Chronic Renal Failure

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.

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.

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).

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

• Polyuria and polydipsia
• Anorexia
• Weight loss
• Blindness/hyphema - related to hypertension
• Dehydration
• Constipation
• Endstage uraemia with clinical signs include oral ulceration, characteristic uraemic breath, vomiting and lethargy.

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

• Small kidneys
• Pale mucous membranes
• Rubber jaw (fairly rare)
• Cervical ventroflexion due to hypokalaemia
• Hypertensive retinopathy
• Hypoproteinaemia

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

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.

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 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

(II) Non/mildly azotaemic with absent/mild clinical signs. Creatinine 125-250 in dogs/140-250 in cats

(III) Mild/moderate azotaemia with or without uraemia. Creatinine 181-440 in dogs/250-440 in cats

(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.

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.

(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'.

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.

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).

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.

Uraemic syndrome

The uraemic syndrome is the clinical signs associated with azotaemia.

Hyperkalaemia/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.

Metabolic Acidosis

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

Anaemia

Several factors contribute to anaemia in 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

(2) Decreased lifespan of red blood cells

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

(4) Iron deficiency

(5) Inhibition of erythropoesis by uraemic inhibition

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 E. coli. The main reason for treatment is to improve quality of life.

Dehydration

Dehydration results in the development of prerenal azotaemia.

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.

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 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.

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.

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

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.

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.