Risk factors for calcium carbonate urolithiasis in goats

Eugene E. Nwaokorie Minnesota Urolith Center, Department of Veterinary Clinical Sciences.

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 DVM, MS
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Carl A. Osborne Minnesota Urolith Center, Department of Veterinary Clinical Sciences.

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 DVM, PhD
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Jody P. Lulich Minnesota Urolith Center, Department of Veterinary Clinical Sciences.

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Thomas F. Fletcher Department of Veterinary Biosciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.

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 DVM, PhD
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Lisa K. Ulrich Minnesota Urolith Center, Department of Veterinary Clinical Sciences.

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Lori A. Koehler Minnesota Urolith Center, Department of Veterinary Clinical Sciences.

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Michelle T. Buettner Minnesota Urolith Center, Department of Veterinary Clinical Sciences.

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Abstract

Objective—To identify demographic or signalment factors associated with calcium carbonate urolith formation in goats.

Design—Retrospective case series and case-control study.

Animals—354 goats with calcium carbonate uroliths (case animals) and 16,366 goats without urinary tract disease (control animals).

Procedures—Medical records of the Minnesota Urolith Center were reviewed to identify case goats for which samples were submitted between January 1, 1984, and December 31, 2012. Control goats evaluated at US veterinary teaching hospitals in the same time period were identified by searching Veterinary Medical Database records. Age, breed, sex, reproductive status, geographic location, season, and anatomic location of collected uroliths were analyzed to identify risk or protective factors associated with calcium carbonate urolithiasis.

Results—Nigerian dwarf goats had higher odds of developing calcium carbonate uroliths than did Pygmy goats (reference group). Several breeds had lower odds of this finding, compared with Pygmy goats; odds were lowest for mixed, Anglo-Nubian, and Toggenburg breeds. Breeds of African origin (Pygmy, Nigerian Dwarf, and Boer) comprised 146 of 275 (53%) case goats with data available. Goats of African descent had a higher risk of developing calcium carbonate uroliths than did goats of non-African descent (reference group). Males and neutered goats had higher odds of calcium carbonate urolithiasis, compared with females and sexually intact goats, respectively. Age category, geographic location, and season were associated with detection of calcium carbonate uroliths.

Conclusions and Clinical Relevance—Goats with calcium carbonate uroliths were typically neutered males, > 1 year of age, and of African descent. This study identified factors associated with calcium carbonate urolithiasis in goats; however, these associations do not allow conclusions regarding cause-and-effect relationships.

Abstract

Objective—To identify demographic or signalment factors associated with calcium carbonate urolith formation in goats.

Design—Retrospective case series and case-control study.

Animals—354 goats with calcium carbonate uroliths (case animals) and 16,366 goats without urinary tract disease (control animals).

Procedures—Medical records of the Minnesota Urolith Center were reviewed to identify case goats for which samples were submitted between January 1, 1984, and December 31, 2012. Control goats evaluated at US veterinary teaching hospitals in the same time period were identified by searching Veterinary Medical Database records. Age, breed, sex, reproductive status, geographic location, season, and anatomic location of collected uroliths were analyzed to identify risk or protective factors associated with calcium carbonate urolithiasis.

Results—Nigerian dwarf goats had higher odds of developing calcium carbonate uroliths than did Pygmy goats (reference group). Several breeds had lower odds of this finding, compared with Pygmy goats; odds were lowest for mixed, Anglo-Nubian, and Toggenburg breeds. Breeds of African origin (Pygmy, Nigerian Dwarf, and Boer) comprised 146 of 275 (53%) case goats with data available. Goats of African descent had a higher risk of developing calcium carbonate uroliths than did goats of non-African descent (reference group). Males and neutered goats had higher odds of calcium carbonate urolithiasis, compared with females and sexually intact goats, respectively. Age category, geographic location, and season were associated with detection of calcium carbonate uroliths.

Conclusions and Clinical Relevance—Goats with calcium carbonate uroliths were typically neutered males, > 1 year of age, and of African descent. This study identified factors associated with calcium carbonate urolithiasis in goats; however, these associations do not allow conclusions regarding cause-and-effect relationships.

Goats are becoming increasingly popular as pets in the United States.1–3 Leading this trend of popular pet goats are breeds of African descent.1–3 The affectionate and docile nature of goats of African origin likely has contributed to their popularity as pets in the United States.1–3 As of January 2014, the population of goats in the United States was estimated to be 2.3 million by the Agricultural Statistics Board.4 Goats, along with being pets, are used for food, fiber, weed control, youth development organization projects, animal cell culture production, pack animal activities, and competition in livestock shows.4 Not much is known about changes in diets and natural habits of these breeds of African goats in their native continent.5 As the population of pet goats increases, uroliths are being detected with increased frequency. One explanation may be that pet goats may receive more intensive medical attention than more traditional livestock. It is also possible that pet goats are more likely to be housed individually or kept at residences because of their small size and therefore are under closer observation than animals not kept as pets. Knowledge of the various mineral compositions of uroliths affecting goats and risk factors for urolith formation are needed to develop effective diagnostic, therapeutic, and preventive strategies.

