Kidneys perform multiple excretory, regulatory, and biosynthetic functions including selective elimination of waste products of metabolism from the body, maintenance of fluid, acid-base and electrolyte homeostasis, and synthesis of a variety of hormones.  Kidney function adequate for homeostasis does not require that all nephrons be functional.  The concept that adequate kidney function is not synonymous with normal kidney function is of importance in understanding the difference between kidney disease and kidney failure, formulating meaningful prognoses and formulating therapy.  In the past, terms such as renal failure, renal insufficiency and renal disease have been used interchangeably.  Renal failure is organ failure in which nephron hypertrophy can no longer maintain adequate renal functions and <25% of original nephrons are functional.  Renal insufficiency implies kidney dysfunction, but at a level less than renal failure.

Staging of CKD:

In the past 5 years, it has become apparent that the traditional ways of classifying renal disease are not applicable to what we know today.  Thankfully, the International Renal Interest Society (IRIS) was formed in 1998 to address these concerns.  CKD is now classified in 4 stages which, along with the accompanying tables, help to improve communications surrounding CKD and link appropriate diagnostic and therapeutic efforts to patients with varying degrees of CKD.  There are 2 major rules:  Azotemia must be interpreted in a stable, hydrated patient, and this method is not to be used with acute or a chronic/acute situation (pre: dehydration, renal: ascending UTI, nephroliths, progression of renal disease, post: obstructive).  This means for classification, treat the presenting signs, repeat lab and then assess the category.

Table 1 IRIS Classification of Chronic Kidney Disease

*Serial creatinine must be evaluated knowing degree of hydration, body mass and urine specific gravity and diet.  BUN affected by many things so best used for therapeutic monitoring.  Evaluate UspG on a case/lab basis always asking is it appropriate for the problem presented.  Normal hydrated and muscled cats should have creatinine.

**Shows that many cats live very well with "controlled" CKD

++Not necessarily progressive at this stage

In addition to classifying based on creatinine levels, cats are evaluated on their degree of proteinuria and hypertension.  It has been determined in cats that earlier intervention assists with slowing renal disease progression and values necessary for cats are much lower than laboratory normal values.  Cats also have unique ways to verify urine protein and the standard SSA test used to confirm protein in dogs and humans is not reliable in cats.

Table 2 Proteinuria
 

* Needs to be consistent and repeatable.  If check every 2 weeks for 3 times and is still positive, proteinuria is a real finding.  Hemorrhage and inflammation need to be eliminated.  Does not need to be sterile.  Must have current urinalysis to be evaluated

** treatment needed

+  recheck every 3 months.

Table 3 Blood Pressure
 

*a normal patient should stabilize blood pressure within 5-10 minutes of "stress”

** latest reports suggesting 150 may be cutoff point for treatment for renal patients whereas 160 and above for most patients.  Target organ damage eyes, brain, heart, kidney can occur with higher levels for an extended time.

Clinical Signs and Diagnosis:  Clinical signs of CKD may not be present in early stages and when present in later stages, are usually nonspecific (lethargy, depression, gastroenteritis and dehydration).  Unique signs of CKD (vs. acute renal disease) include a history of weight loss and polydipsia-polyuria (pu/pd), poor body condition, nonregenerative anemia, small and irregular kidneys and renal secondary hyperparathyroidism.  The classic diagnosis of renal disease based on azotemia (persistent azotemia superimposed on the inability to concentrate urine) pertains to CKD stages late 2-4.  Stage 1 and early Stage 2 could be diagnosed in cats with persistent proteinuria, urine concentrating deficits, increases in s. creatinine over time, even if values remain in the normal range (i.e., s. creatinine that increases from 0.6-1.2 mg/dl could indicate a 50% reduction in GFR), or abnormal renal palpation or renal ultrasound findings.  Once characterized, management can be instituted which is most successful in the early stages of disease.

