Chronic kidney disease and failure is invariably progressive; however, stable disease and a reasonable quality of life can be obtained for some time in most cats. A step-wise therapeutic approach that addresses the potential causes and progressive complications of renal failure is suggested. Dietary modification and judicious use of adjunct medications can reduce signs of uremia and prolong survival. Serial monitoring is recommended to best plan management strategies and to assess long-term prognosis. The typical data base includes body weight, CBC or PCV, biochemistry and acid-base measures, urinalysis, indirect blood pressure measurement, and urine culture.
Pathophysiology of Renal Failure
The kidneys perform many metabolic, excretory and regulatory functions in the body. Progression of renal dysfunction is predictable in chronic renal failure, and likely results from increased function and adaptive processes in surviving nephrons, intraglomerular hypertension or systemic hypertension, hyperphosphatemia and renal mineralization, ongoing inflammation, hypokalemia, and proteinuria which may contribute to tubular damage. Common consequences of renal failure (and the mechanisms involved) include:
Less common consequences of renal failure, usually seen with advanced disease, include bleeding due to platelet dysfunction, uremic encephalopathy, uremic pneumonitis and peripheral neuropathy.
- Uremic gastroenteritis (Stimulation of chemoreceptor trigger zone, hypergastrinemia, uremic vasculitis)
- Systemic hypertension (glomerular capillary injury, decreased vasodilatory substances, enhanced renin-angiotensin-aldosterone activation)
- Hypokalemia and weakness (renal potassium loss, decreased intake)
- Hyperphosphatemia and secondary hyperparathyroidism (decreased GFR, retained phosphorus, decreased activation of vitamin D, decreased calcium absorption)
- Progressive increases in PTH occur to maintain serum calcium concentration
- Metabolic acidosis (retention of acids, failure to resorb bicarbonate, fatigue of ammoniagenesis in nephrons)
- Non-regenerative anemia (decreased erythropoietin production, gastrointestinal loss, shortened RBC lifespan)
- Dehydration and constipation (fluid loss)
Mechanisms of Progression and Possible Renoprotective Strategies
Glomerular hypertension: may be minimized by dietary protein reduction, angiotensin converting enzyme (ACE) inhibitors, fish oil supplementation
Proteinuria: dietary protein reduction, ACE inhibitors, fish oil supplementation
Systemic hypertension: dietary sodium reduction, calcium channel blocking agents, ACE inhibitors
Tubulointerstitial injury: fish oil supplementation
Acidosis:Alkalinizing diet or alkalinizing agents
Mineral Imbalance and Soft Tissue Mineralization: Dietary phosphorus reduction, calcitriol administration, phosphate-binding agents
Epidemiology and Progression of Chronic Kidney Disease in Cats
Chronic kidney disease or failure is common in cats, representing 25 – 50% of cats > 10 years old recorded in the Purdue VM Database in 2000. Regardless of the initial insult or disease process, Chronic Renal Failure is a slowly progressive disorder, beginning with the earliest insult to the kidneys. Some progression may be due to the primary disease process, with natural cycles of progression, remission or exacerbation. Progression is also thought to be due to the long term results of some compensatory mechanisms that occur in remaining nephrons (the "Self perpetuation theory"). The fact that some compensatory mechanisms can lead to deleterious consequences also can be called the "trade off hypothesis". Progression in dogs is fairly linear, whereas clinical research suggests a slower decline in cats, with long periods of stable disease (up to 2 or more years) followed by sudden increases in serum creatinine (Ross et al, 2005). Mechanisms of progression include the effects of glomerular hypertrophy or hypertension in remaining nephrons, deleterious effects of proteinuria and hypokalemia in tubules, ongoing tubulointerstitial inflammation, and damaging effects of the ensuing systemic hypertension, acidosis, and soft tissue mineralization. Current documentation supports systemic hypertension and proteinuria as primary risk factors for progressive renal failure in dogs and cats. Understanding these slowly developing consequences of renal failure provides us the opportunity to intervene with medical strategies designed to blunt the compensatory response or its pathologic results, and can be introduced step-wise at different stages of disease.
Screening for CKD (Early diagnosis)
Geriatric screening: A minimum data base, including complete urinalysis and thyroid hormone measurements in cats can be recommended in cats older than 7 or 8 years. However, changes in urea and creatinine are considered late indicators of renal disease.
Monitor high risk cats: geriatric cats, cats with urolithiasis, history of familial disease, history of urinary tract infections
Chart urine specific gravity: A gradual drop in urine specific gravity may be the earliest laboratory sign of renal disease. Astute owners can monitor urine production or collect samples for periodic assessment
Urine protein measurements: Repeated proteinuria detected by dipstick or screening tests should be quantitated by urine protein:creatinine determination.
Systemic blood pressure measurements and fundic examination: Can be conducted as part of geriatric screen. Measurements of greater than 160 mm Hg systolic should be followed up with reassessments. Persistent measures > 180 mm Hg warrant treatment.
Imaging: Uroliths and changes in renal size or shape can be followed up with more specific testing.
Staging of CKD in Cats
Criteria for staging CKD have been developed by an international group of experts (the International Renal Interest Society, IRIS; see
http://www.iris-kidney.com/) in order to help practitioners in the logical and often stepwise diagnosis and management of renal disease. The staging criteria are based on three primary measures, the creatinine measurement, urine protein concentration, and blood pressure (Table 1). Specific criteria and recommendations are expected to be updated annually. Remember that staging criteria should be based on laboratory and clinical findings during relatively stable disease periods, not during a crisis or in the face of dehydration. Additionally, creatinine measures vary widely among laboratories (and among different sizes and breeds in dogs and cats); some caution must be advised in adhering to these strict creatinine ranges.
Table 1. Current IRIS Staging Criteria for Cats with Chronic Kidney Disease