Persistent proteinuria accompanied by inactive urine sediment is an important diagnostic and prognostic biomarker in dogs and cats with chronic kidney disease (CKD). The urine protein-to-creatinine (UPC) ratio is an important part of the International Renal Interest Society (IRIS) guidelines for staging CKD in dogs and cats. Dogs and cats with a UPC ratio < 0.2 are classified as non-proteinuric; cats with a UPC ratio > 0.4 are considered proteinuric. Those cats with UPC ratios between 0.2 and 0.4 are considered borderline proteinuric. The higher the UPC ratio in a CKD patient with inactive urine sediment, the bigger the risk of progression of CKD, and the poorer the prognosis. Various types of proteins may be present in urine, including albumin, the most common protein found in urine, globulin, Bence-Jones proteins, and many others.
In this evaluation study of 43 client-owned cats, 5 ml of urine was collected as a midstream catch via manual compression of the urinary bladder and then an additional 5 ml of urine was collected via ultrasound-guided cystocentesis. Manual compression was selected as the method to collect a voided urine sample, as collection of a midstream urine catch from a spontaneously voiding cat is usually logistically difficult. Animals likely to have postrenal proteinuria based on the presence of lower urinary tract or genital disease, or a finding of active urine sediment, as well as those in which manual compression of the urinary bladder was difficult, were excluded from the study. Prerenal proteinuria in the cats was considered unlikely based on the results of hematologic and biochemical panels, and absence of hemoglobinuria and myoglobinuria. Patients included in the studies were 34 domestic shorthairs and 9 Persians; 18 were males and 25 were females. Of the 40 cats for which age information was available, the age range was 6 months to 17 years (mean 7.26 years).
Cystocentesis is the most common method of obtaining urine for a UPC ratio, but it may carry some risks or be contraindicated, as in patients with coagulopathy. Previous studies have demonstrated that UPC ratios for voided urine samples in both healthy cats and those with proteinuria correlate well with 24-hour protein excretion determination (the gold standard for determining persistent proteinuria in humans), also in voided urine samples. In healthy cats, the UPC ratios found in urine collected by cystocentesis also correlate with daily protein excretion determined in voided urine samples. Although studies have been performed in dogs confirming that UPC ratios obtained from urine samples collected via cystocentesis are comparable with those obtained from voided urine samples, similar studies have not been performed in cats.
The cats enrolled in the study were either healthy cats requiring a urinanalysis during standard pre-operative screening, or cats with disease requiring urinanalysis as part of their diagnostic plan. For all 43 enrolled cats, the UPC ratios varied from 0.02 to 6.99 for samples collected via cystocentesis; for samples collected via manual compression, the UPC ratios varied from 0.03 to 7.03. Nineteen of the cats were non-proteinuric (UPC ratio < 0.02); 7 were borderline proteinuric (UPC ratio 0.2-0.4), and 17 were proteinuric (UPC ratio > 0.4). In 40 of the cats the UPC ratios for samples obtained by the two methods differed by less than < 0.1; in the other 3 patients, there were differences of 0.13, 0.14, and 1.04. In all patients the UPC ratios for both the cystocentesis samples and the voided samples obtained by manual compression resulted in classification in the same IRIS substage.
The authors point out that manual compression of the urinary bladder to obtain a urine sample is also not without risk, and may result in bladder wall trauma or rupture, or ureteral reflux. This is particularly true in males. None of the cats who were ultimately enrolled in the study suffered any complications from manual expression of the urinary bladder. Most of the cats excluded from the study due to difficulty in manually expressing the urinary bladder were males.
The urine dipstick test is commonly used clinically for detection of proteinuria. These researchers found that the results of this test on the cats enrolled in the study correlated poorly with the UPC ratio, and that the urine dipstick test is neither sensitive nor specific in identifying proteinuria in cats.
Mild iatrogenic hematuria is common in urine samples obtained by cystocentesis. In dogs, the UPC ratio is only significantly influenced by hematuria when the urine is macroscopically bloody (pink or red urine). These researchers share their opinion that this is likely also true for cats, and they state that presence of only low-grade microscopic hematuria should not contraindicate the determination of the UPC ratio. While cystocentesis is still the preferred method for collecting urine for UPC determination, collection of a midstream voided sample is a reliable alternative for obtaining this test. [PJS]
Lyon SD, Sanderson MW, et al. Comparison of urine dipstick, sulfosalicylic acid, urine protein-to-creatinine ratio, and species-specific ELISA methods for detection of albumin in urine samples of cats and dogs. J Am Vet Med Assoc. 2010;236:874-79.