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==Description==

==Description==

Uraemia describes the clinical syndrome caused by [[Azotaemia|azotaemia]], an increase in the blood concentrations of urea and creatinine.  The major cause of azotaemia is [[Kidney Renal Failure - Pathology|renal failure]] but it is an insensitive indicator of this disease, only becoming detectable when more than approximately two thirds of the nephrons are no longer functional.

Uraemia describes the clinical systemic syndrome that occurs in animals suffering from [[Kidney Renal Failure - Pathology|renal failure]].  Traditionally, uraemia was thought to caused by caused by [[Azotaemia|azotaemia]], an increase in the blood concentrations of urea and creatinine, but it is now apparent that multiple '''uraemic toxins''' cause derangements in many metabolic processes.  Azotaemia is important in the diagnosis of uraemia but it is an insensitive indicator of renal failure, only becoming detectable when more than approximately two thirds of the nephrons are no longer functional.

===Pathophysiology===

===Pathophysiology===

Uraemia causes pathological changes of arteriolar fibrinoid degeneration and this affects multiple organ systems and produces marked clinical signs.  It may develop acutely or it may develop gradually in animals with chronic kidney disease.

The kidney has multiple metabolic functions, removing nitrogenous waste from the plasma, maintaining electrolyte and acid/base balance and producing hormones such as erythropoietin (EPO).  Renal failure causes alterations in all of these functions causing the clinical signs of uraemia.

Uraemic toxins - P, CT, PTH.

 

Other uraemic toxins include parathyroid hormone (PTH), phosphate, insulin, gastrin, glucagon and prolactin.  PTH is released due to hypocalcaemia caused by phosphate retention and reduced production of vitamin D and its effects produce '''secondary renal hyperparathyroidism'''.

==Signalment==

==Signalment==

Uraemia is described almost exclusively in animals with renal failure.

Uraemia is described almost exclusively in animals with renal failure.

==Diagnosis==

==Diagnosis==

===Clinical Signs===

===Clinical Signs===

[[Image:uraemia.gif|right|thumb|125px|<center>Lesions due to uraemia associated with pyelonephritis and chronic kidney disease<br><small>Copyright Alun Williams 2007 (RVC))</center></small>]]

[[Image:uraemia.gif|right|thumb|125px|<center>Lesions due to uraemia associated with pyelonephritis and chronic kidney disease<br><small>Copyright Alun Williams 2007 (RVC))</center></small>]]

The most common syndromes encountered in animals with uraemia are:

The most common syndromes encountered in animals with uraemia are:

*'''Oral ulceration''' - This occurs especially at the [[Oral Cavity - Teeth & Gingiva - Anatomy & Physiology|fauces]] of the mouth and on the margins of the [[Oral Cavity - Tongue - Anatomy & Physiology|tongue]].  Halitosis is often a feature of this syndrome as the lesions become secondarily infected oral bacteria such as ''[[Fusobacterium necrophorum]]''.  On clinical examination, there may also be excessive dental calculus in animals with chronic kidney disease.  In severe cases, there may be extensive subepithelial necrosis and sloughing of the tip of the tongue.  The lesions are often very painful and contribute to the anorexia often observed in animals with chronic kidney disease.

*'''[[Gastric Ulceration - all species|Gastric ulceration]]''' - This occurs for two main reasons.  First, urea crosses lipid membranes freely and enters the gastro-intestinal lumen of azotaemic animals.  The urea is degraded to ammonia by bacterial urease and the ammonia irritates the intestinal mucosa.  This is compounded by damage to the blood vessels of the gastric submucosa by the fibrinoid necrosis that is a common feature of the manifestations of uraemia.  Animals with gastro-duodenal ulceration may show '''anorexia, vomiting, haematemesis''' and [[Peritonitis - Cats and Dogs|'''peritonitis''']] if the ulcers perforate.  Similar processes result in the development of '''uraemic colitis'''.

