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Keywords:

  • Anemia;
  • Hyperphosphatemia;
  • Nephrology;
  • Proteinuria

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

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 follow-up 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.

Abbreviations
ACE

angiotensin converting enzyme

CKD

chronic kidney disease

GFR

glomerular filtration rate

IRIS

International Renal Interest Society

ROC

receiver operating characteristic

UPC

urine protein to creatinine ratio

USG

urine specific gravity

Chronic kidney disease (CKD) is common in geriatric cats, but often appears stable for long periods of time. Although several studies have evaluated survival in cats with CKD,[1-6] few have documented changes in renal function. Survival studies also have been confounded by the difficulty of deducing cause of death because geriatric cats often have multiple pathologies and it is difficult to distinguish the cause of clinical deterioration. Furthermore, perceived quality of life has an influence on survival because the majority of cats are humanely euthanized rather than dying naturally.

The first aim of this study was to describe progression of CKD in cats by evaluating changes in renal function over time. Plasma creatinine concentration is the most widely used marker of renal function, but can be affected by hydration status and muscle mass. The gold standard measure of renal function is glomerular filtration rate (GFR). However, GFR assessment consumes both time and resources. Because serial GFR measurements were not possible, changes in renal function were evaluated using the International Renal Interest Society (IRIS) staging system, which is based on plasma creatinine concentration (1.6–2.8 mg/dL for stage 2, 2.9–5 mg/dL for stage 3, and > 5 mg/dL for stage 4).

Several markers have been associated with shorter survival in cats with CKD, including proteinuria,[1] anemia,[2] and hyperphosphatemia.[4] The second aim of this study was to determine which clinicopathological variables could predict further deterioration of renal function in cats newly diagnosed with azotemic CKD.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Case Selection

Cats with CKD were recruited from 1992 onward through geriatric cat clinics held at 2 first opinion London practices: the Peoples Dispensary for Sick Animals, Bow and Beaumont Sainsbury Animal's Hospital, Camden. These cases were recruited for a variety of studies. Diagnosis was based on the concurrent findings of azotemia, which persisted for at least 2 weeks, and urine specific gravity (USG) that was < 1.035. Cases with shorter follow-up were only considered to have CKD if the history and clinical signs were compatible with chronic rather than acute kidney disease. Azotemia was defined as plasma creatinine concentration > 2 mg/dL (ie, above the laboratory reference range). Only cats with azotemic CKD recruited before June 2010 were included in the study and data were analyzed in June 2011.

Clinicopathological Data

Blood and urine samples were obtained by jugular venipuncture and cystocentesis respectively at approximately 4-month intervals once cats were stabilized. These samples were analyzed for routine diagnostic purposes, obtaining plasma biochemical profiles and urine protein-to-creatinine ratio (UPC) from a commercial laboratory. Plasma biochemical profiles were obtained close to the time of sample collection, but UPC were obtained at a later date from urine samples that had been stored at −80°C. Urine protein was measured using a colorimetric pyrogallol red method and creatinine was measured using a colorimetric picric acid method. Sediment analysis was performed on all urine samples before storage and those with bacteriuria or > 5 white blood cells per high power field were cultured. Cats with urinary tract infections were treated with antibiotics for at least 3 weeks according to urine culture and sensitivity results. UPC from urine samples with gross hematuria or cats with urinary tract infections were not used in any analyses. Hypertension was diagnosed in cats with mean systolic blood pressure measurements > 170 mmHg on 2 consecutive visits or on 1 visit in association with hypertensive choroidoretinopathy. All hypertensive cats were treated with amlodipine at a daily dose of 0.625 mg, which was increased to 1.25 mg or subsequently 2.5 mg if blood pressure remained > 160 mmHg. All normotensive cats and hypertensive cats with normalized blood pressure were offered a commercial renal diet as standard care. The renal diets,1,2,3 all clinical examinations, and biochemical tests were provided to clients free of charge. Other treatments were dispensed infrequently, according to the needs of the individual cat. These treatments included dietary phosphate binders, oral potassium supplementation and angiotensin converting enzyme (ACE) inhibitors, but no erythropoiesis-stimulating agents. Cats were routinely screened for hyperthyroidism using plasma total thyroxine concentrations and those that developed the disease at any time during follow-up were excluded from the study.

