Improving management of urolithiasis: diagnostic caveats

Protocols have been developed to promote dissolution of canine and feline struvite uroliths, the dissolution of canine ammonium urate and cystine uroliths, and the prevention of all major types of canine and feline uroliths. However, because the underlying causes of different types of uroliths vary, medical protocols that promote their dissolution and prevention vary.

The objective of the first article in this two-part series is to summarize diagnostic caveats derived from our experience with medical management of urolithiasis during the past 25 years.

When the diagnosis of the underlying causes of urolith formation becomes the rule rather than the exception, therapeutic failures will become the exception rather than the rule. Therapeutic caveats will follow in next month's Diagnotes.

1. Uroliths are always the sequela of one or more underlying inherited, congenital, and/or acquired disorders. Therefore, detection of uroliths should not be accepted as an endpoint of diagnostic investigation.

2. Although some types of uroliths occur with greater frequency in some species and breeds, breed predisposition should not be used as primary criteria for diagnosis of the mineral composition of uroliths. For example, of 9,541 uroliths formed by Dalmatian dogs and submitted to the Minnesota Urolith Center, 9,095 were composed of urates. However, 185 were of mixed composition, 155 were compound stones, 43 were struvite, 21 were composed of calcium oxalate, four were composed of silica, three were composed of cystine and three were composed of calcium phosphate.

3. Urocystoliths and urethroliths that occur in immature dogs and cats are usually composed of struvite caused by infections with urease producing microbes (especially staphylococci). Metabolic uroliths (such as calcium oxalate and cystine uroliths) are uncommonly encountered in immature patients. Two notable exceptions to this generality are the formation of ammonium urate uroliths in dogs with portovascular anomalies, and formation of cystine uroliths by Newfoundlands.

4. Most feline nephroliths are composed of calcium salts (calcium oxalate or calcium phosphate). Calcium containing nephroliths are being recognized with increased frequency in cats with chronic renal failure. Only about 5 percent of feline nephroliths are struvite.

5. Palpation of the urethra (including palpation per rectum) should routinely be performed in patients suspected of having uroliths.

6. Most (~90 percent) urocystoliths in cats cannot be detected by abdominal palpation. Radiographic or ultrasonographic evaluation of the urinary tract is required to detect them consistently.

7. It may be impossible to palpate urocystoliths in a patient with a distended or overdistended urinary bladder. The urinary bladder should be palpated after urine has been eliminated by (depending on circumstances) voiding, manual compression, cystocentesis or catheterization.

8. Detection of crystals in urine is proof that the urine sample is oversaturated with crystallogenic substances. However, in vitro oversaturation may occur in addition to, or instead of, in vivo events. Therefore, care must be used not to over-interpret the significance of crystalluria. In vitro crystal formation may have no clinical relevance to in vivo formation of crystals.

9. Change in temperature associated with preservation of urine by refrigeration is a common cause of in vitro crystalluria. Therefore, presence of crystals in stored samples should be validated by reevaluation of fresh urine.

10. In vitro changes in urine pH also cause changes in crystalluria. When substantial time is expected to lapse between the urine collection and urine analysis, urine pH values should be obtained immediately following collection and again at the time of the analysis. Differences between the two pH values suggest that in-vitro changes have occurred, and should be considered when interpreting the significance of crystalluria. This is especially important when sending samples to diagnostic laboratories.

11. Urine pH values obtained by strips (colorimetric dyes) may vary by as much as 0.5 unit on either side of the observed value. This variation is associated with logarithmic changes in hydrogen ion concentration. Therefore, when precise urine pH values are needed, they should be obtained with the aid of a portable pH meter.

12. Urine samples collected and submitted by clients are often unreliable because unknown variables including contamination, temperature and length of storage, and changes in urine pH may result in formation or dissolution of crystals after sample collection.

13. Consider the patient's diet when interpreting the significance of crystalluria because crystalluria may also be influenced by diet (including water intake). Dietary influence on crystalluria is of diagnostic importance because urine crystal formation that occurs while patients are consuming hospital diets may be dissimilar to urine crystal formation that occurs when patients are consuming diets fed at home.

14. Struvite crystals are often observed when urine pH is slightly acid (6.5) or alkaline. They are unlikely to be observed when urine pH is - 6.3.

15. Urine sediment should be observed for a tendency of crystal aggregation in addition to crystal type. Crystals that aggregate in vivo represent a greater risk for urolith formation than single crystals.

16. Detection of unusual crystals in the urine of patients receiving medications should prompt consideration that they may be drug metabolites. Drug associated crystalluria in dogs and cats includes sulfadiazine and its metabolites.

17. Characterization of amorphous (i.e. without shape) crystals is especially difficult. Calcium phosphate may form amorphous crystals in alkaline urine; ammonium urate and xanthine may form amorphous crystals in acid urine. Other types of crystals may also be amorphous. Addition of 10 percent acetic acid usually results in dissolution of calcium phosphate crystals and often results in formation of characteristic diamond or rhomboid shaped uric acid crystals from amorphous urate crystals.

18. Different types of crystals may have similar shapes. When difficulty is encountered in identifying urine crystals by their light microscopic appearance, their composition may be determined by physical methods of quantitative mineral analysis (infrared spectroscopy, X-ray diffraction, etc.). Contact diagnostic laboratories for details about how to prepare and submit samples.

19. Struvite crystals may on occasion resemble cystine crystals, especially in cats. Addition of 10 percent acetic acid will dissolve struvite crystals, but will not dissolve cystine crystals.

20. Don't rely on microscopic evaluation of urine crystals as the sole criterion of the mineral composition of uroliths. Only quantitative analysis can provide definitive information about the mineral composition of the entire urolith. However, interpretation of crystalluria along with other clinical findings often allows one to establish a tentative identification of the mineral composition of uroliths, especially their outer layers.

