Using information provided by 86 veterinary practitioners who responded to an online questionnaire, we evaluated how veterinarians from Portugal, a country where CanL is endemic, approached the treatment of proteinuria in dogs with leishmaniosis. Specifically, we aimed to clarify the preferred medical management protocol and whether immunosuppressants are considered in the case of glomerular disease. When treating a dog with leishmaniosis, it is important not only to control the infection, but also to treat any complications that develop during the course of the disease, with renal disorders being among the most frequent of complications in such patients . This survey included three virtual scenarios, corresponding to CanL stages IIb, III and IV, in which renal impairment was described. By analyzing the responses of veterinary practitioners to this questionnaire, we were able to assess how these practitioners deal with proteinuria in clinical practice.
With respect to the use of antiproteinuric treatment in daily practice, the results from this survey show that antiproteinuric treatment increased with increasing magnitude of proteinuria (and azotemia). According to some authors [9, 19, 20], given that proteinuria decreases within 4 to 8 weeks following the initiation of antileishmanial treatment, the CanL stages IIb and III scenarios in our survey could be treated only with antileishmanial drugs, and antiproteinuric compounds should only be considered 4 weeks later if the UPC remained > 0.5. However, in our survey, 16.3% and 62.8% of the veterinarians who responded stated that they would apply antiproteinuric treatment in combination with antileishmanial drugs in CanL stages IIb and III, respectively, while almost all respondents (93.8%) stated that antiproteinuric treatment would be appropriate in the CanL stage IV with UPC > 3.0 (creatinine = 3.5 mg/dl and UPC = 6.2 in our scenario). These results reflect that even in early stages of CanL, proteinuria is immediately addressed independently of antileishmanial protocols. As this study was conducted before the publication of a recent consensus on CanL and chronic kidney disease (CKD) , these findings reinforce the inconsistent approach on proteinuria management in daily veterinary practice. Although the publication of recent guidelines can in part contribute to a more homogeneous and step-by-step approach, particularly regarding the treatment of CanL stages IIb and III, the question of whether or not proteinuria should be addressed at the time antileishmanial therapy is initiated or only after 4 weeks of therapy remains controversial.
Regarding the antiproteinuric drugs chosen, ACEI were the preferred compounds. Indeed, ACEI are the most recommended compounds to treat proteinuria in dogs, along with a change in diet to a renal diet [9, 16,17,18, 21,22,23]. To a much lesser extent, some veterinarians selected ARB, CCB and antithrombotic drugs as first-line protocols, with the use of these compounds increasing in line with the severity of renal disease (and CanL). With the advent of ARB for the treatment of canine nephrology disorders [24,25,26], further studies are needed to clarify which drug is more appropriate for cases of CanL with glomerular involvement. The prescription of antithrombotic therapy in CanL stages III and IV may be justified by the hypoalbuminemia described in those scenarios, although guidelines [9, 16] recommend the use of this therapy when hypoalbuminemia is severe, which was not described in the hypothetical clinical cases in this survey.
In addition to the use of pharmacological treatment for CanL, the choice for a renal diet was also seen to have become increasingly accepted therapy, in line with the worsening of renal disease. Recommendations in the most recent literature [9, 16] are that CanL stage IIb would only require monitoring in addition to antileishmanial treatment. According to Roura et al. , CanL stage III should first be monitored, given that UPC is < 3.0, and antiproteinuric treatment should only be considered at follow-up, 4 weeks later. Nevertheless, such protocols may vary according with the clinical status of the patient and should be applied on a per-patient basis . Therefore, it is possible that diet is unnecessarily changed in the treatment of earlier CanL stages, in which, following recent guidelines, proteinuria should be assessed 4 weeks after the onset of antileishmanial treatment.
Even though our results are generally in accordance with the recommendations, the use of non-recommended protocols showed some inconsistency and misinformation among the respondents regarding the management of proteinuria in dogs with leishmaniosis, especially in those with lower UPC values. These results stress the need to increase awareness of the role of medical management in proteinuria.
The use of immunosuppressants in dogs suspected of glomerular disease secondary to leishmaniosis is particularly controversial, as demonstrated by the respondents falling approximately evenly (50%) into the two categories (yes/no), emphasizing the lack of agreement in such cases. The controversy usually focuses on the possibility that these drugs may compromise the immune response against infection and worsen the clinical status rather than help reducing the immune-mediated inflammation. Among those respondents who reported using immunosuppressants, almost all prioritized prednisolone and a small proportion chose mycophenolate mofetil. These results are in contrast with the consensus recommendations for the treatment of immune-mediated glomerular disease , given that glucocorticoids have considerable adverse effects (such as worsening of proteinuria and hypertension); as such, mycophenolate mofetil is the recommended first-choice immunosuppressant for these cases. Nonetheless, the latest recommendations state the use of prednisone at an anti-inflammatory dosage as an effective approach . Only 7.9% (3/38) of the respondents provided details on the dose and frequency of administration used; therefore, it was not possible to properly evaluate this information. Although a recent study  reported the use of prednisolone at 0.7 mg/kg once daily in cases of suspected glomerular disease, further studies are required to clarify the best recommended dose for its use in these patients. These results and the incongruent position of immunosuppressants in the medical management of CanL stress the need for comparative studies to clarify whether immunosupressants are recommended and, if so, which compound provides the best effect.
This study had several limitations that need to be considered. The number of replies (n = 86) was relatively small, considering the estimated number of veterinarians registered in Portugal . However, the number of those actively working as small-animal practitioners and belongs to the network groups where the questionnaire was distributed is unknown, and the number of replies is in line with those reported in other studies [28, 29]. Another limitation was that some details on the clinical cases were absent, with the aim to limit the size of the questionnaire.
Although a recent publication on guidelines addressing the main problems of glomerular disease in dogs with leishmaniosis is helpful , this survey provides a better understanding on how veterinarians currently manage proteinuria in clinical practice.