Chronic Kidney Disease in Cats: Causes, Symptoms, Treatment, and Prognosis Guide
Chronic Kidney Disease in Cats: Causes, Symptoms, Treatment, and Prognosis Guide
Chronic kidney disease (CKD) is a common ailment that affects 1% to 3% of cats, leading to a gradual decline in kidney function. CKD is a serious condition that can persist for months or years, ultimately causing death. While some cats with CKD maintain stable serum creatinine levels for months or even years, the associated nephron damage is progressive and irreversible. Early diagnosis of CKD followed by appropriate treatment can improve survival rates and slow the progression of the disease.
Causes of Chronic Kidney Disease in Cats
The cause of CKD in cats is often difficult to determine. Because the vascular and tubular components of the nephron are interdependent, the endpoint of irreversible glomerular or tubular injury is the same: replacement of nephrons with fibrous scar tissue.
Chronic kidney lesions exhibit morphologic heterogeneity among nephrons, ranging from severely atrophic to markedly hypertrophic. The histologic changes are not process-specific, and therefore, a cause-specific diagnosis is often not possible. The most common histologic diagnosis is chronic tubulointerstitial nephritis. Kidney diseases associated with the development of CKD in cats are listed in Table 1.
Progressive disease that slowly destroys the kidneys causes the intact kidneys to undergo compensatory hypertrophy, which can delay the onset of kidney failure. Therefore, when kidney failure occurs (<25% of the original nephron function), nephron hypertrophy is no longer able to maintain sufficient kidney function. For example, an 80% loss of nephrons may lead to a serum creatinine concentration of 2 mg/dL. As the disease progresses, the serum creatinine concentration should be around 4 mg/dL when 90% of the nephrons are gone.
At the onset of International Renal Interest Society (IRIS) stage 4 CKD (serum creatinine concentration > 5 mg/dL; Table 2), a cat may have fewer than 10% of its original number of nephrons. These numbers highlight the importance of early diagnosis and intervention.
Pathophysiology of Chronic Kidney Disease
The pathophysiology of CKD can be considered at both the organ and the systemic levels.
Decreased glomerular filtration rate
At the organ level, the most basic abnormality is the loss of nephrons and decreased glomerular filtration rate. Decreased GFR leads to an increase in the concentration of substances in plasma that are normally excreted by the kidneys.
Hormonal dysregulation
In addition to excreting metabolic waste products and maintaining fluid and electrolyte balance, the kidneys serve as endocrine organs, metabolizing and excreting a variety of peptide hormones. Therefore, hormonal dysregulation is part of the pathogenesis of CKD as a multisystem disease. For example, decreased production of erythropoietin leads to the nonregenerative anemia of CKD, and decreased metabolism and excretion of parathyroid hormone leads to osteodystrophy.
Compensatory mechanisms
Finally, some of the pathophysiology of CKD is caused by compensatory mechanisms. To maintain adequate kidney function, the individual glomerular filtration rate (GFR) of intact nephrons increases; however, proteinuria and glomerulosclerosis may be a consequence or "trade-off" of this hyperfiltration (Figure 2). In chronic kidney disease, autoregulation of renal blood flow is lost, and the GFR of individual nephrons increases proportionally to the number of nephrons lost. The resultant increase in intraglomerular pressure damages the glomerular capillary wall, increasing plasma protein filtration, leading to subsequent glomerular and tubulointerstitial damage.
Staging of Chronic Kidney Disease in Cats
Many different terms have been used to describe kidney disease and decreased kidney function, and unfortunately, these terms can be confusing due to the lack of standardized definitions and applications.
Kidney disease or kidney failure: Which term?
Chronic kidney disease is more widely preferred than chronic kidney failure because chronic kidney disease can exist without kidney failure, and patients often feel discouraged when "failure" is included in the diagnosis. Kidney failure - defined as persistent azotemia superimposed on an inability to concentrate urine - results when 75% or more of the nephrons in both kidneys are nonfunctional.
