Urolithiasis: past, present and future
Etched In Stone
What do stones and rocks symbolise? The terms “corner stone,” “steady as a rock,” “set in stone,” are commonly used to denote lasting durability. The Rock of Gibraltar on the Iberian Peninsula was mythically depicted as one of the Pillars of Hercules symbolizing that nothing could destroy the Rock or its people. Gibraltar's actual and mythical history has inspired the saying “Solid as the Rock”, which is used to describe a person or situation that cannot be overcome.
The Stone Age
Urinary stone disease has plagued mankind since the beginning of civilization. The discoveries of a bladder stone from an adult female entombed in a cave approximately 8500 years ago, and a Native American mummy estimated to be 1500 years old supports the paradigm of the stability of stones (Streitz and others 1981; D'Alesso and others 2005).
For almost the past 3000 years, the removal of uroliths has been a surgical procedure. Descriptions of cutting for the stone are found in Egyptian, Hindu and Greek writings. Hippocrates refers to lithotomy in the Hippocratic Oath when he stated that “I will not use the knife, not even on suffers from the stone, but will withdraw in favour of such men who are engaged in this work.” Up until the end of the 15th century, stones in the urinary bladders of humans associated with obstructive uropathy were tantamount to a death sentence. Given this probability those afflicted with this excruciating painful disorder turned to lithotomists for help. However, at a time prior to the discovery of general anaesthesia and sterile technique, lithotomists with little knowledge of anatomy and no knowledge of bacterial sepsis, mutilated or killed their patients more often than cured them (Urquhart-Hay, 1999). Complications of the perineal approach to lower urinary tract stones included faecal and urinary incontinence, impotence, urinary fistulas and ruptured bladders. It was not until the end of the 1800s, which also marked the discoveries of aseptic technique by Joseph Lister and improved anaesthesia by Quincy Crawford, William Morton, Crawford Long and others, did success and survival substantially increase.
What about stones in animals? Ashmont (1891) wrote the following about canine bladder stones, “a cure is out of the question”. Subsequently, Muller and Glass (1923) made the following statement about uroliths in dogs, “when the stone is present and causing retention of urine, there is nothing left but to remove the stone by means of an operation called urethrotomy if the stone is lodged in the urethra at the posterior end of the bones of the penis, or a cystotomy if the stone is located in the bladder. Brumley (1943) wrote that surgical treatment is the only satisfactory method of removing calculi from the (canine) bladder. Osborne and others (1972), in a book devoted to urology of small animals, wrote, “In dogs and cats, surgical removal remains the treatment of choice of uroliths in the urinary bladder, ureters and kidneys,” Thus, up until this time, as in humans, removal of uroliths, by consensus, had been the province of the surgeon.
A Paradigm Shift
Our frame of reference regarding the surgical treatment of canine uroliths changed in 1973 after observing in vivo dissolution of a large nephrolith in a four-year-old great Dane dog (Klausner and Osborne 1979). The dog had bilateral struvite nephrolithiasis associated with non-azotaemic pyelonephritis caused by urease-producing Proteus mirabilis. The goal was to surgically remove the stone from the right kidney first, and then 1 month later remove the stone from the left kidney. As planned, the stone in the right kidney was removed and the dog was administered antimicrobial therapy to eradicate bacterial infection. Four weeks later, the planned second surgery was postponed because the 5 × 3 cm nephrolith in the left kidney had completely dissolved. The result of this fortuitous observation of in vivo dissolution crystalised our mission of developing safe and effective non-surgical methods to eradicate uroliths. The tradition that surgery is the only effective treatment for uroliths has changed. Medical protocols for several types of uroliths (struvite, urate, cystine) in dogs and cats have become an accepted mode of therapy, and, in some instances is the preferred choice (e.g. sterile struvite uroliths in cats).
