Natural Causes, Prevention & Treatment of Urolithiosis in Dogs

In the treatment of pet diseases, drugs are often given an inappropriate precedence. Adequate food intake is an important concern for medical and surgical clinicians. In most instances clinical nutrition (enteral and parental) functions as a therapy adjuvant to primary treatment such as surgery, drug therapies and other veterinary therapies. Clinical nutrition is in extensive use since late 1970s in hospitalized canines. The goal of enteral nutrition in anorectic patient is to provide calorie, protein, vitamins and minerals (Madan et al., 1998).

The management of renal disease depends upon its intensity (acute vs chronic). The focus for management of acute renal failure is to eliminate the inciting cause and support of normal renal function. While, management of chronic renal failure is to minimize clinical signs and slowing the progression to end stage renal failure. Dietary management is an important part of medical management of chronic renal failure (Yatiraj, 2004).

Urolothiasis: 

Urolothiasis means presence of calculi in Urinary System. Calculi may be found in the Urinary Tubules (microconcretions), Pelvis of kidney (Nephrolithiasis), Ureter, Urinary bladder (Cysticalculi) or Urethra. The groove of Os penis of the male dog is a frequent site for the lodgement of the calculi. Nephroliths are uroliths located in renal pelvis and/or collecting diverticulla of kidney. Although, it comprises only 1-4% of all uroliths it is an important clinical problem in dogs because of their potential complications. They may obstruct the renal pelvis or ureter, predispose to pyelonephritis or result on compressive injury to renal parenchyma leading to renal failure. Reoccurrence is also a frequent problem (Hoppe, 1998). Nephroliths is dogs most commonly consist of Ca-oxalate (Adems, 1997). Calculi differ in their chemical composition in different species of animals. The difference is largely governed by pH of the urine. In a healthy dog urinary pH is on acid side 5-7.5 depending on the breed. In the dogs, most common uroliths are oxalate, urates, uric acid, cystine, triple phosphates, calcium carbonate and phosphate. Oxalate calculi vary in nature and have spiny and rough surface, so more severe inflammation and irritation is there. While phosphate calculi are chalky and very smooth in nature. Size of calculi depends on its location where it is present (Sastry, 1999). 

Prevelence: 

In a study of composition of naturally developing uroliths removed from the 150 minature Schnauzer dogs from Minnesota urolith center prior to 1981, magnesium ammonium phosphate (struvite) was a predominant mineral in 92% of the uroliths. Uroliths composed of Ca-oxalate were detected only in 6 dogs (4%). By 1988, struvite urolith represented 61% of urolith removed from 1713 dogs. By 1994 the percent of struvite urolith decreased to 54% (n=30,642 dogs). During the same period percent of Ca-oxalate uroliths increased. It was 14% in 1988 and raised to 28% in 1994 and 34% in 1996 (Lulich et al., 2003). Reports from University of California at Davis in 1995 showed approximately 66% of canine uroliths were partially or completely composed of struvite. In Sweden, of 3366 uroliths analysed in 1990-1997, 43% were composed of struvite. Pre struvite uroliths are uncommon because most struvite calculi contain a small quantity of Calcium phosphate and ammonium urate (Hoppe, 1998). 

Epidemilogical studies have shown that the prevalence of Urolithiasis in Dogs in Sweden and Norway is approximately 0.25-0.5%. Proportional morbidity rates in canine urolithiasis have been reported approximately 0.5% in North America and 0.5 – 1.0 % in Germany (Wallerstrom and Wagberg, 1992). These trends suggested a disproportionate increase in the prevalence of Ca-oxalate uroliths to other type of uroliths. The struvite uroliths are commonly diagnosed in younger animals (Lulich et al., 2003). The incidence and composition of uroliths may be influenced by a variety of factors including species, breed, sex, age, diet, anatomical abnormality, urinary tract infection, medication and urine pH. 

Age: Experience from treatment of geriatric dogs in USA with lower urinary tract disease showed that urolithiasis increased with advancing age up to 15 years. Dogs more than 15 years had marked decrease in the frequency of urolithiasis (Lulich and Osborne 1997). 

Breed: The breed of the dog have large influence in the developing of renal calculi, regardless of size, terrier breeds males generally were at high risk of developing renal calculi. Breeds of dogs at low risk for development of renal calculi included crossbreds, German Shepherded, Labrador Retrievers, Golden Retrievers, and female Dachshunds. When only 1 was involved, the risk of left renal calculus was greatest butbilateral; renal involvement was relatively common (Ling et al., 1998). 

Sex: The study found that females has a slight, but statistically higher risk if lower Urinary Tract Diseases than males. Urolithiasis however, predominated in males (63%) compared with females (37%). In Europe no precise epidemiological data are available. However, the prevalence of urolithiasis in German study in 1980s was 1-3%, judged by number of cases treated, and incident was estimated as 0.3 – 0.8%. (Hesse and Buhl, 1988; Hoppe, 1998). Female dogs formed renal calculi containing struvite or oxalate more often than males; males formed calculi containing urate more often than females (Ling et al., 1998). 

