ANOREXIA AND WEIGHT LOSS IN A CAT: DAY 1

A 7-year-old female spayed domestic shorthaired cat was evaluated at the University of Minnesota Veterinary Teaching Hospital (UMVTH) because of partial anorexia and weight loss of several weeks' duration. According to the owners, the cat consumed plenty of water. They were unsure about urine volume; however, there was no evidence of pollakiuria or dysuria. Physical examination revealed mild dehydrated (~ 5% loss of bodyweight). Temperature, respiration, pulse rate, and systolic blood pressure were normal. Abdominal palpation revealed that the left kidney was reduced in size; the urinary bladder was normal.

Results of a serum chemistry profile revealed that the concentrations of creatinine (4.3 mg/dl) and SUN (60 mg/dl) were abnormal. Serum concentrations of phosphorus and calcium were normal. Results of a hemogram revealed values within the normal reference range (HCT = 36%; WBC = 6,300/µl). Analysis of a urine sample collected by cystocentesis prior to any form of therapy revealed aciduria (pH = 6.0) and hematuria. The specific gravity was inappropriately low (SG = 1.014) in the context of clinical dehydration. Crystals were not detected in the urine sediment. Aerobic culture of urine collected by cystocentesis did not result in growth of bacteria. Survey radiography of the abdomen revealed bilateral radiodense nephroliths; uroliths were not detected in the lower urinary tract. Ultrasonography revealed no evidence of urinary outflow obstruction associated with the nephroliths. The left kidney was reduced in size. A diagnosis of chronic azotemic polyuric renal failure associated with nephroliths was made. The owners were given a favorable short-term prognosis for response to treatment of the clinical manifestations of chronic renal failure (CRF).

ARE UPPER TRACT UROLITHS COMMONLY ASSOCIATED WITH RENAL FAILURE?

In cats, approximately 65% of the upper tract uroliths are composed of calcium oxalate CaOx, while less than ~5% are composed of struvite. During recent years, CaOx nephroliths have been encountered with sufficient frequency in cats with CRF to warrant radiography or ultrasonography as a standard component of evaluation. The etiologic interrelationship of CRF and CaOx nephroliths is not known, but risks for both disorders may be linked to hypercalciuria and acidosis.

HOW WOULD YOU TREAT THE RENAL FAILURE?

Our initial therapeutic plans consisted of correcting the dehydration with lactated Ringer's solution given subcutaneously. Supportive management of the renal failure consisted of recommendations to feed a canned nonacidifying renal failure diet with appropriate restrictions in protein, phosphorus, and sodium, and provision of adequate nonprotein calories to minimize catabolism of protein for energy.

HOW WOULD YOU MANAGE THE NEPHROLITHS?

Since composition of the nephroliths was likely to be CaOx, medical dissolution protocols were not considered. However, clinical experience has revealed that increases in size and number of CaOx nephroliths may be minimized with appropriate dietary therapy. Some modifications characteristic of canned renal-failure diets may also minimize some dietary risk factors associated with CaOx uroliths.

SHOULD A NEPHROLITHOTOMY BE CONSIDERED IN THIS CAT?

In cats with CRF and nephroliths, the potential benefit and risk associated with surgical removal of stones should be carefully evaluated. If the kidney(s) with nonobstructing nephroliths is likely to be contributing a significant component of remaining renal function (as was the situation with this cat), the substantial risk of further decline of renal function associated with nephrotomy may negate the potential benefit of surgery. In addition, sudden onset of a uremic crisis associated with outflow obstruction caused by movement of nephroliths into the ureters was deemed to be unlikely in this cat because the stones were too large to pass into the ureteral lumen(s). Therefore, a nephrotomy was not recommended.

The owners were encouraged to return in approximately 2 to 3 weeks for reevaluation of the status of renal function and the nephroliths. However, since the cat's quality of life as judged by the owners' was good, they did not return to the hospital for re-evaluation.

RECURRENCE OF CLINICAL SIGNS: DAY 242

The cat was evaluated 8 months later (Day 242) when the owners became concerned because she developed progressive depression and anorexia over a 2 to 3 day period. They indicated that over the past 2 months the cat was becoming progressively polydipsic and polyuric. However, there was no evidence of pollakiuria or dysuria. Physical examination revealed that the cat was slightly dehydrated (~ 6% loss of bodyweight). Temperature, respiration, pulse rate, and systolic blood pressure were normal. The left kidney was smaller than the right kidney; the urinary bladder was normal.