Risk Factors for Progression within 1 Year of Diagnosis

Associations between clinicopathological variables at diagnosis and progression within 1 year were assessed. Progression was defined as a maximal increase in plasma creatinine concentration of at least 25% relative to the concentration at diagnosis. If there was evidence of dehydration at initial evaluation, baseline was considered to be the date at which normal hydration had been restored with fluid therapy, the azotemia had been stabilized, and fluid therapy had been discontinued for at least 1 week. The figure of 25% was chosen arbitrarily, but it was felt that smaller changes could be caused by lack of precision in the measurement of creatinine rather than actual progression of azotemia. In addition to a combined analysis using all azotemic cats, separate analyses were performed for cats diagnosed in stage 2 and those diagnosed in stage 3. Renal follow-up was defined as the interval between the date of diagnosis and the date of the last available plasma creatinine concentration. Nevertheless, cats often were seen at the clinics beyond the defined follow-up period. Cases that did not demonstrate progression but had renal follow-up < 1 year were excluded from the study.

Changes in IRIS Stage during Follow-Up

Changes in IRIS stage during follow-up were described for the same population of cats, including those that were still alive or eventually lost to follow-up. Only cats with renal function assessed in the last 60 days of life were considered to have been followed to death. Cats that were not followed to death are described separately. Of cats reaching a higher stage, the number that also demonstrated progression within 1 year of diagnosis was recorded.

Statistics

Binary logistic regression was used to assess clinicopathological variables at diagnosis associated with progression within 1 year of diagnosis. Variables associated with progression in the univariate analyses were entered into backward selection multivariable models. USG was multiplied by 1,000 and UPC was multiplied by 10 to facilitate interpretation of the odds ratio. Receiver operating characteristic (ROC) curves were used to find optimal cut-points for variables predicting progression. Summary statistics are presented as median (25th, 75th percentile) and risk factors for progression are presented as odds ratio [95% confidence interval]. No attempt was made to impute missing data. All statistical analyses were performed using computer software4 with significance set at the 5% level.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

From our database of over 2500 cases, 679 cats were diagnosed with CKD, but 212 cats were excluded due to concurrent hyperthyroidism. Two hundred and forty-five cats (118, 70, and 57 diagnosed in IRIS stages 2, 3, and 4, respectively) were excluded due to short biochemical follow-up. Although these cats did not demonstrate progression, they could not be considered stable because they did not have blood samples spanning a year from diagnosis. One hundred and sixty-four (67%) of the cats with short biochemical follow-up are known to have died or been euthanized within 1 year of diagnosis (including 54 of the stage 4 patients) and 81 (33%) were lost to follow-up. The cause of death was known in 45% (73/164) of the cats that died within 1 year of diagnosis and CKD was cited in 74% (54/73) of those cases. Eight further cases were excluded from the study because they showed progression, but this was not documented until after 1 year's follow-up. Their status at 1 year was therefore uncertain. One additional cat with nephrotic syndrome was excluded because it had atypical disease pathology.

These exclusions resulted in a study population of 213 cats including 119 males and 94 females. The majority (175) were nonpedigree domestic cats, but there were 14 Persian or Persian crosses, 14 Burmese, 4 Siamese or Siamese crosses, 4 British shorthairs, 1 Birman, and 1 Devon Rex. At baseline, there were 61 hypertensive cats, 118 normotensive cats, and 34 cats without blood pressure measurements. Thirty cats had urine cultured and 17 of these cultures yielded bacterial growth. At the time of data analysis, 135 cats had been euthanized, 33 had died and for 4 cats, although dead, it was not known whether the cat had died naturally or been euthanized. An additional 14 cats had been lost to follow-up and 27 were still alive.

Risk Factors for Progression within 1 Year of Diagnosis

One hundred and one cats were classed as having progressive disease, having demonstrated an increase in plasma creatinine concentration of at least 25% within 1 year of diagnosis. Plasma creatinine concentration increased by 51 (34, 83)% from 2.7 (2.4, 3.5) to 4.4 (3.5, 6.2) mg/dL in the progressive group. One hundred and twelve cats were considered stable having shown no such increase although they were followed for over a year. Plasma creatinine concentration increased by 7 (0, 16)% from 2.5 (2.3, 3.0) to 2.8 (2.5, 3.3) mg/dL in the stable group. Table 1 illustrates the variables at diagnosis considered in this study for cats in each group. Forty-two percent (56/132) of cats diagnosed in stage 2 progressed within 1 year of diagnosis, whereas the figures were 53% (39/73) and 75% (6/8) for cats diagnosed in stages 3 and 4, respectively.