21. Detection of crystalluria is not synonymous with the presence of uroliths. Crystalluria often is present in absence of uroliths. Conversely, uroliths can be present without concomitant crystalluria.

22. The primary objectives of radiographic evaluation of patients suspected of having uroliths is to determine their site(s), number, density and shape(s). Although properly performed ultrasonography is comparable to survey radiography in detection of uroliths, ultrasonography does not provide information about the relative radiodensity or shape of uroliths. Because the radiodensity, shape and size of uroliths often provides valuable clues as to their mineral composition, we prefer to use survey radiography as the initial imaging procedure when evaluating most patients for uroliths.

23. Once urolithiasis has been confirmed, radiographic and/or ultrasonographic evaluation are important to detect predisposing or complicating abnormalities. Radiographic evaluation of changes in urolith size is also an important index of therapeutic response.

24. Urocystoliths less than 3mm in size are difficult to detect by survey radiography, but may be detected by double contrast cystography or ultrasonography.

25. The radiodensity of uroliths is variable, being dependent on their mineral composition, size, and proportion of matrix. In general, calcium phosphate and calcium oxalate uroliths are the most dense (comparable to the density of bone). In contrast, uroliths composed of urates are often radiolucent (density comparable to soft tissue). Struvite, cystine, and silica uroliths can often be detected by survey radiography, but are substantially less dense than bone.

26. Radiodense uroliths must be differentiated from: a) dystrophic or metastatic calcification of renal parenchyma, b) radiodense ingesta or medications in the gastrointestinal tract, c) calcified mesenteric lymph nodes, d) osseous metaplasia of transitional epithelium or mineralization of a neoplasm, e) radiodensities in the gallbladder and f) large thela of female dogs. Radiodense uroliths within the excretory pathways may disappear or become radiolucent when surrounded by radiopaque contrast agents.

27. Radiolucent uroliths composed of purines (ammonium urate sodium urate, uric acid, and xanthine) can usually be detected by double contrast cystography. Radiolucent uroliths may be distinguished from blood clots with the aid of ultrasonography.

28. Laminations of uroliths detected by survey radiography may be associated with different layers of minerals, or the same type of mineral with different proportions of matrix.

29. The number, location, size and shape of uroliths may rapidly change. For example: infection-induced struvite uroliths may form and grow to a detectable size within one to two weeks. Urocystoliths may also pass into or through the urethra. Likewise, renoliths may pass into the ureters and/or urinary bladder. Following variable periods, new uroliths may form in one or more locations; uroliths may also spontaneously dissolve. Therefore, if significant time has elapsed between the time of diagnostic radiography and the date of initiation of medical or surgical therapy, the number, size, shape and location(s) of uroliths should be reevaluated by radiography or ultrasonography just prior to therapy.

30. In our experience, urocystoliths have been detected in the lower urinary tract in 15 to 20 percent of dogs and cats immediately following cystotomy. If the number of uroliths present in the urinary tract can be accurately determined by survey or contrast radiography, it is usually necessary to obtain immediate postsurgical films to ensure that they have all been removed since they can be accurately counted. However, if the numbers of uroliths detected by radiography are too numerous to count, postsurgical radiographs are indicated to detect uroliths that have been inadvertently allowed to remain in the urinary tract (pseudo-recurrence).

31. Microbes may remain viable within the matrix of uroliths (especially struvite uroliths). In this situation, aerobic culture of surrounding urine may reveal: a) the same type of microbe, b) different types of microbes, or c) no microbes (especially if antimicrobial agents are given prior to collection of urine for culture).

32. Although abnormal serum concentrations of lithogenic metabolites may provide clues about the underlying cause(s) of urolithiasis, normal serum concentrations of potentially lithogenic metabolites are not always associated with normal urine concentrations of those metabolites.

33. The concentrations of lithogenic metabolites in urine is often dependent on the type of diet being consumed, and also whether urine is collected during a non-fasted or fasted state.

34. Although the names of many commercially manufactured diets remain the same over long periods, their composition may change. This fact must be considered when comparing results from one date to another, or between one group of investigators and another.

35. When evaluating the urine concentrations of lithogenic metabolites in urine of patients with urolithiasis, patients should be fed the same type of diet consumed when the uroliths formed, or special diets designed for this purpose.

36. For best results, 24-hour urine collections should be analyzed for concentrations of calculogenic metabolites. Diurnal variation in urinary excretion of lithogenic metabolites decreases the reliability of "spot" urine samples.

37. Laboratory methods designed for measurement of lithogenic metabolites in human urine may not provide reproducible data when used to detect such metabolites in animals. For example, production of ascorbic acid by dogs interferes with commonly used enzymatic tests designed for measurement of urine oxalate concentration in man. Likewise, automated serum chemistry procedures designed to detect relatively high serum uric acid concentrations in man commonly provide irreproducible results of serum uric acid concentrations in dogs and cats.

38. Precipitation of calculogenic metabolites (such as uric acid and ammonium urate) during preservation of urine by refrigeration (or other methods) may result in detection of erroneously low concentrations of these metabolites.

39. If uroliths are removed surgically, consider removing a small biopsy sample for preservation in 10 percent buffered formalin. The sample may be immediately submitted for evaluation, or saved for use in the event that unforeseen difficulties in management of the patient occur.

40. Qualitative methods (such as the Oxford Stone Analysis Kit) or urolith analysis do not provide reliable information about the mineral composition of uroliths. They should only be used as a tentative index of urolith composition, and only then if subsequently validated by quantitative methods of urolith analysis. Additional information may be obtained at our Web site: www.cvm.umn.edu. Click the link to department and centers to find Minnesota Urolith Center.