Trends in the Frequency of Calcium Oxalate Uroliths in the Upper Urinary Tract of Cats
Medical records from cats diagnosed with uroliths at nine United States veterinary teaching hospitals from 1980 to 1999, and records of cats with uroliths submitted for analyses to the Minnesota Urolith Center from 1981 to 2000, were evaluated. A 10-fold increase in frequency of upper tract uroliths occurred in cats during the 20-year interval at the nine veterinary teaching hospitals. Calcium oxalate emerged as the predominant mineral type in upper tract uroliths, having increased more than 50-fold during the study period. These results emphasize the need for increased awareness of the occurrence of upper urinary tract uroliths in cats.
Introduction
The Minnesota Urolith Center has analyzed uroliths from cats for more than two decades. Over this time, calcium oxalate (CaOx) has surpassed struvite as the most common mineral within uroliths. Whereas 78% of all the uroliths submitted in 1981 were primarily composed of struvite and 1% were composed of calcium oxalate, during the year 2000, 54% of all the uroliths were composed primarily of CaOx and 35% were composed of struvite.12 Recent information supports the impression that the frequency of CaOx uroliths affecting the upper urinary tract of cats has also been increasing.34 Clinical experience at the University of Minnesota Veterinary Teaching Hospital (UM-VTH) agrees with this impression. From 1980 to 1989, the hospital proportional morbidity rate (defined here as the frequency with which a disease is diagnosed in a veterinary teaching hospital) of upper tract uroliths at the UM-VTH was 19 cases per 10,000 cats. From 1990 to 1999, the hospital proportional morbidity rate for upper tract uroliths increased to 68 cases per 10,000 cats. With the objective of further evaluating this trend, an epidemiological study was designed to test two hypotheses. One hypothesis was that during the past two decades, there was an increase in the yearly hospital proportional morbidity rate of uroliths in the feline upper urinary tract. The other hypothesis was that during this time interval, the frequency of CaOx urolith occurrence in the upper urinary tract increased.
Materials and Methods
Study Populations
Because ureteral uroliths originate in the kidneys, relevant information about nephroliths and ureteroliths was combined and categorized as upper urinary tract uroliths. Because urethral calculi originate primarily from the urinary bladder, relevant information about cystoliths and urethral calculi was combined and categorized as lower urinary tract uroliths.
Information was retrieved from two databases. One database consisted of information retrieved from medical records of cats evaluated at Veterinary Teaching Hospitals (VTHs) in the United States between 1980 and 1999 and compiled by the Purdue Veterinary Medical Data Base (VMDB). Some colleges of veterinary medicine did not continuously contribute data to the VMDB from 1980 to 1999. Only those records from nine VTHs (i.e., Michigan State University, University of Minnesota, Iowa State University, Purdue University, University of Georgia, University of Illinois, Colorado State University, Auburn University, and Texas A&M University) that submitted data continuously during this time period were reviewed.
Cats evaluated at each VTH were counted only once; data related to readmissions were excluded. Codes from the Purdue VMDB lista were used to identify cats with nephroliths, ureteroliths, or both, and cats with cystoliths, urethral calculi, or both. Cats with uroliths retrieved from both the upper and lower urinary tract were grouped separately (i.e., into a third category). These cats were counted only once; data related to readmissions were excluded. Because of the retrospective nature of this study, it was not possible to determine the extent of the diagnostic evaluations performed on each cat. The Purdue VMDB did not distinguish between uroliths of different mineral composition; therefore, a diagnosis of nephrolith, ureterolith, and cystolith in this study encompassed all types of minerals. The yearly occurrence of upper tract uroliths identified at necropsy at nine VTHs from 1980 to 1999 and submitted to the Purdue VMDB was also evaluated.
The second database included records of cats with uroliths submitted for quantitative analyses to the Minnesota Urolith Center between 1981 and 2000. This database included urolith submissions from the nine VTHs described in the first data set. Uroliths were analyzed by means of optical crystallography, infrared spectroscopy, or X-ray diffraction. A urolith without a nidus or shell that contained ≥70% of one mineral was identified by that mineral. Uroliths retrieved from kidneys, ureters, or both were classified as upper tract uroliths. Lower tract uroliths included uroliths retrieved from the urinary bladder, urethra, or voided urine. Uroliths retrieved from both the upper and lower urinary tract were grouped separately (i.e., into a third category).
Statistical Analysis
The yearly hospital proportional morbidity rate of nephroliths or ureteroliths per 10,000 cats from the Purdue VMDB was calculated by dividing the number of cats diagnosed (with upper tract uroliths) during each year (x 10,000) by the total number of first-visit cats seen during each year. A linear regression (regress y on x; y = the yearly morbidity rate, x = years) method was used to test whether the yearly hospital proportional morbidity rate of nephroliths and/or ureteroliths at the nine VTHs increased from 1980 to 1999.5 In addition, data from necropsied cats with nephroliths and/or ureteroliths from the nine VTHs were also evaluated in the same manner.
