Chronic kidney disease (CKD) is a common problem that affects an estimated 0.5 to 7% of dogs and 1.6 to 20% of cats. Nephron damage associated with CKD is usually irreversible and can be progressive. Renal failure results when three-quarters or more of the nephrons of both kidneys are not functioning.
Chronic kidney disease (CKD) is a common problem that affects an estimated 0.5 to 7% of dogs and 1.6 to 20% of cats. Nephron damage associated with CKD is usually irreversible and can be progressive. Renal failure results when three-quarters or more of the nephrons of both kidneys are not functioning. Whether the underlying CKD primarily affects glomeruli, tubules, interstitial tissue, or renal vasculature, irreversible damage to any portion of the nephron renders the entire nephron nonfunctional. Healing of irreversibly damaged nephrons occurs by replacement fibrosis and therefore a specific etiology is often not determined. Chronic kidney disease occurs over a period of weeks, months, or years and is an important cause of death in dogs and cats. It is often not possible to improve renal function in CKD and therefore treatment is aimed at stabilizing renal function. Importantly, there is increasing evidence that dietary and anti-hypertensive/anti-proteinuric treatments (angiotensin-converting enzyme inhibitors [ACEI]) can decrease the progressive nature of CKD.
The following table was developed by International Renal Interest Society (IRIS) as guide to staging of canine and feline CKD. Importantly, this staging system should only be used in patients with stable CKD.
Serum creatinine concentrations must always be interpreted in light of the patient's urine specific gravity and examination findings in order to rule out pre- and post-renal causes of azotemia. The above stages are further classified by the presence or absence of proteinuria and systemic hypertension as follows:
Clinical signs of CKD may not be present in early stages and when present in later stages, are usually nonspecific (lethargy, depression, anorexia, gastroenteritis, and dehydration). Occasionally uremic breath and/or oral ulcers may be observed. Unique signs of CKD (vs. acute renal disease) include a history of weight loss and polydipsia-polyuria, poor body condition, nonregenerative anemia, small and irregular kidneys, and renal secondary hyperparathyroidism. The classic diagnosis of renal failure based on renal azotemia (persistent azotemia superimposed on the inability to concentrate urine) pertains to CKD stages II-IV. Stage I CKD (non-azotemic CKD) could be diagnosed in cats and dogs with persistent proteinuria or renal origin, urine concentrating deficits due to renal disease, increases in serum creatinine over time, even if the values remain in the normal range (e.g., serum creatinine that increases form 0.6 to 1.2 mg/dl could indicate a 50% reduction in GFR), or abnormal renal palpation or renal ultrasound findings.
In general, the diagnostic approach to patient once CKD has been identified and staged is focused on three areas: 1) characterization of the renal disease, 2) characterization of the stability of the renal disease and function, and 3) characterization of the patient's problems associated with the decreased renal function. Further definition of the renal disease (beyond a standard minimum data base) could include for example, quantitation of proteinuria, measurement of blood pressure, urine culture, kidney imaging, and possibly kidney biopsy. The stability of the renal function would be assessed by serial monitoring of abnormalities identified during the initial characterization of the renal disease. This monitoring should always include serum biochemistry profiles, urinalyses, quantitation of proteinuria, and measurement of blood pressure but may also include follow-up urine cultures and ultrasound examinations. Characterization of the renal disease and its stability is most important in the earlier stages of CKD when appropriate treatment has the greatest potential to improve or stabilize renal function. Characterization of patient problems becomes more important in the later stages of CKD when clinical signs tend to be more severe. In the later stages of CKD, diagnostic (and subsequent therapeutic) efforts should directed at assessing anorexia, vomiting, acidosis, potassium depletion, hypertension, anemia, etc.
Similar to the diagnostic approach to CKD, the therapeutic approach should also be tailored to fit the patient's stage of disease. For example, disease specific treatments for nephroliths and bacterial pyelonephritis as well as treatments designed to slow the progression of renal disease (so called renoprotective treatments) will be of most value in the earlier stages of CKD. Renoprotective treatments include dietary change designed to reduce serum phosphorus concentrations and angiotensin-converting enzyme inhibitors designed to normalize systemic and intraglomerular blood pressures and reduce proteinuria (see proceedings entitled "What's the big deal with proteinuria and hypertension in 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.
Reduction of dietary phosphorus and protein intake is the cornerstone of management of CKD. Dietary management may not only allow the animal to live more comfortably with decreased renal function but may also significantly prolong survival. Ideally, dietary protein reduction allows all essential amino acid requirements to be met without excesses. This is accomplished by feeding lowered quantities of high biological value protein and results in decreased need for renal clearance of urea and other nitrogenous metabolites. Renal diets also have reduced level of sodium and increased level of n-3 fatty acids and alkalinizing agents. 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. Catabolism of endogenous proteins for energy increases the nitrogenous waste the kidney must excrete and exacerbates the clinical signs of renal failure.