Table 1. The percentage occurrence of different types of stones and urethral plugs in dogs in USA (Lulich  et al., 1995)

* Mainly ammonium urate                                   ** Mainly with urea splitting organism 

Table 2. Site for the formation of urinary stonesin Dogs (Lulich et al., 1995) 

Table 3. The male : female ratio of the formation of stones in dogs (Lulich et al., 1995) 

Table 4. Occurrence of stones in popular Dogs (Lulich et al., 1995) 

Table 5.  Factors of calcium stone formation in Dogs (Lulich et al., 1995) 

Table 6 Factors affecting different types of urolithiasis in dogs (Lulich et al., 2000)

Clinical Signs: Urinary calculi are harmful in two ways:

• They may irritate the urinary passage and cause inflammation.
• Obstruction of passage may occur (Sastry, 1999)

Simple urolithiasis causes little or no harm and has relatively little importance. However obstructive urolithiasis is a fatal disease and the obstruction is repaired, it may lead to rapture of the urethra or bladder. This may result in death of animals due to uremia and secondary bacterial infection. Common clinical signs for animal suffering from urolithiasis include dribbling of urine, stranguria, vomiting, tense abdomen with signs of pain and enlarged bladder (Pattanaik and Nanda, 2001) 

Causes: 

For formation of calculi, there must be nucleus or nidus around which salts may be deposited. Different types of nucleus are reported in dogs. They may be cast, bacteria, leucocyte, degenerated cells (from injured nephron) or keratinized desquamated cells, mucoproteins (in vitamin A deficiency). The following factors, singly or combination, may be the cause of nidus formation:  

1. Vitamin A deficiency: In Vitamin A deficiency, the transitional epithelium of urinary tract undergoes metaplasia into keratinized stratified squamous epithelium with exfoliates and may form the nidus calculi (Sastry, 1999). Vitamin A deficiency and Tamm-Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. Vitamin A deficiency may excluded as a potential cause of canine for uroliythiasis. However, the occurrence of Retinol Binding Protein and a concomitant reduction of THP in urine indicate a disturbed kidney function as cause or consequence of stone formation in dogs (Raila et al, 2003).

2. Infection : Certain bacteria viz. Leptospira sp., Leishmania sp., Babesia sp., Streptococci sp., E. coli and micrococci sp may not only cause infection but can also act as nidus for calculi (Sastry, 1999)

3. Concentration of Salts: The concentration of inorganic and organic salts in food and water has influence on the calculi formation. High percent of mineral in water, hypervitminosis and high oxalate containing plants facilitate calculi formation. An in born error in metabolism of these salts, probably predispose the calculi formation (Sastry, 1999).

4. Medication: Sulfonamide when introduced by sodium bicarbonate causes renal degeneration and degenerated renal epithelium may serve as nidus for calculi formation. (Sastry, 1999).

Studies on dogs and humans shown that consumption of high level of sodium increases the renal excretion of calcium and cystein (Lindell et al, 1995; Lulich and Osborne 1997). Urine super saturation of salts is the driving force for the formation of crystals within urinary tract (Balaji and Menon, 1997).

The rate of stone formation is determined by several factors including pH and concentration of urine, composition of calculi, concretion etc. Apart from these, dietary factors for urolithiasis include inadequate liquid intake, sudden change to a dry diet, diet containing excessive total minerals viz phosphorus, magnesium or sodium and inadequate potassium either by deficiency or through excessive sodium or magnesium. Other dietary factors for this being feeding of high concentrate or parallel  feeds, implantation with diethylstilbestrol and hypermineralisation of diets (especially with calcium carbonate). Latter is the main factor for alkaline urinary pH and results in formation of struvite (magnesium ammonium phosphate) stones. Although a direct relationship between any given nutrient and the incidence of urolithiasis is still debatable, many nutrients/ nutritional practice often predispose pet animals to urinary stone formation (Pattanaik and Nanda, 2001).

Treatment:

Calculi in general, can not be dissolved by medical means. It may also be difficult prevent a further increase in size of existing stones or the emergency of new ones, once urolithiasis become clinically apparent in an animal. However, certain measures can be taken to prevent other members of the group exposed to the similar risk factors. In case of simple urolithiasis, especially in early stage, treatment with smooth muscle relaxants may yields results. But treatment of obstructive urolithiasis is mostly done by surgical means (Pattanaik and Nanda, 2001)

Nonspecific therapy to prevent recurrence should include augmentation of water consumption. Animal which consume additional water will be less likely to form highly concentrated urine and, as a result, urine will contain lower concentration of calculogenic mineral. This will in turn minimize formation of crystal and uroliths. The simplest way of reducing the super saturation of urine is to increase the urinary volume (Borgi et al, 1999). The link between dietary sodium and water intake is well documented in dogs and it is well known that NaCl stimulates thirst in animals (Cizek, 1959). The type of therapy is effective, inexpensive and safe. The most practical solution for promoting increase water consumption is to feed canned diets, which contain 70-80% water. If required additional water can be added to the canned foods. To maintain specific gravity of less than 1.020, sodium supplements should be avoided (Hoppe, 1998).

Before nutritional supply is implemented, underlying volume, compositional imbalance of extra cellular fluid should be restored by fluid and electrolyte management. If the oral cavity is normal, appetite may be stimulated or the animal may be force-fed. Appetide could be stimulated by variety of methods viz. clean the nose, warm the food, sprinkle food highly with garlic and onion powder, stay with animal and encourage to eat, Pottasium supplementation (1-2 mg/kg/day), zinc supplementation (1-2 mg/kg/day, post operative) and Vitamin B₁₂ supplementation (100-200 mg/day, post operative) in dogs (Madan et al., 1998).