Assumption of normality (tested by Wilks-Shapiro statistic), linearity (tested by plotting residuals versus fitted values), and constant variance (tested by analysis of residuals) for the yearly submission rates and the yearly morbidity rates were evaluated.6 A linear regression (regress y on x; y = the yearly submission rates, x = years) method was used to determine whether the yearly submission rate of all mineral types of upper tract uroliths (e.g., nephroliths or ureteroliths) from the Minnesota Urolith Center increased (slope of years >0) from 1981 to 2000.5
The test of parallelism of two regression lines was used to assess whether or not the Minnesota Urolith Center’s yearly submission rates of CaOx uroliths affecting the upper urinary tract from 1981 to 2000 were increasing at a faster rate than the CaOx uroliths affecting the lower urinary tract (i.e., slope of the yearly submission rates of upper tract CaOx uroliths was greater than the slope of the yearly submission rates of lower tract CaOx uroliths).7 Statistical analyses were performed using a commercial software program.b Values of P<0.05 were considered significant.
Results
Data From the Purdue Veterinary Medical Data Base
From 1980 to 1999, 390,318 feline records were retrieved. After censoring records of multiple admissions for a single animal, records of 163,999 cats remained. Of nine VTHs that continuously submitted data to the VMDB from 1980 to 1999, the mean hospital proportional morbidity rate for nephroliths or ureteroliths (i.e., upper tract uroliths) was 22 cases per 10,000 cats. The mean morbidity rate for uroliths retrieved from both the upper and lower urinary tract was six cases per 10,000 cats. In contrast, the mean morbidity rate for cystoliths and/or urethral calculi (i.e., lower tract uroliths) was 70 cases per 10,000 cats. When nephroliths or ureteroliths were grouped by year [Table 1], a significant increase in morbidity (slope = 2.7; 95% confidence interval [CI] = 2.2 to 3.2) was observed [Figure 1]. In 1980, the hospital proportional morbidity rate of cats with upper tract uroliths was three cases per 10,000 cats. By 1999, the morbidity rate of cats with upper tract uroliths was 35 cases per 10,000 cats.
From 1980 to 1999, 9402 necropsies were performed on cats at these nine VTHs. Upper tract uroliths were diagnosed in an average of six cases per 1000 necropsies. However, when upper tract uroliths identified at necropsy were grouped by year [Table 2], a significant increase over time was observed (slope = 0.62; 95% CI = 0.25 to 0.98) [Figure 2]. For example, in 1980, the necropsy rate of cats with upper tract uroliths was three cases per 1000 necropsies, whereas by 1998, the rate was 18 cases per 1000 necropsies.
Data From the Minnesota Urolith Center
Records from a total of 32,969 urolith assays were evaluated. Uroliths from the upper urinary tract were identified in 864 (2.6%) cases. Uroliths from only the lower urinary tract were identified in 31,851 (96.6%) cases. Uroliths from both the upper and lower urinary tract were identified in 254 (0.8%) of the cases.
Over the 20-year study period, upper tract uroliths represented approximately 2% to 4% (mean standard deviation [SD], 3.5±1.9) of each year’s total urolith submissions [Table 3]. Evaluation of the yearly submission rates of all mineral types of upper tract uroliths did not reveal a significant time-related increase (slope = −0.10; 95% CI = −0.24 to 0.04) [Figure 3]. Likewise, when this 20-year period was divided into two intervals (1981 to 1990 and 1991 to 2000), a significant increase in the percentage of all upper tract uroliths was not observed. From 1981 to 1990, the yearly totals of upper tract uroliths comprised approximately 4% (mean ± SD, 4.0±2.4) of each year’s total urolith submissions, and from 1991 to 2000, they represented approximately 3% (mean ± SD, 2.9 ±1.1) of each year’s total urolith submissions.
Of 864 upper tract uroliths, CaOx was the major component in 564 (65%) cases. Of 31,281 lower tract uroliths, CaOx was the major component in 15,459 (49%) cases. The yearly percentage of upper tract CaOx uroliths increased significantly (slope = 4.2; 95% CI = 3.2 to 5.1; R2 = 0.81) [Figure 4] from 0% in 1981 to 30% in 1990, and to 75% in 2000 [Table 4]. The yearly percentage of lower tract CaOx uroliths increased (slope = 3.3; 95% CI = 2.7 to 4.0; R2 = 0.84) [Figure 4] from 1.5% in 1981 to 53% in 2000 [Table 4]. The slope of the trend line depicting the yearly frequency of submissions of CaOx uroliths from the upper urinary tract was not significantly different from the slope of the trend line depicting the yearly frequency of submissions of CaOx uroliths from the lower urinary tract. In both the upper and lower urinary tracts, the number of CaOx uroliths increased approximately 3% to 4% per year.
