Chronic kidney disease (CKD) is a very common condition in middle aged to older cats in which kidney function gradually decreases over a period of time. It is a progressive disease that eventually leads to kidney failure, and in fact the condition was once named chronic renal failure (CRF). This nomenclature was somewhat confusing and was therefore changed. Therefore, any literature that refers to either CRF or CKD are in fact describing the same condition.
CKD is a gradual, progressive disease that is staged from 1 through 4. Stage 1 disease is usually diagnosed when some signs of compromised kidney function are present, but the body is still compensating well. For example, a cat that has started to drink and urinate more and has mild hypertension but normal blood work may be in stage 1 CKD. Stage 1 cats are rarely treated medically, but they are monitored closely for signs of progression. On the opposite extreme, stage 4 cats are those that are no longer compensating well and they are showing severe illness. Unfortunately, there is no cure for CKD. It is not possible to reverse kidney damage, and CKD must be regarded as a progressive disease. The good news is that there are multiple treatment approaches that can slow the progression and alleviate some of the clinical signs associated with CKD. An early diagnosis of CKD (stage 1 or 2) provides an opportunity to start management early.
Medical management of CKD may begin at stage 1 if the patient is not drinking well enough to stay hydrated. Patients that are well hydrated usually do not need to begin treatment until stage 2, which is when the blood work is no longer normal. The goals of medical management are to ameliorate clinical signs of uremia, minimize disturbances associated with electrolyte and mineral imbalances, support nutrition, and modify progression of disease. The overall goal is to increase the quality of life for pets and potentially give them more time with their families.
The purpose of this paper is to highlight some of the common management approaches and shed light on the reasons that they may be instituted. Certainly, each patient is unique and not all treatment options are appropriate in every case. It would be uncommon to institute all of the options listed in a single patient.
Adequate hydration is critical to maintain renal blood flow and glomerular filtration rate (GFR). As CKD progresses, especially in stages 3 or 4, dehydration is a common complication that decreases urine output and worsens uremia. While it is well proven that intravenous therapy (with diuretics) is helpful, this method of delivery is not practical for home care. Long term hospitalization defeats the purpose of overall goal of improving quality of life, so fluid delivery at home is usually preferred. Subcutaneous delivery of subcutaneous fluids is often considered a reasonable alternative, and anecdotal evidence suggests that this is a worthwhile option. Due to the absence of controlled studies examining subcutaneous fluid therapy in CKD patients, it is unknown if it truly slows the progression of CKD. However, it is generally accepted that prevention of dehydration should be attempted in spite of the lack of controlled studies with this delivery method.
Calcitriol is the active form of vitamin D3 metabolite, and the normal kidney is primarily responsible for its production. As CKD progresses, the amount of calcitriol in the body is decreased, which leads to a complicated cycle of consequences. Calcitriol is an inhibitor of parathyroid hormone (PTH) by negative feedback, and is also needed for calcium absorption in the gut. PTH stimulates calcitriol production as well as phosphate excretion from the kidney. Unfortunately, compromised kidney function means reduced calcitriol production as well as a decreased ability to clear phosphorous, so phosphorous tends to be retained in spite of the extra PTH. Increased phosphorous further stimulates PTH release in order to keep trying to make calcitriol and clear phosphorous, but the kidney is unable to keep up. Worse yet, PTH itself acts as a toxin and makes the patient feel sick. The further this cycle goes on, the worse it gets. It becomes a vicious cycle.
The physiology is extremely complicated. The bottom line, however, is that CKD patients often develop secondary hyperparathyroidism and hyperphosphatemia. Theoretically, calcitriol supplementation should decrease secondary hyperparathyroidism and prevent some of the above effects. Of course, excess calcitriol would also be detrimental in such a complex system so treatment must be carefully monitored. Unfortunately, the evidence for the benefit of calcitriol therapy is limited.
As described above, hyperphosphatemia is a very common complication in CKD patients. In the early stages, the kidneys' gradual impaired ability to clear phosphorous is masked by a slight increase in PTH, which stimulates more phosphorous excretion. This compensatory mechanism works well for a while, but eventually enters the vicous cycle when the kidney can no longer compensate adequately.
