Abstract Body: Background: As a common complication of diabetes, diabetic kidney disease (DKD) is a chronic progressive disorder that can lead to kidney failure, and it is currently the leading cause of kidney replacement therapy in the USA and worldwide. Although renal denervation (RDNx) has recently been approved by the FDA to treat hypertension, contradictory findings have been reported on the effect of RDNx on the blood pressure and progression of DKD in type 2 diabetic mellitus. Here, we used type 2 diabetic nephropathy (T2DN) rats, a well-established non-obese model that displays similar renal abnormalities and hyperglycemic levels as seen in humans, to evaluate the effect of RNDx on the blood pressure and progression of DKD.

Methods: Bilateral RDNx or sham surgeries were performed on male T2DN rats with mild and severe stages of DN (~20 or >35 weeks old). The blood pressure was monitored chronically using radio telemetry throughout the entire experiment. 24-hr urine collection, glucose tolerance test, and GFR measurement were performed at baseline and at the end of the experiments. Blood and urine electrolytes were measured using a blood gas analyzer. The amount of norepinephrine in the kidney was evaluated by ELISA.

Results: Bilateral RNDx were successfully performed on T2DN rats with a significant reduction of norepinephrine in the kidneys of the RDNx group (244±13 vs. 8±1 pg/mg for >35 weeks old rats). The mean arterial pressure (MAP) and heart rate remain the same between the Sham and RDNx groups. The glucose tolerance test also indicates no difference between the two groups. While there is a significant decrease in the GFR in Sham group from baseline to week 3, the GFRs between Sham and RDNx groups are not different. Similarly, total body weight, kidney to total body weight ratio, heart to total body weight ratio, and blood and urine electrolytes are also not different between Sham and RDNx groups. Analysis of the younger group (~20 weeks old) is in progress.

Conclusion: In summary, our data suggests that RDNx does not affect the blood pressure and progression of DKD in male T2ND rats, at least at the stage of severe kidney injury (>35 weeks old).

Funding sources: National Institute of Health R01 DK135644 and R01 DK129227, Department of Veterans Affairs I01 BX004024 (to AS), and APS Postdoctoral fellowship (to BX).