Between 1981 and 2007, 941 urolith submissions were sent to the Minnesota Urolith Center from 19 ruminant species, and the prevalence of calcium carbonate uroliths was highest in moose, wildebeest, and goats. During this time period, 42% of goat uroliths submitted to this facility were composed of calcium carbonate.6 Urinary tract obstructions resulting from complications of urolithiasis in goats have been observed almost exclusively in males. In male goats, the distal penile urethra forms a lengthy, narrow, and tortuous urethral process that is a common site for uroliths to lodge.2 Published reobstruction rates for goats with obstructive urolithiasis, even after prompt and aggressive treatment, range from 8 of 28 (29%) to 6 of 20 (30%).3,7 A review of uncontrolled clinical studies of obstructive urolithiasis in goats resulted in the observation that the time to reobstruction following initial treatment ranges from 1 to 8 months.3 Our empirical observations suggest that the rate of recurrence may be minimized by modifying dietary ingredients, with the goals of reducing concentrations of lithogenic minerals and increasing urine volume.8

Risk can be defined as the probability of disease developing in an individual during a specific interval.8 As clinicians, we think of risk factors and protective factors as events that will affect the biological behavior of diseases such as urolithiasis.8 Evaluation of risk factors and protective factors through epidemiological studies may be useful in the development of recommendations for the prevention and control of urolithiasis.9

The purpose of the study reported here was to determine the predominant mineral type of uroliths collected from goats and submitted to the Minnesota Urolith Center and to characterize risk factors and protective factors associated with urolithiasis in this species. In addition, we sought to assess associations of potential risk factors (breed, age, sex, reproductive status, anatomic location within the urinary tract, season of sample collection, and geographic location) with calcium carbonate urolith detection. We hypothesized that breed, age, sex, reproductive status, geographic location, and season would be risk factors associated with calcium carbonate urolith detection in goats.

Materials and Methods

Identification of cases and controls and medical records review—Medical records of the Minnesota Urolith Center were reviewed to identify goats for which urolith samples were submitted by veterinarians within the United States between January 1, 1984, and December 31, 2012. The mineral composition of the uroliths was determined by optical crystallography10,11 and, when necessary, by infrared spectroscopy.10 Case animals were identified as goats that had uroliths consisting of ≥ 70% calcium carbonate. Animals with compound uroliths (ie, those containing nuclei, stone, shell, or surface crystal layers with ≥ 2 layers with ≥ 70% different mineral types) were excluded. Preliminary evaluation of case series data indicated that uroliths were not detected in goats < 3 months of age, so goats of this age in the control group were censored.

Goats without urinary tract disorders (control goats) evaluated at the veterinary teaching hospitals in the United States between January 1, 1984, and December 31, 2012, were identified by searching the records of the Veterinary Medical Database.b Only animals that had urinalysis performed and had no urinary tract disease were selected.

The following information was retrieved from urolith submission records of each case animal and medical records of controls when applicable: age, breed, sex, reproductive status (neutered or sexually intact), state of residence, date of urolith submission, anatomic location of the urolith (upper urinary tract [kidneys and ureters], lower urinary tract [bladder, urethra, and voided samples], upper and lower urinary tract, or unknown), and diet (first and second components listed on the record). Distinction between the Anglo-Nubian and Nubian goat breeds could not be consistently determined from medical records of goats with uroliths submitted to the Minnesota Urolith Center. Therefore, goats of these 2 breeds were grouped together in the present study. Geographic regions (Southeast, Southwest, Midwest, Northeast, or West) were determined on the basis of state of residence according to classification established by the National Geographic education division.c Seasons of sample collection were classified as winter (December, January, and February), spring (March, April, and May), summer (June, July, and August), and fall (September, October, and November). Each goat was included only once in the study.

Statistical analysis—Standard statistical software12,d,e was used to determine descriptive statistics (mean, median, and SDs) of age, breed, sex, reproductive status, geographic location of goats, season of urolith submission, and anatomic location of the uroliths within the urinary tract for case animals. Linear regression was used, and ORs and 95% CIs calculated by use of the Woolf method13 to assess whether breed, age, sex, reproductive status, season, and geographic location were associated with the presence of calcium carbonate uroliths. If any expected cell frequency in a contingency table was < 5, the Fisher exact test was used.14 Breeds were further categorized as African (Pygmy, Nigerian Dwarf, and Boer) or non-African (all others) in origin. For analysis of age effects, goats were divided into 6 age groups: < 1 year, 1 to < 2 years, 2 to < 4 years, 4 to < 7 years, 7 to < 10 years, and ≥ 10 years. Data for goats < 4 years of age were also compared with those for goats 4 years old. Referents for the variables (determined on the basis of breaks in the data and mean age) for determination of ORs were as follows: breed, Pygmy; breed origin, non-African; age, < 1 year; sex, female; reproductive status, sexually intact; season, spring; and geographic region, Southwest.

Prevalence of calcium carbonate uroliths was expressed as the relative frequency of all uroliths collected from goats and submitted for analysis to the Minnesota Urolith Center. Relative frequencies also were used to describe the age, breed, sex, reproductive status, and geographic location of goats as well as season of collection and anatomic location of uroliths. Logistic regression was computed to determine whether the percentages of goats of African and non-African origins with calcium carbonate urolithiasis increased or decreased over the study period. The 28-year study was grouped into 2 intervals (1984 through 1998 and 1999 through 2012) to determine whether risk or protective factors changed over time. The Breslow-Day statistic was computed to determine whether ORs were homogenous over the 2 time intervals.15 The Mantel-Haenszel summary of ORs was computed when the results of the Breslow-Day test were not significant. Values of P < 0.05 were considered significant.

Because of the absence of continuous variables, crude ORs were computed by means of hierarchic well-formulated modeling to find the best risk model for the categorical variables of age, breed, sex, reproductive status, geographic location, season, and anatomic location. After adjusting for age, sex, and reproductive status as confounding factors and interactions, risk factors associated with urolith formation were determined from the best model.

Odds ratio estimates were considered significantly different from 1 if the 95% CI did not encompass 1.0.16 On the basis of recommendations by Lilienfeld and Stolley,17 we classified associations with significant ORs between 1.1 and 1.9 or between 0.5 and 0.9 as weak. Significant ORs > 2 (indicating a risk factor) and those < 0.5 (suggesting a protective effect) were interpreted as clinically (biologically) important. All analyses were performed with standard software.12,c,d Results were considered as significant at values of P < 0.05.

