Variation of proteinuria in dogs affected by lehismaniasis trated with maglumine antimoniate and allopurinol : 53 cases

Introduction. Canine leishmaniasis (CanL)-associated proteinuric nephropathy is characterized by glomerular damage primarily attributed to glomerular deposition of circulating immune complexes.1 Results of previously published studies suggest that, in dogs, persistent proteinuria is associated with greater frequency of renal morbidity and mortality.2 A recent study demonstrated a potential reno-protective activity of allopurinol decreasing proteinuria and preventing progression of renal disease in dogs with leishmaniasis and glomerulonephritis.3 Objective. The aim of the study was to investigate whether the degree of proteinuria, evaluated by urine protein-to-creatinine ratio (UP:C), in leishmaniotic dogs classified in clinical stage C according to the staging of Canine Leishmaniasis Working Group,4 changes during anti-protozoan treatment with meglumine antimoniate (MA) and allopurinol (A). Furthermore, we evaluated the variations and correlations between serum concentration of albumin, globulin, total protein and A/G before and after treatment. Material & Methods. Medical records (2006-2010) of the Clinica Veterinaria Pirani (Italy), Veterinary Teaching Hospital of the Universitat Autonoma de Barcelona (Spain) and Centro Veterinario Imperiese (Italy) were reviewed to identify proteinuric leishmaniotic dogs, irrespective of their azotemic status, treated with the combination MA + A for a period ranging between 4 to 8 weeks. Dogs recruited for this study fulfilled the following inclusion criteria: a)diagnosis of leishmaniasis established by clinicopathological abnormalities; b)positive serology for L. infantum and detection of Leishmania amastigotes in lymph node or bone marrow aspiration smears or detection of parasite DNA using PCR; c)negative serology for E. canis and Dirofilaria immitis; d)complete urinalysis, with inactive sediment, and determination of the UP:C just before and after the anti-Leishmania treatment; e)treatment with MA (75-100 mg/kg SC q24h) in combination with A (20 mg/kg PO q24h) for 4 to 8 weeks. Dogs should not have been treated with ACE-inhibitors and/or angiotensin receptor blocker in the 2 months prior to and throughout the anti-Leishmania treatment period. Dogs with clinical signs and clinicopathological findings consistent with neoplastic, endocrine and genetic (inherited nephropathies known or suspected) diseases correlated with proteinuria, were excluded. Results. Before treatment, a significant negative correlation was found between UP:C and both serum albumin concentration (P=0.029, r=-041) and A/G ratio (P=0.006, r=-0.39) and a significant positive correlation was found between UP:C and total globulin (P=0.027, r=0.31). No correlations between UP:C and total protein were found (P=0.062, r=0.27). UP:C, total protein and globulin significantly decreased after treatment, compared with pre-treatment values. Conversely, albumin and the A/G ratio recorded after treatment were significantly higher than those recorded just before treatment. For all parameters, pre-and post-treatment values were always significantly correlated to each other (P<0.001 for all). After treatment: 7 proteinuric or borderline proteinuric dogs (13.4%) became non-proteinuric, 12 proteinuric dogs (22.6%) became borderline proteinuric. 12 dogs (22.6%) modified their IRIS stage based on values of serum creatinine and UP:C. Conclusions. The laboratory findings detected before treatment (hyperproteinemia, hypoalbuminemia, hyperglobulinemia, decreased A/G ratio, proteinuria) are consistent with those previously reported by other authors on CanL.5 The hyperproteinemia caused by hyperglobulinemia observed in this study, corroborates the findings of other Authors who reported that in some leishmaniotic dogs there is an increase in total protein levels due to a greater production of antibodies. Similar to that reported in a recent study,2 the anti-Leishmania treatment reduces the magnitude of proteinuria; nevertheless, in contrast to the aforementioned study, which shows the reduction of proteinuria after 6 months of administration of A, our results show a significant reduction of UP:C after 4-8 weeks of treatment. This result may be related to the mechanism of action of 2 drugs used: the combined use of MA and A could lead to a more rapid reduction of parasitic load, and consequently of the circulating immune complexes that affect the kidneys. In conclusion, is plausible to suggest that is useful, to stage the proteinuric leishmaniotic dog according with the IRIS staging system,6 at the end of the anti-Leishmania treatment in order to correctly identify the dogs that need anti-proteinuric therapy and optimize the conditions for monitoring the therapeutic efficacy.