals had lower BW than CY and NC. In the present work we show increased apoptosis in CYS kidneys compared to NCS and NC, and in CY and NCS compared to NC. Renal weight/BW was higher in CYS mice than NCS and NC but not than CY. Cardiac apoptosis and heart weight/BW did not differ among the groups. Increased fibrosis was found in CYS hearts compared to NCS [1.10% (0.79-2.95) vs 0.26% (0.15-0.45), p<0.05] and NC (p<0.01), and in CY hearts compared to NC [0.82% (0.64-1.60) vs 0.21% (0.09-0.38), p<0.05]. Left ventricle ejection fraction was lower in CYS mice than NCS (35.6±15.1% vs 49.5±11.1%, p<0.05) and NC (vs 52.3±9.5%, p<0.01). CYS animals showed decreased circumferential strain and strain rate compared to CY, NCS and NC; lower values were also found in CY compared to NC. CYS and CY mice presented lower radial strain on the short axis than NC. Radial strain rate on the short axis and longitudinal strain were decreased in CYS and NCS animals in comparison to NC.

Conclusion

Our findings show that smoking worsened the renal and cardiac phenotypes of Pkd1-deficient cystic mice. Detrimental effects also affected noncystic animals. Our results suggest that smoking aggravates the kidney and heart phenotypes associated with ADPKD.

Funding

  • Government Support - Non-U.S.