Results

Uroliths from 832 goats were submitted to the Minnesota Urolith Center for analysis during the study period. Of these, uroliths containing ≥ 70% calcium carbonate were the most common (n = 364 [44%]). After censoring submissions from outside the United States (n = 10), calcium carbonate content of the remaining 354 samples from 354 case goats was as follows: 100%, 337 (95%) samples; 90% to 99%, 8 (2%) samples; and ≥ 70% to 89%, 9 (3%) samples. Calcium carbonate uroliths retrieved from goats were typically spherical and smooth (Figure 1). They were light yellow to golden brown in color and ranged from < 1 mm to > 1 cm in diameter. The number of uroliths submitted from each case goat varied. The control group consisted of 16,366 goats without urinary tract disorders.

Figure 1—
Figure 1—

Photograph of calcium carbonate uroliths (100% CaCO3) from a 4.6-year-old neutered male goat. Measurements are shown in centimeters.

Citation: Journal of the American Veterinary Medical Association 247, 3; 10.2460/javma.247.3.293

Breed—Case goats included 17 breeds and control goats included 11 breeds. Six breeds were excluded from breed-related analysis because of a lack of control animals; these included Pygora (n = 5 case goats), French Alpine (3), Fainting Goat (2), and British Alpine, Cashmere, and Norwegian (1 each). Breed data for 79 of 354 (22%) case and 124 of 16,366 (0.8%) control animals were not provided at the time of urolith submission. The breed with the highest odds of developing calcium carbonate uroliths, compared with Pygmy goats, was Nigerian Dwarf (P ≤ 0.001; Table 1). Breeds with the lowest risk of developing calcium carbonate uroliths, compared with Pygmy goats, included mixed, Anglo-Nubian or Nubian, and Toggenburg. Of the 275 submissions where breed was recorded, 146 (53%) and 129 (47%) were breeds of African and non-African origins, respectively. Goats of African descent had significantly (P < 0.001) higher odds of developing calcium carbonate uroliths than did the referent group (OR, 3.85). From 1984 through 1998, case goats of African descent constituted 17 of 36 (47%) goats with calcium carbonate uroliths. Goat of non-African descent constituted 19 of 36 (53%) of this group. During the same period, 1,579 of 11,205 (14%) controls goats were of African descent, and the remaining 9,626 (86%) were of breeds with other origins. From 1999 through 2012, 129 (54%) and 110 (46%) of 239 case goats were of African and non-African descent, respectively. Among 5,037 control goats seen during this period, breeds of 1,816 (36%) and 3,221 (64%) were of African and non-African origin, respectively. Breed origin data were unavailable for 79 case and 124 control goats seen during 1999 through 2012.

Table 1—

Logistic regression analysis results indicating crude and adjusted ORs and 95% CIs for breed and breed origin of case goats with calcium carbonate uroliths (n = 354) and control goats (16,366).

 No. of animals*      
BreedCasesControlsCrude OR95% CIAdjusted OR†95% CIP value
Pygmy1052,7151.0NANANAReferent
Boer317941.0090.67–1.511.0020.59–1.490.986
Alpine241,4150.440.28–0.690.3250.27–0.650.003
Saanen319970.800.54–1.210.760.51–1.110.294
Angora104400.590.30–1.130.540.27–1.100.112
La Mancha66550.240.103–0.5420.210.100–0.480.006
Mixed104,2140.0610.032–0.120.0510.022–0.110< 0.001
Nigerian Dwarf102211.755.43–25.4510.985.42–24.68< 0.001
Anglo-Nubian or Nubian253,9000.170.11–0.260.150.10–0.25< 0.001
Oberhasli31200.650.203–2.080.630.20–2.040.468
Toggenburg79700.1870.087–0.4020.170.073–0.38< 0.001
Goats of non-African origin12912,8031.0NANANAReferent
Goats of African origin1463,4394.213.32–5.363.853.10–4.77< 0.001

Case animals were defined as goats for which the uroliths were submitted to the Minnesota Urolith Centera between January 1, 1984, and December 31, 2012, and were found to contain ≥ 70% calcium carbonate. Control animals were goats without urinary tract disease evaluated at veterinary teaching hospitals during the study period (identified through use of the Veterinary Medical Databaseb).

Breed-specific analysis excluded case goats (n = 13, all of non-African descent) of various breeds for which no controls were available and case (79) or control goats (124) for which breed was not recorded. Breed origin analysis excluded 79 case and 124 control goats for which this variable was unknown. †Adjusted for age, sex, and reproductive status as confounding factors and their interactions.

NA = Not applicable.

Age—Mean ± SD age of 296 case goats for which data were available was 3.8 ± 1.8 years (range, 3.8 months to 14 years). One hundred sixty-five (56%) of these goats were < 4 years and 131 (44%) were ≥ 4 years of age. The odds of developing calcium carbonate uroliths were significantly greater for goats in all other age groups, compared with odds for the referent group of < 1 year of age (Table 2). When combined age groups were evaluated, goats that were < 4 years old were significantly less likely (adjusted OR, 0.26) to develop calcium carbonate uroliths than goats ≥ 4 years old (referent group).

Table 2—

Logistic regression analysis results indicating crude and adjusted ORs and 95% CIs of demographic variables for case goats with calcium carbonate uroliths (n = 354) and control goats (16,366).

