Management
Quality of medical care and the level of owner commitment are two major determinants of treatment success. Treatment goals include slowing down the disease progression rate, while providing a good quality of life.
The former is achieved by feeding a designated diet, minimizing the pathophysiological consequences of the disease, and identifying and controlling known risk factors for rapid progression. Therapeutic targets should all be met even if clinical signs are absent.There is good evidence that feeding a “kidney diet” is associated with slower progression rate and lower frequency of uremic crises (Jacob et al. 2002; Ross et al. 2006). Diets specifically designed for animals with CKD are modified from typical maintenance diets in several ways, therefore, diets only lower in protein content, are not satisfactory. Clinicians are advised to spend the time explaining the importance of consuming an appropriate diet, as an educated client is more likely to follow therapeutic recommendations. Transition to a new diet should be made gradually and only when clinical signs are controlled. Dogs and cats are often presented for medical care during an acute exacerbation of the disease, when they are unwilling to consume their regular diet, and are therefore even less likely to consume a therapeutic diet. An attempt to transition the animal to a therapeutic diet before clinical signs are controlled is more likely to fail and end up in food aversion.
Decreased appetite and weight loss are likely the most pronounced clinical signs of animals with advanced CKD. When animals are reluctant to eat, owners often replace the therapeutic diet by a more palatable diet; however, the latter might exacerbate the clinical manifestation of the disease (i.e., worsening azotemia, hyperphosphatemia and acid-base disorders), and consequently promote disease progression.
When animals are reluctant to eat, owners often perceive quality of life as substantially deteriorated and might even elect euthanasia. In such instances, a variety of therapeutic diets, both dry and wet, should offered with concurrent use of medications such as anti-emetics (metoclopramide, maropitant, ondansetron), H2 blockers (e.g., famotidine), proton pump inhibitors (e.g., omeprazole) and appetite stimulants (e.g., mirtazapine), so the animal will continue consuming the appropriate amount of a therapeutic diet. When these interventions are no longer effective, the use of feeding tubes should be considered.Additional therapies are tailored for each patient according to the disease stage, the clinical signs and the presence and severity of secondary complications, such as hyperphosphatemia, hypertension, proteinuria, acid-based disorders, anemia, urinary tract infection, and dehydration. Each of these should be monitored regularly and treated until predetermined therapeutic goals have been achieved (IRIS-website, 2017). When all therapeutic targets are met, quality of life is likely to improve and progression rate is likely to be slower. In this chapter, only a brief description of the management of CKD patients is provided. For a more detailed discussion, the reader is referred elsewhere (Polzin 2010).
Phosphorous control is achieved by prescribing a phosphorous restricted kidney diet and phosphorous binders, which should be mixed with food. The most common phosphorous binders are aluminum and calcium based. Lanthanum-based binders and Sevelamer are being used more frequently, but are also more costly. Recommended therapeutic goals are to maintain phosphorus concentration < 4.5 mg/dL in CKD stage II, < 5.0 mg/dL in stage III, and < 6.0 mg/dL in stage IV, but the accompanying risk of developing hypercalcemia or aluminum accumulation should not be overlooked.
Hypertension is another common complication of CKD and has been shown to be (directly or indirectly) associated with higher progression rates (Jacob et al.
2003; Syme et al. 2006). Thus, blood pressure should be monitored and controlled in any animal with CKD, but treatment should be initiated only when hypertension is documented persistently or when it is concurrent to documented damage to one of the end organs (e.g., eye). The most commonly used drugs to control systemic hypertension are angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers, and calcium channel blockers (e.g., amlodipine) with the goal of reducing systemic blood pressure to < 150/95 mmHg.Renal proteinuria is more common in dogs compared to cats but is associated with progression of CKD in both species (Jacob et al. 2003; Syme et al. 2006). Renal proteinuria is managed using a low protein diet, omega 3 supplementation, ACEi, thromboxane inhibitors, angiotensin receptor blockers (e.g., telmisartan), and when indicated, immunosuppressant agents (Segev et al. 2013).
Metabolic acidosis is common in late Stage III and Stage IV CKD. The decision to institute alkalinization therapy is mostly based on serum pH and bicarbonate concentration. Treatment consists of sodium bicarbonate or potassium citrate administration.