Management:  The therapeutic approach is tailored to fit the patient's stage of disease.  For example, treatment of stones and infections, combined with renoprotective measures such as diet changes are of the most value in early stages of CKD.  In the later stages of CKD, treatment tends to be focused on decreasing the patient's clinical signs associated with the decreased renal function.  Many of the treatments are designed to slow the fibrosis and scarring of the kidneys as well as to slow the onset of secondary signs such as tissue mineralization and anemia.  In addition, concurrent diseases such as inflammation, hyperthyroidism, diabetes and periodontal disease should be controlled to decrease load on kidneys.

Diet through reduction of phosphorus and protein intake is the cornerstone of management of CKD.  Studies have shown that diet not only allows the patient to live more comfortably with decreased renal function but may also significantly prolong survival.  It is important to keep in mind when feeding reduced protein diets, that the energy requirements of the body have a higher priority than does protein anabolism and therefore, if the available carbohydrates and fats are insufficient to meet caloric requirements, endogenous proteins will often be broken down as a source of energy.  This breakdown for energy increases the nitrogenous waste and exacerbates the clinical signs of kidney disease.

Ideally, cats with CKD should receive a minimum of 3.3-3.5 g protein/kg/day.  Twenty percent of the caloric intake should be high quality protein.  A good recommendation for dietary protein reduction is to feed the maximum amount of high biological value, highly digestible protein that the animal can tolerate at his/her level of renal function.  (Dietary protein reduction refers to decreased protein intake compared to normal protein intake.  Most commercial pet foods contain relatively high levels of protein.  Dietary protein should never be restricted, that is less than the patient's dietary requirements.)  A favorable response to therapy is a stable body weight and serum creatinine and albumin concentrations and decreasing BUN and phosphorus concentrations.  Moderate dietary protein reduction should be employed early in the course of renal failure and use of markedly reduced protein diets should be reserved for patients that are refractory to moderate dietary protein reduction.

Besides protein, phosphorus levels need to be managed to prevent secondary hyperparathyroidism which can lead to osteodystrophy, bone marrow suppression and soft tissue mineralization.  This soft tissue mineralization, if present in the kidney, markedly speeds up the progression of renal disease by increasing the rate of fibrosis.  Fortunately, renal diets have reduced levels of phosphorus and some cats benefit from the addition of phosphate binders as well.  Phosphate binders must be given with the meal and have a much greater efficacy rate if given with a renal diet.

Table 4: Acceptable phosphorus levels for stage of chronic renal disease**

**Increased levels are common in acute renal disease and will usually decrease once disease is controlled.

Vomiting and anorexia are common in CKD and can result in decreased caloric intake.  Causes include stimulation of chemoreceptor trigger zone (CTZ) by uremic toxins, decreased excretion of gastric and increased gastric acid production and gastrointestinal irritation secondary to uremia.  Fortunately, antiemetics and gi protectors work very well in cats and starting early tends to decrease rate of body mass loss.  If vomiting is controlled yet anorexia persists, feeding tubes are a great way to assist with maintenance of caloric intake and hydration status.  Additionally, try to avoid negative changes such as force feeding (vs. tube) and sudden diet changes.  Do not do negative reinforcement when feeding such as giving pills or subcutateous fluids.

Urinary tract infections are rare in healthy cats, but are more common in cats with CKD since the antibacterial properties of urine decline as urine concentration decreases.  Uroliths common in older cats can predispose to infection or trauma of the urinary tract and need to be monitored as indicated.

The nonregenerative anemia observed in cats with CKD occurs as a combination of decreased erythropoietin production, shortened red blood cell survival, gastrointestinal tract blood loss, and the effects of uremic toxins such as PTH on red cell production.  In addition, nutritional deficiencies (i.e. vitamins B6 and B12, niacin, and folic acid) and iron depletion can contribute to the anemia.  Multiple treatments have been tried with little success due to the cat's formation of antibodies to the compounds.  Until feline specific treatments become commercially available, human products (erythropoietin) should be reserved for those cats with weakness and lethargy attributable to their anemia.