 No. of animals*      
VariableCasesControlsCrude OR95% CIAdjusted OR†95% CIP value
Age       
< 1 year56,2901.0NANANAReferent
1 to < 2 years392,28921.438.44–54.4520.567.92–53.62< 0.001
2 to < 4 years1213,31945.8618.73–112.2944.4317.33–112.13< 0.001
4 to < 7 years982,04460.3224.52–148.3559.4623.66–147.17< 0.001
7 to < 10 years2763153.8320.66–140.2752.6320.26–139.44< 0.001
≥ 10 years631723.817.22–78.4422.67.12–77.48< 0.001
Combined age category       
≥ 4 years1312,9921.0NANANAReferent
< 4 years16511,8980.320.251–0.3990.260.23–0.0.34< 0.001
Sex       
Female310,2481.0NANANAReferent
Male3435,921197.8963.48–616.89196.3662.59–612.52< 0.001
Reproductive status       
Sexually intact3814,1601.0NANANAReferent
Neutered3082,00957.1340.66–80.2856.4839.43–78.95< 0.001
Season       
Spring425,2551.0NANANAReferent
Winter783,3892.881.97–4.2012.881.97–4.201< 0.001
Summer874,2972.531.75–3.672.531.75–3.67< 0.001
Fall1473,4255.373.80–7.595.373.80–7.59< 0.001
Geographic location       
Southwest151,7681.0NANANAReferent
Southeast522,7732.211.24–3.942.211.24–3.940.007
Midwest949,9561.110.64–1.921.110.64–1.920.070
West1541,47912.277.19–20.9512.277.19–20.95< 0.001
Northeast3939011.796.43–21.6011.796.43–21.79< 0.001
Breed origin and study period 1984–1998       
Non-African breeds199,6261.0NANANAReferent
African breeds171,5796.093.12–11.975.532.87–10.66< 0.001
1999–2012       
Non-African breeds1103,2211.0NANANAReferent
African breeds1291,8162.081.60–2.701.871.56–2.40< 0.001

Age-specific analysis excluded 58 case and 1,476 control goats for which age was not recorded. Sex and reproductive status analysis excluded 8 case and 197 control goats for which information was not provided. Breed origin analysis for the 2 study periods excluded 79 case and 124 control goats for which this variable was unknown.

See Table 1 for remainder of key.

Sex and reproductive status—Of 354 case goats, sex was recorded for 346 (98%). Of the 346, 343 (99%) were males and 3 (1%) were females. Males were approximately 196 times as likely to develop calcium carbonate uroliths as were females (referent group; Table 2). Reproductive status for 346 of 354 (98%) case goats was recorded; 308 (89%) of these were neutered and 38 (11%) were sexually intact. A higher proportion of neutered male goats (307/343 [90%]) had calcium carbonate uroliths, compared with sexually intact males (36/343 [10%]; P < 0.001). Neutered goats were approximately 56 times as likely to have calcium carbonate uroliths as were sexually intact goats (Table 2).

Anatomic location—Sites from which the uroliths were collected were reported for 342 case animals and unknown for 12. Three hundred thirty-six of 342 (98%) goats had samples obtained from the lower urinary tract (urinary bladder, urethra, voided uroliths, or some combination of these). Uroliths from 3 (1%) goats included material collected from both the upper (kidney or ureter) and lower urinary tract. Submitted uroliths were from the bladder only for 93 (27%) goats, and from the urethra only for 137 (40%) goats. Submission of uroliths from the kidney (n = 1) or ureter alone (2) was uncommon.

Seasonal distribution—Collection and submission of uroliths for the 354 case goats took place in fall (n = 147 [42%]), summer (87 [25%]), winter (78 [22%]), and spring (42 [12%]). Calcium carbonate uroliths were significantly (P < 0.001 for all comparisons) more likely to be collected and submitted in fall, summer, and winter than in spring (Table 2).

Geographic distribution—Ninety-four of 354 (27%) case goats were from the Midwest, 39 (11%) were from the Northeast, 52 (15%) were from the Southeast, 15 (4%) were from the Southwest, and 154 (44%) were from the West geographic zones. The frequency of submission of calcium carbonate was approximately 2 times as great in the Southeast as in the Southwest (P = 0.007). Likewise, the frequency of submission of calcium carbonate uroliths in the West and Northeast was approximately 12 times that in the Southwest (Table 2; P < 0.001).

Diet—The primary types of diet were recorded for 311 of 354 (88%) case goats. One hundred seven of the 311 (34%) goats were fed grass or kept on pasture, 74 (24%) were fed grass hay, 37 (12%) were fed alfalfa hay, 55 (18%) were fed commercial foods (type not specified on the submission forms), 26 (8%) were fed whole grains (eg, corn or wheat), and 12 (4%) were fed hay and pelleted grain mixture (pelleted grains blended with vitamins and minerals).

Discussion

The results of the present study supported our hypothesis that multiple risk factors such as age, breed, sex, reproductive status, geographic location, and season play a role in the development of calcium carbonate uroliths. Our results were in agreement with reports by other investigators.18,19 However, those studies18,19 were performed without controls. Instead, generalities they observed were based on uncontrolled empirical observations.

As theorized in urolith formation in other species, it is probable that when several risk factors occur together, their individual effects may be enhanced. Thus, each risk factor or protective factor may play either a limited or a major role in the development or prevention of calcium carbonate uroliths.8 However, case-control studies usually cannot demonstrate that risk factors are the cause of a disease. The case animals in the present study were likely goats with clinical signs and may not have included subclinically affected animals, such as goats that voided uroliths uneventfully, or those whose uroliths were not collected and submitted to the Minnesota Urolith Center for analysis for various reasons (eg, goats that died as a result of urinary tract obstruction or goats that were euthanized because of complications). As a result of these limitations, this study may not have fully represented the population of all goats with calcium carbonate uroliths.

