Changes

==Introduction==

==Introduction==

'''Chronic renal failure''' is the end result of persistent, chronic renal disease - it is usually '''irreversible''' and involves the '''gradual and progressive loss of nephrons'''. Clinical signs include '''polyuria/polydypsia (PU/PD)''' and '''uraemia''', and blood sample analysis shows '''azotaemia''', '''non-regenerative anaemia''' and '''hyperphosphataemia'''. Often presented as 'end stage kidney' disease, on gross pathology kidneys are '''shrunken, fibrosed, pale and firm'''.

'''Chronic renal failure''' is the end result of persistent, chronic renal disease - it is usually '''irreversible''' and involves the '''gradual and progressive loss of [[Nephron - Anatomy & Physiology|nephrons]]''' resulting in loss of function. Clinical signs include '''polyuria/polydipsia (PU/PD)''' and [[Uraemia|'''uraemia''']], and blood sample analysis shows [[Azotaemia|'''azotaemia''']], [[Regenerative and Non-Regenerative Anaemias|'''non-regenerative anaemia''']] and '''hyperphosphataemia'''. Often presented as 'end stage kidney' disease, on gross pathology kidneys are '''shrunken, fibrosed, pale and firm'''.

==Signalment==

==Signalment==

Chronic kidney disease is most common in '''geriatric cats'''. In these cases the cause is generally unknown. It can also occur in younger cats, but in these cases there tends to be an underlying intrinsic cause such as pyelonephritis, FIP, lymphoma, hypercalcaemia, polycystic kidney disease, amyloidosis, obstructive disease, glomerulonephritis, toxins or acute renal failure. It can also occur in the dog in one of the following three presentations; young dogs with heritable or breed associated disease; geriatric dogs suffering from chronic kidney disease; and dogs presenting with proteinurea or nephrotic syndrome at any age. Disease in this final group of dogs can be caused by a number of things such as pyelonephritis, leptospirosis, hypercalcaemic nephropathy, neoplasia, amyloidosis, obstructive disease, glomerulonephritis, toxins or acute renal failure.  

Chronic kidney disease is most common in '''geriatric cats'''. In these cases the '''cause''' is generally '''unknown''' and assumed to be '''age-related'''. It can also occur in '''younger cats''', but in these cases there tends to be an underlying intrinsic cause such as '''[[Pyelonephritis|pyelonephritis]], [[FIP|FIP]], [[Lymphoma|lymphoma]], [[Hypercalcaemia|hypercalcaemia]], polycystic kidney disease, [[Amyloidosis|amyloidosis]], obstructive disease, [[Glomerulonephritis|glomerulonephritis]], [[Toxicology|toxins]] or [[Acute Renal Failure|acute renal failure]]'''. It can also occur in the '''dog''' in one of the following three presentations; young dogs with '''heritable''' or breed associated disease; '''geriatric dogs''' suffering from chronic kidney disease; and dogs presenting with '''proteinurea or nephrotic syndrome''' at any age. Disease in this final group of dogs can be caused by a number of things such as '''[[Pyelonephritis|pyelonephritis]], [[Leptospirosis - Cats and Dogs|leptospirosis]], [[Hypercalcaemia|hypercalcaemic]] nephropathy, [[Neoplasia - Pathology|neoplasia]], [[Amyloidosis|amyloidosis]], obstructive disease, [[Glomerulonephritis|glomerulonephritis]], [[Toxicology|toxins]] or [[Acute Renal Failure|acute renal failure]]'''.  

==Clinical Signs==

==Clinical Signs==

'''Clinical signs''' do not tend to develop until damage to the kidneys is quite '''advanced''', as they can function adequately with destruction of up to three quarters of the nephrons. The severity of clinical signs normally correlates to the severity of renal failure. Prior to the development of clinical signs, the cat may be suffering chronic kidney disease (CKD) but it is only with the development of clinical signs that the disease complex is known as chronic renal failure (CRF).

'''Clinical signs''' do not tend to develop until damage to the kidneys is quite '''advanced''', as they can function adequately with destruction of up to three quarters of the [[Nephron - Anatomy & Physiology|nephrons]]. The severity of clinical signs normally correlates to the severity of renal failure. Prior to the development of clinical signs, the cat may be suffering chronic kidney disease (CKD) but it is only with the development of clinical signs that the disease complex is known as chronic renal failure (CRF).

