Chronic kidney disease is a common condition in geriatric cats and an important cause of illness and death in this species.1 The mean age of affected cats ranges from 9 to 12 years depending on the population examined, and the prevalence of the disease increases with age.2 Chronic kidney disease is a degenerative condition that often results from chronic tubulointerstitial nephritis of unknown etiopathogenesis.3 The IRIS has developed guidelines for staging of CKD on the basis of blood creatinine concentration.4 Staging has allowed for determination of disease severity and for treatment strategies to be implemented according to the stage of disease.3,4 The general goals of treatment are to slow the progressive loss of kidney function by addressing underlying or concurrent disease processes, improve clinical and biochemical consequences of CKD, and maintain adequate nutrition.5 However, few studies have described risk factors for the development and progression of CKD in cats.6
In a large cross-sectional analysis, CKD was found to affect approximately 13% of people in the United States, and prevalence of the disease from 1999 to 2004 was higher than it was from 1988 to 19947 Urolithiasis and, more specifically, nephrolithiasis, are recognized as risks factors for CKD in human patients. Patients with CKD were found to have 1.9 times the odds of a previous diagnosis of urolithiasis as were matched control patients without CKD,8 and a history of nephrolithiasis was found to be associated with an increased risk of CKD and end-stage renal failure in people.9
Theories have been proposed to explain the formation of uroliths in cats, and various risk factors for the development of urolithiasis have been proposed.10–13 Calcium oxalate and struvite uroliths are most commonly identified in cats.11 To the authors' knowledge, an association between CKD and urolithiasis in cats has not previously been established.
The veterinary literature regarding risk factors associated with the development and progression of CKD in cats is sparse. The purpose of the study reported here was to investigate whether an association exists between urolithiasis and CKD in cats. We hypothesized that there would be a positive association between urolithiasis and CKD in the feline population evaluated.
Materials and Methods
Case selection
Electronic and hard-copy medical records of the Faculté de Médecine Vétérinaire of the Université de Montréal were searched to identify cats that were admitted to the hospital between June 1, 2006, and July 31, 2013, and underwent abdominal or urinary tract ultrasonography. Affected cats (the urolithiasis group) included patients that had urolithiasis identified by ultrasonography and for which serum creatinine concentration and USG data were obtained within 14 days before or after the hospital visit. These cats were identified by a keyword search of ultrasonographic reports for the terms nephrolith, ureterolith, urolith, stone, pelvis, kidney disease, nephropathy, nephritis, vesical, and sand. Still ultrasound images were reviewed by a board-certified radiologist (KA) to verify the findings prior to study inclusion. The control group included cats that had no evidence of urolithiasis on ultrasonographic examination and for which serum creatinine concentration and USG data were obtained within 14 days before or after the examination. Control cats were randomly selected by use of a random numbers generator. Cats were excluded from the study group and the control group if there was evidence of a urinary tract obstruction, if a urinary catheter was present, or if renal mineralization was identified or could not be distinguished from nephrolithiasis. Each cat was included in the study only once. The first ultrasonographic evaluation was used for cats that underwent multiple ultrasonographic examinations during their hospital visit or during the study period; similarly, the first laboratory data (serum creatinine concentration and USG) obtained were used.
Medical records review
For each cat enrolled in the study, data extracted from the medical record included the date of evaluation, signalment, body weight, serum creatinine concentration, and USG as measured by refractometry For the urolithiasis group, the location and number of uroliths were recorded. The uroliths were classified according to location as nephroliths, ureteroliths, cystoliths, or urethroliths. When nephroliths or ureteroliths were present, they were further characterized as being unilateral or bilateral. Nephroliths were also characterized by location as follows: within the diverticula, within the renal pelvis, or both. Uroliths were also described as being single or multiple.
For cats in each group, the presence of CKD was determined on the basis of the IRIS guidelines.4 A serum creatinine concentration ≥ 140 μmol/L and a USG < 1.035 g/L were considered to confirm a diagnosis of CKD, and cats with CKD were categorized by stages from 2 to 4 according to serum creatinine concentrations (stage 2, 140 to 250 μmol/L; stage 3, 251 to 440 μmol/L; and stage 4, ≥ 440 μmol/L).4 The IRIS substages (proteinuria, hypertension) were not evaluated.