Goat breeds of African descent (Pygmy, Nigerian Dwarf, and Boer) were overrepresented among those with calcium carbonate uroliths (ie, case animals) in our study. This higher prevalence of calcium carbonate uroliths in goat breeds of African descent may be associated with a trend of keeping them as pets. As pets, they may be more likely to receive veterinary care when sick, compared with animals kept for other purposes. The number of goats with calcium carbonate uroliths in this study may reflect an increased awareness that uroliths can cause urethral obstruction and increased use of diagnostic methods to detect uroliths such as survey radiography and abdominal ultrasonography in the latter half of the study period. This may also be associated with an increased awareness of the availability of complimentary urolith analysis that influenced submissions made during these 2 periods (1984 through 1998 and 1999 through 2012).a

The results of our study indicated that goat breeds of African origin were at increased risk for calcium carbonate urolithiasis, compared with others breeds (ie, those of non-African origin). Familial predisposition for urolithiasis has been well documented for some mineral types.20 For example, genetic mutations causing cystine urolithiasis have been identified in dogs21 and humans.22 To the authors’ knowledge, a genetic predisposition for calcium carbonate uroliths in goats has not been explored. In our study, the observation that calcium carbonate uroliths more commonly affected goats of African descent, compared with other breeds, may suggest genetic predisposition of these breeds to calcium carbonate urolithiasis. Prospective studies evaluating the effects of diet, housing, body condition score, and other potential risk factors in addition to breed are necessary to further investigate a potential predisposition to this type of urolithiasis.

In our study, age was significantly associated with development of calcium carbonate uroliths in goats, with all age groups having significantly higher odds of this finding, compared with the < 1-year-old category. Epidemiological data derived from studies23–25 of dogs, cats, and humans have suggested that advancing age is a risk factor for urolithiasis.

Our results also indicated that calcium carbonate uroliths almost exclusively affected males (343/346 [99%]), compared with females (3 [1%]). The adjusted OR for this finding in males, relative to females, was 196.36 (95% CI, 62.59 to 612.52). This is likely related to the fact that male urethras are much longer and narrower than those of females.26 As urocystoliths pass into the distal end of the male urethra (urethral process), obstructive urolithiasis is a likely consequence. The S-shaped sigmoid flexure located just caudodorsal to the testes is another potential site for uroliths to lodge. It is likely that calcium carbonate uroliths are not commonly detected in female goats because the wider and shorter urethra allows uroliths to be passed in the urine stream before they can cause clinical signs. A higher proportion of case goats (308/346 [89%]) were neutered than were sexually intact (38 [11%]), and odds of calcium carbonate urolithiasis were significantly greater for neutered goats (OR, 56.48; 95% CI, 39.43 to 78.95). Given that only 1 of the 3 female case animals in this study was neutered, this statement may most appropriately be applied to the males only. This observation suggests that neutering may be a risk factor for urolithiasis. One group of investigators generated convincing evidence that early neutering may result in underdevelopment of the urethra and thus predispose adult goats to urethral obstruction.27 The same group of investigators showed that neutering reduces production of testosterone, which normally aids in the development of urethral lumen.27 A reduced circulating testosterone concentration is also believed to diminish normal preputial-penile attachments.27 Because the ages at which case goats were neutered was not provided, we were unable to determine whether there was a significant association between urolithiasis and early neutering.

Three hundred thirty-six of 342 (98%) case animals in this study had calcium carbonate uroliths retrieved from the lower urinary tract. The predominant location of uroliths in the lower urinary tract of other domestic animals has been described.28 In our experience in other species, the development of uroliths in the upper urinary tract is likely underreported because survey radiography and ultrasonography are often omitted during initial evaluation of animals with clinical signs of urolithiasis. Clinical signs caused by uroliths in the lower urinary tract (increased voiding frequency, straining to void, and dribbling urine) are more likely to be observed than are clinical signs caused by uroliths located in the upper urinary tract (polyuria and hematuria without obvious signs of pain, which may go unrecognized). In case animals of the present report, uroliths were more commonly retrieved from the urethra only (137/342 [40%]) than from the bladder only (93 [27%]). These localizations are important when considering dietary modification for dissolution of uroliths. It has been recommended that attempts to dissolve urethral uroliths by dietary modification be avoided.28 Uroliths lodged in the ureters or urethra cannot be dissolved by medical protocols because urolith dissolution requires sustained contact with urine that has been modified and therefore is undersaturated with lithogenic mineral.28

In our study, goats residing in the West, Northeast, and Southeast regions of the United States had significantly higher odds of developing calcium carbonate uroliths than did goats in the Southwest. These observations indicate that geographic location may be a risk factor for urolithiasis. Geographic prevalence of urolithiasis has been reported in dogs and humans.29,30 Our study was not designed to determine the reason for the variations among geographic locations. Further research is needed to assess the factors that contribute to such differences.

Calcium carbonate uroliths were significantly (P < 0.001 for all comparisons) more likely to be collected and submitted for case goats during the summer, fall, and winter than in spring. The association between season and presence of urolithiasis was in agreement with findings of other investigators that detection of urolithiasis in cats, sheep, and humans varies by season (with odds in summer, fall, and winter being greater than in spring [OR, 2.5, 5.4, and 2.9, respectively; P < 0.001]).31–33 This may be partly attributable to higher seasonal temperatures observed during the summer and fall (leading to heat-induced water loss) in comparison to winter and spring,31–33 and it is also possible that reduced water intake during the winter season could lead to increased urine concentration. We did not investigate possible associations between calcium carbonate urolithiasis and these factors.

