Improving management of urolithiasis: Feline calcium oxalate uroliths

Calcium oxalate (CaOx) was the most common (47 percent) mineral in feline uroliths submitted to the Minnesota Urolith Center during 2003 (Table 1). More than two-thirds of feline nephroliths were composed of CaOx.

Medical protocols that will promote dissolution of CaOx uroliths are not yet available. Urocystoliths small enough to pass through the urethra may be removed with the aid of voiding urohydropropulsion. Surgery is currently the only practical alternative for removal of larger active CaOx uroliths. In some patients, uroliths may be eliminated with the aid of lithotripsy.

Cats that have formed CaOx uroliths are at substantial risk of stone recurrence within 12 to 24 months. Therefore, medical protocols should be considered to minimize urolith recurrence. The objective of Part 3 of this series is to provide insight into the risks and benefits associated with therapeutic strategies designed to prevent recurrence of feline CaOx uroliths.

Table 1.

Therapeutic caveats associated with other types of uroliths will be the subject of future Diagnotes.

Risk factors

1. CaOx urolith formation does not occur as a result of a single cause. Rather it is the result of varying combinations of risk factors that promote precipitation of calcium and oxalic acid in urine.

2. As clinicians, we think of risk factors and protective factors as events that affect the likelihood of urolithiasis occurring. There are many types of risk factors, but, in general they may be listed under three categories:

• etiological risk factors such as infections and endocrinopathies,
• demographic risk factors such as breed, age, gender, and
• genetic predisposition, and environmental risk factors such as living conditions and sources of water and food.

3. When used in a qualitative (rather than a quantitative) way, the significance of risk (or protective) factors should not be assigned an "all or none" or "always or never" interpretation. Each contributing risk factor may play either a limited or significant role in the development of uroliths. In some situations, individual risk factors may not be a factor in every exposed patient. Furthermore, identifying one event in a chain of etiologic events is not the same as identifying all components in the etiologic chain.

4. In general, prevention strategies are designed to eliminate or control risk factors associated with calculogenesis. Exposure to some risk factors can be eliminated or controlled; others cannot (Table 2, p. 6S). Preventative therapy is especially important for patients with a large number of persistent risk factors for CaOx uroliths.

5. Epidemiological studies indicate that males (~60 percent) are more commonly affected than females (~40 percent). In one study, neutered cats were seven times more likely to develop CaOx uroliths than sexually intact cats.

6. Whereas struvite uroliths are more commonly detected in young to middle age cats (2 to 6 years old), the mean age of cats at the time of detection of calcium oxalate uroliths is ~8 years. However, CaOx uroliths have been detected in cats ranging in age from less than 1 year to more than 15 years.

7. Epidemiological studies indicate that CaOx uroliths have been observed in most breeds of cats. However, Himalayan, Persian, Ragdoll, Havana Brown and Scottish Fold cats were at increased risk for CaOx uroliths, while Siamese and Abyssinian cats had a reduced risk of urolith formation.

8. Hypercalciuria is a major risk factor for CaOx urolith formation. Hypercalciuria may be associated with 1) hypercalcemia, 2) hyperabsorption of calcium from the intestinal tract, 3) impaired renal reabsorption of calcium, and/or, 4) excessive mobilization of skeletal calcium. Other risk factors that have been associated with calcium oxalate uroliths include acidosis, hyperoxaluria, hypocitrituria, hypomagnesuria, decreased urinary concentration of crystallization inhibitors and formation of small volumes of concentrated urine.

9. Empirical clinical observations indicate that mild hypercalcemia may be present in approximately one-third of cats with CaOx uroliths. Although serum total calcium concentration and blood-ionized calcium have been mildly increased, parathyroid concentrations have not been elevated. Unfortunately, the underlying cause of hypercalcemia in most of these cats has not yet been identified. Causes of hypercalcemia excluded in these patients include primary hyperparathyroidism, hypervitaminosis D and hypercalcemia of malignancy.

10. Intestinal absorption of excessive calcium will result in hypercalciuria. Therefore, it would seem logical that restriction of dietary calcium would minimize calcium oxalate urolith formation. However, dietary restriction of calcium may actually increase the risk for CaOx urolith formation. Why? As in the urinary tract, calcium and oxalic acid in the intestinal lumen may combine to form an insoluble complex that is not absorbed. However, reducing dietary calcium without an appropriate reduction in oxalate will increase the solubility of unbound oxalic acid in the intestinal lumen This promotes absorption and subsequent excretion of oxalic acid in urine. Hyperoxaluria is a greater risk factor for CaOx urolith formation than hypercalciuria of equivalent magnitude because smaller increments of oxalic acid are required for formation of insoluble CaOx. This provides a plausible explanation as to why calcium oxalate uroliths recur more frequently in humans consuming calcium-restricted diets compared to those consuming diets with adequate calcium. It follows that the quantity of dietary calcium should not be altered without considering an appropriate reduction in the quantity of dietary oxalic acid.