Beyond The Stone Age
Innovative thinking and technology have transformed the ways in which urinary stones in dogs and cats are managed today. In 1971, a non-surgical technique (retrograde urohydropropulsion) designed to rapidly repel urethroliths back into the bladder lumen with the goal of reestablishing urethral patency was reported (Piermattei and Osborne 1971). Later, voiding urohydropropulsion paved the way for minimally invasive stone extraction with a simple and quick method of removing small stones (<3 to 4 mm in diameter) without making an incision into the urinary bladder (Lulich and others 1993). With the aid of a cystoscope, stone retrieving baskets can excavate small stones in minutes. To manage larger stones, two modified cystotomy procedures, laproscopic-assisted cystotomy and cystoscopic-assisted cystotomy, provide safe and effective alternatives with the benefit of minimising the surgical incision (Rawlings and others 2003; Runge and others 2011). The use of lasers to fragment stones into pieces sufficiently small enough to be evacuated through the urethra has increased the possibility of non-surgical removal of stones from the bladder or urethra feasible in almost all dogs, and female cats greater than 4 to 5 kg in body weight (Lulich and others 2009). To manage stones in the kidney, extracorporeal shock wave lithotripsy has been successful in the dog (Adams and Senior 1999). Management of uroliths in the veterinary profession has come a long way.
Leaving No Stone Unturned
Although much has been accomplished in the past four decades, there is still a lot of work to be done before the “War on Urolithiasis” is complete (Osborne and Klausner 1978). Uroliths composed of calcium oxalate remain a formidable foe because the exact mechanisms underlying calcium oxalate urolith formation are not known and no therapy has been proven to consistently prevent recurrence. The difficulty is magnified in cats with chronic renal failure in which partial or complete obstruction of a ureter with a urolith may precipitate an acute uraemic crisis (so-called “acute-on-chronic” renal failure). Results of a recent retrospective study concluded that medical and surgical management of ureteroliths in cats were associated with high morbidity and mortality (Kyles and others 2005). Because of the complex nature of this clinical syndrome, no routine approach is appropriate for every patient.
Albert Szent-Györgyi, the 1937 Nobel prize recipient in physiology/medicine from Hungary said “discovery consists of looking at the same thing as everyone else and thinking something different”. In other words, maintain a questioning mind. The aetiopathogenesis of calcium oxalate urolith formation is currently unknown and likely due to a variety of risk factors. Yet, for years, we have relied solely on the belief that supersaturation is the primary driving force. Although supersaturation may be a significant risk factor, other risk factors may be equally important. It has been reported that calcium oxalate supersaturation in healthy dogs can be just as high as in dogs with calcium oxalate uroliths (Robertson and others 2002).
In this issue of JSAP, two manuscripts provide additional insight on calcium oxalate urolith formation. Jozef and others (2012) exquisitely reconstructed the nidus of uroliths utilising contemporary techniques of x-ray microtomography and mass spectrometry with the skill and detail of a forensic detective. The paper by Roe and others (2012) used epidemiological procedures to demonstrate strong breed associations for calcium oxalate and other urolith types. Individual dog breeds represent ideal opportunities for studying genetic determinants of disease because specific breeds have relatively little genetic diversity, and disease traits are often controlled by a small number of loci with strong effect (Lindblad-Toh and others 2005). Research has repeatedly identified shared susceptibility genes between dogs and humans. For example, urate uroliths in Dalmatian dogs and humans can develop from mutations in Slc2a9 (Bannasch and others 2008; Dinour and others 2010). Cystine stones in Newfoundland dogs and humans have been described secondary to mutations in Slc3a1 gene (Henthorn and others 2000; Ito and others 2000). Studying genetic determinants in particular dog breeds is likely the efficient path to better understanding this problem in humans. The War on Urolithiasis is not complete. But these two papers provide new information as to how we can continue the fight.
Drs Lulich and Osborne are co-directors of the Minnesota Urolith Center. In 1981, they established the Minnesota Urolith Center to investigate the causes, cures, and prevention of urolithiasis. The Centre has analysed approximately 750,000 uroliths from more than 90 species of companion animals sent from veterinarians in more than 67 countries. The purpose is to help animals by collecting, evaluating, and sharing epidemiologic data about naturally occurring stone disease and by providing diagnostic information about risk factors to our veterinary colleagues.