Diet has been incriminated as an important risk factor for calcium carbonate urolithiasis in goats.34 In our study, we encountered a lack of detailed information regarding diet composition and variability in the reported diets fed to case goats. Lack of consistency in response to our requests for dietary history prevented evaluation of dietary components as risk factors for this disease. To our knowledge, controlled, blinded clinical studies have not been performed to evaluate associations between most dietary factors and urolith formation in goats. Our study was also not designed to explore this factor, and we were unable to test for such associations, although it is likely that diet has a role in the pathogenesis of calcium carbonate urolithiasis. Most case goats for which diet was reported primarily received alfalfa hay or grass hay (111/311 [36%]). Alfalfa and grass hay have a high calcium-to-magnesium concentration ratio and low phosphorus concentration and are also rich in oxalate. Further prospective studies are needed to define the role played by each of these factors singly and in combination as they relate to calcium carbonate urolithiasis.

Healthy goats normally excrete urine that is alkaline (pH range, 7.5 to 8.5). Sheep, horses, rabbits, and guinea pigs also normally excrete alkaline urine. Production of alkaline urine and calcium carbonate urolithiasis are shared characteristics among these herbivorous species. Most of the plants used to feed goats in this study (eg, grass, grains, and alfalfa) are associated with alkaline urine production.35 Although not investigated in the present study, it is probable that alkaline urine pH is a risk factor for calcium carbonate urolithiasis in goats, and this should be investigated in future studies.

Although information derived from the extensive urolith database compiled by the Minnesota Urolith Center,a together with data from the Veterinary Medical Database,b provides a unique resource for retrospective evaluation of the epidemiological features of this disorder, it is important to note that case-control studies and retrospective case series do not prove cause-and-effect relationships. Additional prospective or interventional studies are needed to prove hypotheses derived from such studies. Knowledge of the predominant mineral types of uroliths in specific species, along with insight into etiologic, demographic, and environmental risk and protective factors for urolithiasis may facilitate development of surveillance strategies that result in earlier detection of uroliths in goats. Modification of risk factors, where possible, may help to minimize urolith formation, dissolve existing uroliths, and minimize recurrences.

ABBREVIATION

CI

Confidence interval

a.

Minnesota Urolith Center, University of Minnesota, Saint Paul, Minn.

b.

Veterinary Medical Database, Urbana, Ill.

c.

National Geographic Society. Education: United States regions. Available at: education.nationalgeographic.com/education/maps/united-states-regions/?ar_a=1. Accessed Oct 23, 2014.

d.

Statistical consulting service, School of Statistics, University of Minnesota, Minneapolis, Minn. www.stat.umn.edu/consulting/. Accessed Oct 23, 2014.

e.

Epi-Info, version 6.04b, CDC, Atlanta, Ga. Available at: wwwn.cdc.gov/epiinfo/. Accessed Oct 23, 2014.

f.

Minnesota Urolith Center Quantitative Urolith Analysis submission form. Available at: www.cvm.umn.edu/depts/MinnesotaUrolithCenter/submissionform/home.html. Accessed Oct 23, 2014.

References

  • 1. Harwood D. Goat health and welfare. A veterinary guide. Ramsbury, Marlborough, Wiltshire, England: The Crowood Press Ltd, 2006.

  • 2. Smith MC, Sherman DM. Urinary system. In: Cann CC, ed. Goat medicine. Philadelphia: Lea & Febiger Publishing Co, 1994;398402.

  • 3. van Weeren PR, Klein WR, Voorhout G. Urolithiasis in small ruminants 1. A retrospective evaluation of urethrostomy. Vet Q 1987; 9: 7679.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. USDA Agricultural Statistical Board. National Agricultural Statistics Services. Available at: usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1145. Accessed Oct 23, 2014.

    • Search Google Scholar
    • Export Citation
  • 5. Kabasa JD, Opuda-Asibo J, Thinggaard G, et al. The mineral scoring technique and evaluation of indigenous browse species as natural mineral phytocentres for goats in African rangelands. Trop Anim Health Prod 2004; 36: 365380.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Osborne CA, Albasan H, Lulich JP, et al. Quantitative analysis of 4468 uroliths retrieved from farm animals, exotic species, and wildlife submitted to the Minnesota Urolith Center: 1981–2007. Vet Clin North Am Small Anim Pract 2009; 39: 6578.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Janke JJ, Osterstock JB, Washburn KE, et al. Use of Walpole's solution for treatment of goats with urolithiasis: 25 cases (2001–2006). J Am Vet Med Assoc 2009; 234: 249252.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Osborne CA, Lulich JP. Risk and protective factors for urolithiasis. What do they mean? Vet Clin North Am Small Anim Pract 1999; 29: 3943.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Nwaokorie EE, Osborne CA, Lulich JP, et al. Epidemiology of struvite uroliths in ferrets: 272 cases (1981–2007). J Am Vet Med Assoc 2011; 239: 13191324.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Ulrich LK, Bird KA, Koehler LA, et al. Urolith analysis. Submission, methods and interpretation. Vet Clin North Am Small Anim Pract 1996; 26: 393400.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Volmer M, De Vries JCM, Goldschmidt MJ. Infrared analysis of urinary calculi by a single reflection accessory and a neutral network interpretation algorithm. Clin Chem 2001; 47: 12871296.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. SAT/STAT user's guide: version 8 edition. Cary, NC: SAS Institute Inc, 1999;26: 393400.

  • 13. Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1955; 19: 251253.

  • 14. Schlessman JJ. Basic methods in cancer analysis. In: Schlesselman JJ, ed. Case-control studies. Oxford, England: Oxford University Press, 1982;171226.

