Renal Papillary Necrosis in Horses after Phenylbutazone and Water Deprivation

Abstract

Abstract. Acute renal papillary necrosis occurred in five horses given normal therapeutic doses of phenylbutazone and deprived of water for 36 to 48 hours prior to euthanasia. Five horses given phenylbutazone alone and four horses subjected to water deprivation alone did not develop papillary necrosis. Urinalyses were normal prior to water deprivation, and also after water deprivation in the horses that did not receive phenylbutazone, but the waterdeprived, phenylbutazone-treated horses had many red blood cells, transitional epithelial cells, and large numbers of oxalate crystals in their urine.Ulceration of the alimentary tract was seen in more than 50% of these horses. Tongue ulceration was present in one of five horses given phenylbutazone and one of five horses which had phenylbutazone and water deprivation. Ulceration of the gastric mucosa was seen in two of the five phenylbutazone-treated horses, four of five horses with phenylbutazone treatment and water deprivation, and one of four horses with water deprivation alone. Severe colonic ulceration with perforation and peritonitis was present in one horse given phenylbutazone for three months. No other significant changes in the small or large intestine were seen in the other 13 horses.It generally has been thought that phenylbutazone is not toxic to horses [ 10, 151, although deaths have resulted from its use in man [ 15 I. Recently, however, severe adverse effects have been described in eight of ten ponies given normal therapeutic doses of phenylbutazone [20]. It was concluded that ponies were much more susceptible than horses to severe side effects during phenylbutazone treatment [3, 201. Ulceration of the alimentary canal is a relatively common side effect of phenylbutazone therapy in equidae [5, 6, 10, 20, 211 and other species [15, 191, and recently gastrointestinal protein loss has been reported in both horses and ponies [2 11. Although there is decreased urinary excretion of sodium and chloride [ 11, and raised blood urea nitrogen has been noted [20], no renal lesions have been described in any of these studies [l, 5, 6, 10, 20, 211. Renal papillary necrosis has been seen, however, in a series of 16 horses in which therapy with antiprostaglandin drugs, mostly phenylbutazone, was an almost constant feature, as was dehydration or impaired water intake [8]. The present study was undertaken to determine 603

Detecting early kidney damage in horses with colic by measuring matrix metalloproteinase -9 and -2, other enzymes, urinary glucose and total proteins

“…Moreover, a deterioration in renal function may become evident for the first time or may progress after the drug has been discontinued [8]. Gunson et al [9] reported that horses with both water deprivation and concurrent administration of the non-steroidal drug developed acute necrosis of the renal papilla, whereas the groups of horses that received either non-steroidal drug or water deprivation alone did not develop kidney damage.…”

Effects of using Flunixin Meglumine, Metamizole, and Phenylbutazone on equine kidney functions, urinary mucus, and secretory Immunoglobulin A (IgA) concentrations

“…Using PHZ did not affect the UUN concentration, however, it caused a significant increase of FECa and FEMg in comparison with the control group, which suggests that using of PHZ in horses with orthopaedic pain can affect the reabsorption of Ca and Mg at the thick ascending loop of Henle. Previous studies pointed to renal crest necrosis as a side effect of using PHZ, since the PHZ can cause inadequate blood supply in the renal medulla in waterdeprived horses (Gunson andSoma 1983, MacAllister 1993). However, the difference between the latter studies and our study is that, unlike these two studies, the horses in group 3 of our study were hydrated (as their PCV showed), and these horses were administered the recommended dose of PHZ.…”

“…Although several studies have been conducted to investigate the adverse effects of NSAIDs on horses, only a few reports have described their effects on the equine urinary system, probably because they happen rarely under recommended doses and are associated mainly with hypovolaemia. Horses have the potential to develop renal papillary necrosis if they are treated with overdoses of phenylbutazone (PHZ) or, to a lesser extent, FM (MacAllister et al 1993), or when they are treated with PHZ and are deprived of water (Gunson and Soma 1983). Side effects that have been reported after using metamizole (MZ) in human and veterinary medicine include mild GI tract disorders, aplastic anaemia, skin allergy and renal dysfunctions (Jasiecke et al 2014, Bentz 2015.…”

Gastrointestinal diseases of athletic horses

“…86 Cyclooxygenases metabolize arachidonic acid for the synthesis of the various prostanoids such as prostaglandins PGD 2 , PGE 2 , PGF 2 , prostacyclin, and thromboxane A 2 . 92,93 Phenylbutazone is the most commonly used NSAID due to its efficacy, availability and affordability. 88 The NSAID phenylbutazone is used in horses for the treatment of osteoarthritis and other musculoskeletal disorders.…”