The prevalence of chronic kidney disease (CKD) among dogs and cats is unknown. Estimations range between 0.5–7% in dogs and up to 30% in geriatric cats. Chronic kidney disease is irreversible and progressive in nature even if the inciting cause can be eliminated. Due to the reduced number of nephrons, each remaining nephron is undergoing hypertrophy (and is becoming a “super nephron”), but this compensatory mechanism eventually leads to additional nephron loss.
The current terminology of the disease, as suggested by the International Renal Interest Society (IRIS), is “chronic kidney disease” and it is classified into four stages (see below) to guide therapeutic guidelines and predict the prognosis. Classification into the stage is determined by plasma creatinine concentration, but is done only when the animal is in steady state. The disease is further classified based on renal proteinuria and blood pressure. Both have been incorporated in the disease staging because there is solid evidence to suggest that proteinuria and hypertension influence the survival of dogs and cats with CKD. The degree of renal proteinuria is determined by the urine protein to creatinine (UPC) ratio. Blood pressure should be determined using appropriate technique and equipment, as stress and anxiety might dramatically influence the blood pressure (“white coat effect”).
The diagnosis of CKD is based on clinical signs, which are often nonspecific, and is confirmed by laboratory tests. Serum creatinine, symmetric dimethylarginine (SDMA), urea concentration, urine concentration ability, presence of proteinuria, imaging techniques, blood pressure, and kidney biopsy can all be used to diagnose and classify the disease. Early diagnosis is critical, as nephron loss is an irreversible process, thus early intervention slows down the disease progression, and delays onset of clinical signs.
Management of Chronic Kidney Disease
Treatment goals are to slow down the progression rate and to control the clinical signs and clinicopathologic abnormalities. These include polyuria and polydipsia, anorexia, vomiting, diarrhea, weight loss, anemia, bleeding, protein loss, hypertension, acid base and electrolytes imbalances. Management should be tailored to the specific patient according to its IRIS stage. While most of the clinical manifestations are expected when the animal is in CKD stage III or above, some of the complications (e.g., hypertension, proteinuria) might be present even in stage I CKD.
Nutritional management is a cornerstone in the management of CKD. Evidence suggests that consuming a therapeutic kidney diet is associated with lower number of uremic crises and decreased mortality rate compared to patients consuming maintenance diets. Yet, anorexia and weight loss are major factors that influence owners of dogs and cats with CKD to elect euthanasia, and thus many owners and veterinarians elect to feed free choice diets, despite the fact that the latter facilitate uremic crisis and progression. Thus, before offering a therapeutic kidney diet, clinical signs (especially gastrointestinal signs) must be controlled. A variety of commercial diets should be offered, and any transition to a kidney diet must be done gradually and only when clinical signs are controlled. Any attempt to transition a patient to a kidney diet when the animal is presented to the clinic for the first time, before clinical signs are controlled, is doomed for failure.
Hypertension is common in dogs and cats with CKD and is associated with rapid progression of the disease. When systemic hypertension is documented or suspected, the risk for end organ damage (i.e., kidney, heart, eye, brain) needs to be evaluated. Typically, hypertension is not considered an emergency unless it is extreme or when evidence for end organ damage is apparent. The most commonly used drugs to control hypertension are ACE inhibitors (ACEi) (e.g., enalapril, benazepril), angiotensin receptor blockade (ARBs) (e.g., telmisartan) and calcium channel blockers (e.g., amlodipine). Caution should be used not to administer ACEi to dehydrated animals, as glomerular filtration rate may drop precipitously if these drugs are introduced before the patient is adequately hydrated or in uremic crisis. In dogs, the IRIS recommendation is to combine ACEi and calcium channel blockers, but in cats calcium channel blockers are usually sufficient to control hypertension. The target blood pressure is systolic blood pressure < 160 mmHg.
When present, the initial goal is to identify the origin of the proteinuria and its cause, as anti-proteinuric therapies should be administered only to animals with renal proteinuria. Common causes (e.g., infectious, inflammatory, neoplastic processes) should be looked for and eliminated if possible. If the initial cause can neither be eliminated nor can be identified, the treatment is symptomatic. Kidney biopsy should be considered as a diagnostic aid to identify the underlying disease and presence of immune complexes. The treatment goals are to decrease the magnitude of proteinuria and to prevent complications that may be associated with it (e.g., edema, decreased antithrombin concentration leading to hypercoagulability). The treatment includes dietary modification, ACEi/ARBs, and immunosuppression, if the process is immune mediated. ACEi and ARBs decrease proteinuria by decreasing the resistance of the afferent glomerular arteriole, and consequently decrease the intraglomerular pressure. Thus, serum creatinine concentration should be monitored ~ 5 days following initiation of treatment to identify any decrease in GFR in a timely manner. Low dose aspirin has also been recommended if albumin concertation is < 2.0 g/dL. When histology supports presence of immune complexes, immunosuppression should be considered.
Hyperphosphatemia and Secondary hyperparathyroidism
Hyperphosphatemia and secondary hyperparathyroidism are inevitable consequences of CKD. Hyperphosphatemia and secondary hyperparathyroidism are controlled using phosphorus restricted diets and phosphorus binders. These drugs bind the phosphorus in the food, thus should not be administered without it. The most commonly used phosphate binders are aluminum based or calcium based. In stage I–III, phosphorous concentration needs to be maintained at the range of 2.7–4.6 mg/dL, and at stage III and IV < 5.0 mg/dL and < 6.0 mg/dL, respectively. Evidence suggests that judicious use of calcitriol (1.5–3.5 ng/kg), prolongs survival in dogs in stage III when phosphate is controlled and ionized calcium and PTH are monitored.
Anemia is evident mostly in animals in stage III CKD. There are many potential causes for anemia in patients with CKD, including decreased erythropoietin production, bleeding (mostly to the gastrointestinal tract) and bone marrow dysfunction. The timing for treatment initiation is determined by the severity of the anemia, the degree of clinical signs associated with it, and when the clinician is convinced that its origin is erythropoietin deficiency. In most animals anemia is treated when hematocrit is < 20%. The two common therapies include erythropoietin and blood transfusions. The latter are used mainly in crisis or when a rapid response in needed. The main complication of erythropoietin treatment is antibody production.
Metabolic acidosis is a common complication of CKD and is to be expected in late stage III and stage IV CKD. The diagnosis of metabolic acidosis is based on total venous CO2 or bicarbonate concentration. Treatment of metabolic acidosis is to be initiated when bicarbonate is < 18 mmol/L and includes administration of sodium bicarbonate or potassium citrate.
The main goal of subcutaneous fluid administration is to prevent dehydration. It is likely that patients that maintain hydration status by drinking enough water to compensate for their fluid losses do not benefit from subcutaneous fluids. Moreover, fluid administration should not be regarded is risk free. Potential side effects of subcutaneous fluids include hypernatremia and worsening preexisting hypertension, negative effect on the owner-pet interaction and decrease the patient quality of life. In animals that tend to get dehydrated (especially cats), subcutaneous fluid administration is beneficial and thus might be used on a regular basis. As the disease progresses, this treatment becomes more and more common both in dog and cats.