Results of a serum chemistry profile indicated an increase in the severity of azotemia (SUN = 126 mg/dl and serum creatinine = 8.3 mg/dl), hyperphosphatemia (9.6 mg/dl), and acidemia (TCO2 = 15.6 mEq/L). Results of a hemogram revealed immature neutrophilia (WBC = 19,600/µl) associated with leukocytosis and hypoproliferative anemia (HCT = 27%). Survey radiographs of the urinary tract revealed that the nephroliths were similar in size and number to those evaluated 6 months previously. Ultrasonography revealed no evidence of urinary outflow obstruction associated with the nephroliths.

Analysis of a pretreatment sample of urine collected by cystocentesis revealed that the urine specific gravity was inappropriately low (SG = 1.017) in the context of clinical dehydration. There was evidence of infectious inflammation. Crystals were not detected in the urine sediment.

Problems identified included: 1) primary chronic polyuric azotemic renal failure, 2) bilateral nephroliths, and 3) secondary bacterial urinary tract infection probably involving the kidneys.

WHY DID THIS CAT DEVELOP BACTERIAL UTI?

Since the urinary tract is inherently resistant to bacterial UTI, underlying abnormalities in one or more of this cat's host defenses against UTI was likely. Bacterial UTI can be a cause, or, as was likely in this patient, a consequence of renal failure. In a study of cats with renal failure evaluated at the UMVTH, approximately 20% had concomitant bacterial UTI. Abnormalities associated with renal failure that increase the risk for secondary bacterial UTI's include decreased urine concentration, altered urine composition, and impaired cellular and humoral immune responses. In addition, the nephroliths predisposed this patient to secondary bacterial UTI. Detection of abnormalities related to the structure and function of the kidneys, along with the absence of abnormalities related to the lower urinary tract, suggested that the infection in this cat primarily involved the kidneys.

WHAT IS YOUR PROGNOSIS?

The answer to this question is linked to localization of the azotemia. Did this cat have prerenal, primary renal, or postrenal azotemia? Our interpretation of this case was that the underlying causes of azotemia were multifactorial. In this patient, clinical signs of dehydration indicated that a component of the azotemia was prerenal in origin. The prognosis for correction of the prerenal component of the azotemia was good since it could be rapidly corrected by restoring vascular volume and intrarenal blood pressure with replacement fluids. This cat also clearly had chronic primary (or intrarenal) azotemia. Although the initiating cause of the CRF had not been identified at the time of initial evaluation (Day 1), structural and functional kidney changes in patients with CRF are typically progressive and irreversible. Did this indicate that the decline in the intrarenal component of the azotemia was irreversible? The answer is, not necessarily. In this cat, acute decompensation of CRF associated with the uremic crisis was likely related, at least in part, to a recent onset of secondary bacterial UTI (so-called "acute-on-chronic" renal failure). Eradication of the bacterial UTI by appropriate antimicrobic therapy selected on the basis of antimicrobial susceptibility tests had the potential to result in reduction in the intrarenal component of the azotemia, recompensation of the CRF, and substantial improvement in the cat's quality of life. Although the uremic crisis could also have been related to urine outflow obstruction caused by the nephroliths, this was considered to be unlikely based on evaluation of the upper urinary tract by ultrasonography.

HOW WOULD YOU MANAGE THE RENAL FAILURE?

Lactated Ringer's solution (LRS) was given intravenously to correct the dehydration and to restore renal perfusion. Because the owners did not want to hospitalize the patient, they were taught how to continue fluid therapy with LRS given subcutaneously at home. They were instructed to continue feeding the renal failure diet.

WHAT DRUG WOULD YOU SELECT TO MANAGE THE UTI?

Evaluation of the in vitro susceptibility of infecting bacteria to specific antimicrobial agents is the most reliable guide for choice of drugs because different bacterial pathogens isolated from cats with UTI vary widely in their susceptibility to various antimicrobics. Especially Pseudomonas aeruginosa and Klebsiella species, but also Enterobacter species, E. coli, and Proteus species are examples of urinary pathogens that may be associated with polyresistant strains.

