Nephroliths and bacterial UTI in a cat with chronic renal failure

Anorexia and weight loss in a cat: Day 1

What is your diagnosis?

A 7-year-old female spayed domestic short-hair cat was evaluated at the University of Minnesota Veterinary Medical Center because of partial anorexia and weight loss of several weeks' duration. The cat had been recently adopted from owners who were informed that they were in violation of policies related to housing of animals. The new owners wanted an opinion as to the likelihood that the anorexia and weight loss were related to a change in living environment. According to them, the cat consumed plenty of water. They were unsure about urine volume; however, there was no evidence of pollakiuria or dysuria.

Physical examination revealed that the cat was mildly dehydrated (estimated to be 5 percent loss of body weight). Temperature (101 F), respirations, pulse rate and systolic blood pressure were normal. Abdominal palpation revealed that the left kidney was somewhat reduced in size; the urinary bladder was normal.

Table 1. Hematology and serum biochemical values

Results of a serum chemistry profile revealed that the concentrations of creatinine and SUN were abnormal (Table 1). Serum concentrations of phosphorus and calcium were normal. Results of a hemogram revealed values within the normal reference range (Table 1). Analysis of a urine sample collected by cystocentesis prior to any form of therapy revealed that the specific gravity was inappropriately low in the context of clinical dehydration. The urine was acid and contained evidence of hematuria (Table 2).

Crystals were not detected in the urine sediment. Aerobic culture of an aliquot of urine collected by cystocentesis did not result in growth of bacteria. Survey radiographs of the urinary tract revealed bilateral radiodense nephroliths; there was no evidence of uroliths 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 advised of the likelihood of a favorable short-term prognosis for response to treatment of the clinical manifestations of chronic renal failure.

What clinical signs are commonly associated with early renal failure in cats?

The frequency of occurrence of renal failure in cats substantially increases when they reach 7 to 8 years of age. However, early detection of chronic renal failure (CRF) is often difficult in cats because early premonitory signs [anorexia (80 percent), weight loss (72 percent), dehydration (70 percent), depression (68 percent), poor nutritional status (58 percent), and weakness (47 percent)] are nonlocalizing and therefore do not direct the clinician's attention to the urinary tract. Signs indicative of renal involvement, such as polyuria and polydipsia (40 percent) and abnormal kidney size (25 percent) occur less frequently. Therefore, appropriate tests of renal function, initially including urinalysis and serum creatinine concentration, should be routinely performed in older cats with the aforementioned non-localizing clinical signs.

Are upper tract uroliths commonly associated with renal failure?

In cats, approximately 65 percent of the upper-tract uroliths are composed of calcium oxalate, while less than 5 percent are composed of struvite. During recent years, calcium oxalate 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 calcium oxalate nephroliths is not known, but risks for both disorders may be linked, at least in part, to hypercalciuria and acidosis.

How would you treat this patient?

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 non-acidifying renal-failure diet with reduced quantities of phosphorus, sodium and high-quality protein, and adequate non-protein calories to minimize catabolism of protein for energy.

How would you manage the nephroliths?

Because the composition of the nephroliths was very unlikely to be struvite, medical dissolution protocols were not considered. Would you recommend that a nephrolithotomy be performed in this cat? In cats with CRF and nephroliths, the potential benefit and risk associated with surgical removal of the stones should be carefully evaluated. If the kidney(s) with non-obstructing nephroliths is likely 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 the 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. Clinical experience has revealed that increases in the size and number of many metabolic nephroliths may be minimized with appropriate dietary therapy. Some of the modifications characteristic of canned renal-failure diets may also minimize some dietary risk factors associated with calcium oxalate uroliths. However, the serum concentration of calcium should be monitored if renal failure diets with increased levels of vitamin D are fed.

The owners were encouraged to return in approximately two to three weeks for re-evaluation of the status of renal function and the nephroliths. But because the cat's quality of life as judged by the owners was good, they did not return to the hospital for re-evaluation at that time.

Recurrence of clinical signs: Day 242

What's your diagnosis?

The cat was evaluated eight months later (day 242) when the owners became concerned because she developed progressive depression and anorexia over a two- to three-day period. They indicated that during the past two 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 (estimated to be 6 percent loss of body weight). Temperature (101.5 F), respirations, 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, hyperphosphatemia and acidemia (i.e. reduction in the serum concentration of total carbon dioxide; Table 1). Results of a hemogram revealed immature neutrophilia associated with leukocytosis and non-regenerative anemia (Table 1). Survey radiographs of the urinary tract revealed that the nephroliths were similar in size and number to those evaluated six months previously. Ultrasonography revealed no evidence of urinary outflow obstruction associated with the nephroliths.

Table 2. Urinalysis and urine culture results

Analysis of a pretreatment sample of urine collected by cystocentesis revealed that the urine specific gravity was inappropriately low in the context of clinical dehydration. There was evidence of infectious inflammation (pyuria, hematuria, proteinuria and bacteriuria; Table 2). Crystals were not detected in the urine sediment.

