Epidemiology

3. Epidemiology

Causes

Urolithiasis is the result of underlying inherited, congenital or acquired disorders, resulting in increased urinary excretion of certain minerals and/or predisposition to urolith formation (Osborne et al., 1995). Urine composition may be altered by metabolic abnormalities. An inherited mechanism has been proven in Dalmatians (urate) and Newfoundland dogs (cystine) (Sorenson & Ling, 1993; Henthorn et al., 2000), and the predilection in several other breeds suggests a possible genetic basis. Congenital causes can directly (e.g., congenital cystinuria) or indirectly (e.g., urogenital malformations) predispose an individual to form uroliths. Acquired disorders include UTI with urease forming bacteria as well as metabolic disorders that result in an increased mineral excretion (e.g., hypercalcemia). Administration of drugs may be an aggravating cause in some cases (Osborne et al., 1999f).

Predisposition and Risk Factors

Breed, Sex, Age

Urolithiasis tends to affect smaller dog breeds more often than larger breeds (Lulich et al., 2000). The predisposition for smaller breeds may be related to their lower urine volume, fewer numbers of micturitions, and therefore increased mineral concentrations (Ling, 1998; Stevenson & Markwell, 2001) (Table 4).

The incidence and mineral composition of uroliths may be influenced by a complex interaction of multiple factors, including age, sex, genetic predisposition and breed, diet, water consumption, lifestyle and the presence of UTI.

Breed predisposition for specific mineral types may suggest a genetic basis, and is often significantly correlated with the sex (Table 3) (Stevenson, 2002). The genetic mode of inheritance has been determined for cystinuria in Newfoundland dogs, where it has been shown that the disease is transmitted in a simple autosomal recessive pattern (Casal et al., 1995; Henthorn et al., 2000).

Most forms of urolithiasis are more common in male dogs, whereas struvite urolithiasis has a high incidence in female dogs, probably related to their greater susceptibility to develop bacterial UTIs (Table 5).

Urolithiasis usually occurs in mature dogs, although the age range is wide. Calcium containing stones (phosphate and oxalate) tend to be found in older dogs.

Diet and Water Consumption

Diet can influence urine composition and dietary factors therefore play a significant role in increasing the risk of urolithiasis, although this may differ for certain mineral types (Table 6).

Several dietary factors have been suggested to play a role in the development of calcium oxalate urolithiasis, including low dietary moisture and sodium, and high protein content. A greater risk is associated with dry formulations (Ling et al., 1998; Lekcharoensuk et al., 2002a, 2002b). High moisture diets and a moderate increase in dietary sodium have been shown to reduce the risk of calcium oxalate formation in susceptible breeds of dog (Stevenson et al., 2003b; 2003c). Severe purine restriction has been found to reduce urinary urate excretion in both healthy dogs and Dalmatians. There is also a strong link between silica urolithiasis and the feeding of diets high in plant ingredients such as bran or soybean hulls (Lulich et al., 2001).

Urinary Tract Infections (UTIs)

UTIs predispose an individual to struvite urolithiasis, especially when associated with urease-forming bacteria. As urinary infections are more frequent in females than in males, this helps to explain why struvite uroliths occur more frequently in females and in particular spayed females.

Environment

Differences in the pattern of urolith formation are observed between countries. Factors that predispose an individual to dehydration (e.g., hot climate, limited access to fresh water), or urinary retention in the bladder (indoor lifestyle) can increase the likelihood of urolith formation (Franti et al., 1999).

Drug Administration

Diagnostic and therapeutic drugs may enhance urolithiasis by altering urine pH, tubular reabsorption or secretion, and precipitation of drugs and their metabolites (Osborne et al., 1999b,1999f). The prevalence of drug-induced urolithiasis is unknown, although drugs and their metabolites are more likely to precipitate in urine if uroliths are already present. The older generation sulfonamides have been most frequently implicated, although precipitation and urolithiasis may also occur with the newer generations drugs when given for prolonged times at high concentrations.

Metabolic Influences

Prolonged hypercalcemia and subsequent calciuria may increase the risk of calcium containing stones. Hyperadrenocorticism has been associated with calcium oxalate stones, since glucocorticosteroids increase mobilization of calcium from bone and reduce tubular resorption, resulting in calciuria (Hess et al., 1998; Lulich et al., 1999).

Chronic metabolic acidosis may also contribute to calcium oxalate urolithiasis, which is attributed to buffering of excess hydrogen ions by bone phosphorus and carbonates, with concurrent release of calcium (Lulich et al., 1999) (Figure 13).

Figure 13. The effect of metabolic acidosis on urinary calcium excretion. In the presence of metabolic acidosis the bone is stimulated to release calcium phosphates and carbonate buffers into the blood stream. The excess calcium is excreted into the urine, which increases the risk of calcium oxalate formation.

Cystinuria is an inherited inborn error of metabolism that predisposes to cystine urolith formation, although not all dogs with cystinuria or cystine crystalluria form uroliths.