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.
Many different terms have been used to describe renal disease and decreased renal function. Unfortunately, these terms can
be confusing due to lack of standard definition and application. For example, there are no uniform definitions for terms like
"early renal disease," "renal insufficiency," or "end-stage renal disease." Recently, a staging system for CKD was proposed
by the International Renal Interest Society (IRIS). This group consists of approximately 20 independent veterinary nephrologists
from ten countries with the mission of helping practitioners better diagnose, understand, and treat canine and feline renal
disease. The following system was developed by the IRIS Board in order to improve communications surrounding CKD and link
appropriate diagnostic and therapeutic efforts to patients with varying stages of CKD. This staging system has been adopted
(after input and modification) by both the American and European Societies of Veterinary Nephrology and Urology (see Table 1).
Table 1 Stages of Chronic Kidney Disease (CKD)
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.