Due to lack of effective medical solutions nutritional management seems to be the best way for preventing the occurrence or to deal with urinary calculi in pet animals.for treatment of chronic renal disease in dogs, the main objective is to ameliorate azotaemia and associated signs by reducing protein breakdown to a value that meets just requirements thus avoiding excessive nitrogen waste and excretion of urea. Diets required for dissolution of struvite stone should have a low content of magnesium and phosphorus. Urine pH should be lower and volume increased by measures such as feeding low protein, high sodium diets. To avoid any health risk in long term application, diets formulated should be of low base excessive and contain a few alkalizing compounds as possible. The compounds if present must be neutralized by acidifiers. In this respect, maize gluten and DL-methionine appeared to be potent acidifier (Pattanaik and Nanda, 2001).

Dietary Management:

Dietary protein restriction is employed on dogs with chronic renal failure for two reasons.  

Ø      To reduce the extent of uremia.

Ø      To slow rate of progression of renal disease.

Protein restriction should be used as needed to control clinical sign of uraemia in dogs with chronic renal failure but may not prevent progression of renal failure. In ureamic condition, guanidinosuccinic acid and other byproducts of protein metabolism are toxic and ureamic animals should be fed a low protein diet. Protein should be of high biological value and quantity recommended is 2.0 -3.5 gm per kg body weight per day. Protein malnutrition may lead to protein catabolism and generation of ureamic toxins (Yatiraj, 2004).

Diets for dogs should have a low level of high quality protein, low phosphorus and magnesium and high sodium. A typical diet for treatment of   Urolithiasis in dogs should contain 8% protein, 0.3% calcium, 0.12% magnesium and 1.2% sodium on dry matter basis. Research findings indicate that clinical recurrence rate of Urolithiasis in dogs fed a protein restricted diet is 27% as compared to 36% in dogs fed commercial diets. In dogs with metabolic disorders, organically based stone such as purine, cystine are often found. This can be treated by decreasing dietary purine and protein intake. Besides, drug treatment can be given to inhibit uric acid synthesis (Pattanaik and Nanda, 2001).

Dry/pelleted proprietary feeds should be sold with instruction advising gradual introduction in to the diet. There should be provision of adequate fresh water or milk available at all time. Strategies should be made to ensure higher water intake especially in winter season. This can be done by supplemental feeding of sodium chloride which also helps in decreasing the rate of deposition of magnesium and phosphate around the nidus of a calculus. To sum up, a typical diet for effective management of feline and canine urolithiasis should have a low level of high quality protein and low phosphorus and magnesium. Further, it should have high sodium and suitable acidifiers/alkalizer for acidification/alkalization of urine (Pattanaik and Nanda, 2001).

Calcium Oxalate Urolithisis :

In pets the greatest increased percentage of Ca-oxalate increased from 6-30%. It has been suggested that during the same time, dietary manufacturers, in efforts to minimize struvite uroliths formation, formulated diet that provide reduce Mg and promote the formation of acid urine which are risk factor for Ca-oxalate uroliths formation. Irrespective of the type of diet consumed, many other factors are highly associated with Ca-oxalate formation. For example, the majority of uroliths only occur in few breeds of dogs, with a higher propensity among the smaller breed such as Miniature Schnauzer, Pomeranian, Lhasa Apso, Miniature Poodles, Bichon Frises and Shihtzus, than among larger breeds such as Labrador Retriever (Stevenson and Markwell, 2001). However in case of small dogs, females are at higher risk of developing renal calculi than males. Pet animals suffering from simple urolithiasis or one kidney is involved, the chances of left renal calculi is greater than right one. In female this occurs due to formation of stones containing struvite or oxalate where as males form calculi containing urate stones (Pattanaik and Nanda, 2001).

Likewise, Ca-oxalate uroliths primarily occur in males. As discussed previously, Ca-oxalate is primarily a disease of middle age and older dogs. These variables are independent of diet. For uroliths to form, urine must be over saturated with respect to that crystal system. Alteration in the balance between urine concentration of calculogenic minerals (Ca and Oxalate) and crystallization inhibitors (including citrate, P, Mg and K) have been associated with initiation and growth of Ca-oxalate uroliths. In addition to urine concentration of calculogenic minerals and other ions, large molecular weight protein in urine has a profound ability to enhance solubility to Ca-oxalate. One such protein, called Nephrocalcin, was found to be defective in dogs with Ca-oxalate (Lulich et al,2003). In most of the cases Calcium oxalate uroliths are found mixed with Calcium phosphate (Osborne et al.,2005).

Calcium oxalate calculi are most commonly found in the bladder and less often in the upper urinary tract. Several conditions are associated with an increased risk of Calcium oxalate urolithiasis, including hyperparathyroidism, hyperradrenocorticisn, hypervitaminosis, D, and paraneoplastic hypercalcemia. The etiology of calcium oxalate Urolithiasis in dogs is thought to be multi factorial (Hand et al.,2000).

Dietary Causes:

Stone forming dogs had significantly lower intake of sodium, calcium, potassium and phosphorus and significantly higher urinary calcium and oxalate concentrations, calcium concentration and ca-oxalate relative super saturation (RSS). Hypercalciuria and hyperoxaluria contribute to formation of ca-oxalate uroliths in dogs (Stevenson et al.,2004).

Role of pH: During metabolic acidosis, acidifying metabolites are neutralized by phosphate and carbonates mobilized from bone. Bone calcium is released with the phosphorus, resulting in hypercalciuria. Thus, reduction in urine pH contributes to the increased urinary calcium concentration (Stevenson et al.,2003)

Role of Dietary Calcium: Available reports indicate that higher intake of calcium increases, the risk of urolithiasis and decrease calcium consumption lowers the risk. But evidences indicate that calcium restriction below a certain level may increase the risk of stone formation by stimulating vitamin D₃ metabolite secretion which, in turn increases bone resorption and promotes calciuria. Besides, low level of elementary calcium while causing hypocalciuria in preferential intestinal absorption of  oxalates leading to hyperoxaluria (Pattanaik and Nanda, 2001).