Table 1. Summary statistics for clinicopathological variables at diagnosis in cats with chronic kidney disease. Data presented as median (25th, 75th percentile) or prevalence (%).
Clinicopathological VariableStable (n = 112)Progressive (n = 101)
Year of diagnosis2004 (2000, 2007)2003 (1999, 2006)
Age (years)14 (11, 16)14 (11, 16)
% Male5557
Weight (kg)4.2 (3.5, 4.9)3.9 (3.2, 4.5)
Plasma creatinine concentration (mg/dL)2.5 (2.3, 3.0)2.7 (2.4, 3.5)
Plasma urea nitrogen concentration (mg/dL)49 (40, 60)56 (45, 74)
Plasma inorganic phosphorus concentration (mg/dL)4.4 (3.6, 5.2)5.1 (4.0, 6.8)
Plasma total calcium concentration (mg/dL)10.3 (9.9, 10.7)10.2 (9.6, 10.8)
Plasma potassium concentration (mEq/L)4.0 (3.7, 4.4)3.9 (3.6, 4.3)
Plasma cholesterol concentration (mg/dL)212 (162, 247)204 (166, 250)
Plasma total protein concentration (g/dL)7.7 (7.4, 8.2)7.7 (7.3, 8.3)
Plasma albumin concentration (g/dL)3.2 (3.0, 3.4)3.1 (2.9, 3.3)
Plasma globulin concentration (g/dL)4.5 (4.1, 4.9)4.6 (4.1, 5.2)
Packed cell volume (%)35 (32, 38)31 (25, 35)
Urine protein to creatinine ratio0.14 (0.08, 0.24)0.27 (0.17, 0.68)
Urine specific gravity1.020 (1.016, 1.024)1.016 (1.014, 1.020)
% with urinary tract infection115
Systolic blood pressure (mmHg)147 (134, 164)155 (132, 177)
% with systolic hypertension2940
Renal follow-up (days)744 (576, 1014)209 (99, 347)
Median survival with 95% confidence interval (days)1021 [861, 1181]264 [186, 342]

The clinicopathological variables associated with progression within 1 year of diagnosis in the combined univariate analysis of all azotemic cats included low body weight, PCV, USG and plasma albumin concentration, high UPC, plasma creatinine, urea and phosphate concentrations. These data are shown in Table 2. The multivariable model (Table 3) predicting progression of CKD within 1 year of diagnosis included UPC and plasma phosphate concentration. An increase in UPC of 0.1 was associated with a 24% increase in the risk of progression, and an increase in plasma inorganic phosphorus concentration of 1 mg/dL was independently associated with a 41% increase in the risk of progression.

Table 2. Univariate binary logistic regression analysis of clinicopathological variables at diagnosis associated with progression of chronic kidney disease in all azotemic cats. Only variables with P < .2 are presented here.
Clinicopathological VariableOdds Ratio with  95% Confidence intervalNP
Weight (kg)0.68 [0.50, 0.93]194.016
Plasma creatinine  concentration (mg/dL)1.47 [1.06, 2.05]213.022
Plasma urea nitrogen  concentration (mg/dL)1.02 [1.01, 1.03]213.008
Plasma inorganic  phosphorus  concentration (mg/dL)1.34 [1.14, 1.57]212<.001
Plasma albumin  concentration (g/dL)0.28 [0.12, 0.70]212.006
Packed cell volume (%)0.92 [0.88, 0.96]207<.001
Urine protein to creatinine  ratio × 101.30 [1.12, 1.52]150.001
Urine specific gravity × 10000.93 [0.88, 0.97]213.002
Presence of urinary  tract infection0.43 [0.15, 1.28]213.130
Presence of systolic  hypertension1.65 [0.89, 3.08]179.113
Table 3. Multivariable binary logistic regression analysis of clinicopathological variables at diagnosis associated with progression of chronic kidney disease in all azotemic cats (n = 150).
Clinicopathological VariableOdds Ratio with 95%  Confidence intervalP
Plasma inorganic phosphorus  concentration (mg/dL)1.41 [1.08, 1.84].012
Urine protein to  creatinine ratio × 101.24 [1.06, 1.45].008

