Staging and management of canine chronic kidney disease
Chronic kidney disease (CKD) occurs over a period of months to years and is a leading cause of morbidity and mortality in dogs. Nephron damage associated with CKD is usually irreversible and can be progressive. Whether the underlying disease primarily affects glomeruli, tubules, interstitial tissue, or renal vasculature, irreversible damage to any portion of the nephron renders the entire nephron nonfunctional. The histologic appearance of CKD caused by different primary diseases is often similar since the healing of irreversibly damaged nephrons occurs by replacement fibrosis. It is usually not possible to improve renal function in CKD; therefore, treatment is aimed at stabilizing renal function. Increasing evidence indicates that dietary and antihypertensive/antiproteinuric treatments can decrease the progressive nature of canine CKD.
The pathophysiology of CKD can be considered at both the organ and systemic level. At the level of the kidney, the primary pathology of CKD is loss of nephrons and decreased glomerular filtration. Reduced glomerular filtration results in increased plasma concentrations of substances that are normally eliminated from the body by renal excretion. In addition to excretion of metabolic wastes and maintenance of fluid and electrolyte balance, the kidneys also function as endocrine organs and catabolize several peptide hormones. Therefore, hormonal disturbances also play a role in the pathogenesis of CKD. For example, decreased production of erythropoietin contributes to the nonregenerative anemia of CKD and decreased metabolism and excretion of parathyroid hormone and gastrin contribute to osteodystrophy and gastritis, respectively. Finally, part of the pathophysiology of CKD is brought about by compensatory mechanisms like the hyperparathyroidism that develops in an attempt to maintain normal plasma calcium and phosphorus concentrations. Similarly, the individual glomerular filtration rate of intact nephrons increases in CKD in an attempt to maintain adequate renal function; however, proteinuria and glomerulosclerosis may be consequences or trade-offs of this hyperfiltration.
Due to the interdependence of the vascular and tubular components of the nephron, the end point of irreversible glomerular or tubular damage is the same. Morphologic heterogeneity between nephrons exists in the chronically-diseased kidney with changes ranging from severe atrophy and fibrosis to marked hypertrophy. Progressive diseases that destroy nephrons at a slow rate allow intact nephrons to undergo compensatory hypertrophy, which can delay the onset of renal failure (persistent azotemia superimposed on the inability to concentrate urine). Therefore, when renal failure finally occurs, nephron hypertrophy can no longer maintain adequate renal function and usually < 20 percent of the original nephrons are functional. Renal diseases that have been associated with the development of CKD in dogs include glomerulonephritis, amyloidosis, tubulointerstitial disease, pyelonephritis, nephrolithiasis, leptospirosis and neoplasia.
This system uses serum creatinine concentrations as the major determinate for the four stages. Serum creatinine concentrations should always be interpreted in light of the patient's urine specific gravity, body condition score, and examination findings in order to rule out pre- and post-renal causes of azotemia. In addition, the staging system should only be applied to dogs with stable CKD since in other forms of renal disease (e.g., acute renal failure or acute decompensation of CKD) the plasma creatinine concentration can change significantly over a short period of time.
Management of CKD
Reduction of dietary phosphorus is one of the cornerstones of CKD management and can be accomplished by feeding specifically formulated diets for CKD. From a practical nutrition standpoint, dietary phosphorus reduction is combined with dietary protein reduction. If after three to four weeks of dietary phosphorus restriction serum phosphorus concentrations remain high, enteric phosphate-binding agents containing calcium, aluminum, sevelamer, or lanthanum should be administered with meals (initial dosage of 30 mg/kg body weight to achieve normophosphatemia). Physiologic dose replacement of vitamin D3 (calcitriol) is the third line of defense in the treatment of hyperphosphatemia and hyperparathyroidism and has been used successfully in dogs with CKD.
Treatment of patient symptoms becomes a higher priority in the later stages of CKD when the decreased renal function has a more pronounced effect on the patient's quality of life. In addition to phosphorus restriction and protein reduction, dietary management includes omega-3 fatty acid supplementation, salt reduction, and alkalinization—all of which are designed to reduce patient symptoms and slow disease progression. Acceptance of a renal diet is enhanced with early initiation (while the patient still has a good appetite) and gradual implementation. Vomiting and anorexia are common patient symptoms in dogs with later stage CKD and can often result in decreased caloric intake. 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, 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 one of the drugs of choice for vomiting associated with renal failure. H2-receptor blockers (e.g., famotidine or ranitidine) have been shown to effectively decrease gastric acid secretion, which may attenuate vomiting in dogs 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 feeding tube (esophagostomy or gastrostomy tube) will often facilitate the maintenance of caloric intake and hydration status. In many stage III and IV dogs without feeding tubes, fluid therapy with polyionic solutions, given intravenously or subcutaneously in the hospital or subcutaneously by owners at home (10-50 ml/kg every one to three days), will help improve the patient's quality of life.
Dr. Grauer is professor and Jarvis chair of small animal internal medicine at Kansas State University in Manhattan, Kan. Dr. Grauer's expertise involves small animal urinary system diseases and disorders.