IRIS seeks to promote the scientific understanding of small animal kidney disease, specifically helping practitioners better diagnose, understand, and treat kidney disease in dogs and cats. IRIS has developed guidelines (Table 2) - adopted by the American and European Societies of Veterinary Nephrology and Urology - for staging stable feline CKD to:
Improve communication about CKD
Provide appropriate diagnostic and therapeutic approaches for patients with different degrees of CKD
Serum creatinine concentration
The staging system outlined in Table 2 is not used until CKD is confirmed. The system categorizes kidney disease into one of four stages based on the serum creatinine concentration of a hydrated and stable cat with CKD; stability is demonstrated by a serum creatinine concentration variation of less than 20% over at least 2 weeks. Note that this staging system indicates that azotemia in cats begins at a serum creatinine concentration of 1.6 mg/dL or higher. However, serum creatinine concentration must always be interpreted in light of the patient's muscle mass, urine specific gravity (USG), and physical examination findings to rule out pre-renal and post-renal causes of azotemia. This staging system does not apply to patients with pre-renal or post-renal azotemia or those with an acute exacerbation of either acute or chronic kidney disease.
Proteinuria
The stages in Table 2 are further subdivided by the presence or absence of proteinuria, renal proteinuria being:
Persistent (at least 2 positive test results 10-14 days apart)
Associated with an inactive urine sediment
Of glomerular or tubular origin (ie, overfiltration, decreased tubular reabsorption, or both)
A urine protein-to-creatinine ratio > 2 indicates glomerular-range proteinuria, which is uncommon in cats compared to dogs. It is important to realize that this ratio cannot differentiate between renal proteinuria and proteinuria associated with lower urinary tract inflammation. Clinicians need to differentiate between proteinurias by evaluating the urine sediment.
Systolic blood pressure
Systolic blood pressure in cats is usually measured using a Doppler technique. IRIS blood pressure segmentation is based on the risk of target organ damage (eyes, brain, heart, and kidneys). Most clinicians consider systolic hypertension to be systolic blood pressure > 160 mm Hg, and treatment is initiated at this point.
Clinical Signs and Diagnosis of Chronic Kidney Disease in Cats
Clinical signs
Clinical signs of CKD may be absent in the early stages, while in the later stages, they are typically nonspecific, such as lethargy, weakness, anorexia, vomiting, and dehydration. Occasionally, uremic breath or oral ulcers may be observed. Unique signs of CKD (compared to acute kidney injury) include long-term weight loss and a history of polydipsia/polyuria, poor body condition, small and irregular kidneys, and secondary hyperparathyroidism.
Diagnostic findings
The classic diagnosis, based on renal azotemia (persistent azotemia superimposed on an inability to concentrate urine), falls into stages 2-4 of chronic kidney disease. Some cats with renal azotemia retain the ability to produce a concentrated urine (USG > 1.035), and in these cases In these cases, the response to fluid therapy can help differentiate between pre-renal and renal azotemia.
Stage 1 CKD can be diagnosed based on the following:
Abnormal findings on renal palpation or ultrasound/radiographic examination
Persistent renal proteinuria
Inability to concentrate urine due to kidney disease
An increase in serum creatinine over time, even if values remain within the normal range
For example, a serum creatinine concentration that increases from 0.6 mg/dL to 1.2 mg/dL over several years may indicate a GFR reduction of at least 50% (at least 50% of nephrons lost because the compensatory hypertrophy of remaining nephrons increases their functional capacity).
Serum symmetric dimethylarginine
Serum symmetric dimethylarginine (SDMA) is a novel marker of kidney function that may aid in the early diagnosis of feline CKD. In a recent longitudinal study of cats with CKD, SDMA levels were elevated above normal for approximately 17 months before serum creatinine levels exceeded the reference range (> 2.1 mg/dL). Notably, if a serum creatinine concentration ≥ 1.6 mg/dL was considered abnormal in this study, then serum creatinine and SDMA identified renal azotemia at virtually the same time.