Diagnostic imaging
Ultrasonography of the abdomen or of the urinary tract specifically was performed by various board-certi-fied radiologists and radiology residents. Ultrasonography equipmenta,b was used with a 5- to 8-MHz microconvex or 7- to 12-MHz or 7- to 18-MHz linear transducer. Patients were positioned in dorsal recumbency for the examination, and acoustic gel was used on skin clipped of hair. For study purposes, mineralization was denned as a moderately hyperechoic, linear interface that could be nonuniform with only mild acoustic shadowing; it followed the normal renal architecture, such as the margins of the renal pelvis and diverticula. Within the renal diverticula, mineralization was considered present when a pattern of 2 parallel lines was identified (Figure 1). Nephroliths were defined as a strongly hyperechoic, curved interface suggesting a measurable space-occupying structure that displaced the surrounding renal tissue or protruded into the renal pelvis. A prominent acoustic shadow was associated with nephroliths (Figure 2).
Representative ultrasonographic image of the right kidney (sagittal view) in a cat depicting findings considered to indicate mineralization (arrowhead). For study purposes, mineralization was identified by presence of a moderately hyperechoic, linear interface that could be nonuniform with only mild acoustic shadowing. It followed the normal renal architecture (eg, the margins of the renal pelvis and diverticula). Within the renal diverticula, mineralization was considered present when a pattern of 2 parallel lines was identified.
Citation: Journal of the American Veterinary Medical Association 250, 7; 10.2460/javma.250.7.770
Representative ultrasonographic image of a kidney (transverse view) in a cat with nephrolithiasis. Nephroliths were identified by a strongly hyperechoic, curved interface, suggesting a measurable space-occupying structure that displaced the surrounding renal tissue or protruded into the renal pelvis. A prominent acoustic shadow was associated with nephroliths.
Citation: Journal of the American Veterinary Medical Association 250, 7; 10.2460/javma.250.7.770
Statistical analysis
Normality of the data was assessed with the Anderson-Darling test, and deviations from normality were found to be slight or nonsignificant. A Student t test was used to determine whether mean age or mean weight differed between cats in the urolithiasis and control groups. The exact χ2 test was used to test for associations between group and categorical variables including sex, breed, presence of renal disease, renal disease stage, and presence of urolithiasis. The association between CKD and presence of uroliths was then evaluated for each anatomic location individually by use of the exact χ2 test. This test was also used to determine the association between CKD and the number of uroliths (single vs multiple). Statistical analysis was performed with commercially available computer-based statistical software.c Values of P < 0.05 were considered significant.
Results
Fifty-nine cats (33 males, 25 females, and 1 with sex unrecorded) were included in the urolithiasis group. Forty-eight were domestic shorthair or domestic longhair cats, and 11 were purebred (Siamese [n = 3], Himalayan [3], Persian [2], Pixie-Bob [1], Birman [1], and Bengal [1]). The mean ± SD age of cats with urolithiasis was 8.3 ± 3.8 years (range, 0.4 to 18.0 years), and mean ± SD body weight was 4.5 ± 1.5 kg (9.9 ± 3.3 lb; range, 2.3 to 9.3 kg [5.1 to 20.5 lb]). Sixty-seven cats (39 males and 28 females) were included in the control group (group numbers were unequal because some cats tentatively included in the urolithiasis group were subsequently excluded on review of the records). Forty-five were domestic shorthair or domestic longhair cats, and 22 were purebred (Himalayan [n = 5], Persian [4], Siamese [3], Abyssinian [2], Bengal [2], Balinese [1], Tonkinese [1], Cornish Rex [1], Pixie-Bob [1], Bombay [1], and Birman [1]). The mean ± SD age of control cats was 8.7 ± 4.7 years (range, 1.0 to 18.0 years), and mean ± SD body weight was 4.5 ± 1.5 kg (9.9 ± 3.3 lb; range, 2.1 to 8.1 kg [4.6 to 17.8 lb]). There was no significant difference in age (P = 0.65) or weight (P = 0.95) between groups. There was also no significant heterogeneity between groups for sex (P = 1.0) or breed (P = 0.10).
CKD
The prevalence of CKD was significantly (P = 0.003) higher in the urolithiasis group (33/59 [56%]) than in the control group (20/67 [30%]). Of the 33 cats with CKD in the urolithiasis group, 11 (33%) had stage 2, 10 (30%) had stage 3, and 12 (36%) had stage 4 disease. Of the 20 cats with CKD in the control group, 9 (45%), 8 (40%), and 3 (15%) had stage 2, stage 3, and stage 4 disease, respectively. There was no significant (P = 0.27) association between the presence of urolithiasis and the stage of CKD.
Urolithiasis
Among the 59 cats with urolithiasis, nephroliths were identified in 39 (66%), cystoliths in 30 (51%), urethroliths in 5 (8%), and ureteroliths in 2 (3%). Twenty-five of 39, 12 of 30, 3 of 5, and 2 of 2 cats with nephroliths, cystoliths, urethroliths, and ureteroliths, respectively, had a diagnosis of CKD. Evaluation of cats with urolithiasis identified no significant association between CKD and the presence of nephroliths (P = 0.1), ureteroliths (P = 0.5), or urethroliths (P = 1); however, there was a significant (P = 0.02) negative association between CKD and presence of cystoliths.
Sixteen of the 59 (27%) cats with urolithiasis had uroliths present in multiple parts of the urinary tract, and 8 of 16 had a diagnosis of CKD. Of the 16 cats with urolithiasis in multiple parts of the urinary tract, 11 had both nephroliths and cystoliths, 3 had cystoliths with urethroliths, 1 had nephroliths with ureteroliths, and 1 had a combination of nephroliths, ureteroliths, and cystoliths. The prevalence of CKD when uroliths were present in a single location (25/43 [58%]) did not differ from the prevalence of CKD when uroliths were present in multiple locations in the urinary tract (8/16 [50%]; P = 0.77).
For the 39 cats with nephroliths, the stones were present in the renal pelvises of 19 (49%), the diverticula of 9 (23%), and both locations in 11 (28%) cats that had the condition. Fifteen of 19, 3 of 9, and 7 of 11 cats with nephroliths present in the renal pelvises, diverticula, or both locations, respectively, had a diagnosis of CKD. There was no association between the prevalence of CKD and the location of nephroliths within the kidney (P = 0.07). Nephroliths were unilateral in 18 of 39 (46%) and bilateral in 21 of 39 (54%) cats. Of the 2 cats with ureteroliths, 1 was affected unilaterally and 1 was affected bilaterally.
Discussion
The present study found a positive association between CKD and urolithiasis in a population of hospitalized cats evaluated during a 7-year study period. The prevalence of CKD among feline patients with urolithiasis (33/59 [56%]) was significantly (P = 0.003) higher than that of patients without urolithiasis (20/67 [30%]). A similar association has been found in human patients.8 A positive association has also been identified between nephrolithiasis and CKD, and the presence of nephroliths has been identified as a risk factor for the development of kidney disease in people.14,15 Results of 1 study14 also suggested that patients with nephroliths may warrant more aggressive screening for subclinical CKD and that aggressive medical treatment to prevent recurrent nephroliths may decrease the risk of CKD in human patients. Our study did not identify a significant association between the presence of nephroliths and CKD in cats. Moreover, the present study was not designed to assess causality, and the results do not suggest that urolithiasis is a risk factor for the development and progression of CKD or vice versa. However, the positive association between urolithiasis and CKD in our study suggests that feline patients with urolithiasis should be evaluated for CKD.