Increased gastrointestinal absorption of Ca is an important pathophysiologic mechanism to sustain excessive urine, Ca excretion in patient with Ca-oxalate urolithiasis. Epidemiological studies have provided evidence that consuming diets with higher levels of Ca are at reduced risk for Ca-oxalate uroliths formation than those consuming diet with lower Ca contents. In contrast Ca supplementation between meals promotes hypercalciuria and is therefore is a risk factor for Ca-oxaltate uroliths formation (Lulich et al,2003).

Dietary calcium had a far greater effect on calcium oxalate super saturation. Thus, dietary calcium restriction without concurrent oxalate restriction would increase the risk of calcium oxalate crystal formation in dogs. Urinary oxalate concentration does not increase when oxalate was supplemented in the presence of moderate or high calcium (Stevenson et al., 2003)

Role of Dietary Oxalate: Hyperoxaluria promotes recurrence of Ca-oxalate uroliths because comparative small increments in Oxalate excretion markedly increase the activity product for Ca-oxalate. Oxalate is the metabolic end product of glycine utilization. This accounts for about 60% of the total urinary oxalate. Approximately 25-30% is derived from the metabolism of dietary Ascorbic acid. Vitamin B₆ also plays a key role in oxalate metabolism; B₆ deficiency results in increased formation of oxalate and hyperoxaluria. The remaining 10-15% is received from dietary oxalate out of which 8-12% is absorbed (Lulich et al,2003).

Oxalate is the simple dicarbooxilic acid present in many foods, particularly cereal grains and leafy plants, as oxalic acid (Holmes & Kennedy, 2000). Its content is thought to be typically low except in foods such as spinach, rhubarb, peanuts, chocolate and tea. Unabsorbed Ca in intestinal luman complexes with oxalates ions and prevents oxalate and Ca absorption. Conversely, with a reduction in intestinal Ca, oxalate absorption and excretion is increased. Therefore to reduce Ca-oxalate uroliths recurrence, diets supplemented with Ascorbic acid or restricted with Vitamin B₆ and Ca should be avoided (Lulich et al,2003).

Oxalate- induced cell injury of the renal epithelium plays and important role in promoting CaOx nephrolithiasis (Iida et al,2003) observed acute exposure to a high concentration of oxalate challenges the renal cells, diminishes their viability and induces changes in cytosolic Ca²⁺ levels. Heparin and Heparin Sufate, which are known as potent inhibitors of CaOx crystallization, may also prevent oxalate induced cell changes by stabilizing the cytosolic Ca²⁺ level.

Role of Dietary Sodium: Studies have shown hat supplemental dietary sodium given to dogs had no effect on urinary calcium or oxalate (Allen et al., 1989 and Lulich et al., 2000). However, reports indicates that increased dietary sodium increases sodium excretion which encourages urolith formation by inhibiting renal tubular absorption of calcium, resulting hypercalciuria (Sakhaee et al., 1993). Further, high sodium content in the diet increases the chance of formation of urinary calcium and monosodium urate crystals. The latter can act as an epitaxial nidus for calcium crystallization. Besides, high urinary sodium excretion also increases the relative saturation of calcium phosphate with a concomitant decrease in urinary citrate. All these factors can lead to higher incidence of urolithiasis (Pattanaik and Nanda, 2001).

Role of Phosphorus: Urinary phosphorus concentration in dietary correlated with calculi formation. A high phosphate intake although decreases the urinary calcium through a decrease in vitamin D and subsequent intestinal calcium absorption but increases urinary phosphate. A low urinary phosphate is therefore desirable to avoid struvite urolithiasis. But dietary phosphate restriction hand increases calcium excretion, which may promote calculi formation. A balanced ratio of calcium and phosphorus, therefore, is required in the diet to avoid precipitation of excess phosphorus in the urine (Pattanaik and Nanda, 2001). 

Role of Magnesium and Potassium: Diets supplemented with magnesium decreases nucleation and growth of calcium oxalate crystals thus reducing the rate of stone formation. This may be due to binding of magnesium to intestinal and urinary oxalate producing a magnesium oxalate complex and increases urinary citrate excretion. Similarly, deficiency of potassium may increase the risk for stone formation and calciuria because of increase in urinary calcium (Pattanaik and Nanda, 2001). 

Role of Fluids intake: low fluid intake or chronic dehydration is one of the major factors associated with urolithiasis in pet animals. Chronic dehydration on the one hand raises urine specific gravity and uric acid, but on the other hand decreases urinary pH. This results in formation of urinary urate crystals which act as epitaxial for growth of calcium containing stones. High water intake with supplemental magnesium may lessen urinary saturation of calcium phosphate, calcium oxalate and monosodium urate with decreased severity of calculi formation as compared to given restricted water (Pattanaik and Nanda, 2001). 

Role of Animal Protein: Consumption of animal protein increases urinary Ca excretion and decreases urinary citrate excretion (a chelator of Ca) and is directly associated with an increased risk of Ca-oxalate and uric acid uroliths in dogs. One explanation of hypercalciuria associated with dietary proteins is increased endogenous acid production and thus increased urinary net acid excretion. Increased acid excretion is thought to decrease Ca resorption in distal nephron and increased urine citrate uptake in the proximal nephron. Mobilization of carbonate and phosphate from bone to buffer acid dietary metabolites may also contribute to hypercalciuria. Dietary protein may also promote hypercalciuria by increasing GFR (Lulich et al,2003). 