Diagnostic Approach to Feline CKD
In general, once CKD is identified and staged, the diagnostic approach for patients is focused on 3 areas (Table 3):
Characterizing the primary kidney disease and/or complicating disease processes
Analyzing the stability and functional characteristics of the kidney disease
Assessing patient problems related to declining kidney function
Further investigation of kidney disease (in addition to a complete blood count, serum biochemical analysis, and urinalysis) includes:
Proteinuria quantification
Blood pressure measurement
Urine culture
Urinary system radiographs and ultrasound
The stability of kidney function is assessed by monitoring for changes in the abnormalities found during the initial characterization of the kidney disease. This monitoring should always include:
Serum biochemical markers
Urinalysis
Proteinuria quantification
Blood pressure measurement
Monitoring may also include follow-up urine cultures and ultrasound examinations. In the early stages of CKD, further investigation of kidney disease is most important because correction of the underlying disease or complicating disease processes has the greatest potential to improve or stabilize kidney function. In the early stages of CKD, characterizing the stability of the disease is most important because appropriate treatment at this time has the greatest potential to stabilize kidney function. In the later stages of CKD, when clinical signs tend to be more severe, characterizing patient problems becomes more important. In this situation, diagnostic (and subsequent therapeutic) efforts should be directed towards the patient's problems, including anorexia, vomiting, dehydration, acidosis, hypokalemia, and anemia.
Treatment Approach to Feline CKD
Similar to the diagnostic approach to CKD (see Diagnostic Approach to Feline CKD), treatment should be adjusted based on the patient's stage of disease (Table 3). For example, in the early stages of CKD, disease-specific treatment aimed at kidney stones and bacterial pyelonephritis, as well as treatment aimed at slowing the progression of kidney disease (nephroprotective treatment), is most valuable. Nephroprotective treatment includes dietary modifications, lowering serum phosphorus concentrations, and reducing soft-tissue mineralization (Figure 3).
Proteinuria is an important risk factor for the development and progression of azotemia and decreased survival in cats. Angiotensin receptor blockers and calcium channel blockers are used to reduce proteinuria and normalize systemic and intraglomerular blood pressure. In the later stages of CKD, treatment tends to focus on mitigating clinical signs associated with declining kidney function.
Acute Decompensation of CKD
Causes of acute or chronic decompensation are generally categorized into three groups (Table 4):
Pre-renal: The most common pre-renal cause is dehydration/hypovolemia and decreased renal perfusion; decreased renal perfusion may also be associated with decreased cardiac output and thromboembolic disease
Renal: Renal causes include ascending urinary tract infection (ie, pyelonephritis that may or may not be associated with kidney stones), renal neoplasia, and a rapid progression of an underlying kidney disease (rare)
Post-renal: Post-renal causes include obstructive uropathy - most commonly, migration of kidney stones into the ureter (less commonly, inflammatory debris or strictures), leading to partial or complete obstruction.
Prognosis for Feline CKD
In a recent retrospective study, survival time was correlated with the IRIS CKD staging system (Table 5). In Table 5, IRIS CKD stage 2 was modified to stage 2b, which included only cats with stable serum creatinine concentrations between 2.3 and 2.8 mg/dL. This change was made because the upper limit of the normal reference range for serum creatinine at the study center was 2.3 mg/dL; in other words, the researchers were unable to retrospectively identify cats with serum creatinine concentrations between 1.6 and 2.3 mg/dL. The rest of the staging system used in this study correlated with standard IRIS staging.
Note that survival rates progressively decrease with increasing CKD stage: 1151 days for stage 2b cats (which would be higher if all stage 2 cats were included), 679 days for stage 3 cats, and 35 days for stage 4 cats. This trend is not surprising, but the actual numbers help with better predictions and highlight the importance of early diagnosis.
Summary
Chronic kidney disease (CKD) is a serious condition that can affect a cat's health and lifespan. Early diagnosis and treatment are crucial.
Key Takeaways
Here are some important points to remember about CKD in cats:
Early diagnosis: Early diagnosis and treatment can significantly improve survival rates. Regular checkups and monitoring serum creatinine and SDMA levels are crucial.
Dietary management: A low-phosphorus, low-protein diet can help slow the progression of CKD.
Medication: Angiotensin receptor blockers and calcium channel blockers can reduce proteinuria and blood pressure, protecting the kidneys.
Hydration: Ensuring adequate water intake can help dilute urine, reducing the burden on the kidneys.
Regular monitoring: Regular monitoring of a cat's kidney function, including serum creatinine, SDMA, blood pressure, and proteinuria, can help understand the disease's progression and adjust treatment plans.