Phosphorous binders should decrease the amount of phosphorous that is absorbed in the gut. The goal is to make phosphorous in the food unavailable for absorption while not interfering with the absorption of needed nutritional components. This option may be offered in cases where the patient will not eat a reduced phosphorous renal diet or when the phosphorous and PTH levels are in excess in spite of a renal diet.
Hypertension is a well known side effect of CKD. Uncontrolled hypertension leads to "end organ damage" such as blindness, neurologic disorders, and heart disease, but also causes increased pressure on the kidney and may damage the delicate glomeruli. Hypertension is associated with advancement of CKD and protein losses in the urine.
Amlodipine is currently the drug of choice for most patients with systemic hypertension and is often very effective given alone. In some cases, additional treatment with ACE inhibitors such as benazepril may be offered if amlodipine alone is insufficient. The biggest challenge with treating blood pressure in the feline patient is getting an accurate reading of blood pressure to begin with. However, an experienced veterinarian will take all of the variables into consideration and look at trends and changes in the individual.
As mentioned above, ACE inhibitors are sometimes added to amlodipine treatment to control systemic hypertension. ACE inhibitors are not usually sufficient to control systemic hypertension alone. However, ACE inhibitors alone may be renoprotective. Research in rodents suggests that treatment lowers glomerular capillary pressure and glomerular size. The ACE inhibitor benazepril has been licensed for use in cats with CKD and seems to be effective at decreasing proteinuria.
Erythropoietic Hormone (EPO) is produced in the kidney and is needed to produce red blood cells in the bone marrow. Patients in advanced CKD (stage 3 or greater) commonly develop anemia due to a decreased ability to make new blood cells. There is a human recombinant EPO that has been shown to be effective in cats. However, this treatment is considered a last resort because cats sometimes have severe immune reactions to it. In a worst case scenario, a patient may develop antibodies to the EPO that is given that cross react and cause them to also attack their own. Due to the severity of this possible complication, EPO therapy is only used when it is absolutely necessary. The risks of EPO treatment may be lessened in the future when, hopefully, a feline EPO product will be available.
Moderate to severe hypokalemia is a common finding in cats with CKD, although it is unclear if this is initially a cause or effect of progression of disease. Regardless, the evidence shows that persistent hypokalemia and acidosis leads to a self-perpetuating cycle of declining renal function and it is well accepted that potassium supplementation is beneficial. As such, renal diets contain added potassium.
Metabolic acidosis is a common complication in cats with CKD, in part due to uremia. In some cases, sodium bicarbonate or potassium citrate may be offered once acid base imbalances are detected. While it makes sense to immediately address acidosis with alkalinization therapy for immediate relief, this therapy is often not well tolerated by the patient especially since it must be given multiple times per day. Many patients do better with a diet with increased buffering capacity. Patients with severe acidosis may be admitted to the hospital for intravenous treatment in the short term and then controlled with renal diets.
Renal diets have been prescribed for over 50 years in veterinary patients with CKD and have been proven, time and time again, to decrease uremic episodes and reduce premature mortality. The strongest evidence is in patients at stage 2 or above. The composition of renal diets includes decreased protein, phosphorous, and sodium. Additionally, they contain added buffers, soluble fiber, B-complex vitamins, antioxidants, potassium, and omega-3 fatty acids. The biggest challenge reported by cat guardians is that renal diets are notoriously less palatable than traditional diets. However, most cats will accept at least one brand of renal diet if it is introduced gradually. For those that do not, supplementing with alkalinizing agents, potassium, antioxidants, vitamins, and omega-3 fatty acids is certainly possible. Additionally, phosphorous binders may be beneficial as described above. Another alternative is to feed a published, well described home-made renal diet. This option requires great commitment on the part of the guardian and it is critical that the home-made diet is formulated carefully and with proper guidance from a nutritionist. When prepared correctly, however, this is sometimes a great solution for owners that want the benefit of a renal diet and a cat that will not eat the commercially available prescription foods.