Portal de Pesquisa da BVS Veterinária

Tese em Português | VETTESES | ID: vtt-212908

Resumo

A doenca renal cronica (DRC) e uma afeccao prevalente em caes, de carater irreversivel e de natureza progressiva. Ferramentas terapeuticas que possam retardar a progressao desta enfermidade tem sido objeto de pesquisas; dentre as novas modalidades de tratamento sob investigacao, esta a terapia celular. Estudos em modelos pre-clinicos de DRC demonstraram que as celulas-tronco mesenquimais (CTMs) exercem efeito prorregenerativo, associado a liberacao de fatores antifibroticos e vasculotroficos. Diante destes resultados promissores, aventa-se a aplicabilidade das CTMs como recurso terapeutico na DRC de ocorrencia natural em caes. Os disturbios do metabolismo mineral, frequentemente associados a esta condicao, constituem importantes fatores de progressao e implicam no aumento da mortalidade; recursos terapeuticos que possam retardar a DRC e, por conseguinte, o desenvolvimento destes disturbios sao de grande relevancia clinica. Desta forma, a hipotese do presente estudo e que a terapia com CTMs possa atenuar o desenvolvimento dos disturbios do metabolismo mineral em caes doentes renais cronicos, e o objetivo e avaliar os efeitos da terapia celular sobre o metabolismo mineral na doenca renal cronica, nestes animais. Para tanto, foram selecionados 28 caes, nos estagios 2 (grupo A) e 3 (grupo B) da DRC (IRIS), provenientes da rotina de atendimento do Servico de Clinica Medica do Hospital Veterinario da FMVZ/USP (HOVET/USP). Os animais foram, entao, divididos em subgrupos, conforme o tratamento com solucao fisiologica (A SF, n= 6; ou B SF, n= 7) ou celulas-tronco-mesenquimais (A CTM, n= 6; ou B CTM, n= 9), e acompanhados clinicamente por um ano, ou ate o obito. Nao houve diferenca entre os tratamentos para as variaveis do metabolismo mineral; entretanto, a tendencia de incremento nas medias das mensuracoes sericas de 1,25(OH)2D3 e 25(OH)D3 nos grupos A CTM e B CTM, em comparacao ao placebo, foi observada. O delta dos valores de 25(OH)D3 apresentou diferenca significativa (p <0,05) entre os subgrupos A CTM e A SF, de modo que o grupo que recebeu a terapia celular apresentou maiores concentracoes deste metabolito. Quanto as variaveis PTH, calcio ionico, calcio total, fracao de excrecao urinaria de calcio, FGF-23, fosforo serico e fracao de excrecao urinaria de fosforo, nao houve diferenca entre os tratamentos com solucao fisiologica ou celulas-tronco mesenquimais, nos grupos A e B. O delta dos valores de ureia e fosforo serico tenderam a ser menores no subgrupo A CTM, em comparacao ao placebo. A analise de sobrevida, nao houve diferenca entre os tratamentos com terapia celular ou placebo, tanto para o grupo A, quanto para o B. Independentemente do tratamento, a proporcao de sobrevida tendeu a ser menor naqueles caes doentes renais cronicos que apresentaram as determinacoes sericas de 1,25(OH)2D3 < 35 pg/mL. No atinente ao PTH, os caes que obtiveram valores < 8,0 pmol/L apresentaram proporcoes de sobrevida significativamente menores, em comparacao aos demais, independente do tratamento recebido (p< 0,0001). A partir dos resultados obtidos no presente estudo, nao e possivel concluir acerca dos efeitos da terapia celular sobre o metabolismo mineral na doenca renal cronica em caes, nos estagios 2 e 3; por ora, sugere-se que o tratamento com celulas-tronco mesenquimais possa trazer maiores beneficios para aqueles caes em estagios iniciais da DRC.

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Chronic Kidney Disease in dogs is a highly prevalent illness, which is irreversible and progressive. A variety of therapeutic approaches that aim to slow CKD progression have been investigated, including the therapy with mesenchymal stem cell (MSC). Several studies performed with preclinical models showed positive results, regarding the antifibrotic effects of MSC on experimental CKD. However, it remains to be determined the benefits of MSC in dogs with naturally occurring CKD. One of the most concerning issue in patients with CKD is the development of Mineral Disorders (MD-CKD), since it is associated with disease progression and mortality. Our hypothesis is that MSC therapy could attenuate the development of MD-CKD in dogs; our aim is to evaluate the effects of MSC therapy on mineral metabolism in dogs with CKD. We recruited 28 CKD dogs with stages 2 (group A) and 3 (group B), in accordance with IRIS criteria. All of the dogs were treated at the Clinic of the Veterinary Teaching Hospital of the University of Sao Paulo, School of Veterinary Medicine and Animal Science. The dogs were assigned to receive placebo (A SF, n= 6; B SF, n= 7) or MSC therapy (A CTM, n= 6; B CTM, n= 9), and they were then followed up during one year or until death. There was no difference between the effects of placebo or MSC therapy on mineral metabolism. A trend was note regarding the serum concentrations of 1,25(OH)2D3 and 25(OH)D3, which seemed to be increased in dogs that received MSC therapy (A CTM and B CTM), in comparison with placebo. The delta of 25(OH)D3 was significantly higher (p< 0,05) in dogs from the A CTM group, in comparison with those from A SF group. There were no differences between placebo or MSC therapy for both groups (A and B), regarding PTH, ionized calcium, total calcium, urinary fractional excretion of calcium, FGF-23, serum phosphorus and urinary fractional excretion of phosphorus. A trend was note in the delta of urea and phosphorus, which were lower in the A CTM group, in comparison with placebo. There was no difference in the survival rates of dogs whose received placebo or MSC therapy, in both goups (A and B). Regardless the applied treatment, the dogs that had the lowest values of calcitriol (1,25(OH)2D3 < 35 pg/mL) showed a trend to exhibit the lowest rate of survival. Similar results were obtained in those dogs that had the lowest levels of PTH (PTH < 8,0 pmol/L), whose showed the lowest survival rates (p< 0,0001). It is not possible to conclude the effects of MSC therapy on mineral metabolism in CKD dogs with stages 2 and 3. Our results suggest that the MSC therapy may have some benefit in the early stages of CKD in dogs.

Biblioteca responsável: BR68.1