    • Search Google Scholar
    • Export Citation
  • 15. Breslow NE, Day NE. Statistical methods in cancer research, volume 1: the analysis of case-control studies. Lyon, France: International Agency for Research on Cancer, 1980;142.

    • Search Google Scholar
    • Export Citation
  • 16. Fletcher RH, Fletcher SW, Wagner EH. Clinical epidemiology: the essentials. 3rd ed. Baltimore: Williams & Wilkins, 1996;186207.

  • 17. Lilienfeld DE, Stolley PP. Foundation of epidemiology. 3rd ed. Oxford, England: Oxford University Press, 1994;198225.

  • 18. Sun WD, Zhang KC, Wang JY, et al. The chemical composition and ultrastructure of uroliths in Boer goats. Vet J 2010; 186: 7075.

  • 19. Mavangira V, Cornish JM, Angelos JA. Effect of ammonium chloride supplementation on urine pH and urinary fractional excretion of electrolyte in goats. J Am Vet Med Assoc 2010; 237: 12991304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Bartges JW, Osborne CA, Lulich JP, et al. Prevalence of cysteine and urate uroliths in bulldogs and urate uroliths in Dalmatians. J Am Vet Med Assoc 1994; 204: 19141918.

    • Search Google Scholar
    • Export Citation
  • 21. Bannasch D, Henthorn PS. Changing paradigms in diagnosis of inherited defects associated with urolithiasis. Vet Clin North Am Small Anim Pract 2009; 39: 111125.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Schmidt C, Vester U, Wagner CA, et al. Significant contribution of genomic rearrangement in SLCA1 and SLC7A9 to the etiology of cystinuria. Kidney Int 2003; 64: 15641572.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Lekcharoensuk C, Lulich JP, Osborne CA, et al. Patient and environmental factors associated with calcium oxalate urolithiasis in dogs. J Am Vet Med Assoc 2000; 217: 515519.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Lekcharoensuk C, Lulich JP, Osborne CA, et al. Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiasis in cats. J Am Med Assoc 2001; 219: 12281237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Osborne CA, Polzin DJ, Abdullahi SU, et al. Struvite urolithiasis in animals and man: formation, detection, and dissolution. In: Cornelius CE, Simpson CF, eds. Advances in veterinary science and comparative medicine. Vol 29. New York: Academic Press, 1985;2733.

    • Search Google Scholar
    • Export Citation
  • 26. Dyce KM. Sack WO, Wensing CJG. The pelvis and reproductive organs of male ruminants. In: Textbook of veterinary anatomy. 3rd ed. Philadelphia: Saunders, 2002;713722.

    • Search Google Scholar
    • Export Citation
  • 27. Kumar R, Kumar A, Singh H, et al. Effect of castration on urethral and accessory sex glands in goats. Indian Vet J 1982; 59: 304308.

    • Search Google Scholar
    • Export Citation
  • 28. Osborne CA, Lulich JP, Polzin DJ, et al. Medical dissolution and prevention of canine urolithiasis. Vet Clin North Am Small Anim Pract 1999; 29: 73111.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Franti CE, Ling GV, Ruby AL, et al. Urolithiasis in dogs V: regional comparisons of breed, age, sex, anatomic location, and mineral type of calculus. Am J Vet Res 1999; 60: 2942.

    • Search Google Scholar
    • Export Citation
  • 30. Takemoto K. An epidemiological overview of canine and feline urolithiasis in Japan. J Jpn Assoc Vet Nephrol Urol 2010–2011; 3(1):3645.

    • Search Google Scholar
    • Export Citation
  • 31. Jackson OF. Springtime rise in the incidence of feline urolithiasis. Vet Rec 1974; 95: 540.

  • 32. Nottle MC. Renal calculi in apparently normal sheep. Aust Vet J 1982; 58: 256259.

  • 33. Sourcie JM, Coates RJ, McClellan W, et al. Relationship between geographic variability in kidney stones prevalence and risk factors for stones. Am J Epidemiol 1996; 143: 491495.

    • Search Google Scholar
    • Export Citation
  • 34. MacLeay JM. Urolithiasis. In: Smith BP, ed. Large animal internal medicine. 4th ed. St Louis: Mosby, 2008;9501958.

  • 35. McIntosh GH. Urolithiasis in animals. Aust Vet J 1978; 54: 267271.

  • Figure 1—

    Photograph of calcium carbonate uroliths (100% CaCO3) from a 4.6-year-old neutered male goat. Measurements are shown in centimeters.

  • 1. Harwood D. Goat health and welfare. A veterinary guide. Ramsbury, Marlborough, Wiltshire, England: The Crowood Press Ltd, 2006.

  • 2. Smith MC, Sherman DM. Urinary system. In: Cann CC, ed. Goat medicine. Philadelphia: Lea & Febiger Publishing Co, 1994;398402.

  • 3. van Weeren PR, Klein WR, Voorhout G. Urolithiasis in small ruminants 1. A retrospective evaluation of urethrostomy. Vet Q 1987; 9: 7679.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. USDA Agricultural Statistical Board. National Agricultural Statistics Services. Available at: usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1145. Accessed Oct 23, 2014.