CKD is a challenging condition, but with early diagnosis, appropriate treatment, and careful care, we can help cats better manage this disease, improving their quality of life and lifespan.
Chronic kidney disease (CKD) is a common ailment that affects 1% to 3% of cats, leading to a gradual decline in kidney function. CKD is a serious condition that can persist for months or years, ultimately causing death. While some cats with CKD maintain stable serum creatinine levels for months or even years, the associated nephron damage is progressive and irreversible. Early diagnosis of CKD followed by appropriate treatment can improve survival rates and slow the progression of the disease.
Causes of Chronic Kidney Disease in Cats
The cause of CKD in cats is often difficult to determine. Because the vascular and tubular components of the nephron are interdependent, the endpoint of irreversible glomerular or tubular injury is the same: replacement of nephrons with fibrous scar tissue.
Chronic kidney lesions exhibit morphologic heterogeneity among nephrons, ranging from severely atrophic to markedly hypertrophic. The histologic changes are not process-specific, and therefore, a cause-specific diagnosis is often not possible. The most common histologic diagnosis is chronic tubulointerstitial nephritis. Kidney diseases associated with the development of CKD in cats are listed in Table 1.
Progressive disease that slowly destroys the kidneys causes the intact kidneys to undergo compensatory hypertrophy, which can delay the onset of kidney failure. Therefore, when kidney failure occurs (<25% of the original nephron function), nephron hypertrophy is no longer able to maintain sufficient kidney function. For example, an 80% loss of nephrons may lead to a serum creatinine concentration of 2 mg/dL. As the disease progresses, the serum creatinine concentration should be around 4 mg/dL when 90% of the nephrons are gone.
At the onset of International Renal Interest Society (IRIS) stage 4 CKD (serum creatinine concentration > 5 mg/dL; Table 2), a cat may have fewer than 10% of its original number of nephrons. These numbers highlight the importance of early diagnosis and intervention.
Pathophysiology of Chronic Kidney Disease
The pathophysiology of CKD can be considered at both the organ and the systemic levels.
Decreased glomerular filtration rate
At the organ level, the most basic abnormality is the loss of nephrons and decreased glomerular filtration rate. Decreased GFR leads to an increase in the concentration of substances in plasma that are normally excreted by the kidneys.
Hormonal dysregulation
In addition to excreting metabolic waste products and maintaining fluid and electrolyte balance, the kidneys serve as endocrine organs, metabolizing and excreting a variety of peptide hormones. Therefore, hormonal dysregulation is part of the pathogenesis of CKD as a multisystem disease. For example, decreased production of erythropoietin leads to the nonregenerative anemia of CKD, and decreased metabolism and excretion of parathyroid hormone leads to osteodystrophy.
Compensatory mechanisms
Finally, some of the pathophysiology of CKD is caused by compensatory mechanisms. To maintain adequate kidney function, the individual glomerular filtration rate (GFR) of intact nephrons increases; however, proteinuria and glomerulosclerosis may be a consequence or "trade-off" of this hyperfiltration (Figure 2). In chronic kidney disease, autoregulation of renal blood flow is lost, and the GFR of individual nephrons increases proportionally to the number of nephrons lost. The resultant increase in intraglomerular pressure damages the glomerular capillary wall, increasing plasma protein filtration, leading to subsequent glomerular and tubulointerstitial damage.
Staging of Chronic Kidney Disease in Cats
Many different terms have been used to describe kidney disease and decreased kidney function, and unfortunately, these terms can be confusing due to the lack of standardized definitions and applications.
Kidney disease or kidney failure: Which term?
Chronic kidney disease is more widely preferred than chronic kidney failure because chronic kidney disease can exist without kidney failure, and patients often feel discouraged when "failure" is included in the diagnosis. Kidney failure - defined as persistent azotemia superimposed on an inability to concentrate urine - results when 75% or more of the nephrons in both kidneys are nonfunctional.
