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Abstract: FR-PO293

Expression of Sodium Renal Transporters in Urinary Exosomes from Patients with Edema Associated with Cirrhosis, Heart Failure, or Nephrotic Syndrome

Session Information

Category: Fluid and Electrolytes

  • 902 Fluid and Electrolytes: Clinical

Authors

  • Hurtado, Ivonne, INCMNSZ, MEXICO, Mexico
  • Bazua-Valenti, Silvana, IIB, UNAM, Mexico City, Mexico
  • Rojas, Lorena Leonor, INCMNSZ, MEXICO, Mexico
  • Gallardo, Fabiola, INCMNSZ, MEXICO, Mexico
  • Carrillo Perez, Diego Luis, INCMNSZ, MEXICO, Mexico
  • Marfil-Garza, Braulio A., INCMNSZ, MEXICO, Mexico
  • Galindo, Pablo Enrique, Instituto Nacional de ciencias medicas y nutrición salvador Zubiran, CUERNAVACA, Mexico
  • Becerra-Gamba, Tomas Alexis, INCICH, Mexico City, Mexico
  • Madero, Magdalena, INCICH, Mexico City, Mexico
  • Gamba, Gerardo, INCMNSZ, MEXICO, Mexico
Background

The formation of edema requires sodium retention along the nephron. The molecular pathways in humans leading to salt retention in edematous states remain elusive. The use of urinary exosomes (UE) is a non-invasive powerful tool to study the pathophysiology of renal diseases. Here we analyzed the expression of a variety of renal sodium transporters in UE from patients with and without edema diagnosed with chronic failure of the liver or heart, as well as from patients with nephrotic syndrome.

Methods

We conducted a prospective and observational study. We obtained clinical and biochemical data, as well as urinary samples from adult patients with liver cirrhosis (LC), heart failure (HF) or nephrotic syndrome (NS) (N=9 with, N=9 no-edema for each group) and 5 healthy volunteers as controls. UE from 8 ml of urine were obtained by ultracentrifugation for western blot analysis of SGLT2, NHE3, NKCC2, NCC and ENaC. The amount of UE used per patient was adjusted to urinary creatinine.

Results

Clinical and biochemical data from edema and non-edema patients were similar, except for mild hyponatremia and lower MAP in LC and HF patients with edema, respectively. Analysis of UE of patients with LC showed a significant increase in NHE3 and SGLT2 only in the edema group, while there was decreased NCC expression in the non-edema group. Conversely, NS and HF patients showed increased proximal tubule transporters even in the non-edema group. These patients were also characterized by increased ENaC expression. NKCC2 was only increased in HF patients with or without edema. Interestingly, NCC did not increase in any of the groups.

Conclusion

Our observations suggest that in edematous patients, regardless of the underlying syndrome, the proximal tubule transporters are upregulated and may be the most important cause of sodium retention. Interestingly, NKCC2 was increased in HF patients, but not in LC or NS patients. Down regulation of NCC in some groups suggests that the distal nephron is trying to compensate proximal reabsorption. These results suggest that diuretic therapy in patients with edema could be revisited to explore the use of proximal tubule inhibitors.

Funding

  • Government Support - Non-U.S.