**'''Oral ulceration''' - This occurs especially at the [[Oral Cavity - Teeth & Gingiva - Anatomy & Physiology|fauces]] of the mouth and on the margins of the [[Oral Cavity - Tongue - Anatomy & Physiology|tongue]].  Halitosis is often a feature of this syndrome as the lesions become secondarily infected with oral bacteria such as ''[[Fusobacterium necrophorum]]''.  In severe cases, there may be extensive subepithelial necrosis and sloughing of the tip of the tongue.  The lesions are often very painful and contribute to the anorexia often observed in animals with chronic kidney disease.  Excessive dental calculus may be evident in animals with chronic kidney disease on oral examination.

*'''[[Pulmonary Oedema|Pulmonary oedema]]''' - Damage to the small vessels of the pulmonary vasculature may result in pulmonary oedema and pleural effusion with dyspnoea, tachypnoea and coughing.

**'''[[Gastric Ulceration - all species|Gastric ulceration]]''' - This occurs for three main reasons.  First, urea crosses lipid membranes freely and enters the gastro-intestinal lumen of azotaemic animals.  The urea is degraded to ammonia by bacterial urease and the ammonia irritates the intestinal mucosa.  This is compounded by damage to the blood vessels of the gastric submucosa by the fibrinoid necrosis that is a common feature of uraemia.  Elevated serum concentrations of gastrin (which is normally metabolised in the kidney) also lead to excessive production of gastric acid from parietal cells in the stomach.  Animals with gastro-duodenal ulceration may show '''anorexia''', '''vomiting''', '''haematemesis''' and [[Peritonitis - Cats and Dogs|'''peritonitis''']] and '''haemorrhage''' if the ulcers perforate.  Hypergastrinaemia may also cause incompetence of the pyloric sphincter of the stomach, permitting relfux of irritant bile into the stomach.  Similar processes result in the development of '''uraemic colitis'''.

*'''Electrolyte imbalances''' - The failure to excrete phosphate through the damaged kidneys results in hyperphosphataemia.  This complexes with calcium and also prevents the activation of vitamin D (dihydroxycholecalciferol), resulting in hypocalcaemia.  This hypocalcaemia directly stimulates the production of parathyroid hormone (PTH) to try to maintain normal blood calcium levels and, in ~10% dogs with renal failure, hypercalaemia may develop due to an alteration in the set-point at which PTH is secreted.  In the remaining 90%, calcium is mobilised from bone causing '''secondary renal hyperparathyroidism''' with pathological fractures of various bones.

*'''[[Peritonitis - Cats and Dogs|Uraemic peritonitis]]''' - This is a form of chemical [[peritonitis]] that results from inflammation of the small mesothelial blood vessels.

*'''Atrial rupture''' - Mineralisation of the atria reduces their normal compliance and renders them susceptible to rupture.  The resultant haemopericardium is often fatal as it causes acute cardiac tamponade.

**'''[[Pulmonary Oedema|Pulmonary oedema]]''' - Damage to the small vessels of the pulmonary vasculature may result in the development of vasogenic pulmonary oedema and pleural effusion with dyspnoea, tachypnoea and coughing.

*'''Metastatic mineralisation''' - The presence of excessive blood concentrations of phosphate leads to metastatic calcification in multiple tissues, particularly the rugae of the gastric mucosa, the pulmonary parenchyma, the heart ...

*'''Thrombocytopathia'''.

**'''Electrolyte imbalances''' - The failure to excrete phosphate through the damaged kidneys results in hyperphosphataemia.  This electrolyte complexes with calcium and also prevents the activation of vitamin D (dihydroxycholecalciferol), resulting in hypocalcaemia.  This hypocalcaemia directly stimulates the production of parathyroid hormone (PTH) to try to maintain normal blood calcium levels and, in ~10% dogs with renal failure, hypercalaemia may develop due to an alteration in the set-point at which PTH is secreted.  In the remaining 90%, calcium is mobilised from bone causing '''secondary renal hyperparathyroidism''' with resorption of bone, pathological fractures and fibrous osteodystrophy of the bones of skull ('rubber jaw').

*'''[[Arrhythmias Overview|Arrhthymias]]'''.

**'''Metastatic mineralisation''' - The presence of excessive blood concentrations of phosphate leads to metastatic calcification in multiple tissues, particularly the rugae of the gastric mucosa, the pulmonary parenchyma and the heart.

*'''Neurological disease''' - The presence of extremely high concentrations of urea and creatinine may induce '''uraemic seizures''' and this is usually a terminal event.

