Stage of Kidney Disease

Recent studies have shown that the International Renal Interest Society (IRIS) stage of kidney disease predicts survival.^3,4 The IRIS stage is based on serum creatinine, with subcategories for blood pressure and proteinuria (Table 48-1) (see Chapters 47 and 49). The IRIS staging system is intended for use with cats who have been diagnosed already with CKD and are clinically stable. In one study that applied IRIS staging criteria to cats at initial diagnosis and after stabilization, 30 per cent of cats categorized initially as stage IV were classified in a lower stage after they had been stabilized.³ It is likely that the prerenal component of azotemia in several of the cats caused them to be categorized initially in a more advanced stage. The prerenal component of azotemia is rapidly reversible with fluid therapy. Median survival time for cats with stage IIb CKD (after rehydration) in that study was 3.1 years (1151 days), compared to 1.9 years (679 days) for cats with stage III CKD, and 35 days for cats with stage IV CKD.³ These results are similar to a study evaluating survival of 50 cats with CKD based on IRIS stage at diagnosis.⁴ In that study, survival times of cats in stage IIb kidney disease were reported as 1.4 years (504 days) in normotensive patients, but only 187 days in stage IIb cats with hypertension. Stage III cats had a reported survival time of 154 days (normotensive patients) and 281 days (hypertensive patients); because of the small number of cats in this group, there was not a statistically significant difference in survival times between normotensive and hypertensive cats. Cats in stage IV CKD were found to have a survival time of 57 days (normotensive patients) and 21 days (hypertensive patients).⁴

Table 48-1 IRIS Staging System*

A prospective study determined that an increased serum creatinine was associated with a shorter survival time.⁵ In that study, the relative risk of reaching a renal endpoint, defined as death or euthanasia from renal failure or need for parenteral fluid therapy, was 2.3 times higher in cats with stage III CKD than for those in stage II (p = not significant), 3.8 times higher for those in stage IV than for those in stage III, and 9.3 times higher for those in stage IV than for those in stage II.⁵ Median survival times estimated from a Kaplan Meier survival curve were 60 days for cats in stage IV CKD and 475 days for cats in stage III disease.⁵ A study comparing cats who survived to those who did not survive for more than 1 month from diagnosis found that patients with a higher serum creatinine concentration at diagnosis were more likely to die of kidney disease within the first month after diagnosis.⁶ At diagnosis, the surviving cats had a median serum creatinine concentration of 2.7 mg/dL and the nonsurvivors had a median serum creatinine concentration of 5.5 mg/dL.⁶

Median survival time in one study was 123 days once the serum creatinine concentration exceeded 4 mg/dL and 44 days when the creatinine exceeded 5 mg/dL.³ In another study, cats who developed a serum creatinine concentration greater than 4.5 mg/dL died within 5 to 63 days and typically presented 3 weeks after the increase in serum creatinine with dehydration and complete anorexia.⁷ Another study found the serum creatinine concentration at the time of diagnosis to be a poor predictor of survival time in uremic cats.⁸ In that study, 10 per cent of the cats were assessed as being dehydrated at diagnosis. Mean serum creatinine concentration in those cats at diagnosis was 3.6 mg/dL.⁸

The results of these studies indicate that IRIS stage of kidney disease, based on serum creatinine concentration, is associated with survival in cats. Cats discharged in IRIS stage IIb kidney disease have only a 42 per cent chance of dying of renal disease, compared to a 68 per cent chance for cats in stage III and an 86 per cent chance for cats in stage IV CKD.³ Thus more than one half of cats with stage IIb CKD develop another disease process that leads to death. This is not surprising considering that the mean age at diagnosis of CKD in all cats is 12.3 years and the mean survival time from that point is 2.3 years.³ However, this information can be valuable when counseling owners on what to expect once their cat is diagnosed with CKD.

Proteinuria

The urine protein:creatinine ratio (UPC) is a spot measurement of urinary protein excretion that predicts 24-hour urine protein excretion accurately without the inconvenience of trying to collect urine from a cat for a full 24 hours. Urine albumin-to-creatinine ratio is no more accurate than UPC and is not readily available.^4,9 A rapid and easy semiquantitative assay is available for microalbuminuria in cats, defined as urinary albumin concentration of less than 30 mg/dL, which is the lower limit of detection of standard urine dipsticks. Although microalbuminuria testing may prove to be an early predictor of renal damage, at this time we lack clinical correlates of microalbuminuria. In one study of more than 300 feline urine samples, more than 100 tested positive for microalbuminuria but only 16 had a UPC higher than 0.4.⁹ Thus the role of testing for microalbuminuria in feline CKD remains to be clarified.

Significant proteinuria is not a common finding in cats with CKD. From 50 to 66 per cent of affected cats have UPCs lower than 0.2 and only 20 per cent or less have UPCs higher than 0.4.^4,5 Multiple studies have shown that proteinuria is associated with a shorter survival time.^4–6 An increased UPC was the most likely variable to be associated with increased mortality in cats with CKD.⁶ Cats with CKD and UPCs higher than 0.4 had a fivefold higher risk of reaching a renal endpoint than cats with UPCs below 0.2, and median survival time of cats with UPCs higher than 0.4 is about 1 year, compared to a median survival time of about 3 years in cats with UPCs lower than 0.2.^4,5 The results of survival analyses of cats with CKD and UPCs between 0.2 and 0.4 vary; one study showed no difference in survival between this group and cats with UPCs below 0.2, while another study showed survival times intermediate between survival in cats with UPCs lower than 0.2 or higher than 0.4.^4,5 From these findings, we can conclude that a UPC over 0.4 is detrimental but values from 0.2 to 0.4 remain equivocal.

Angiotensin-converting enzyme (ACE) inhibitors, such as enalapril and benazepril, are known to decrease proteinuria, and benazepril has been found to decrease proteinuria in cats with naturally occurring CKD.^10–12 In a study of surgically induced CKD, benazepril did not decrease proteinuria; however, the degree of proteinuria at the start of treatment was small.¹³ Despite its antiproteinuric effects, benazepril did not improve survival times in cats with CKD when compared to placebo.¹⁰ That study also did not find a survival advantage from benazepril in a subset of cats with UPCs above 1; however, there were only 13 cats in that group. Because of day-to-day variation, the UPC must change by more than 80 per cent in dogs with UPCs around 0.5 to represent an actual change in value.¹⁴ Similar data are not available for cats. Although side effects of ACE inhibitors are uncommon in stable, well-compensated cats, complications include worsening azotemia, hyperkalemia, and a decrease in blood pressure, and these parameters should be monitored shortly after starting therapy or following dose adjustments. (See Chapter 45 in the fifth volume of this series for further discussion on proteinuria.)

Hypertension

Hypertension is a poor prognostic indicator in dogs with CKD. Dogs with a systolic blood pressure above 160 mm Hg were three times more likely to develop a uremic crisis or die than dogs with a systolic blood pressure less than 143 mm Hg. Survival times were shorter and progression of azotemia was more rapid in the hypertensive dogs. However, blood pressure remained above 160 mm Hg in 10 of 11 dogs treated with antihypertensive medications.¹⁵

Although systolic blood pressure in cats is correlated to magnitude of proteinuria, cats treated for hypertension did not have a reduced survival time compared to cats without hypertension.⁴ This may have occurred because cats with hypertension treated with amlodipine had a significant reduction in blood pressure over the follow-up period.⁴ (See Chapter 49 for further discussion of hypertension.)

Biochemical Parameters

Serum phosphorus concentration was correlated to survival in several studies.^3,5,6 In one study, serum phosphorus was considered a dependent variable because the increase in phosphorus concentration was correlated to the independent variable serum creatinine.⁵ In another study, serum phosphorus was predictive of survival in a multivariate model. For each 1 mg/dL increase in serum phosphorus, there was an 11.8 per cent increase in the risk of death.³ Other commonly measured biochemical parameters are not correlated consistently with survival. Serum urea concentration was correlated to survival in two studies^5,6 but not in a third.³ However, in one study serum urea was considered a dependent variable correlated to serum creatinine and not a separate indicator.⁵ Serum concentrations of potassium, calcium, bicarbonate, and albumin were not predictive when evaluated.^3,5,6