When cats with urolithiasis were evaluated according to the anatomic site of uroliths, our results revealed a significant negative association between CKD and the presence of cystoliths. To the authors’ knowledge, this association has not previously been identified in the veterinary or human literature. The design of the present study did not allow for conclusions to be drawn regarding the clinical relevance of this association. However, it may reflect a difference between the local environments of the kidneys and the bladder, and we speculate that the factors driving the formation of urolithiasis in these 2 areas of the urinary tract may differ.
The prevalence of CKD in the urolithiasis and control groups of the present study was much higher than previously reported. It has been estimated that CKD develops in 1% to 3% of the general feline population and 30% of cats > 15 years of age.16 In our study, CKD was diagnosed on the basis of serum creatinine concentration and USG. There were several limitations to our study, mostly owing to its retrospective nature. The study population, which consisted of cats admitted to a teaching hospital and included only those that underwent diagnostic ultrasonography, likely did not reflect the more general population of cats. Moreover, the reasons for evaluation, the hydration status of each patient, and whether patients had received fluid therapy prior to collection of blood and urine samples could not be retrieved from the medical records, and this could have biased our results.
Our results indicated that sex, age, and breed did not differ between the urolithiasis and control groups; however, a larger sample size could have allowed for better representation of some breeds or the creation of larger subgroups on the basis of urolith location, thus increasing the power to detect differences if they existed. The inclusion and exclusion criteria were also limitations; specifically, the presence of mineralization as an exclusion factor decreased the number of cats in the urolithiasis group by nearly half. Although the ultrasonographic appearance of renal mineralization has been described in the literature,17 it can be difficult to differentiate from nephroliths, particularly on still images. For this reason, we developed definitions to differentiate between these 2 entities. In several instances, it remained impossible to differentiate nephroliths from mineralization. It is unknown whether there is an association between nephroliths and renal mineralization and what role these variables may have in relationship to CKD or other disease processes. In the absence of more information regarding renal mineralization, it was designated as an exclusion criterion in our study to rule out potential bias. The combination of ultrasonography and radiography has been shown to allow optimal diagnosis of nephrolithiasis, and their combined use may have allowed better differentiation between nephrolithiasis and renal mineralization.18 The use of both forms of diagnostic imaging may have allowed for the identification of a greater number of patients with urolithiasis than were found by use of ultrasonography as a single modality, and this also represented a limitation of the study.
Calcium oxalate and struvite uroliths are the most commonly identified uroliths in cats.11 Feline struvite urolithiasis is most often sterile and is associated with metabolic factors, including urine concentration, pH, and excess consumption or excretion of calculogenic minerals.19 Calcium oxalate uroliths are the most common type of feline nephroliths and ureteroliths and are also commonly found in the lower urinary tract.20 These have been associated with dietary factors, including a decreased magnesium content and an increased acid content, and have also been associated with breed, age, and sex.21 Metabolic disorders such as hypercalcemia leading to hypercalciuresis and metabolic acidosis have also been proposed as risk factors for calcium oxalate urolithiasis.20,21 Nephrolithiasis and ureterolithiasis can potentially cause intermittent obstruction, which could lead to nephron damage and the development of CKD. Alternatively, urolith formation could result from underlying CKD, leading to abnormal handling of certain minerals and metabolites.
Although the present study identified a positive association between urolithiasis and CKD in cats, it remains unknown whether urolithiasis is a predictive factor for, or a consequence of, CKD. Further prospective studies are necessary to identify specific risk factors for urolithiasis formation and for the development and progression of CKD in cats and to better understand the association between these conditions.
Acknowledgments
No funding or support was received in connection with this study or the writing or the publication of this manuscript. The authors declare that there were no conflicts of interest.
Presented in abstract form at the American College of Veterinary Internal Medicine Forum, Nashville, Tenn, June 2014.
ABBREVIATIONS
| CKD | Chronic kidney disease |
| IRIS | International Renal Interest Society |
| USG | Urine specific gravity |
Footnote
ATL HDI 5000, Advanced Technology Laboratories Inc, Bothell, Wash.
Toshiba Aplio 4000, Toshiba Medical Systems, Zoetermeer, The Netherlands.
SAS, version 9.3, SAS Institute Inc, Cary, NC.
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