IRIS seeks to promote the scientific understanding of small animal kidney disease, specifically helping practitioners better diagnose, understand, and treat kidney disease in dogs and cats. IRIS has developed guidelines (Table 2) - adopted by the American and European Societies of Veterinary Nephrology and Urology - for staging stable feline CKD to:
Improve communication about CKD
Provide appropriate diagnostic and therapeutic approaches for patients with different degrees of CKD
Serum creatinine concentration
The staging system outlined in Table 2 is not used until CKD is confirmed. The system categorizes kidney disease into one of four stages based on the serum creatinine concentration of a hydrated and stable cat with CKD; stability is demonstrated by a serum creatinine concentration variation of less than 20% over at least 2 weeks. Note that this staging system indicates that azotemia in cats begins at a serum creatinine concentration of 1.6 mg/dL or higher. However, serum creatinine concentration must always be interpreted in light of the patient's muscle mass, urine specific gravity (USG), and physical examination findings to rule out pre-renal and post-renal causes of azotemia. This staging system does not apply to patients with pre-renal or post-renal azotemia or those with an acute exacerbation of either acute or chronic kidney disease.
Proteinuria
The stages in Table 2 are further subdivided by the presence or absence of proteinuria, renal proteinuria being:
Persistent (at least 2 positive test results 10-14 days apart)
Associated with an inactive urine sediment
Of glomerular or tubular origin (ie, overfiltration, decreased tubular reabsorption, or both)
A urine protein-to-creatinine ratio > 2 indicates glomerular-range proteinuria, which is uncommon in cats compared to dogs. It is important to realize that this ratio cannot differentiate between renal proteinuria and proteinuria associated with lower urinary tract inflammation. Clinicians need to differentiate between proteinurias by evaluating the urine sediment.
Systolic blood pressure
Systolic blood pressure in cats is usually measured using a Doppler technique. IRIS blood pressure segmentation is based on the risk of target organ damage (eyes, brain, heart, and kidneys). Most clinicians consider systolic hypertension to be systolic blood pressure > 160 mm Hg, and treatment is initiated at this point.
Clinical Signs and Diagnosis of Chronic Kidney Disease in Cats
Clinical signs
Clinical signs of CKD may be absent in the early stages, while in the later stages, they are typically nonspecific, such as lethargy, weakness, anorexia, vomiting, and dehydration. Occasionally, uremic breath or oral ulcers may be observed. Unique signs of CKD (compared to acute kidney injury) include long-term weight loss and a history of polydipsia/polyuria, poor body condition, small and irregular kidneys, and secondary hyperparathyroidism.
Diagnostic findings
The classic diagnosis, based on renal azotemia (persistent azotemia superimposed on an inability to concentrate urine), falls into stages 2-4 of chronic kidney disease. Some cats with renal azotemia retain the ability to produce a concentrated urine (USG > 1.035), and in these cases In these cases, the response to fluid therapy can help differentiate between pre-renal and renal azotemia.
Stage 1 CKD can be diagnosed based on the following:
Abnormal findings on renal palpation or ultrasound/radiographic examination
Persistent renal proteinuria
Inability to concentrate urine due to kidney disease
An increase in serum creatinine over time, even if values remain within the normal range
For example, a serum creatinine concentration that increases from 0.6 mg/dL to 1.2 mg/dL over several years may indicate a GFR reduction of at least 50% (at least 50% of nephrons lost because the compensatory hypertrophy of remaining nephrons increases their functional capacity).
Serum symmetric dimethylarginine
Serum symmetric dimethylarginine (SDMA) is a novel marker of kidney function that may aid in the early diagnosis of feline CKD. In a recent longitudinal study of cats with CKD, SDMA levels were elevated above normal for approximately 17 months before serum creatinine levels exceeded the reference range (> 2.1 mg/dL). Notably, if a serum creatinine concentration ≥ 1.6 mg/dL was considered abnormal in this study, then serum creatinine and SDMA identified renal azotemia at virtually the same time.