**'''Metabolic acidosis''' - The kidney plays a vital role in the regulation of the normal acid/base balance.

*'''Anaemia''' - The diseased kidenys produce less erythropoietin than normal but the uraemic toxins also decrease the lifespan of existing red blood cells.  Erythrocytes may also be damaged as they pass along inflamed vessel walls, a form of microangiopathic haemolysis.

**'''Atrial rupture''' - Mineralisation of the atria reduces their normal compliance and renders them susceptible to rupture.  The resultant haemopericardium is often fatal as it causes acute cardiac tamponade.

**'''[[Arrhythmias Overview|Arrhthymias]]'''

**'''Thrombocytopathia''' - The reduction in platelet function occur due to multiple alterations in normal [[Thrombocyte|thrombocyte]] metabolism.

**'''Anaemia''' - This occurs because the diseased kidenys produce less erythropoietin than normal and the uraemic toxins (especially PTH) decrease the lifespan of existing red blood cells.  Erythrocytes may also be damaged as they pass along inflamed vessel walls, a form of microangiopathic haemolysis.  Chronic gastro-intestinal haemorrhage may also result in iron deficiency.

*'''Neurological disease''' - The presence of extremely high concentrations of urea and creatinine may induce '''reduced conciousness''' or '''uraemic seizures''' and this is usually a terminal event.  PTH has also been implicated in the development of uraemic encephalopathy, possibly due to alterations in calcium pumps.  Animals may enter a so-called '''twitch-convulsive''' state where they suffer concurrent tremors, myoclonus and seizures.  Peripheral neuropathies may contribute to the reduced hindlimb function that is commonly ascribed to hypokalaemic myopathy.

*'''Myopathy''' - Hypokalaemic animals with chronic kidney disease may suffer severe muscle weakness with a plantigrade stance and cervical ventroflexion in cats which lack a nuchal ligament.

===Laboratory Tests===

===Laboratory Tests===

Serum biochemistry will show elevated levels of [[Urea|urea]] and [[Creatinine|creatinine]].  Animals with acute renal failure may by '''hyperkalaemic''' and '''hyperphosphataemic''' but cats with chronic renal failure are often '''hypokalaemic''' and '''hyponatraemic'''.   

Serum biochemistry will show elevated levels of [[Urea|urea]] and [[Creatinine|creatinine]].  Animals with acute renal failure may by '''hyperkalaemic''' and '''hyperphosphataemic''' but cats with chronic renal failure are often '''hypokalaemic''', '''hyperphosphataemic''' and '''hyponatraemic'''.  Blood ionised calcium concentration may be reduced (in ~90% cases) or elevated (in ~10% cases).

In cases of chronic renal failure, there may be a '''normocytic, normochromic, non-regenerative anaemia'''.

In cases of chronic renal failure, there may be a '''normocytic, normochromic, non-regenerative anaemia'''.  Platelet levels are usually normal despite any reduction in function.

===Other Tests===

===Other Tests===

===Diagnostic Imaging===

===Diagnostic Imaging===

Imaging may show the presence of metastatic calcification in multiple organs, including...

Imaging may show the presence of metastatic calcification in multiple organs, including...

===Other Tests===

===Other Tests===

==Treatment==

==Treatment==

The underlying cause of the renal failure should be treated.  To alleviate the clinial signs of uraemia, it is particularly important to restrict phosphate by feeding a '''low phosphate diet''' and using '''phosphate-binding drugs''' such as aluminium hydroxide or chitosan.

The underlying cause of the renal failure should be treated.  To alleviate the clinial signs of uraemia, it is particularly important to restrict phosphate by feeding a '''low phosphate diet''' and using '''phosphate-binding drugs''' such as aluminium hydroxide or chitosan.  Deficient electroylytes should be supplemented but calcium should only be administered after hyperphosphataemia has been corrected to prevent further mineralisation of soft tissues.

 

A major advance in the management of uraemia has been the introduction of '''recombinant erythropoietin''' which can be administered to anaemic animals as a series of subcutaneous injections.  Some animals may become resistant to its effects over time due to the development of an immune response to the recombinant protein.

==Prognosis==

==Prognosis==

==References==

==References==