    

    

For renal failure to be classed as chronic, clinical signs should be of '''two weeks or more duration''':

For renal failure to be classed as chronic, clinical signs should be of '''two weeks or more duration''':

* Polyuria and polydipsia

* '''Polyuria and polydipsia'''

* Anorexia

*''' Anorexia'''

* Weight loss

*''' Weight loss'''

* Blindness/hyphema - related to hypertension

* '''Blindness/hyphema - related to [[Systemic Hypertension|hypertension]]'''

* Dehydration

* '''[[Dehydration|Dehydration]]'''

* Constipation

* [[Colonic Impaction - Dog and Cat|'''Constipation''']]

* Endstage uraemia with clinical signs include oral ulceration, characteristic uraemic breath, vomiting and lethargy.

* '''Endstage [[Uraemia|uraemia]] with clinical signs include oral ulceration, characteristic uraemic breath, [[Vomiting|vomiting]] and lethargy'''

Following physical exam and basic diagnostics the following features may be evident:

Following physical exam and basic diagnostics the following features may be evident:

* Small kidneys

* '''Small kidneys'''

* Pale mucous membranes

* '''Pale mucous membranes'''

* Rubber jaw (fairly rare)  

* '''Rubber jaw (fairly rare)'''

* Cervical ventroflexion due to hypokalaemia

* '''Cervical ventroflexion due to [[Hypokalaemia|hypokalaemia]]'''

* Hypertensive retinopathy

* '''[[Systemic Hypertension|Hypertensive retinopathy]]'''

* Hypoproteinaemia

* '''Hypoproteinaemia'''

On post mortem, gross pathology will reveal kidneys that are '''shrunken, fibrosed, pale and firm'''.

On post mortem, gross pathology will reveal kidneys that are '''shrunken, fibrosed, pale and firm'''.

==Diagnosis==

==Diagnosis==

Depending on the clinical presentation and the wishes of the owner, a full work-up to diagnose an underlying cause may not be necessary (particularly in geriatric cats). If the cause for nephron dysfunction is pursued '''haemotology, biochemistry and urinalysis''' should be performed as standard. Additionally '''imaging''' of the urinary system by '''ultrasound''' or '''radiography''' can be performed. Finally, renal '''biopsy''' may be indicated, especially in the cases where a lesion has been identified. However these often fail to provide a conclusive diagnosis, with histopathology showing '''interstitial fibrosis''' regardless of the original cause.

Depending on the clinical presentation and the wishes of the owner, a full work-up to diagnose an underlying cause may not be necessary (particularly in geriatric cats). If the cause for nephron dysfunction is pursued '''haemotology, biochemistry and [[Urine Analysis - Pathology|urinalysis]]''' should be performed as standard. Additionally '''imaging''' of the urinary system by '''ultrasound''' or '''radiography''' can be performed. Finally, renal '''biopsy''' may be indicated, especially in the cases where a lesion has been identified. However these often fail to provide a conclusive diagnosis, with histopathology showing '''[[Interstitial Nephritis|interstitial fibrosis]]''' regardless of the original cause.

 

'''Plasma [[Urea|urea]] and [[Creatinine|creatinine]]''' are normally measured in early diagnostics, however they are relatively insensitive - only demonstrating renal disease when over two thirds of the nephrons no longer function. '''[[Urine Analysis - Pathology|Urine specific gravity]]''' is a more useful tool, as cats suffering from CRF begin to lose the ability to concentrate urine appropriately early in the disease. Measuring the '''[[Glomerular Filtration Rate|GFR]]''' is the '''ideal''' measurement of renal excretory function.

==Staging/Classification==

==Staging/Classification==

The disease can be staged. This helps to guide the prognosis and diagnostic plan. In addition it allows the clinician to monitor the progression of the disease over time in an indivdual animal.

The disease can be staged. This helps to guide the prognosis and diagnostic plan. In addition it allows the clinician to monitor the progression of the disease over time in an indivdual animal.

