Feline Chronic Kidney Disease

Chronic kidney disease (CKD) affects an estimated 1% to 3% of all cats.¹ This important cause of mortality in cats develops over a period of months or years. The associated nephron damage is progressive and irreversible even though some cats with CKD have stable serum creatinine concentrations for months to years.

Diagnosis of early CKD, followed by appropriate treatment, may result in improved survival. There is solid evidence that dietary treatments, and increasing evidence that antiproteinuric treatments, can slow the progression of CKD.

Profile

Prevalence of feline CKD increases with age; as many as 30% to 50% of cats older than 15 years of age have CKD.^2–4 Frequency of CKD in male and female cats is similar, but male cats are often diagnosed at a younger age than female cats.⁵ Certain breeds appear to be overrepresented, including Maine Coon, Abyssinian, Siamese, Burmese, and Russian blue.⁴

Etiology

The cause of feline CKD is usually difficult to determine. Due to the interdependence of the nephron’s vascular and tubular components, the end point of irreversible glomerular or tubular damage is the same: fibrous scar tissue replacement of nephrons (Figure 1).

FIGURE 1. Histopathologic image from a feline kidney with CKD. Note the fibrous scar tissue replacement (arrows); and mononuclear cell infiltrates.

Morphologic heterogeneity between nephrons exists in the chronically diseased kidney, with changes ranging from severe atrophy to marked hypertrophy. Histologic changes are not process specific and, therefore, an etiologic diagnosis is frequently not established. The most common histologic diagnosis is chronic tubulointerstitial nephritis.⁶

Renal diseases associated with development of feline CKD are listed in Table 1.⁶ Progressive diseases that slowly destroy nephrons allow intact nephrons to undergo compensatory hypertrophy, which can delay onset of renal failure. Therefore, when renal failure occurs (< 25% of the original nephrons functional), nephron hypertrophy can no longer maintain adequate renal function. For example, 80% nephron loss may result in a serum creatinine concentration of 2 mg/dL. With progression, serum creatinine concentration should be approximately 4 mg/dL when 90% nephron loss has occurred.

At the onset of International Renal Interest Society (IRIS) Stage 4 CKD (serum creatinine concentration > 5 mg/dL; Table 2), it is likely cats have < 10% of their original nephron population. These figures emphasize the need for early diagnosis and intervention.

Pathophysiology

Pathophysiology of CKD can be considered at both the organ and systemic level.

Decreased Glomerular Filtration
At the level of the kidney, the fundamental abnormality 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.

Hormonal Disturbances
In addition to excreting metabolic wastes and maintaining fluid and electrolyte balance, the kidneys function as endocrine organs and catabolize several peptide hormones. Therefore, hormonal disturbances are part of the pathogenesis of multisystem disorders associated with CKD. For example, decreased production of erythropoietin contributes to the nonregenerative anemia of CKD, and decreased metabolism and excretion of parathyroid hormone contributes to osteodystrophy.

Compensatory Mechanisms
Finally, part of the pathophysiology of CKD is brought about by compensatory mechanisms. The individual glomerular filtration rate (GFR) of intact nephrons increases in an attempt to maintain adequate renal function; however, proteinuria and glomerulosclerosis may be consequences or “trade-offs” of this hyperfiltration (Figure 2). In CKD autoregulation of renal blood flow is lost, and single nephron GFR increases in proportion to the number of nephrons lost. The resulting increased intraglomerular pressure damages the glomerular capillary wall and increases plasma protein filtration, leading to subsequent glomerular and tubulointerstitial damage.

FIGURE 2. Potential mechanisms of progressive loss of nephrons in CKD. Courtesy Mal Hoover Rooks, CMI, Kansas State University

Staging Feline CKD

Many different terms have been used to describe renal disease and decreased renal function, and unfortunately, these terms can be confusing due to lack of standard definitions and application.

Therapeutic Approach

Similar to the diagnostic approach to CKD (see Diagnostic Approach to Feline CKD), the therapeutic approach should be tailored to the patient’s disease stage (Table 5).

For example, in the earlier stages of CKD, disease-specific treatments for nephroliths and bacterial pyelonephritis, as well as treatments designed to slow the progression of renal disease (renoprotective treatments), provide the most value. Renoprotective treatments include dietary change that reduces serum phosphorous concentrations⁹ and decreases soft tissue mineralization (Figure 3).

Proteinuria is an important risk factor for the development and progression of azotemia and for decreased survival in cats.^10-13 Angiotensin-converting enzyme inhibitors and calcium-channel blockers are used to reduce proteinuria and normalize systemic and intraglomerular blood pressure.^14-16

In later stages of CKD, treatment tends to focus on limiting clinical signs associated with decreased renal function.

FIGURE 3. Ultrasound of the stomach of a cat with IRIS Stage 4 CKD demonstrating soft tissue mineralization (A). The cat was euthanized, and the gritty stomach tissue texture was observed at necropsy (B) and on a high-detail postmortem radiograph of the stomach (C). Soft tissue mineralization is most likely to occur in acid-secreting tissues, such as the stomach and kidney.

Acute Decompensation of CKD

The cause of acute-on-chronic decompensation usually falls into 1 of 3 categories (Table 6):

1. Prerenal: Most common prerenal causes are dehydration/hypovolemia and decreased renal perfusion; decreased renal perfusion can also be associated with decreased cardiac output and thromboembolic disorders
2. Renal: Renal causes include ascending urinary tract infections (ie, pyelonephritis that may or may not be associated with nephroliths), renal neoplasia, and precipitous progression of underlying renal disease (rare)
3. Postrenal: Postrenal causes include obstructive uropathies—most commonly a nephrolith that migrates into a ureter (less commonly inflammatory debris or stricture), resulting in partial or complete obstruction.