Fifty-one (91%) of the progressive cats and 12 (16%) of the stable cats diagnosed in stage 2 reached stage 3 within 1 year of diagnosis. Table 4 shows the clinicopathological variables associated with progression within 1 year of diagnosis in the univariate analysis of cats diagnosed at stage 2. Low PCV and high UPC remained in the multivariable model (Table 5). An increase in PCV of 1% was associated with a 10% reduction in the risk of progression and an increase in UPC of 0.1 was independently associated with a 23% increase in the risk of progression within 1 year of diagnosis. UPC was 0.23 (0.15, 0.40) in progressive cases and 0.13 (0.07, 0.24) in stable cases, whereas PCV was 33 (28, 36)% in progressive cases and 36 (33, 39)% in stable cases. Only 10 cats in the progressive group (18%) and 3 cats in the stable group (4%) were anemic (PCV < 27%).

Table 4. Univariate binary logistic regression analysis of clinicopathological variables at diagnosis associated with progression of chronic kidney disease in cats diagnosed at International Renal Interest Society stage 2. Only variables with P < .2 are presented here.
Clinicopathological VariableOdds Ratio with  95% Confidence  intervalNP
Weight (kg)0.75 [0.50, 1.12]122.157
Plasma urea nitrogen  concentration (mg/dL)1.02 [0.99, 1.05]132.145
Plasma inorganic  phosphorus  concentration (mg/dL)1.34 [1.02, 1.77]131.036
Plasma total calcium  concentration (mg/dL)0.77 [0.53, 1.13]131.180
Plasma potassium  concentration (mEq/L)0.53 [0.26, 1.06]132.074
Plasma albumin  concentration (g/dL)0.36 [0.11, 1.20]131.097
Plasma globulin  concentration (g/dL)1.39 [0.86, 2.25]131.182
Packed cell volume (%)0.89 [0.84, 0.96]128.001
Urine protein to  creatinine ratio × 101.23 [1.01, 1.51]89.045
Urine specific gravity × 10000.94 [0.88, 1.00]132.043
Table 5. Multivariable binary logistic regression analysis of clinicopathological variables at diagnosis associated with progression of chronic kidney disease in cats diagnosed at International Renal Interest Society stage 2 (n = 86).
Clinicopathological VariableOdds Ratio with 95%  Confidence intervalP
Packed cell volume (%)0.90 [0.82, 0.99].023
Urine protein to  creatinine ratio × 101.23 [1.01, 1.50].037

Twenty-seven (69%) of the progressive cats and 1 (3%) of the stable cats diagnosed in stage 3 reached stage 4 within 1 year of diagnosis. Table 6 shows the clinicopathological variables associated with progression within 1 year of diagnosis in the univariate analysis of stage 3 cats. The multivariable model included only high plasma phosphate concentration and an increase in plasma inorganic phosphorus concentration of 1 mg/dL was associated with a 43% increase in the risk of progression within 1 year of diagnosis. Exceeding the IRIS target for plasma inorganic phosphorus concentration in stage 3 cats (5 mg/dL)[7] had a sensitivity of 74%, a specificity of 50%, a positive predictive value of 63%, and a negative predictive value of 63% for predicting progression within 1 year. Analysis of the ROC curve indicated no better cut-point.

Table 6. Univariate binary logistic regression analysis of clinicopathological variables at diagnosis associated with progression of chronic kidney disease in cats diagnosed at International Renal Interest Society stage 3. Only variables with P < .2 are presented here.
Clinicopathological VariableOdds Ratio with  95% Confidence  intervalNP
Weight (kg)0.61 [0.37, 1.01]66.056
Plasma creatinine  concentration (mg/dL)2.06 [0.81, 5.19]73.128
Plasma urea nitrogen  concentration (mg/dL)1.03 [1.00, 1.05]73.042
Plasma inorganic  phosphorus  concentration (mg/dL)1.43 [1.08, 1.89]73.012
Plasma albumin  concentration (g/dL)0.24 [0.06, 1.02]73.053
Packed cell volume (%)0.95 [0.89, 1.01]71.118
Urine protein to  creatinine ratio × 101.37 [1.04, 1.79]56.024
Urine specific gravity × 10000.92 [0.83, 1.02]73.098
Systolic blood pressure (mmHg)1.02 [1.00, 1.04]59.028
Presence of systolic hypertension3.71 [1.12, 12.27]58.032

