Kidney Week

Abstract: FR-PO1076

Novel Model of Kidney-Cardiovascular-Metabolic Injuries by Unilateral Nephrectomy and an Extreme Western Diet: Beneficial Effects by a Natural Food Additive (FLX)

Session Information

• Kidney Nutrition and Metabolism
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1500 Health Maintenance, Nutrition, and Metabolism

Authors

• Fellstrom, Bengt C., Dept Medical Sciences, Nephrology, Uppsala, Sweden

Bengt C. Fellstrom, MD, PhD

• Carvalho, Lucas, Dept Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

Lucas Carvalho

• Tydén, Maria, Dept Medical Sciences, Nephrology, Uppsala, Sweden

Maria Tydén, MD

• Monteiro, Matheus, Dept Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

Matheus Monteiro, PhD

• Andersson, Daniel C., Dept Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

Daniel C. Andersson, MD, PhD

• Schiffer, Tomas A., Dept Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

Tomas A. Schiffer, PhD

• Carlstrom, Mattias, Dept Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

Mattias Carlstrom, PharmD, PhD

Background

CV complications are severe in renal failure and patients continue to die from CVD. A novel mouse model with progressive renal, CV and metabolic injuries was developed. Beneficial results from preventive treatment with a food additive were found. We aimed to characterize reno-cardio-metabolic dysfunctions, induced by renal failure and Western diet (WD) rich in sugar, fat and salt, and explore preventive effects by a novel food additive.

Methods

C57BL/6J mice (n=18) were subject to unilateral nephrectomy (UNX), fed a WD rich in fat, carbs and salt and followed for 12 weeks compared with SHAM-operated mice on standard chow. A group of UNX+WD mice (n=8) was fed a food additive (FLEXOVITAL [FLX]: extracts of Rhodiola, beetroot, L-arginine and citrulline). Body weight (BW), blood pressure (BP), endothelial-dep. vasorelaxation (myograph), glucose metabolism (IPGTT), body fat-lean mass (DEXA), adipocyte area, renal function (GFR : FITC-inulin), and mitochondrial function (Highresolution respirometry) were measured plus markers of heart injury (TnI), inflammation (IL6) and histology.

Results

In the UNX+WD group, notable increases in BW were observed along with higher fat/lean-mass ratio (17%) and adipocyte area (31%), all of which were mitigated by FLX. Fasting glucose levels were elevated but decreased with FLX. BP was increased (MAP of 78 to 90 mmHg, p<0.001), substantially attenuated by FLX. Endothelial dysfunction in UNX+WD mice was partially preserved with FLX. GFR decreased by 60%, yet a 75% protective effect by FLX. Glomerular and tubular injuries emerged, but less severe in the FLX group. TnI levels increased 2-3-fold but normalized with FLX. Additionally, FLX reduced IL6 levels. Mitochondrial dysfunction in kidneys and hearts improved with FLX.

Conclusion

Cardiovascular, renal and metabolic dysfunction/injuries emerge in this model and significant protection were demonstrated with the food additive FLEXOVITAL

Funding

• Commercial Support – BioConcept AB, Stockholm, Sweden