Effects of Allopurinol Treatment on the Progression of Chronic Nephritis in Canine Leishmaniosis (Leishmania infantum)

Abstract

Forty dogs with canine leishmaniosis (CL) participated in this study, which was designed to investigate the effect of allopurinol on the progression of the renal lesions associated with this disease. The animals were allocated into 5 groups. Group A dogs (n = 12) had neither proteinuria nor renal insufficiency, group B dogs (n= 10) had asymptomatic proteinuria, and group C dogs (n = 8) were proteinuric and azotemic. Two more groups, CA and CB, comprising 5 dogs each, served as controls for groups A and B, respectively. Group A, B, and C dogs received allopurinol PO (10 mg/kg q12h) for 6 months, whereas group CA and CB dogs were placebo-treated. Serum biochemistry profile, urinalysis, urine protein/creatinine ratio, and glomerular filtration rate (GFR) measurements were carried out at the beginning of the study, the 3rd month, and the 6th month, whereas renal biopsies were carried out only at the beginning and the end of the trial. Membranoproliferative glomerulonephritis was the most common cause of chronic renal failure. Mesangioproliferative and tubulointerstitial nephritis were detected even in group A and CA dogs. Allopurinol not only lowered proteinuria in group B dogs but also prevented the deterioration of GFR and improved the tubulointerstitial, but not the glomerular, lesions in both group A and group B dogs. Further, it resolved the azotemia in 5 of the 8 dogs admitted with 2nd stage chronic renal failure (group C). Consequently, treatment with allopurinol is advisable in CL cases with asymptomatic proteinuria or 1st-2nd stage chronic renal failure.

Pathologic Mechanisms Underlying the Clinical Findings in Canine Leishmaniosis due to Leishmaniainfantum/chagasi

“…30 Renal histopathology of these nephritic dogs almost always reveals glomerulonephritis, usually mesangioproliferative and membranoproliferative, and tubulointerstitial nephritis, whereas amyloidosis is a rare occurrence. 8,29,72,116,118 Tubulointerstitial lesions appear secondarily to glomerular pathology as well as to immune complex-mediated inflammation and the fibrosis of renal interstitium. 8,29,116,153 This proteinuric nephropathy progressively leads to excretory dysfunction or sometimes to decreased or increased glomerular filtration rate and to systemic hypertension that can establish a vicious cycle, thus amplifying the underlying glomerular pathology.…”

“…8,29,72,116,118 Tubulointerstitial lesions appear secondarily to glomerular pathology as well as to immune complex-mediated inflammation and the fibrosis of renal interstitium. 8,29,116,153 This proteinuric nephropathy progressively leads to excretory dysfunction or sometimes to decreased or increased glomerular filtration rate and to systemic hypertension that can establish a vicious cycle, thus amplifying the underlying glomerular pathology. 25,26 Ocular disease is quite common in CanL and can be the only or the main clinical manifestation in 3.7% to 16% of the affected dogs.…”

“…13,18,21,27,44,74,96,141 Renal disease, a common entity and occasionally the sole clinical manifestation of CanL, may progress from asymptomatic proteinuria to nephrotic syndrome and/or end-stage kidney disease (uremic syndrome), and it is the principal cause of death among the affected leishmanial dogs. 29,73,116,118 Since renal disease plays a pivotal role in the prognosis and outcome of these animals, it has been adopted as a major criterion in the clinical staging of CanL by Leishvet. 137 In most cases, the only indication of renal involvement is asymptomatic proteinuria, which, due to its severity, may contribute to muscular wasting and cachexia and occasionally lead to pulmonary thromboembolism.…”

Questionnaire-based survey on canine leishmaniosis (Leishmania infantum) in Greece

“…Η κλινική εικόνα της ΛΣ, όπως καταγράφηκε α πό τους Έλληνες κτηνιάτρους, ουσιαστικά είναι η ί δια με εκείνη που περιγράφεται σε προηγούμενες με λέτες που έγιναν στη χώρα μας (Kontos 1986, Koutinas et al 1992, Kontos and Koutinas 1993, Koutinas et al 1999, Vamvakidis et al 2000, Papadogiannakis et al 2005, Rallis et al 2005, Plevraki et al 2006, Petanides et al 2008. Ενδιαφέρον, όμως, προκαλεί ότι από το σΰ-νολο σχεδόν των κτηνιάτρων (92,6%) διαπιστώθηκε η συνύπαρξη της ΛΣ με άλλα νοσήματα ή παθήσεις.…”

Determination of Allopurinol and Oxypurinol in Dogs Plasma by High- Performance Liquid Chromatography with an Ultraviolet Detector: Application for Pharmacokinetic Studies

“…Its use also extends to the treatment of canine visceral leishmaniasis (LV) therapy. In leishmaniostatic treatment is utilized either as monotherapy [6,7] or associated with leishmanicidal drugs [8][9][10].…”