Kidney Week

Abstract: SA-OR067

Expression Pattern of Renal Transporters in Urinary Exosomes from Patients with Edematous States

Session Information

• Tipping the Balance: Fluid and Electrolytes in Health and Disease
  November 04, 2017 | Location: Room 385, Morial Convention Center
  Abstract Time: 05:42 PM - 05:54 PM

Category: Fluid, Electrolytes, and Acid-Base

• 704 Fluid, Electrolyte, Acid-Base Disorders

Authors

• Bazua-Valenti, Silvana, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico

Silvana Bazua-Valenti, MBBS

• Rojas, Lorena Leonor, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico

Lorena Leonor Rojas,

• Gallardo, Fabiola, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico

Fabiola Gallardo,

• Carrillo Perez, Diego Luis, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico

Diego Luis Carrillo Perez,

• Marfil, Braulio Alejandro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico

Braulio Alejandro Marfil,

• Galindo, Pablo Enrique, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico

Pablo Enrique Galindo,

• Gamba, Gerardo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico

Gerardo Gamba,

Background

The use of urinary exosomes (UE) is a non-invasive powerful tool to study the pathophysiology of renal diseases and also as a diagnostic tool for assessment of human samples. For instance, we have shown that in renal transplant patients, tacrolimus increases expression and phosphorylation of NCC in UE. Here we analyzed UE from patients with liver cirrhosis or chronic kidney disease (CKD) with and without edema to assess the expression of a variety of renal transporters.

Methods

We conducted a prospective and observational study. We obtained clinical and biochemical data, and urinary samples from adult patients with liver cirrhosis (Child B) (N=6 with, N=6 no-edema), with CKD (KDIGO G3-G5) (N=6 with, N=6 no-edema) and healthy subjects (N=5), as controls. UE from 8 ml of urine were obtained by ultracentrifugation for western blot analysis of SGLT2, NHE3, NKCC2, NCC and CaSR. The amount of UE used per patient was adjusted to urinary creatinine.

Results

We found no significant differences in laboratory findings of cirrhotic patients with or without edema, except for higher serum Na⁺ in the edema group (133.9±4.9 vs. 140.1±2.1 p<0.05). In CKD patients, however, we found differences in the BMI (31±6.9 vs. 25±3 p<0.01), serum K⁺ (5.2±0.39 vs. 4.6±0.55 p<0.01) and serum Ca²⁺ (8.6±0.47 vs. 9.3±0.75 p<0.05) in the edema vs. no-edema group, respectively. Analysis of UE showed a significant increase in NCC phosphorylation, SGLT2, NHE3 and CaSR expression in both cirrhotic and CKD patients when compared to healthy controls. In the cirrhotic patients, those with edema showed increased expression of SGLT2, NHE3 and CaSR vs. the non-edema group. In CKD patients, although the expression of these transporters looks higher in the edema group, the difference did not reach significance. Interestingly, NKCC2 expression showed no changes in any group.

Conclusion

We observed different expression patterns for five proteins in UE of cirrhotic and CKD patients. Moreover, in cirrhotic patients the expression of the transporters was higher in the edema group. These results suggest that the analysis of renal transporters using UE can give insights into the molecular mechanisms of salt retention in patients with edematous states and may contribute to the design of early therapeutic strategies.

Funding

• Government Support - Non-U.S.