ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1826

Contributions of Obesity and Hypertension to Progression of Cardiorenal Syndrome in Non-Diabetic Obese Female ZSF1 Rats

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Nguyen, Isabel T.N., Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
  • Joles, Jaap A., Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
  • Verhaar, Marianne C., Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
Background

Obesity and hypertension are highly prevalent in patients with cardiorenal syndrome (CRS). Insight in how these comorbidities individually contribute to disease progression is required to improve treatment strategy. We dissected the separate contribution of obesity and worsening hypertension by deoxycorticosterone acetate (DOCA) plus high salt diet in the obese female ZSF1 rat, a model of metabolic CRS in the absence of diabetes [Nguyen, PLoS One 2020]. We hypothesize that in obese non-diabetic female ZSF1 rats obesity has a profound effect on functional progression of CRS while hypertension mainly affects fibrosis and inflammation.

Methods

Systolic blood pressure (SBP), renal and cardiac function were assessed biweekly in lean and obese female ZSF1 rats from 12 to 26 weeks of age. From 19 weeks, rats were implanted with either a DOCA pellet and fed a high salt (6% w/w) diet or with a placebo pellet and fed a normal salt diet. At 26 weeks of age, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were assessed under isoflurane anesthesia. Subsequently, rats were sacrificed and tissues processed for analysis of renal and cardiac damage and inflammation.

Results

Obese versus lean placebo rats showed elevated E/e’ ratio from 12 weeks, indicative of diastolic dysfunction. From 24 weeks obese compared to lean placebo rats developed proteinuria with lower GFR at 26 weeks of age. DOCA-salt markedly increased SBP in obese but not lean rats, despite similarly high natriuresis compared to placebo rats. ERPF was increased by DOCA-salt in lean but not obese rats. DOCA-salt worsened proteinuria and glomerulosclerosis in obese rats. Cardiac fibrosis and glomerular hypertrophy, present in obese rats, were not aggravated by DOCA-salt. However, DOCA-salt increased the number of macrophages in heart, but not in glomeruli of obese ZSF1 rats.

Conclusion

Obesity leads to renal and cardiac dysfunction and damage in female ZSF1 rats. Even without worsening of hypertension (DOCA+salt), cardiac dysfunction preceded proteinuria, suggestive of CRS type 2. Our findings suggest that antihypertensive and antiproteinuric treatment at a later stage without initially addressing metabolic risk, even in the absence of diabetes, will not provide adequate functional protection in CRS type 2.

Funding

  • Private Foundation Support