11. In contrast to dietary calcium, consumption of non-dietary calcium supplements between meals has minimal effect on the intestinal absorption of oxalic acid derived from the diet. As a result, non-dietary calcium supplements increase the risk for CaOx urolith formation.

12. Dietary phosphorus restriction is a risk factor for increased urinary calcium excretion because diets deficient in phosphorus stimulate renal activation of vitamin D. Vitamin D, in turn, promotes intestinal absorption and subsequent urinary excretion of calcium. Reduction of dietary phosphorus may also result in reduced formation of relatively insoluble calcium phosphate complexes in the intestinal lumen, thereby enhancing intestinal absorption and renal excretion of calcium. Therefore, to minimize recurrence of CaOx uroliths, dietary phosphorus should not be restricted.

13. Diets formulated to acidify urine promote calcium oxalate uroliths by inducing hypercalciuria. The association between persistent aciduria and increased urolith formation is not directly related to decreased solubility of CaOx crystals in acid urine. CaOx crystals can form in acid and alkaline urine. The association between aciduria, acidemia, and calcium oxalate urolithiasis may be explained at least in part, by the fact that acidemia promotes mobilization of carbonate and phosphate from bone to buffer hydrogen ion. Concomitant mobilization of bone calcium results in hypercalciuria. In addition, metabolic acidosis may induce hypocitrituria. Hypocitrituria may increase the risk for CaOx uroliths because citrate is an inhibitor of CaOx crystal formation.

14. Dietary ingredients that contain substantial quantities of oxalate (spinach, soybeans, sardines, sweet potatoes, asparagus, tofu) promote hyperoxaluria. They are well-documented risk factors of CaOx uroliths in humans. However, these foods are infrequently associated with feline CaOx urolith formation.

15. Excessive dietary levels of vitamin D (which promotes intestinal absorption of calcium) and ascorbic acid (a precursor of oxalic acid) should be avoided. The diet should be adequately fortified with vitamin B6 because vitamin B6 deficiency promotes endogenous production and subsequent urinary excretion of oxalic acid.

16. Although increased dietary sodium is associated with increased urinary excretion of calcium, recent studies indicate that calcium concentration may not rise because of a concomitant increase in urine volume. In addition, increased urine volume may decrease urine oxalic acid concentration. Thus, the overall effect of adding sodium chloride to the diet may be increased urine volume and reduced supersaturation with CaOx. Current evidence suggests that restriction of dietary sodium is not of benefit in prevention of CaOx uroliths.

17. Epidemiological studies indicate that cats fed high moisture (canned) diets are three times less likely to develop CaOx uroliths as cats fed low-moisture (dry) diets. High moisture diets are preferred over dry formulations because by promoting increased fluid intake they reduce urinary concentration of calulogenic substances in urine. By increasing urine volume and frequency of voiding, they also minimize the time that crystals can grow by remaining within the urinary tract.

18. Epidemiological studies indicate that cats fed diets with a lower quantity of magnesium had a higher risk for CaOx uroliths than cats fed moderate quantities of magnesium. However, supplemental magnesium may contribute to hypercalciuria, and may also increase the risk for struvite urolith formation. Pending further studies, we do not recommend dietary magnesium restriction or supplementation to minimize recurrence of CaOx uroliths in cats.

19 Epidemiological studies indicate that diets high in potassium were associated with a decreased risk for CaOx uroliths. Studies in humans suggest that oral potassium supplements may reduce urinary excretion of calcium. In addition, oxalic acid forms salts with potassium that are more soluble than CaOx.

Dietary recommendations

1. The goals of dietary prevention include:

• reducing calcium concentration in urine,
• reducing oxalate concentration in urine,
• promoting higher concentrations and activity of inhibitors of calcium crystal growth and aggregation, and
• reducing urine concentration and minimizing urine retention.