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 fed at a level 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 with decreasing serum urea nitrogen and phosphorus concentrations. Moderate dietary protein reduction should be employed early in the course of renal failure and use of more severely reduced protein diets should be reserved for patients that are refractory to moderate dietary protein reduction.
Management of the hyperphosphatemia that occurs in CKD is closely related to dietary protein reduction inasmuch as protein reduced diets are also phosphorus reduced. An increase in plasma phosphorus concentration occurs in CKD as a result of decreased renal excretion. Concurrently, decreased renal production of the active form of vitamin D3 decreases intestinal absorption of calcium which, in conjunction with impaired renal reabsorption of calcium, decreases plasma ionized calcium concentrations. Decreased vitamin D3 and serum calcium concentrations stimulate parathyroid hormone (PTH) secretion which facilitates renal excretion of phosphorus and increases serum calcium concentrations by increasing renal calcium reabsorption and calcium absorption from bones and the gastrointestinal tract. The "trade-offs" for this hyperparathyroidism, however, can be severe and include osteodystrophy, bone marrow suppression, and soft tissue mineralization. Soft tissue mineralization occurs predominately in damaged tissue and if mineralization occurs in renal tissue the result may be a progressive decline in renal function. If the product of the serum calcium and phosphorus concentrations is greater than 50-70 mg/dl, the patient is at risk for soft tissue mineralization. Studies in cats with remnant kidney CKD have shown that normal dietary phosphorus intake is associated with microscopic renal mineralization and fibrosis and these changes were prevented by reducing dietary phosphorus. Similarly in both cats and dogs with naturally occurring CKD, feeding a diet specifically formulated to meet the needs of cats with CKD, together with phosphate binding drugs if required, controls hyperphosphatemia and secondary renal hyperparathyroidism, and is associated with an increased survival time.
In addition to feeding a phosphorus-restricted diet, administration of enteric phosphate binders will help combat hyperphosphatemia. Enteric phosphate binders do not directly lower plasma phosphorus but bind phosphorus in the intestinal tract and prevent absorption. Enteric phosphate binders are generally ineffective if dietary phosphorus intake is not restricted. In many cases of canine CKD, low dosages of 1, 25-dihdroxycholecalciferol (calcitriol) have been associated with decreased PTH concentrations and decreased renal mortality. Conversely, preliminary studies in cats with CKD have not demonstrated a benefit to calcitriol treatment.
Decreased appetite, nausea, vomiting, and weight loss become more pronounced as CKD progresses and these symptoms are of major concern to most owners. Causes of vomiting and anorexia include: 1) stimulation of chemoreceptor trigger zone by uremic toxins, 2) decreased excretion of gastrin and increased gastric acid secretion (plasma gastrin concentrations in cats with chronic renal failure may be as high as 20 times the normal concentrations), and 3) gastrointestinal irritation secondary to uremia. Vomiting may be treated with metoclopramide, which blocks the chemoreceptor trigger zone. Metoclopramide also increases gastric motility and emptying without causing gastric acid secretion and is the drug of choice for vomiting associated with renal failure. H2 receptor blockers (famotidine and ranitidine) have been shown to effectively decrease gastric acid secretion, which may attenuate vomiting in cats with CKD. Oral ulcers, stomatitis, and glossitis may occur as a result of gastritis and vomiting or the effect of uremic toxins on mucosal membranes and will often also result in anorexia. If vomiting has been controlled but anorexia persists, placement of a gastrostomy tube (especially in cats) will often facilitate the maintenance of caloric intake and hydration status.
Urinary tract infections (UTI) are rare in healthy cats but are more common in cats with CKD since the antibacterial properties of urine decline as urine concentration decreases. The prevalence of UTI in dogs with CKD is also thought to be increased. In a study of cats with naturally-occurring CKD, 29% had occult UTI. Bacterial infection of the renal pelvis and parenchyma can then result from an ascending urinary tract infection. Initially the renal cortex is not affected; however with chronic pyelonephritis the entire kidney may become involved. Pyelonephritis can precipitate the development of renal calculi and conversely renal calculi can increase the risk of pyelonephritis. Calcium oxalate uroliths are the most common type of renoliths in older cats. Appropriate, long term antibiotic therapy may halt the renal damage associated with pyelonephritis, however if renoliths are present, antibiotic therapy alone is usually ineffective. Since calcium oxalate uroliths can not be dissolved, surgery is necessary for stone removal. Anesthesia and surgery however have the potential to further compromise renal function in the CKD cat.