Abstract
For millennia, removal of uroliths has been the province of the surgeon. However, a paradigm shift in management of canine uroliths occurred beginning in 1973. Translating the science associated with medical dissolution of canine uroliths into a form that would serve companion animals involved the interdependent knowledge, skills, and desire of many individuals. By practicing the principles of being proactive, defining clear objectives, agreeing how to accomplish these objectives, and empathetically listening to each others ideas and concerns, the surgical removal of uroliths will one day become a subject of historic interest.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-15, ix |
| Journal | The Veterinary clinics of North America. Small animal practice |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1999 |
Bibliographical note
Funding Information:Blocking Urease With Acetohydroxamic Acid: Our next step was to determine if blocking the action of bacterial urease with a urease inhibiting drug would interrupt the pathogenic chain of events with the result that struvite uroliths would dissolve. This phase of the project involved collaboration with Dr. Donald Griffith, Baylor College of Medicine, who had performed elegant studies in the cause and treatment of struvite urolithiasis in humans.'9-21 We were particularly interested in his work with acetohydroxamic acid, a urease inhibitor. As a portion of his doctoral studies, Dr. Donald Kraweic in collaboration with the Minnesota team evaluated the ability of orally administered acetohydroxamic acid (AHA) to dissolve induced struvite urocystoliths in dogs with persistent staphylococcal UTI. A research proposal entitled "Investigation of the Effect of Acetohydroxamic Acid on the Formation and Dissolution of Phosphate Urinary Calculi" was funded by the Morris Animal Foundation. Results of these studies revealed that high doses of AHA could cause struvite urolith dissolution.28 Unfortunately, administration of AHA at doses high enough to cause
Funding Information:
stone dissolution was associated with a mild degree of hemolytic anemia. When the dosage of AHA was reduced so that it was nontoxic, it inhibited further stone growth but did not result in struvite urolith dissolution. In a related study, nontoxic doses of AHA were effective in preventing formation of uroliths in dogs with persistent staphylococcal UTI.29 However, in a study (Evaluation of the Teratogenic Effect of Acetohydroxamic Acid in Normal Beagle Dogs) funded by the Baylor College of Medicine and conducted as part of a Master of Science thesis by Dr. Norma Bailie in collaboration with the Minnesota team, AHA was found to be teratogenic when given to pregnant dogs.• Although the results of our studies with AHA were disappointing in context of our goal to safely and effectively dissolve struN"ite uroliths, they were highly significant from an etiopathogenic point of view. How so? They provided convincing evidence that interruption of the chain of events leading to struvite urolith formation could result in in vivo stone dissolution. Substrate Depletion by Dietary Modification: The results of our study with acetohydroxamic acid led us to hypothesize that reduction of the urine concentration of urea, the substrate of bacterial urease, would provide similar results. A research proposal entitled "Investigation of the Effects of Diets on Dissolution of Struvite Urinary Calculi" was designed to test this hypothesis. It was submitted to the Morris Animal Foundation. However, it was not approved by the Foundation's Scientific Advisory Board apparently because some were of the opinion that surgery was the accepted standard of treatment for canine urocystoliths by the veterinary profession. In addition, the opinion was expressed to me that the pet food industry would be a more suitable source of funding. We submitted our proposal to Dr. Mark L. Morris, Jr. and colleagues at Mark Morris Associates. They enthusiastically accepted the proposal, and together we formulated a prototype calculolytic diet that contained a reduced quantity of high quality protein and reduced quantities of calcium, phosphorus, and magnesium. The diet contained an increased amount of sodium chloride to promote increased thirst and increased urine formation. Other required nutrients were included to meet normal adult maintenance requirements. Reduction in the quantity of urea produced by catabolism of dietary protein reduced renal medullary urea concentration, further contributing to formation of unconcentrated urine. The study became a part of the doctoral thesis conducted by Dr. Shehu Abdullahi in collaboration with the research team at the University of Minnesota. The calculolytic diet was found to be highly effective in causing struvite urolith dissolution in 5 of 6 Beagle dogs with persistent staphylococcal UTI.' Uroliths dissolved in an average of 14 weeks (range, 8-20 weeks) despite the fact that no antibiotics were given. The urolith in the remaining dog decreased to less than half its pretreatment size at the end of the 6-month study. In the corresponding control group of 6 Beagle dogs fed an adult maintenance diet, uroliths increased in size by a mean of 5 times their pretreatment size. In a related study of sterile struvite uroliths, consumption of the calculolytic diet induced stone dissolution in a mean of 3.3 weeks (range, 2-4 weeks).' In a corresponding control group of Beagle dogs fed an adult maintenance diet, stones in 4 dogs dissolved in a mean period of 14 weeks. In the remaining 2 dogs, the stones were one fifth of their initial size at the end of the 6 month study. Combinations of Dietary and Pharmacologic Therapy: A subsequent study entitled "Investigation of the Effects of Antimicrobial Agents Acetohydroxamic Acid and Diet on Dissolution of Canine Struvite Urinary Calculi" was funded by the Paralyzed Veterans of America Technology and Research Foundation and
Funding Information:
The dogs arrived in Paul Bunyan land when they were 5 weeks old. They became a part of the thesis project of Dr. Jeffrey Klausner. A research proposal entitled, "Investigation Of The Etiopathogenesis Of Urinary Calculi In Miniature Schnauzers" was funded by the American Miniature Schnauzer Club Inc., the Morris Animal Foundation, and the Graduate School of the University of Minnesota.