The '''IRIS (International Renal Insufficiency Society) Staging System''' is a system based on '''creatinine values''', which are an approximately equal to the Glomerular Filtration Rate (GFR):

The [http://www.iris-kidney.com/guidelines/en/staging_ckd.shtml|'''IRIS (International Renal Insufficiency Society) Staging System'''] is a system based on '''creatinine values''', which are an approximately equal to the Glomerular Filtration Rate (GFR):

(I) Non-azotaemic but some palpable and functional renal abnormalities. Creatinine <125 in dogs/<140 in cats

(I) Non-azotaemic but some palpable and functional renal abnormalities. Creatinine <125 in dogs/<140 in cats

(IV) Creatinine levels of > 440 with or without signs of uraemia

(IV) Creatinine levels of > 440 with or without signs of uraemia

Renal failure can also be classed according to protein:creatinine ratios and blood pressure readings.  

Renal failure can also be classed according to '''protein:creatinine ratios''' and '''blood pressure readings'''.  

==Management==

==Management==

(1) Search for an underlying cause - this may only be appropriate in young cats, cats with enlarged kidneys and in dogs. Otherwise it is very likely to be tubulointerstitial nephritis which is very common in elderly cats.

(1)''' Search for an underlying cause''' - this may only be appropriate in young cats, cats with enlarged kidneys and in dogs. Otherwise it is very likely to be [[[[Interstitial Nephritis|tubulointerstitial nephritis]] which is very common in elderly cats.

(2) Control any factors important in disease progression - these are normally self perpetuating.

(2) '''Control any factors important in disease progression''' - these are normally self perpetuating.

(3) Control factors that increase patient morbidity and quality of life, these are mainly complications of the 'uraemic syndrome'.  

(3) '''Control factors that increase patient morbidity and quality of life''', these are mainly complications of the '''[[Uraemia|'uraemic syndrome']]'''.  

==Maladaptive mechanisms==

==Maladaptive mechanisms==

Multiple maladaptive mechanisms are associated with CRF. They are the body's attempt to minimise the detrimental effects of the renal disease, but in time these mechanisms are damaging in themselves and actually cause the progression of the disease.  

Multiple maladaptive mechanisms are associated with CRF. They are the body's attempt to minimise the detrimental effects of the renal disease, but in time these mechanisms are damaging in themselves and actually cause the progression of the disease.  

===Secondary renal hyperparathyroidism===  

===[[Hyperparathyroidism|Secondary renal hyperparathyroidism]]===  

A reduction in the number of nephrons causes a reduction in the excretion of phosphate. As the level of phosphate in the body increases, parathyroid hormone (PTH) is stimulated. Over time this causes parathyroid gland hypertrophy and further increases in PTH secretion. This causes the release of calcium and phosphorous from the bones and deposition of these minerals in soft tissue. The end result is mineralisation of soft tissues and loss of bone density (rubber jaw).

A reduction in the number of nephrons causes a reduction in the excretion of phosphate. As the level of phosphate in the body increases, [[Parathyroid Hormone|parathyroid hormone (PTH)]] is stimulated. Over time this causes parathyroid gland hypertrophy and further increases in PTH secretion. This causes the release of [[Calcium|calcium]] and [[Phosphorus|phosphorus]] from the bones and deposition of these minerals in soft tissue. The end result is [[Mineralisation - Pathology|mineralisation]] of soft tissues and loss of bone density (rubber jaw).

Increased levels of phosphate in the plasma increase parathyroid hormone release by direct action, mass action and by inhibition of renal tubular production of calcitriol.  

Increased levels of phosphate in the plasma increase [[Parathyroid Hormone|parathyroid hormone]] release by direct action, mass action and by inhibition of renal tubular production of [[Calcitriol|calcitriol]].  

===Uraemic syndrome===

===[[Uraemia|Uraemic syndrome]]===

The uraemic syndrome is the clinical signs associated with azotaemia.

The uraemic syndrome is the clinical signs associated with [[Azotaemia|azotaemia]].

===Hyperkalaemia/Hypokalaemia===

===Hyperkalaemia/[[Hypokalaemia|Hypokalaemia]]===

Hyperkalaemia normally occurs in cases of acute renal failure, but may also occur in endstage CRF, especially the animal is treated with ACE-inhibitors. Hypokalaemia can also occur, this may be caused by mineral deficiency in the diet and poor appetite.  