Changes in IRIS Stage during Follow-Up

At diagnosis, 62% (132) of the cats were in stage 2, whereas 34% (73) were in stage 3 and 4% (8) were in stage 4. Figure 1 shows the changes in IRIS stage for these cats. Of the cats diagnosed in stage 2, 5% (7) progressed directly to stage 4 and 62% (82) reached stage 3. Additionally, 33% (43) remained in stage 2 during follow-up, but some of these cats (41%; 18/43) were not followed up to death. They were, however, followed up for 641 (520, 1141) days from diagnosis. Thirteen percent (11) of the cats that reached stage 3 proceeded to stage 4 before they died, whereas 87% (71) remained in stage 3. Twenty-four percent (20) of the cats remaining in stage 3 were not followed up to death, but these cats were followed up for 592 (226, 1005) days from diagnosis.

image

Figure 1. Flow chart illustrating International Renal Interest Society stage at diagnosis and peak stage in cats with CKD diagnosed at 2 first opinion clinics between 1992 and 2010. Only cats that had renal function assessed in the last 60 days of life were considered to have been followed up to death.

Download figure to PowerPoint

Overall, 18 of the cats diagnosed in stage 2 reached stage 4 before they died and 76 did not, whereas the remaining 38 cats were not followed up to death. Of the 18 cats that reached stage 4, 12 progressed (plasma creatinine concentration increased by 25%) within 1 year of diagnosis and 6 had stable renal function in the year after diagnosis. Of the 71 cats that reached stage 3, 40 progressed within 1 year of diagnosis and 31 had stable renal function in the year after diagnosis. The cats with stage 2 CKD that reached stage 3 did so in 112 (56, 504) days and those that reached stage 4 did so in 679 (273, 961) days from diagnosis.

Thirty-four of the cats diagnosed in stage 3 reached stage 4, whereas 20 did not, and the remaining 19 cats were not followed up to death. The last group was, however, followed up for 665 (469, 1064) days from diagnosis. Of the 34 cats that reached stage 4, 28 progressed within 1 year of diagnosis and the remaining 6 did not. Cats diagnosed in stage 3 that reached stage 4 did so in 106 (46, 174) days.

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

This study demonstrates that a substantial number of cats with CKD have nonprogressive or slowly progressive disease. A minority of cats diagnosed in IRIS stage 2 progressed to stage 4 before they died. Models using surgical reduction of renal mass in cats have similarly found that renal function remains stable for a substantial period of time after the procedure.[8, 9] However, rapidly progressive cases in the present study might have been euthanized without blood tests documenting that they had reached stage 4. The proportion of cats reaching stage 4 thus could be underestimated. Furthermore, our criterion (an increase in plasma creatinine concentration of at least 25%) might fail to detect progression if losses in muscle mass decrease creatinine production over time. Many cats were excluded from the progression study because they had insufficient follow-up biochemical data. Because it is unknown whether or not these cats progressed, their exclusion introduces a source of bias. Notably, the study excludes cats diagnosed in stage 4 that died or were euthanized before further progression could be documented biochemically. Only 4% (8/213) of the cats in the progression study population were diagnosed in stage 4, whereas the figure was 23% (57/245) for cats with short follow-up. Thus, a separate analysis for predictors of progression was not undertaken in cats diagnosed at stage 4.

Higher UPC was associated with progression in this study, and proteinuria may be a marker for a subtype of CKD that is likely to progress. Alternatively, it might be a mediator of progression. Previous studies also have found high UPC to be associated with shorter survival in cats with CKD independently of plasma creatinine[1] or urea[2] concentration. Furthermore, high UPC predicts development of azotemia in cats.[10] If proteinuria contributes to disease progression in cats with CKD, therapies that decrease proteinuria would be expected to improve survival. Several studies have evaluated the effects of the ACE inhibitor benazepril in cats with CKD. Although this drug decreases proteinuria, it has not been shown to significantly improve survival[11] or slow CKD progression in cats.[12]

Proteinuria can be considered a marker of tubular function because filtered proteins are reabsorbed in the proximal tubule. If the glomerular filtration barrier is compromised, excess filtered protein could overload proximal tubular epithelial cells, triggering these cells to secrete cytokines into the interstitial compartment. Proteinuria may lead to progression of kidney disease via inflammation initiated by such cytokines. However, the evidence in favor of these theories is largely derived from models of severe experimental protein overload in rodents,[13, 14] which might misrepresent the mild proteinuria seen in naturally occurring CKD in cats.

