Publicação
Endothelial glycocalix shedding as a proposed pathophysiological pathway for proteinuria in canine hypercortisolism
| Resumo: | Proteinuria is a common finding in dogs with naturally occurring Cushing´s syndrome, with an estimated incidence as high as 75%. Although hemodynamic factors such as hypertension and consequent changes on glomerular filtration rate may contribute to proteinuria, its etiology is still poorly understood. Emerging studies have revealed a compelling correlation between endothelial glycocalyx (eGlx) breakdown and proteinuria in humans. Serum circulating hyaluronan has been considered a reliable biomarker of eGlx shedding not only in humans but in various animal models. Although growing evidence highlights the role of eGlx shedding in the pathophysiology of various diseases, its impact in canine naturally occurring Cushing`s syndrome remains poorly understood. This study aims to evaluate serum hyaluronan in dogs with Cushing`s syndrome and its possible relationship with proteinuria. A cross-sectional multicentric study was conducted, including leftover samples from dogs with Cushing´s syndrome diagnosed from 2022 to 2024 before initiating trilostane therapy. Stored and frozen at -20 or -80°C until processing, serum hyaluronan was measured using a sandwich ELISA Kit (Hyaluronan Quantikine ELISA kit) previously validated for dogs. Concurrent urinary protein- creatinine ratio (UPC) and hematobiochemical values for each animal were obtained from medical records. Gathered values were compared with historic controls from previous studies. Dogs were grouped regarding their degree of proteinuria: non-proteinuric (UPC<UPC2). The serum hyaluronan concentrations (median [min-max range]) obtained for dogs with hypercortisolism (45.94 [9.70- 265.07] ng/mL) showed a similar range to those previously described in dogs in hypercoagulable states (92.40 [16.9-247.6] ng/mL), and median value either higher or similar to those observed in healthy dogs, depending on the study (45.7 vs 17.4 vs 17,9 ng/mL). The difference in serum hyaluronan concentrations between different degrees of proteinuria did not reach statistical significance (p = 0.062). No correlation was found between serum hyaluronan and UPC (p = 0.119). This study documents an increase in serum hyaluronan concentrations in dogs with Cushing´s syndrome. Despite no apparent association with proteinuric status, the serum hyaluronan values obtained in this study are similar in range to those found on dogs with in a hypercoagulable status, pointing towards an association between eGlx breakdown and the hypercoagulability in patients with naturally occurring Cushing’s syndrome |
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| Autores principais: | Silva, David Vieira da |
| Assunto: | Cushing's syndrome Proteinuria Endothelial Glycocalyx Hyaluronan ELISA Síndrome de Cushing Proteinúria Glicocálice endotelial Hialuronato ELISA |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Proteinuria is a common finding in dogs with naturally occurring Cushing´s syndrome, with an estimated incidence as high as 75%. Although hemodynamic factors such as hypertension and consequent changes on glomerular filtration rate may contribute to proteinuria, its etiology is still poorly understood. Emerging studies have revealed a compelling correlation between endothelial glycocalyx (eGlx) breakdown and proteinuria in humans. Serum circulating hyaluronan has been considered a reliable biomarker of eGlx shedding not only in humans but in various animal models. Although growing evidence highlights the role of eGlx shedding in the pathophysiology of various diseases, its impact in canine naturally occurring Cushing`s syndrome remains poorly understood. This study aims to evaluate serum hyaluronan in dogs with Cushing`s syndrome and its possible relationship with proteinuria. A cross-sectional multicentric study was conducted, including leftover samples from dogs with Cushing´s syndrome diagnosed from 2022 to 2024 before initiating trilostane therapy. Stored and frozen at -20 or -80°C until processing, serum hyaluronan was measured using a sandwich ELISA Kit (Hyaluronan Quantikine ELISA kit) previously validated for dogs. Concurrent urinary protein- creatinine ratio (UPC) and hematobiochemical values for each animal were obtained from medical records. Gathered values were compared with historic controls from previous studies. Dogs were grouped regarding their degree of proteinuria: non-proteinuric (UPC<UPC2). The serum hyaluronan concentrations (median [min-max range]) obtained for dogs with hypercortisolism (45.94 [9.70- 265.07] ng/mL) showed a similar range to those previously described in dogs in hypercoagulable states (92.40 [16.9-247.6] ng/mL), and median value either higher or similar to those observed in healthy dogs, depending on the study (45.7 vs 17.4 vs 17,9 ng/mL). The difference in serum hyaluronan concentrations between different degrees of proteinuria did not reach statistical significance (p = 0.062). No correlation was found between serum hyaluronan and UPC (p = 0.119). This study documents an increase in serum hyaluronan concentrations in dogs with Cushing´s syndrome. Despite no apparent association with proteinuric status, the serum hyaluronan values obtained in this study are similar in range to those found on dogs with in a hypercoagulable status, pointing towards an association between eGlx breakdown and the hypercoagulability in patients with naturally occurring Cushing’s syndrome |
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