Problems identified included:

1) primary chronic polyuric azotemic renal failure,

2) bilateral nephroliths,

3) secondary bacterial urinary tract infection probably involving the kidneys.

Why did this cat develop bacterial UTI?

Because the urinary tract is inherently resistant to bacterial urinary tract infection, underlying abnormalities in one or more of this cat's host defenses against UTI were 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 University of Minnesota Veterinary Teaching Hospital, approximately 20 percent had concomitant bacterial infections. Abnormalities associated with renal failure that increase the risk for secondary bacterial UTIs 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.

Can you localize the 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 primarily involved the kidneys. Localization of infection within the urinary tract should be considered because it might influence:

• the prognosis,

• the type, dosage and dose interval of antimicrobial agent selected,

• the duration of therapy.

What is your prognosis?

The answer to this question is linked to localization of the azotemia. Did this cat have pre-renal, primary renal or post-renal azotemia? Our interpretation of this case was that the underlying causes of azotemia were multifactorial. In this patient, clinical signs of dehydration were reliable evidence that a component of the azotemia was pre-renal in origin. The prognosis for correction of the pre-renal component of the azotemia was good because it could be corrected rapidly by restoring vascular volume and intrarenal blood pressure with replacement fluids.

Key Points

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 outflow obstruction of urine 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?

An appropriate quantity of lactated Ringer's solution 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 lactated Ringer's solution given subcutaneously at home.

What drug would you select to manage the UTI?

Pending results of urine culture and susceptibility tests, initial therapy of the bacterial UTI consisted of parenterally administered ampicillin, followed by oral amoxicillin. Subsequently, results of aerobic bacterial culture of an aliquot of urine collected by cystocentesis revealed significant in vitro growth of Escherichia coli (Table 2) that was sensitive to several antimicrobics including amoxicillin, enrofloxacin, trimethoprim-sulfonamide, chloramphenicol and nitrofurantoin.

What dose of antimicrobial agent would you recommend?

In general, dosages of antimicrobics and intervals between maintenance dosages should conform to the recommendations of the manufacturer. Whereas emphasis is placed on selecting drugs that attain high urine concentrations for treatment of lower UTI, selection of drugs likely to attain high serum concentrations is recommended for treatment of bacterial infections of the renal parenchyma. Why? Because concentrations of antimicrobics in the renal interstitial tissue are more likely to correspond to serum concentrations of antimicrobics than urine concentrations.

What effect could reduced renal function have on drug metabolism?

When treating patients with renal failure, the probable benefits of therapy should be considered in the context of probable risks. If the standard dose and dose interval of drugs dependent on the kidneys for elimination or metabolism are given to patients with reduced renal function, increased serum concentrations of these drugs might predispose the patient to adverse drug reactions. When therapy of renal failure patients with drugs dependent on renal excretion is essential, consider adjusting the dose or dose interval in context of the magnitude of renal dysfunction and potential toxicity of the drug. The goal is to maintain comparable serum (or plasma) concentrations of the drug known to be safe and effective in patients with normal renal function. The decision as to whether to alter the drug dose or the maintenance interval between doses should be based on the best balance of efficacy and potential toxicity. Because the serum half-life of amoxicillin is prolonged in patients with renal failure and because the efficacy of amoxicillin is dependent on the time the concentration of this drug remains above the minimum inhibitory concentration, the dose was reduced by 50 percent and given twice per day. [See the "Chronic Kidney Disease" chapter in the second volume, sixth edition of the textbook of Veterinary Internal Medicine (Elsevier Saunders) for further information about modification of drug doses and maintenance intervals in patients with renal failure].

How would you monitor response to therapy?

Follow-up bacterial culture of a urine sample collected by cystocentesis three to five days after initiation of antibacterial therapy was recommended because complete inhibition of bacterial growth in urine at that time provides evidence of effectiveness of therapy.

Although there might 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 only has 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 from the cat five days (day 247) after initiation of amoxicillin therapy was bacteriologically sterile; the magnitude of the inflammatory response was substantially less (Table 2). Likewise, the leukocytosis (Table 1), immature neutrophilia, and the magnitude of azotemia and hyperphosphatemia were also reduced.

Length of treatment

How long should the patient be treated for bacterial infection of the kidneys?

Because 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 three weeks. Deep-seated or severe renal infections may require more prolonged therapy. Re-evaluations of urinalyses and urine cultures within seven to 10 days after discontinuation of therapy are recommended to detect recurrent UTIs (relapses or re-infections) 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 one month (day 273) after initiation of treatment of the bacterial UTI revealed that the magnitude of the azotemia had continued to decline (Table 1). Because there was no evidence of E. coli UTI (Table 2), 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 (Table 2); the magnitude of renal dysfunction was stable (Table 1). 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 every two to three months was recommended.

Dr. Osborne, a diplomate of the American College of Veterinary Internal Medicine, is professor of medicine in the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota.