Clinicopathological Variables Predicting Progression of Azotemia in Cats with Chronic Kidney Disease

Abstract

Background: Chronic kidney disease (CKD) is common in geriatric cats, but often appears to be stable for long periods of time.Objectives: To describe CKD progression and identify risk factors for progression in newly diagnosed azotemic cats. Animals: A total of 213 cats with CKD (plasma creatinine concentration > 2 mg/dL, urine specific gravity < 1.035) were followed up until progression occurred or for at least 1 year; 132, 73, and 8 cats were in International Renal Interest Society (IRIS) stages 2, 3, and 4, respectively.Methods: Progression was defined as a 25% increase in plasma creatinine concentration. Logistic regression was used to assess variables at diagnosis that were associated with progression within 1 year. Changes in IRIS stage during followup also were described. Cases that remained in stages 2 or 3, but did not have renal function assessed in the last 60 days of life, were excluded from analysis of the proportion reaching stage 4.Results: Of the cats, 47% (101) progressed within 1 year of diagnosis. High plasma phosphate concentration and high urine protein-to-creatinine ratio (UPC) predicted progression in all cats. Low PCV and high UPC independently predicted progression in stage 2 cats, whereas higher plasma phosphate concentration predicted progression in stage 3 cats; 19% (18/94) of cats diagnosed in stage 2; and 63% (34/54) of cats diagnosed in stage 3 reached stage 4 before they died.Conclusions: Proteinuria, anemia, and hyperphosphatemia may reflect more progressive kidney disease. Alternatively, they may be markers for mechanisms of progression such as tubular protein overload, hypoxia, and nephrocalcinosis.

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

“…UPC has previously been shown to be an independent predictor of survival time in cats with CKD,31 and in this study being classified as borderline proteinuric (UPC 0.2–0.4) or proteinuric (UPC > 0.4) under the IRIS proteinuria classification scheme6 was associated with a greater than 2‐times increase in risk of death. A previous study found UPC to be an independent predictor of progression of CKD;18 however, UPC did not remain in the multivariable model in the present analysis. A placebo‐controlled interventional study failed to demonstrate a significant increase in survival time when feline CKD patients with proteinuria were administered an angiotensin converting enzyme (ACE) inhibitor, despite a significant lowering of UPC with treatment 38.…”

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

“…4 Equally important, many animals with recognized CKD maintain relatively "static" or non-progressive kidney function over extended periods of time. 40,41 These patients may justify different diagnostic, monitoring, and therapeutic attention. An important outcome of the Napa Meeting was establishment of a strategic hypothesis for the recognition and understanding of early (IRIS CKD Stage 1) kidney disease.…”

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

“…The cats in these studies diagnosed with systemic hypertension however, were always treated with the calcium channel blocker, amlodipine besylate, and therefore the true effect of systemic hypertension on the development and/or progression of CKD may have been masked. [38][39][40]  Diabetes mellitus: Unlike in human medicine, to date no association has been identified between diabetes mellitus and CKD in cats or the development of a diabetic nephropathy, although it remains possible that this reflects the relatively shorter life expectancy of diabetic cats compared to diabetic humans. 23,41  Hyperthyroidism: Hyperthyroidism is a common condition in the older cat and therefore is often diagnosed concurrently with CKD.…”

“…114 In one study 29% of cats with IRIS stage 2 disease and 63% of IRIS stage 3 CKD cats progressed to IRIS stage 4 before death. 40 Epidemiological studies have evaluated factors associated with the development of azotemia, survival of cats with CKD and also demonstrating a more progressive phenotype of CKD. 24,[38][39][40][115][116][117] From the experimental and human literature there are a number of key pathophysiological mechanisms which have been implicated in both the development and progression of CKD.…”

“…40 Epidemiological studies have evaluated factors associated with the development of azotemia, survival of cats with CKD and also demonstrating a more progressive phenotype of CKD. 24,[38][39][40][115][116][117] From the experimental and human literature there are a number of key pathophysiological mechanisms which have been implicated in both the development and progression of CKD. An understanding of these mechanisms is important not only because many may be applicable and translated to feline CKD but also because they provide potential targets for therapy in order to slow disease progression.…”