    • Search Google Scholar
    • Export Citation
  • 5. Kabasa JD, Opuda-Asibo J, Thinggaard G, et al. The mineral scoring technique and evaluation of indigenous browse species as natural mineral phytocentres for goats in African rangelands. Trop Anim Health Prod 2004; 36: 365380.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Osborne CA, Albasan H, Lulich JP, et al. Quantitative analysis of 4468 uroliths retrieved from farm animals, exotic species, and wildlife submitted to the Minnesota Urolith Center: 1981–2007. Vet Clin North Am Small Anim Pract 2009; 39: 6578.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Janke JJ, Osterstock JB, Washburn KE, et al. Use of Walpole's solution for treatment of goats with urolithiasis: 25 cases (2001–2006). J Am Vet Med Assoc 2009; 234: 249252.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Osborne CA, Lulich JP. Risk and protective factors for urolithiasis. What do they mean? Vet Clin North Am Small Anim Pract 1999; 29: 3943.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Nwaokorie EE, Osborne CA, Lulich JP, et al. Epidemiology of struvite uroliths in ferrets: 272 cases (1981–2007). J Am Vet Med Assoc 2011; 239: 13191324.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Ulrich LK, Bird KA, Koehler LA, et al. Urolith analysis. Submission, methods and interpretation. Vet Clin North Am Small Anim Pract 1996; 26: 393400.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Volmer M, De Vries JCM, Goldschmidt MJ. Infrared analysis of urinary calculi by a single reflection accessory and a neutral network interpretation algorithm. Clin Chem 2001; 47: 12871296.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. SAT/STAT user's guide: version 8 edition. Cary, NC: SAS Institute Inc, 1999;26: 393400.

  • 13. Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1955; 19: 251253.

  • 14. Schlessman JJ. Basic methods in cancer analysis. In: Schlesselman JJ, ed. Case-control studies. Oxford, England: Oxford University Press, 1982;171226.

    • Search Google Scholar
    • Export Citation
  • 15. Breslow NE, Day NE. Statistical methods in cancer research, volume 1: the analysis of case-control studies. Lyon, France: International Agency for Research on Cancer, 1980;142.

    • Search Google Scholar
    • Export Citation
  • 16. Fletcher RH, Fletcher SW, Wagner EH. Clinical epidemiology: the essentials. 3rd ed. Baltimore: Williams & Wilkins, 1996;186207.

  • 17. Lilienfeld DE, Stolley PP. Foundation of epidemiology. 3rd ed. Oxford, England: Oxford University Press, 1994;198225.

  • 18. Sun WD, Zhang KC, Wang JY, et al. The chemical composition and ultrastructure of uroliths in Boer goats. Vet J 2010; 186: 7075.

  • 19. Mavangira V, Cornish JM, Angelos JA. Effect of ammonium chloride supplementation on urine pH and urinary fractional excretion of electrolyte in goats. J Am Vet Med Assoc 2010; 237: 12991304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Bartges JW, Osborne CA, Lulich JP, et al. Prevalence of cysteine and urate uroliths in bulldogs and urate uroliths in Dalmatians. J Am Vet Med Assoc 1994; 204: 19141918.

    • Search Google Scholar
    • Export Citation
  • 21. Bannasch D, Henthorn PS. Changing paradigms in diagnosis of inherited defects associated with urolithiasis. Vet Clin North Am Small Anim Pract 2009; 39: 111125.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Schmidt C, Vester U, Wagner CA, et al. Significant contribution of genomic rearrangement in SLCA1 and SLC7A9 to the etiology of cystinuria. Kidney Int 2003; 64: 15641572.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Lekcharoensuk C, Lulich JP, Osborne CA, et al. Patient and environmental factors associated with calcium oxalate urolithiasis in dogs. J Am Vet Med Assoc 2000; 217: 515519.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Lekcharoensuk C, Lulich JP, Osborne CA, et al. Association between dietary factors and calcium oxalate and magnesium ammonium phosphate urolithiasis in cats. J Am Med Assoc 2001; 219: 12281237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Osborne CA, Polzin DJ, Abdullahi SU, et al. Struvite urolithiasis in animals and man: formation, detection, and dissolution. In: Cornelius CE, Simpson CF, eds. Advances in veterinary science and comparative medicine. Vol 29. New York: Academic Press, 1985;2733.

    • Search Google Scholar
    • Export Citation
  • 26. Dyce KM. Sack WO, Wensing CJG. The pelvis and reproductive organs of male ruminants. In: Textbook of veterinary anatomy. 3rd ed. Philadelphia: Saunders, 2002;713722.

    • Search Google Scholar
    • Export Citation
  • 27. Kumar R, Kumar A, Singh H, et al. Effect of castration on urethral and accessory sex glands in goats. Indian Vet J 1982; 59: 304308.

    • Search Google Scholar
    • Export Citation
  • 28. Osborne CA, Lulich JP, Polzin DJ, et al. Medical dissolution and prevention of canine urolithiasis. Vet Clin North Am Small Anim Pract 1999; 29: 73111.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Franti CE, Ling GV, Ruby AL, et al. Urolithiasis in dogs V: regional comparisons of breed, age, sex, anatomic location, and mineral type of calculus. Am J Vet Res 1999; 60: 2942.

    • Search Google Scholar
    • Export Citation
  • 30. Takemoto K. An epidemiological overview of canine and feline urolithiasis in Japan. J Jpn Assoc Vet Nephrol Urol 2010–2011; 3(1):3645.

    • Search Google Scholar
    • Export Citation
  • 31. Jackson OF. Springtime rise in the incidence of feline urolithiasis. Vet Rec 1974; 95: 540.

  • 32. Nottle MC. Renal calculi in apparently normal sheep. Aust Vet J 1982; 58: 256259.

  • 33. Sourcie JM, Coates RJ, McClellan W, et al. Relationship between geographic variability in kidney stones prevalence and risk factors for stones. Am J Epidemiol 1996; 143: 491495.

    • Search Google Scholar
    • Export Citation
  • 34. MacLeay JM. Urolithiasis. In: Smith BP, ed. Large animal internal medicine. 4th ed. St Louis: Mosby, 2008;9501958.

  • 35. McIntosh GH. Urolithiasis in animals. Aust Vet J 1978; 54: 267271.

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