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Abstract: PO2038

Is Basal Nitric Oxide Activity of the Renal Vasculature Altered? Analysis of a Randomized Controlled Trial Comparing Two Combination Therapies

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Kannenkeril, Dennis, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Ott, Christian, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Bosch, Agnes, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Striepe, Kristina, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Pietschner, Robert, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Schiffer, Mario, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
  • Schmieder, Roland E., Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
Background

Recently we demonstrated that a combination therapy with empagliflozin and linagliptin in patients with type 2 diabetes mellitus(T2DM) induce changes in renal hemodynamics. The purpose of this study was to analyze the influence of basal nitric oxide(NO) activity of the renal vasculature on the described changes of the renal hemodynamic profile.

Methods

In this study patients with T2DM were randomized to receive either empagliflozin and linagliptin(E+L group, n=50) or metformin and insulin glargine(M+I group, n=46), for 3 months. Renal hemodynamics were assessed with constant-infusion input-clearance technique with p-aminohippuric acid and inulin at baseline and after treatment. Due to withdrawal of inulin from the market during the study, glomerular filtration rate and filtration fraction(FF) were measured only in a sub-group of patients(E+L: n=34; M+I: n=31). Intraglomerular hemodynamics were calculated according the model established by Gomez. The basal NO activity in the renal circulation has been assessed by analyzing change in renal plasma flow(RPF) in response to intravenously administrated NG-monomethyl-l-arginine(NO inhibitor).

Results

After 3 months of treatment, we did not observe any change in basal NO activity compared to baseline in either of the groups. In the E+L group, we found a correlation between basal NO activity of the renal vasculature after 3 months of treatment and change in RPF(r=-0.535, p<0.001), renal blood flow(r=-0.468, p=0.001) and renal vascular resistance(r=0.377, p=0.007) induced by treatment. Similar correlations with change in FF(r=0.639, p<0.001), preglomerular(r=0.350, p=0.046) and postglomerular resistance(r=0.588, p<0.001) have been found. No such relationships were found in the M+I group after 3 months and with basal NO activity at baseline in both treatment groups.

Conclusion

Basal NO emerged as a determinant of the renal hemodynamic response in the combination therapy of empagliflozin and linagliptin, but not in the combination therapy of insulin and metformin.