Increases in plasma phosphate concentration have been associated with shorter survival in cats with CKD,[4] and feeding a phosphorus-restricted diet improves survival.[5, 6] Because phosphate is freely filtered at the glomerulus, plasma phosphate concentration can be considered a marker of GFR. However, increases in plasma phosphate concentration also can result in soft tissue mineralization due to precipitation of calcium-phosphate crystals. A phosphorus-restricted diet has been compared with a high-phosphorus diet in cats with surgically reduced renal mass. The low-phosphorus diet decreased renal tubular mineralization and interstitial inflammation in this model.[9] However, both dietary protein and phosphorus were restricted in all the intervention studies referenced above.

In human patients with CKD, hyperphosphatemia also is associated with progression. Phosphate binders decrease vascular calcification in human hemodialysis patients[15] and renal artery calcification is a superior predictor of progression to serum phosphorus concentration in human patients with diabetic nephropathy.[16] Higher plasma phosphate concentrations might therefore lead to CKD progression via calcification of the renal vasculature and subsequent ischemia.

The present study also found that low PCV was predictive of CKD progression in cats diagnosed at stage 2. The anemia of CKD is believed to be multifactorial. A reduction or relative deficiency in erythropoietin production is considered the main cause[17] because erythropoietin is produced by peritubular fibroblasts.[18] In human patients, gastrointestinal blood loss, anemia of inflammatory disease, and hemolysis due to uremic toxins also are believed to be etiological factors. Few cats in the present study were actually anemic, and the mild reduction in PCV seen in the progressive group would not be expected to compromise systemic oxygen delivery. However, the kidney operates at low oxygen tensions even in physiological conditions. In CKD, tubulointerstitial fibrosis and renal vascular lesions could result in hypoxia, which might be exacerbated by small changes in PCV.

If hypoxia is the link between low PCV and CKD progression, correction of anemia with erythropoietic drugs could delay disease progression. In human patients too, anemia has been associated with an increased rate of CKD progression,[19, 20] which can be reversed by erythropoietin therapy.[21, 22] Erythropoietin might improve oxygenation of renal tissues by increasing PCV. However, there have been very few placebo-controlled trials of erythropoietic factors due to the widespread assumption that these drugs are beneficial and concern that it would be unethical to deprive patients of treatment. It also has been suggested that erthyropoietin might be beneficial due to its anti-apoptotic effects.[23] Human recombinant erythropoietin has been used to treat anemia in cats with CKD, but this treatment results in a high incidence of antibody formation and red cell aplasia.[24] Even trials with recombinant feline erythropoietin have not prevented this serious complication.[25] Consequently, it has not been possible to evaluate whether treatment of anemia could delay progression in cats with CKD. Although associated with renal survival, PCV does not predict the development of azotemia in cats.[10]

It was not always possible to undertake thorough clinical evaluations on these cats, due to the first opinion setting. More thorough evaluations and diagnostic imaging, in particular, might have helped to identify causes of CKD progression. Furthermore, the effects of treatments such as renal diet and blood pressure therapy could not be evaluated in this study because treatments were introduced at different time points relative to diagnosis and tailored to individual cases. The treatments offered were those considered the current standard care for cats with CKD and are thus representative of first opinion practice. Prospective randomized controlled clinical trials would be indicated to evaluate the effects of such treatments on CKD progression. It also should be highlighted that treatments produced confounding effects. For example, treatment of hypertensive cats with amlodipine confounded the analysis of the role of hypertension in the progression of feline CKD. The incentives offered to clients encouraged good follow-up care in the present study. A large number of cats were included and changes in renal function were tracked over long periods of time for many of these cases.

In conclusion, the results of this study suggest that proteinuria, anemia, and hyperphosphatemia predict progression in feline CKD. These changes might reflect more progressive types of renal disease. Alternatively, they might reflect mechanisms of CKD progression such as tubular protein overload, hypoxia, and nephrocalcinosis.

Acknowledgment

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

The work was funded by Vetoquinol as part of a PhD studentship.

Footnotes
  1. 1

    Waltham feline renal diet

  2. 2

    Royal Canin feline renal diet

  3. 3

    Royal Canin feline renal special diet

  4. 4

    PASW version 18, SPSS Inc, Chicago, IL

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References