A high protein diet increase the risk of urolithiasis by increasing the urinary level of urolith constituents viz. oxalate and uric acid. Protein load increases glomerular filtration rate, calciuria, oxaluria, uricosuria and decreases urinary citrate excretion besides causing a metabolic acidosis in animals. The latter results because of transient increase in endogenous acid production and excretion in urine which may increase calcium resorption from bone with a concomitant increase in filtered calcium through glomeruli. The hypercalciuria effect of protein is further enhanced hen sulphur containing amino acids content of protein is high. This increases urinary sulphate level which promotes calciuria by forming a complex with calcium, thus preventing its absorption in renal tubules. All these factors facilitate an optimal environment for stone growth (Pattanaik and Nanda, 2001). 

Role of Fatty Acids: The dietary content of arachidonic acid was positively correlated with urinary oxalate excretion. The association between arachidonic acid and oxalate excretion suggests that arachodonic acid increases the intestinal absorption of oxalate and increases the clearance of oxalates in kidneys (Naya et al,2002). Canned diets with highest amount of carbohydrate were associated with an increased risk of CaOx urolith formation (Lekcharoensuk et al,2001).

Treatment: 

The main of dietary modifications are to decrease calcium and oxalate concentration in the urine, to promote the high concentration of crystal formation inhibitors in the urine and to decrease urine concentration (Ling, 1995; Lulich and Osborne, 1995; Hand et al, 2000 and Dolinsek, 2004). 

Stevenson et al,(2004) used a diet therapy with higher intake of water, sodium and fat and lower intake of potassium and calcium in dogs for treatment of canine lower urinary tract disease for one month and observed that there was decreased urinary calcium and oxalate concentrations and Ca-oxalate relative super saturation (RSS). No clinical signs of disease recurrence were observed in the stone forming dogs when the diets were fed for additional eleven months. 

Role of Calcium: Restricting Ca was at one time thought to be logical step to minimize Ca-oxalate uroliths formation. However, results from recent studies suggest that Ca restriction is inappropriate because decrease dietary calcium may promote increased absorption of dietary oxalic acid leading to hyperoxaluria and potential negative Ca balance. Hence, to reduce calcium oxalate urolith recurrence, diets supplemented with Ascorbic acid or restricted with Vitamin B-6 and Calcium should be avoided (Lulich et al,2003). But studies indicate that restricted dietary Ca between 0.3% and 0.6% DM reduces the chance of excessive absorption and excretion of calcium. Further, vitamin D and vitamin C supplements should be avoided, since the former will enhance the intestinal absorption of calcium and latter serves as a precursor for oxalate (Ling, 1995; Lulich and Osborne, 1995; Hand et al, 2000 and Dolinsek, 2004).  

Role of Dietary Sodium: the possibility that reducing dietary Na might be beneficial in treatment of Ca-oxalate urolithiasis is based on the observation that increased Na consumption by dogs was associated with increased urinary Na and Ca excretion. Likewise, urinary Ca excretion is highly correlated with urinary Na clearance in dogs given isotonic saline, hypertonic mannitol and hypertonic glucose parenterally. These observations are physiologically sound, since Ca and Na are absorbed at various common sites along the renal tubule. Two decades ago oral NaCl was recommended to minimize uroliths recurrence in dogs including diuresis. However, it is apparent that dietary Na should be restricted when designing protocols to minimize Ca-oxalate uroliths recurrence (Lulich et al,2003).  

Dietary sodium should be restricted to < 0.3% DM, because urinary sodium excretion is directly correlated with urinary calcium excretion. This includes avoiding table scraps and commercial pet treats that tend to be high in sodium (Ling, 1995; Lulich and Osborne, 1995; Hand et al, 2000 and Dolinsek, 2004). When dietary sodium was increased (0.3 g sodium/100 kcal), calcium oxalate RSS was reduced in Labrador dogs compare with low sodium diet (0.05 g sodium/100 kcal). These findings should be considered when evaluating methods for preventing calcium oxalate formation within the high risk groups (Stevenson and Markwell, 2003). 

Role of phosphorus: In man, neutral potassium phosphate (1500 mg/day) lowers urinary Ca excretion. The ability of phosphorus to reduce uroliths recurrence rates is often attributed to its role in minimizing renal production of calcitriol and enhancing urinary excretion of pyrophosphate, an inhibitor of Ca-oxalate crystallization (Lulich et al,2003). 

Role of potassium : Epidemiologic studies in dogs have revealed an association between higher K consumption with reduced Ca-oxalate formation. The beneficial effects of  K may be due to high alkali content of many K rich foods which can lead to increased urine citrate, a natural inhibitor of Ca crystal in urine (Lulich et al,2003). 

Dietary potassium citrate supplementation has also been advocated in the prevention of recurrence of calcium oxalate uroliths in dogs. Potassium citrate maintains a higher urinary pH. Inclusion amounts of 0.2 to 0.5% in canned food and 1 to 2% in dry food have been recommended for modifying urinary pH. Diets containing potassium citrate should be fed twice daily (Stevenson et al,2000). Pattanaik and Nanda (2001) indicated that supplementation of potassium citrate in the diet decreases the incidences of recurrence of stone formation because of significantly increase in pH and citrate level of urine.  