Anemia is another sequel of advanced CKD, resulting from erythropoietin deficiency, blood loss (mostly to the gastrointestinal tract), reduced red blood cell lifespan, bone marrow toxicity, and nutritional (e.g., iron) deficiencies. Prior to erythropoietin treatment initiation, the clinician must be convinced that the main cause of anemia is erythropoietin deficiency. Premature treatment might result in antibody production and worsening of the anemia. When indicated (based on hematocrit level and presence of clinical signs), erythropoietin is administered together with iron supplementation.
Urinary tract infections (UTI) should be monitored on a regular basis to prevent pyelonephritis and acute exacerbation of CKD, as often UTIs are clinically silent and may not be diagnosed until they progressed to pyelonephritis and further decrease in kidney function.
UTI should be treated based on culture and sensitivity results until clinical signs resolve and culture results are negative.Subcutaneous (SQ) fluid administration is used to prevent dehydration. Although some veterinarians routinely administer SQ fluids to all CKD patients, it should not be considered as risk free. Adverse effects include sodium loading, overhydration, hypertension and an undesired interaction between owners and pets. Therefore, judicious amounts of SQ fluids should only be offered to patients with a risk of (or documented) dehydration. Cats, and animals with advanced CKD, appear to be more susceptible to chronic dehydration.
Managing Advanced CKD Patients
With further progression, clinical signs worsen and can no longer be controlled using conventional medical management. Some animals, however, (e.g., with congenital kidney disease) are more adapted or resilient than others to the consequences of uremia, and can therefore be managed successfully even when the disease is very advanced.
When clinical signs cannot be controlled using conventional management, owners might elect euthanasia or one of several other options, some of which might not be readily feasible. The first and most practical option is placing a feeding tube. The importance and utility of feeding tubes in animals with advanced CKD cannot be overemphasized. When the disease is very advanced, animals are not likely to consume enough food of the appropriate type. At this point owners also need to provide a myriad of medications to control clinical signs and clinicopathologic abnormalities. Placement of feeding tubes (esophagostomy or gastrostomy tubes) overcomes most of these obstacles. Feeding tubes are used to provide the amount of calories required (and not less importantly, of the appropriate diet), and to administer almost all the medication, some of which are being directly mixed with the food. Lastly, feeding tubes enable fluid administration in a more physiologic way, avoiding the undesired sodium load that is associated with SQ fluid administration, and the negative interaction between the owner and the pet.
Unfortunately, many owners perceive an animal being fed with a feeding tube as having a poor quality of life, but the reality is that many CKD patients managed with a feeding tube have an excellent quality of life. When animals are being fed the appropriate type and amount of diet, and receive all the required medications and fluids, clinical signs often subside and consequently animals might even begin to re-consume the appropriate diet voluntarily. Nonetheless, before considering this option, owners need to be committed to this highly demanding type of care, as feeding 3-4 times a day (20-30 minutes each time) is required.Chronic dialysis is performed successfully in dogs and cats and might provide an excellent quality of life for patients with advanced CKD that can no longer be medically managed. However, realistically speaking,
this is not applicable for most owners due to financial constrains. Chronic dialysis is not only a financial commitment, but also a time commitment as the animal has to be presented for treatment twice or thrice weekly (for a whole day procedure), and the treatment does not replace the need for intense medical management. Nonetheless, if owners are willing to accept this commitment, animals can be successfully maintained on chronic dialysis even for years.
Kidney transplantation is another therapeutic intervention for animals with advanced CKD, but might be cost prohibitive. Kidney transplantation has been performed in both dogs and cats, but is substantially more successful in the latter. The perioperative mortality rate among cats undergoing kidney transplantation is 10-20%, with an additional 10-20% mortality during the 6 postoperative months due to various complications (Adin et al. 2001; Schmiedt et al. 2008). Nevertheless, those that survive may have an excellent quality of life for years with an overall 3-year survival rate of40-50% (Adin et al. 2001; Schmiedt et al. 2008). In dogs, mortality rates are higher. In one study 15 and 100 days survival probability was 50% and 36%, respectively (Hopper et al. 2012).