2. Results of epidemiological studies in humans, dogs and cats indicate CaOx urolith recurrence may be minimized by feeding a nonacidifying, high-moisture diet formulated to avoid excessive protein, calcium, oxalate and sodium. The diet should contain adequate quantities of phosphorus so as to minimize renal activation of vitamin D, adequate quantities of magnesium, adequate quantities of potassium, and adequate quantities of vitamin B6.

3. Increased water intake is the cornerstone of therapy to prevent urolith recurrence.

High-moisture diets are preferred over dry formulations because by promoting increased fluid intake they reduce urinary concentration of calulogenic substances in urine. By increasing urine volume and frequency of voiding, they also minimize the time that crystals can grow by remaining within the urinary tract. The goal is to promote urine with a specific gravity value ≤ 1.025. Alternatively, water or other liquids may be added to the patient’s usual diet. Living conditions should be adjusted so that the frequency of micturition is not restricted.

4. It is unlikely that water hardness plays a significant role in the formation of uroliths. The quantity of water consumed is much more important. Therefore, use of distilled water is of questionable value, unless it can be documented that it enhances a patient's water consumption and urine volume.

5. As with calcium supplements given independently of the diet, vitamin C and D supplements are not recommended.

Pharmacologic recommendations

1. Detection of persistent calcium oxalate crystalluria or recurrence of uroliths may prompt consideration of other therapeutic strategies. Before considering adding drugs to the prevention protocol, appropriate consideration should be given to owner and patient compliance with dietary recommendations.

2. In general, pharmacological agents should be added in stepwise fashion, with the goal of reducing the urine concentration of calculogenic substances. Medications that have the potential to induce a sustained alteration in body composition of metabolites, in addition to urine concentration of metabolites, should be reserved for patients with active or frequently recurrent uroliths. Caution must be used so that the side effects of treatment are not more detrimental than the effects of the uroliths.

3. Oral administration of potassium citrate is of proven value in minimizing recurrence of CaOx uroliths in humans. The benefit is related to increased urinary excretion of citric acid and subsequent formation of calcium citrate. Calcium citrate is much more soluble in urine than calcium oxalate. However, oral administration of calcium citrate to dogs is not associated with increased urinary excretion of citric acid.

The effect of potassium citrate on urine citric acid concentrations in cats with CaOx uroliths has not been well documented. Even though oral administration of potassium citrate may not be associated with a sustained increase in urine citrate excretion, it may be useful in patients with acidosis-induced hypercalciuria because of its alkalinizing effects. The oral dosage commonly used is 40 to 75 mg/kg every 12 hours. The dose may be adjusted by evaluation of serum total carbon dioxide concentrations, blood bicarbonate concentrations and/or urine pH. Appropriate precautions should be taken to prevent iatrogenic hyperkalemia.

4. Vitamin B6 has been recommended for management of calcium oxalate uroliths because it reversed hyperoxaluria in kittens fed a vitamin B6 deficient diet. The efficacy of supplemental vitamin B6 in reducing urinary oxalate excretion in cats with CaOx uroliths has not been determined. However, empirical use of this inexpensive nutrient at an oral dose of 2 to 4 mg/kg is apparently safe.

5. Thiazide diuretics decrease urinary excretion of calcium in humans and dogs with CaOx uroliths. However, the safety and efficacy of thiazides has not been documented in cats. Because they have the potential to induce dehydration and electrolyte imbalances (hypokalemia and hypercalcemia), we cannot recommend their routine use.

6. Glucocorticoids promote urinary excretion of calcium and therefore have been empirically recommended to treat cats with CaOx uroliths and idiopathic hypercalcemia. However, the long-term safety and efficacy of glucocorticoids in this situation have not been documented in controlled clinical trials. Therefore, they should be used with appropriate caution.

7. We have had some success in correcting idiopathic hypercalcemia associated with CaOx uroliths by feeding a high fiber diet (Prescription Diet Feline w/d-Hill's) and supplemental oral potassium citrate. As with glucocorticoid therapy, further clinical studies are needed to evaluate the long-term safety and efficacy of this regimen.

Monitoring response

Medical prevention protocols should be consistently monitored by appropriate indices of therapeutic response. These typically include timely urinalyses, serum chemistry profiles, and radiography or ultrasonography. Therapy should be adjusted to meet each individual patient's needs. The degree to which risk factors have been eliminated or modified should be considered when determining the frequency of re-evaluations (Table 2).

Table 2.

A large number of persistent risk factors warrants more frequent rechecks. If urocystoliths recur despite efforts to minimize risk factors, early detection will facilitate their removal by voiding urohydropropulsion.