Role of fluid intake and pH: In excessive fluid dilutes crystallization inhibitors, it could paradoxically increase the risk of urine concentration of lithogenic constituents by increased urine volume may more than offset the potential detrimental effect of crystallization inhibitors and thus to prove to be beneficial.  

High water intake with supplemental magnesium may lessen urinary saturation of calcium phosphate, calcium oxalate and monosodium urate with decreased severity of calculi formation as compared to these given restricted water (Pattanaik and Nanda, 2001). Diuresis associated with increased fluid intake has been associated with decreased risk of urolithiasis in people. Dogs and cats consuming canned diet have one third risk for Ca-oxalate uroliths formation compared to other dietary formulation (Lulich et al,2003). 

Diets that promote relatively alkaline urine (pH 6.8 to 7.0) are encouraged to minimize oxalate crystal formation. Lastly, water should be provided ad libitum, and the dog should be encouraged to drink. Ideally, urine specific gravity should be maintained at < 1.020. the chance of crystal formation and precipitation increases as the urine becomes more saturated with solutes. However, to prevent crystal formation the addition of crystal formation inhibitors may be necessary. The most suitable inhibitors for calcium oxalate urolithiasis is citrate, because it forms a soluble salt with calcium and decreases precipitation (Ling, 1995; Lulich and Osborne, 1995; Hand et al, 2000 and Dolinsek, 2004).  

Role of Protein: Dietary protein should be restricted to 10% to 18% on a dry matter basis (DM). Higher protein intake has been shown to significantly increase urinary calcium and oxalate excretion. Protein fed should be of high biological value. Thus, it would be utilized maximum and would exceed minimum through urine (Ling, 1995; Lulich and Osborne, 1995; Hand et al, 2000 and Dolinsek, 2004).  

Role of fatty acids: The dietary content of arachidonic acid was positively correlated with urinary oxalate excretion. Thus, in urolithiasis diets should be provided containing low level of arachidonic acid (Naya et al, 2002). 

Struvite Urolithiasis:

Aetiopathogenesis: 

Struvite (MgNH₄PO₄.6H₂O) is one of the most common mineral found in canine uroliths. Over saturation of urine with Magnesium Ammonium Phosphate is a prerequisite for struvite urolith formation. Several observations suggest dietary or metabolic factors may be involved in the formation of such uroliths. Pilot studies of clinical cases have revealed dogs with frequently alkaline urine but without identifiable bacteria or no detectable urease (Hoppe , 1998).

Approximately 70 % of dogs with struvite urolithiasis have an associated urinary tract infection with urease producing bacteria, such as Staphylococci sp. and Proteus sp.Hydrolysis of urea by the enzyme urease ultimately results in the formation of ammonia and carbonate which creates an increasingly alkaline environment in urine. These conditions are ideal for development of struvite uroliths, but they also favour the formation of other uroliths including calcium carbonate (Osborne et al., 1995).

Characteristics:

Struvite uroliths are white or pale yellow dominantly found in the bladder from there they often pass into the urethra. They may be present singly or in large numbers, grow rapidly and sometimes become rather large in size (Hoppe, 1998).

Treatment and Prevention:

Management of struvite urolithiasis includes: 

Ø      Relief of obstruction to urine outflow if necessary

Ø      Elimination of existing uroliths

Ø      Eradication of urinary tract infection

Ø      Prevention of recurrence of uroliths (Hoppe, 1998) 

Medical dissolution: 

The objective and current recommendation of medical treatment of uroliths are: 

Ø      To increase the solubility of crystalloids in urine, urine acidifiers should be used. In this respect maize gluten and DL-methionine appeared to be potent acidifiers. A dose of 1-2 g DL-methionine helps in acidifying urine to enhance dissolution of struvite crystals (Pattanaik and Nanda, 2001). 

Ø      To eradicate or control the urinary tract infection. Because of the quantity of urease produced by bacterial pathogens, it may be impossible to acidify urine. Therefore, sterilization of urine with appropriate microbial agents should be an important objective in decreasing the concentration of struvite crystals, thereby preventing further growth of uroliths or even promoting their dissolution. 

Ø      To decrease the concentration of crystalloids in urine by stimulating thirst, thereby increasing the urine volume (Hoppe, 1998). 

Dietary Considerations: 

Calculolytic diets have been formulated to reduce the urine concentration of urea, phosphorus and magnesium. These diets contain low quantity of high quality protein, phosphorus and magnesium, and are supplemented with Sodium Chloride to stimulate the thirst. The efficacy of diets in including urolith dissolution has been confirmed by controlled experimental and clinical studies in dogs. (Osborne, 1986; Hoppe, 1987; Hoppe, 1998).

If found to be infection induced, appropriate antimicrobial agents form an essential component of therapy for struvite urolithiasis in dogs (Stevenson and Smith, 1998). Response to therapy should be evaluated every fourth week with dissolution and growth of uroliths measures radiographically. Antibiotic therapy should be maintained until urolith dissolution occurs, which can take 1 – 6 months (Hoppe, 1987; Osborne, 1986). Usually, less time is required to induce dissolution of sterile struvite than of infection induced struvite (Hoppe, 1998). 

Dietary measures may also be employed in the control of struvite associated urinary tract infection. Urea concentration in the urine is directly affected by the dietary level of protein. A reduction in dietary protein intake, therefore, has beneficial effect by reducing the amount of substrate available for the urease producing bacteria. Although less common, struvite uroliths may also form alkaline urine in the absence of urinary tract infection. A reduction in urinary pH is thus a prime consideration in the management of sterile struvite uroliths and feeding of a commercial acidifier diet can help to achieve this goal (Stevenson and Smith, 1998). 

