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Título/Title/Titulo

Use of urine progenitors cells for in vivo renal repair in a new non-invasive rat kidney injury model using high sodium oxalate-diet

Introdução/Introduction/Introdución

Chronic Kidney Disease (CKD) is a major worldwide public health issue affecting 14% of the general population. Despite the elevated costs in dialysis and extended waiting list for renal transplantation, the research focusing on CKD mechanisms and treatment is limited. Moreover, animal models accurately recapitulating the human physiopathology of the disease with systemic complications are limited.

Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados

We propose a new non-invasive model of CKD in rats and assessed the potential benefits of human Urine Progenitors Cells (UPC) injection to trigger kidney repair. 25 male Wistar rats 7 weeks-old, 250-300g, were obtained from animal care of Heart Institute (São Paulo, Brazil). They received a diet with low calcium concentration (control diet) plus 50 μmol/g of sodium oxalate (OXA diet) for 3 weeks to induce CKD. Control rats received only the control diet. After the induction of the renal dysfunction, we injected UPCs (106 cells / per animal) directly in the renal parenchyma (10 injection points) or under the renal capsule. 7 weeks after injection, to assess renal function, the animals were left for 24 hours in the metabolic cage and had their urine and blood collected. Blood gases, caudal pressure, echocardiography and histological analyzes were evaluated. First, we analyzed the effects of OXA diet and showed that, compared to control rat, rats treated with OXA diet developed a stable CKD with a 60% reduction of the Glomerular Filtration Rate (GFR), elevated blood urea levels and proteinuria. Histological analyzes showed an important tubular atrophy and deposition of collagen, proving a high cortical disorganization and fibrosis, besides the accumulation of OXA crystals in the atrophied tubules. Rats treated with OXA diet also displayed classical complications of CKD, such as elevated blood pressure and reduced hematocrit. In addition, functional cardiac analyses revealed that OXA diet triggered diastolic dysfunction, presented with higher E/e’ ratio accompanying significant cardiac hypertrophy. In addition, we showed that both types of UPC injections increased significantly GFR and prevent the GFR decrease after 7 weeks of treatment. The rats treated with injected cells in the renal parenchyma showed an increase in blood urea levels and reduction in blood pressure, reversing completely the effects caused by OXA diet. Altogether, our results showed the feasibility to use a convenient and non-invasive strategy based on a diet rich in sodium oxalate to induce CKD and its classical systemic complications in rats. As this rat model does not involve kidney mass loss or acute toxicity it has a strong potential for research on CKD mechanisms and treatments.

Considerações Finais/Final considerations/Consideraciones finales

Finally, preliminary results of UPC injection provide evidence that these cells may contribute to improve kidney function and systemic complication, such as blood pressure.

Palavras-chave/Key words/Palabras clave

Chronic kidney disease; rat model; oxalate; human urine progenitors cells, cardiac function

Área

Cell Therapy

Autores

THAYANE ANTONIOLLI CRESTANI, Clara Steichen, Renato O Crajoinas, Leonardo Jensen, Leno L Dima, Adriana C Girardi, Jose E Krieger