Hyperkalaemia normally occurs in cases of acute renal failure, but may also occur in endstage CRF, especially the animal is treated with ACE-inhibitors. [[Hypokalaemia|Hypokalaemia]] can also occur, this may be caused by mineral deficiency in the diet and poor appetite.  

===Metabolic Acidosis===

===Metabolic Acidosis===

This is common is cases that have acutely decompensated, and can be diagnosed by measuring bicarbonate levels in the plasma.  

This is common is cases that have acutely decompensated, and can be diagnosed by measuring bicarbonate levels in the plasma.  

===Anaemia===

===[[Regenerative and Non-Regenerative Anaemias|Anaemia]]===

Several factors contribute to anaemia in Chronic Renal failure:

Several factors contribute to the non-regenerative anaemia of Chronic Renal failure:

(1) Low levels of Erythropoetin (as it is produced in the kidney) - this is the most significant cause and the limiting factor in the cats recovery from the anaemia

(1) Low levels of Erythropoetin (as it is produced in the kidney) - this is the most significant cause and the limiting factor in the cats recovery from the anaemia

(2) Decreased lifespan of red blood cells

(2) Decreased lifespan of [[Erythrocytes|red blood cells]]

(3) Blood loss through regular blood sampling, surgical procedures and GI ulceration

(3) Blood loss through regular blood sampling, surgical procedures and GI ulceration

(4) Iron deficiency

(4) [[Iron|Iron]] deficiency

 

(5) Inhibition of erythropoesis by uraemic inhibition

===[[Urinary System (Content Map) - Pathology|Urinary Tract]] Infection===

These are very common in CRF cases. It can cause decompensation and a worsening of clinical signs. In some cases it may develop into pyelonephritis, ultimately causing progression of disease. In cats the most common causative organism is [[Escherichia coli|''E. coli'']]. The main reason for treatment is to improve quality of life.

===Urinary Tract Infection===

===[[Dehydration|Dehydration]]===

These are very common in CRF cases. It can cause decompensation and a worsening of clinical signs. In some cases it may develop into pyelonephritis, ultimately causing progression of disease. In cats the most common causative organism is ''E. coli''. The main reason for treatment is to improve quality of life.  

Dehydration results in the development of prerenal [[Azotaemia|azotaemia]].

===Dehydration===

===[[Systemic Hypertension|Systemic Hypertension]]===

Dehydration results in the development of prerenal azotaemia.

A proportion of cats with CRF develop hypertension. The consequence of this may be cardiac, ocular, renal and neurological damage.

==Treatment==

==Treatment==

The feeding of a phosphate restricted diet (Renal Care Diet) is proven to extend lifespan. In addition intestinal phosphate binders such as aluminium hydroxide can be added to food.

The feeding of a '''phosphate restricted diet''' (Renal Care Diet) is proven to extend lifespan. In addition intestinal phosphate binders such as aluminium hydroxide can be added to food.

 

Feeding of a '''protein restricted diet''' (Renal Care Diet) is ideal as this reduces the amount of uraemic toxins produces, improving the quality of life of the animal. The disadvantage of this that the diet is '''unpalatable''' so in an anorexic cat this may not be appropriate. It is better to have a cat eating on a high protein diet that have a cat anorexic on a low protein diet. It is suggested that the cat be started on the diet whilst it is feeling systemically well, rather than introducing it when the effects of CRF make it less likely to eat.  

Feeding of a protein restricted diet (Renal Care Diet) is ideal as this reduces the amount of uraemic toxins produces, improving the quality of life of the animal. The disadvantage of this that the diet is unpalatable so in an anorexic cat this may not be appropriate. It si better to have a cat eating on a high protein diet that have a cat anorexic on a low protein diet. It is suggested that the cat be started on the diet whislt it is feeling systemically well, rather than introducing it when the effects of CRF make it less likely to eat.  

In cases of hypokalaemia, '''potassium supplements''' may be given in food, however they are quite '''unpalatable''' so this may be difficult. Following treatment appetite and muscle strength should improve.

In cases of hypokalaemia potassium supplement s may be given in food, however they are quite unpalatable so this may be difficult. Following treatment appetite and muscle strength should improve.