For some years, manipulation of urinary pH through diet has been the key in the management of struvite urolithiasis. Uine pH is much more important determinant for struvite formation than is the magnesium content of diet. This is because the changes in urinary pH have a proportionately much greater effect on struvite activity product then changes in concentration of one or more the crystalloid components of struvite. Reduction in urine pH through dietary manipulation is, therefore, one of the most reliable therapeutic strategies that can contribute to the successful management of struvite urolithiasis.  

In dogs, diets designed to produce acidic urine, with a target urine pH of 5.5 – 6.0 have been identified as suitable for the dissolution and prevention of recurrence of struvite uroliths. This urine pH range is known to be safe for long term feeding and will not predispose dog to metabolic acidosis (Shaw, 1989). These calculolytic diets should not be given to patients with heart failure, nephritic syndrome or hypertension or in growing dogs (Abdullahi  et al., 1984). 

Cystine Urolithiasis  

Aetiopathogenesis and Biological Behavior: 

Cystinuria is inborn metabolic disease characterized by excessive urinary excretion of cystine and dibasic amino acid lysine, arginine and ornithine. Compared with normal dogs, most Cystinuric dogs showed significantly increased excretion of cystine, lysine, ornithine, cystathionine, glutamic acid, threonine and glutamine (Casal et al., 1995). 

The solubility of cystine in urine is pH dependent, and it is relatively insoluble in acid urine but becomes more soluble in alkaline urine. The exact mechanism of cystine urolith formation is unknown. Cystine uroliths are often not recognized until maturity with the average age of detection being approximately 3-5 years. Because cystinuria is an inherited defect, uroliths commonly reoccur in 6-12 months (in some dogs within 4-6 weeks) unless prophylactic therapy is initiated. Apart from uroliths, cystinuric dogs have no other defects and normal renal function and the disease would have remained a psychological curiosity if cystine had not been the least soluble naturally occurring amino acids, and thus potentially leading to the formation of Cystine Uroliths (Hoppe, 1998). 

Characteristics, Prevalence and Diagnosis:  

Cystine uroliths accounts for 305 – 27%, probably depending on the breed of dogs encountered in specific survey. Many breeds of dogs have been reported to develop cystine uroliths. In Sweden and Germany, cystine uroliths is particularly a problem in the Dachshund and it accounts approximately 4 and 18.8%, respectively (Hoppe, 1998). 

Treatment and Prevention: 

Current recommendation for dissolution and prevention of cystine uroliths encompass reduction in the urine concentration of cystine and increasing the solubility of Cystine in urine. Therapeutic approaches may be divided into four categories: 

·        Reduction and change in dietary protein intake, aimed at reducing cystine production and excretion. 

·        Increase of diuresis 

·        Increase of Cystine solubility 

·        Conversion of Cystine to a more soluble compound. 

Dietary modification: 

For pet animal suffering from Cystine urolith, a diet with low protein and low sodium is suggested. Although of alkaline urinary conditions help in treating cystine urolithiasis, that with calcium oxalate stone need diets promoting aciduria (Pattanaik and Nanda, 2001).

Attempts have been made to design low in methionine to decrease the excretion of cystine. Hoppe et al. (1993) used a protein restricted diet, designed for dissolution of canine struvite uroliths, in two dogs with cystine uroliths, the uroliths did not dissolve.

Despite of proximal tubular reabsorption of Cystine in Cystinuria, the resorption can be increased by dietary sodium restriction (Lindell et al. 1995). 

·        Increase in Diuresis: Increase in water intake provides a progressive restriction in urinary Cystine concentration and reduces the likelihood precipitation. 

·        Alteration in solubility: Cystine solubility can be enhanced by including an alkaline pH is above 7.5. Administration of bicarbonate and citrate, for example, has been advocated for improving solubility. 

·        Conversing to more soluble compound: Chemical modification of cystine molecule into a more soluble form with D-penicillamine or 2-mercaptopropionylglycine (2-MPG) has been suggested. This decrese the cystine excretion into the urine and diminish the likelihood of urolith formation. Although D-penicillamine is effective in preventing the formation and some time the dissolution, of crystal urolith, there are frequent complications that limit its use. In dogs the most prominent side effect is vomiting. Another property of penicillamine is chelation of metals. In a study of 11 normal beagles given D-penicillamine orally or intravenously, significantly increase excretion of Calcium, Copper, Zinc, Chromium, Cobalt, Iron, and Magnesium were found. 2-MPG is chemically related to D-penicillamine but has a higher oxidation – reduction potential and therefore be more effective in disulphide exchange reaction (Hopp, 1998). 

Urate Urolithiasis :

Aetiopathogenesis:

Urate uroithiasis are relatively uncommon in dogs, comparing 2-8% of urolith analyzed (Boove and Mc. Guire, 1984 and Hesse and Bruhl, 1988). These uroliths most commonly comprise ammonium acid urate (known as ammonium urate) (Hoppe, 1998). 

Various breeds of dogs have been reported develop urate urolithiasis. While this is commonly encountered in Dalmatians, approximately30-60% is found in other breeds (Boove and Mc. Guire, 1984). In both Dalmatian and other breeds, the urolith most frequently occur in males (70%) and are most frequently detected in dogs aged 3-6 years (Osborne et al. 1986). Following surgical removal, the recurrence rate has been found to be as high as 33-50% in all breeds (Hoppe, 1998). 