Discussion
Until the 1990s, the prevailing opinion was that uroliths uncommonly affected the upper urinary tract of cats.8–12 Furthermore, the occurrence of CaOx nephroliths was considered to be rare. However, results of the study reported here indicated a 10-fold increase in the frequency of upper tract uroliths in cats evaluated at nine VTHs in the United States during the 20-year study period. Surprisingly, a corresponding increase in the percentage of upper tract uroliths submitted to the Minnesota Urolith Center was not observed during the same time interval. This difference was likely related, at least in part, to the fact that many upper tract uroliths (especially small nephroliths) diagnosed by radiography or ultrasonography were not removed surgically.13–15 In addition, the majority of uroliths received at the Minnesota Urolith Center were submitted by colleagues in private practice. It is probable that proportional morbidity rates of upper tract uroliths are higher at VTHs than in private practices, because cats with upper tract uroliths were more likely to be referred to specialists for diagnostic evaluations and/or surgery.
Results of this study indicated that CaOx is currently the predominant mineral type in upper tract uroliths submitted to the Minnesota Urolith Center. The frequency of CaOx uroliths increased more than 50-fold since 1981. Although the mineral types of upper tract uroliths were not specified in information compiled by the Purdue VMDB, the combined results derived from the Purdue VMBD and the Minnesota Urolith Center supported the hypothesis that the yearly percentage of upper tract CaOx uroliths of cats increased substantially during the 20-year study period. It should be noted that in the study reported here, the hospital proportional morbidity rate of upper tract uroliths represented the percentage of cats with nephroliths admitted to nine VTHs that submitted appropriate data to the Purdue VMDB continuously over a 20-year period. This morbidity rate may not have reflected the morbidity rate of upper tract uroliths diagnosed in private practice or the true incidence of upper tract uroliths in the general population of cats.
This study was not designed to identify factors associated with the increased occurrence of CaOx in upper tract uroliths. However, results of epidemiological studies indicate that some dietary factors (e.g., urine acidifying potential, magnesium restriction, moisture reduction) may increase the risk for CaOx uroliths in cats.1617 Other factors such as age, sex, reproductive status, breed, and environment may also be involved.1618 Nutritional and environmental factors have also been incriminated in the dramatic increase of CaOx upper tract uroliths observed in humans during the 20th century.1920
Upper urinary tract uroliths should be suspected in cats with clinical signs related to the kidneys (e.g., intrarenal azotemia, abdominal pain, renomegaly) and in cats with hematuria not associated with signs of lower urinary tract disease (e.g., dysuria, pollakiuria, urinating outside the litterbox). At the UM-VTH, nephroliths have been unexpectedly detected by survey radiography in 83 of 189 cats with naturally occurring chronic renal failure and intrarenal azotemia.c Results of this study also emphasize the need to use caution when considering use of modified diets to dissolve nephroliths. Although protocols have been developed that are effective in dissolving feline sterile struvite uroliths, in the year 2002 only 9.4% of the upper tract uroliths submitted to the Minnesota Urolith Center were composed primarily of struvite.21
Conclusion
The frequency of detection of upper tract uroliths has significantly increased during the past 2 decades. Diagnosticians should increase their index of suspicion of upper urinary tract uroliths in cats, especially those with chronic renal failure.
Purdue Veterinary Medical Data Base, 1248 Lynn Hall, Purdue University, West Lafayette, IN 47906. Nephrolith is coded “722061500” and “710061500;” ureterolith is coded “723061500” and “723034324;” cystolith is coded “730061500,” “730061504,” and “730061505;” and urethral calculus is coded “740061500” and “740061505.”
PROC GLM; SAS Institute, Cary, NC 27513-2414
Unpublished data from ongoing clinical study of chronic renal failure in cats; 2000 to 2003.
Acknowledgment
The authors gratefully acknowledge the assistance of Yun Shen, Veterinary Medical Data Base, Purdue University, West Lafayette, Indiana.
Citation: Journal of the American Animal Hospital Association 41, 1; 10.5326/0410039
Citation: Journal of the American Animal Hospital Association 41, 1; 10.5326/0410039
Citation: Journal of the American Animal Hospital Association 41, 1; 10.5326/0410039
Citation: Journal of the American Animal Hospital Association 41, 1; 10.5326/0410039
Trend line (solid line) and the hospital morbidity rates per 10,000 cats (black bars) of all mineral types of upper urinary tract uroliths diagnosed at nine veterinary teaching hospitals from 1980 to 1999.
Trend line (solid line) and the yearly rates of cats per 1000 cats necropsied (black bars) diagnosed with upper tract uroliths upon necropsy at nine veterinary teaching hospitals from 1980 to 1999.
Trend line (solid line) and frequency of all types of upper tract uroliths as a percentage of the total number of uroliths (black bars) submitted to the Minnesota Urolith Center from 1981 to 2000.
Trend lines and frequency of upper and lower calcium oxalate (CaOx) uroliths submitted to the Minnesota Urolith Center from 1981 to 2000. Upper CaOx uroliths (black bars) are expressed as a percentage of total upper tract uroliths. Lower tract CaOx uroliths (gray bars) are expressed as a percentage of total lower tract uroliths. The solid line represents trend of upper tract CaOx uroliths. The interrupted line represents trend of lower tract CaOx uroliths.
Contributor Notes