Pending results of urine culture and susceptibility tests, initial therapy of the bacterial UTI consisted of parenterally administered ampicillin, followed by oral amoxicillin to be given by the owners at home. Because the serum half-life of amoxicillin is prolonged in patients with renal failure, the dosage interval was lengthened from twice per day to once per day. Reducing the frequency of administration of amoxicillin also enhanced owner and patient compliance with therapeutic recommendations. Results of aerobic bacterial culture of an aliquot of urine collected by cystocentesis on day 242 revealed significant in vitro growth of Escherichia coli that was sensitive to several antimicrobics including amoxicillin, enrofloxacin, trimethoprim-sulfonamide, chloramphenicol, and nitrofurantoin. Therefore, the owners were instructed to continue oral therapy with amoxicillin and to return to the hospital for re-evaluation of the patient in approximately five days.

MONITORING RESPONSE TO THERAPY: DAYS 247, 273, AND 395 HOW WOULD YOU MONITOR RESPONSE TO THERAPY?

Follow-up tests consisting of bacterial cultures of urine samples collected by cystocentesis three to 5 days after initiation of antibacterial therapy are desirable. Complete inhibition of bacterial growth in urine after initiation of therapy provides evidence of effectiveness of therapy. Although there may be viable bacteria in surrounding tissues, the urine should be sterile. Hematuria, pyuria, and proteinuria associated with compensatory inflammation may still be present even though the urine contains no viable microbes. Treatment is considered to be ineffective and relapse will likely occur if the bacterial colony count has only been reduced (for example, from 10⁵ colony forming units [CFU] per ml to 10² CFU/ml). In this situation, re-evaluate the therapeutic protocol, including the basis for selection and dosage of antimicrobic drugs and the likelihood of client compliance with treatment instructions.

A urine sample collected 5 days (Day 247) after initiation of amoxicillin therapy was bacteriologically sterile; the magnitude of the inflammatory response was substantially less. Likewise, the leukocytosis (WBC = 15,500 /µl), immature neutrophilia, and the magnitude of azotemia (SUN = 90 mg/dl, serum creatinine = 6.7 mg/dl) and hyperphosphatemia (5.9 mg/dl) were also reduced.

HOW LONG SHOULD THE PATIENT BE TREATED FOR BACTERIAL INFECTION OF THE KIDNEYS?

Since response to treatment of bacterial UTI varies from patient to patient, it is not possible to establish rigid generalities about the optimum duration of therapy. Duration of antimicrobial therapy should be individualized by monitoring each patient's response via serial evaluation of clinical and laboratory findings. For patients with upper UTI, therapy is usually continued for a minimum of 3 weeks. Deep-seated or severe renal infections may require more prolonged therapy. Re-evaluations of urinalyses and urine cultures within 7 to 10 days after discontinuation of therapy are recommended to detect recurrent UTIs (relapses or reinfections) at a subclinical stage. Ultimately duration of therapy for each patient should be based on persistent elimination of UTI as determined by urine culture in addition to amelioration of pyuria and clinical signs

The owners were instructed to continue amoxicillin therapy for an additional three weeks, to continue feeding the renal-failure diet indefinitely, and to give subcutaneous fluids as needed. Re-evaluation of the patient was scheduled three weeks later.

Re-evaluation of the patient one month (Day 273) after initiation of treatment of the bacterial UTI revealed that the magnitude of the azotemia had continued to decline (SUN = 77 mg/dl, serum creatinine = 5.1 mg/dl). Since there was no evidence of E. coli UTI, the owners were advised to discontinue therapy with amoxicillin. Follow-up evaluation of a urine sample collected by cystocentesis 10 days later revealed no evidence of bacteria or inflammation. Likewise, re-evaluation of the cat four months later (Day 395) revealed no evidence of recurrent UTI; the magnitude of renal dysfunction was stable (SUN = 67 mg/dl and serum creatinine = 5.0 mg/dl). There was no significant change in the size, number, or location of the nephroliths. The owners were advised to continue with dietary therapy and to give subcutaneous fluids as needed to minimize dehydration. Re-evaluation of the cat in two to three months was recommended.

REFERENCES

1.  Osborne CA, Stevens B. Treatment of bacterial urinary tract infections: Basic concepts and their applications. In, Urinalysis: A clinical guide to compassionate patient care. Bayer Corp, Shawnee Mission, Kansas, 1999.