Diagnostic Approach to Feline CKD
In general, once CKD is identified and staged, the diagnostic approach for patients is focused on 3 areas (Table 3):
Characterizing the primary kidney disease and/or complicating disease processes
Analyzing the stability and functional characteristics of the kidney disease
Assessing patient problems related to declining kidney function
Further investigation of kidney disease (in addition to a complete blood count, serum biochemical analysis, and urinalysis) includes:
Proteinuria quantification
Blood pressure measurement
Urine culture
Urinary system radiographs and ultrasound
The stability of kidney function is assessed by monitoring for changes in the abnormalities found during the initial characterization of the kidney disease. This monitoring should always include:
Serum biochemical markers
Urinalysis
Proteinuria quantification
Blood pressure measurement
Monitoring may also include follow-up urine cultures and ultrasound examinations. In the early stages of CKD, further investigation of kidney disease is most important because correction of the underlying disease or complicating disease processes has the greatest potential to improve or stabilize kidney function. In the early stages of CKD, characterizing the stability of the disease is most important because appropriate treatment at this time has the greatest potential to stabilize kidney function. In the later stages of CKD, when clinical signs tend to be more severe, characterizing patient problems becomes more important. In this situation, diagnostic (and subsequent therapeutic) efforts should be directed towards the patient's problems, including anorexia, vomiting, dehydration, acidosis, hypokalemia, and anemia.
Treatment Approach to Feline CKD
Similar to the diagnostic approach to CKD (see Diagnostic Approach to Feline CKD), treatment should be adjusted based on the patient's stage of disease (Table 3). For example, in the early stages of CKD, disease-specific treatment aimed at kidney stones and bacterial pyelonephritis, as well as treatment aimed at slowing the progression of kidney disease (nephroprotective treatment), is most valuable. Nephroprotective treatment includes dietary modifications, lowering serum phosphorus concentrations, and reducing soft-tissue mineralization (Figure 3).
Proteinuria is an important risk factor for the development and progression of azotemia and decreased survival in cats. Angiotensin receptor blockers and calcium channel blockers are used to reduce proteinuria and normalize systemic and intraglomerular blood pressure. In the later stages of CKD, treatment tends to focus on mitigating clinical signs associated with declining kidney function.
Acute Decompensation of CKD
Causes of acute or chronic decompensation are generally categorized into three groups (Table 4):
Pre-renal: The most common pre-renal cause is dehydration/hypovolemia and decreased renal perfusion; decreased renal perfusion may also be associated with decreased cardiac output and thromboembolic disease
Renal: Renal causes include ascending urinary tract infection (ie, pyelonephritis that may or may not be associated with kidney stones), renal neoplasia, and a rapid progression of an underlying kidney disease (rare)
Post-renal: Post-renal causes include obstructive uropathy - most commonly, migration of kidney stones into the ureter (less commonly, inflammatory debris or strictures), leading to partial or complete obstruction.
Prognosis for Feline CKD
In a recent retrospective study, survival time was correlated with the IRIS CKD staging system (Table 5). In Table 5, IRIS CKD stage 2 was modified to stage 2b, which included only cats with stable serum creatinine concentrations between 2.3 and 2.8 mg/dL. This change was made because the upper limit of the normal reference range for serum creatinine at the study center was 2.3 mg/dL; in other words, the researchers were unable to retrospectively identify cats with serum creatinine concentrations between 1.6 and 2.3 mg/dL. The rest of the staging system used in this study correlated with standard IRIS staging.
Note that survival rates progressively decrease with increasing CKD stage: 1151 days for stage 2b cats (which would be higher if all stage 2 cats were included), 679 days for stage 3 cats, and 35 days for stage 4 cats. This trend is not surprising, but the actual numbers help with better predictions and highlight the importance of early diagnosis.
Summary
Chronic kidney disease (CKD) is a serious condition that can affect a cat's health and lifespan. Early diagnosis and treatment are crucial.
Key Takeaways
Here are some important points to remember about CKD in cats:
Early diagnosis: Early diagnosis and treatment can significantly improve survival rates. Regular checkups and monitoring serum creatinine and SDMA levels are crucial.
Dietary management: A low-phosphorus, low-protein diet can help slow the progression of CKD.
Medication: Angiotensin receptor blockers and calcium channel blockers can reduce proteinuria and blood pressure, protecting the kidneys.
Hydration: Ensuring adequate water intake can help dilute urine, reducing the burden on the kidneys.
Regular monitoring: Regular monitoring of a cat's kidney function, including serum creatinine, SDMA, blood pressure, and proteinuria, can help understand the disease's progression and adjust treatment plans.
CKD is a challenging condition, but with early diagnosis, appropriate treatment, and careful care, we can help cats better manage this disease, improving their quality of life and lifespan.
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