Immedite treatment of metabolic acidosis is with '''IVFT''', with a product containing low levels of bicarbonate such as Hartmanns. Longterm an '''alkali dietary supplements''' can be fed.

Immedite treatment of metabolic acidosis is with IVFT, with a product containing low levels of bicarbonate such as Hartmanns. Longterm an alkali dietary supplements can be fed.

Therapy of anaemia should be aimed at '''reducing blood loss''' and '''increasing RBC production''' where appropriate. '''Iron supplementation''' should be given. A specific therapy for low erythropoetin levels is the administration of '''recombinant human erythropoetin'''. However it is expensive and cross reactions are common (occuring at any point during the treatment course). Therefore its use should be carefully considered, and it should not be used unless the animal is demonstrating clear clinical signs associated with anaemia. Darbepoetin is an alternative with potentially fewer side-effects.  

Therapy of anaemia should be aimed at reducing blood loss and increasing RBC production where appropriate. Iron supplementation should be given. A specific therapy for low erythropoetin levels is the administration of recombinant human erythropoetin. However it is expensive and cross reactions are common (occuring at any point during the treatment course). Therefore its use should be carefully considered, and it should not be used unless the animal is demonstrating clear clinical signs associated with anaemia. Darbepoetin is an alternative with potentially fewer side-effects.  

Patients with chronic kidney disease should be monitored for UTI's - ideally '''cystocentesis''' should be performed at the time of each blood test. Treatment should be with an appropriate '''antibiotic''' and the animal should be encouraged to drink.  

Patients with chronic kidney disease should be monitored for UTI's - ideally cystocentesis should be performed at the time of each blood test. Treatment should be with an appropriate antibiotic and the animal should be encouraged to drink.  

In dehydrated animals, '''fluids''' should be administered by; '''promoting oral intake'''; '''subcutaneous fluid administration'''; '''IVFT'''; or by '''oesophageal tube'''.

In dehydrated animals, fluids should be administered by; promoting oral intake; subcutaneous fluid administration; IVFT; or by oesophageal tube.

'''Blood pressure readings''' should be taken regularly and any cat with a reading consistently higher than '''170mmHg''' should receive anti-hypertensive treatment. Treatment is staged, involving a combination of a '''low-sodium diet''' and the administration of the '''calcium-channel blocker amlopidine'''. Additional treatment with ACE-Inhibitors can be considered. The cat should be monitored closely for signs of hypotension when treatment is introduced.  

In the early stages of disease it may be appropriate to treat the animal with ACE-Inhibitors. The drug dilates the efferent arterioles of the glomerulus, thus decreasing glomerular capillary pressure and periability - which decreases proteinurea and slows the progression of glomerulosclerosis. It should be noted that the administration of this drug to advanced cases of CRF may in fact be detrimental.

In the early stages of disease it may be appropriate to treat the animal with '''[[Angiotensin Converting Enzyme|ACE]]-Inhibitors'''. The drug dilates the efferent arterioles of the [[Glomerular Apparatus and Filtration - Anatomy & Physiology|glomerulus]], thus decreasing glomerular capillary pressure and permeability - which '''decreases proteinurea''' and '''slows the progression of glomerulosclerosis'''. It should be noted that the administration of this drug to '''advanced cases''' of CRF may in fact be '''detrimental'''.

==Prognosis==

==Prognosis==

The disease is progressive and gradually more nephrons fail to function and fibrose. Eventually the cat will succumb to the disease, with the progression of clinical signs and a drop in the quality of life. However with appropriate management it may be several years before this occurs. Prognosis is clearly directly correlated to the stage of renal failure, with a worse stage indicating a poorer prognosis and shorter survival time.

The disease is '''progressive''' and gradually more nephrons fail to function and fibrose. Eventually the cat will succumb to the disease, with the progression of clinical signs and a drop in the quality of life. However with appropriate management it may be several years before this occurs. '''Prognosis''' is clearly directly '''correlated to the stage of renal failure''', with a worse stage indicating a poorer prognosis and shorter survival time.

 

 

 

 

[[Category:Renal Failure]]

[[Category:Renal Failure]]

[[Category:To Do - Urinary]]

[[Category:To Do - Urinary]]

[[Category: To Do - Siobhan Brade]]

[[Category: To Do - Siobhan Brade]]