Dalmatians are unique among in dogs in that they excrete uric acid in their urine as the end product of purine metabolism rather than allantoin as do other breeds of dogs. Urinary calculi formed from urate can cause urethral obstruction in male Dalmatians. Calculi formation might have a genetic component and high heritability that segregates within the breed. The prevalence of the disease was 34% (24.99 – 43.70%) among male Dalmatians (Bannasch et al. 2004). 

In non-Dalmatian breeds, almost all the urate formed from degradation of purine nucleotides is metabolized by hepatic uricase to allantoin, which is excreted by the kidney and is very soluble. In Dalmatians, only 30-40% of uric acid is converted to allantoin. The defective uric acid metabolism in Dalmatians is thought to be impaired transport of urate across the hepatocyte cell membrane. Also, intestinal uptake of hypoxanthine and urate is delayed and renal reabsorption of the urate in the renal proximal tubules is reduced in Dalmatians. Regardless of cause, severe hepatic dysfunction may predispose dog to urate urolithiasis, especially ammonium urate urolithiasis. A high incidence of ammonium urate uroliths has been observed in dogs with portal vascular anomalies. Hepatic dysfunctions in these dogs are associated with reduced hepatic conversion of uric acid to allontoin and ammonia to urea. Potential risk factor for ammonium urolithiasis in dogs include increase renal excretion and urine concentration of uric acid; increased renal excretion and renal concentration of ammonia; low urine pH; presence of promoters of ammonium urate crystal formation; and absence of inhibitors of ammonium urate crystal formation and aggregation (Hoppe, 1998). 

Treatment and Prevention:  

Recommendation in medical dissolution of canine ammonium acid urate uroliths include: 

Feeding of calculolytic diet restricted in purine: The aim of dietary modification is to reduce urine concentration of ammonium and urate. Studies have shown that protein restricted diet, formulated to minimize uric acid excretion and supplemented with potassium citrate to promote urine alkalization, is associated not only with reduction in urinary excretion but also with alkalinuria and polyuria, which may be beneficial in the management of ammonium urate uroliths on dogs (Barget et al. 1996). It was also shown that this diet was associated with the dissolution of ammoninium urate uroliths. However, urate uroliths can be trated effectetively by feeding low protein diets along with xanthine oxidase inhibitors. Literature indicates that diets containing around 10% protein and 70% moisture are ideal for dissolution and prevention of urate uroliths in dogs. 

Administration of Xanthine Oxidase Inhibitors (allopurinol): Therapy should be initiated with Allopurinol. Allopurinol binds to and inhibits the action of Xanthine Oxidase, there by decreasing the production of uric acid by inhibiting the conversion of hypoxanthine to xanthine and xanthine to uric acid. Within few days, this results in reduction in the concentration of uric acid in the serum and urine. The recommended for the dissolution of ammonium acid urate uroliths in dogs is 30 mg/kg/day. To determine the safe and effective dosage of allopurinol in dogs, measurement of uric acid and/or Xanthine concentration is important (Silberman, 1967).  

Alkalization of Urine: If necessary, supplement the diet with potassium citrate to achieve urine pH 7.0. Ammonium ions appeared to precipitate the urates in dog urine, and administration of alkaline agents, such as Sodium bicarbonate or Potassium citrate, appears to prevent renal tubular production of ammonia and subsequent acid metabolites. Dosage of urine alkalisers should be individualized for each patient (Hoppe, 1998).

Conclusion: 

Urolithisis means present of calculi in urinary system. The important uroliths are Calcium Oxalate, Struvite, Cystine and urate crystals common in dogs. Ca oxalates uroliths are more commonly found in the bladder. Hypercalciurea and Hyperoxalurea contribute mainly for formation of Ca oxalate uroliths. Higher intake of Ca, acidic pH of urine hypercalciurea, high dietary intake of sodium and phosphorus, low magnesium and arachidonic acid increases the formation of Calcium oxalate uroliths. Higher intake of fluid reduces the concentration of Ca, P and oxalate in the urine which leads to reduction in the urolith formation in the dogs.  

Struvite uroliths are mainly predisposed due to over saturation of urine with magnesium-aluminum-phosphate. Dietary management to reduce the concentration of urea, P and Mg in the urine prevents the formation of struvite uroliths. Reduction in the pH of urine even by using acidifiers helps in the prevention of urolith formation.  

Cystine uroliths are mainly developed due to excessive exertion of cystine and dibasic amino acids like lysine, arginine and ornithine. These are soluble in alkaline pH of urine and insoluble in the acidic pH. Diet with low protein and low sodium is beneficial.  

Urate urolithiasis occurs mainly in Dalmatians, which uniquely excrete uric acid as end product of purine metabolism rather than allantone hepatic dysfunction also predisposes urate crystal formation. Feeding of restricted protein, xanthine oxidase inhibitor and alkalizer may prevent the urolith formation.  

Thus, dietary management can be a great tool in preventing the urolithiais in dogs and for dissolution of already formed uroliths in dogs.  

References:  

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Barget, J.W., Osborne, C.A. and Felice, L.J. (1996). Influence of four diets in uric acid metabolism and endogenous acid production in healthy Beagles. Am.J.Vet.Res. 57:Pp 324-328 

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Hesse, A. and Bruhl, M (1988). Comparative aspect of urolithiasis in Man and Animals (Dogs, Cats). Proc. 3^rd Annual Symposium, ESVNU, Barcelona. Pp183-194 

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