Urinary

• The kidneys have a large functional reserve and as such detectable renal dysfunction will only manifest when this reserve capacity is exceeded. All components of the kidney are interdependent, and once renal maturity is established, no new nephrons can be formed.
• The renal arteries and branches are end arteries, meaning they have no potential for collateral supply. Occlusion to any branch will lead to infarction. Kidneys are very vulnerable to toxic damage. They receive 20% of cardiac output , with the large glomerular capillary surface area providing a lot of space for toxicant-endothelium interaction.
• Progressive renal disease develops through overlapping stages: a diminished reserve leads to insufficiency. Insufficiency will progress to failure, then eventually end stage renal disease where the kidney is fibrosed.
• In chronic renal failure, kidneys appear shrunken and fibrosed. They are pale and firm with scarring and fibrosis. The cortex and medulla will vary in thickness by area.
• Renal insufficiency is a GFR which is 20-50% of normal, with polyuria and decreased concentrating ability. Chronic renal failure is less than 20% normal GFR, polyuria, decreased concentrating ability and subsequent metabolic effects.
• To assess a kidney at post-mortem, cut in a saggital plane. Remove the capsule; it should come off easily and the underlying surface should be smooth. The corticomedullary ratio should be about 1:2. Assess the overall contour of the cortex and medulla.
• Azotaemia is an abnormal increase in non-protein nitrogenous substances in the blood, usually developing due to decreased renal excretion of urea and creatinine. Mat be pre-, renal or post-renal.

  Uraemia is the clinical signs of azotaemia.
• Pre-renal azotaemia occurs due to reduced renal perfusion e.g. dehydration, cardiac insufficiency, shock. Urine specific gravity will rise as urine output is decreased to increase blood volume.
• Renal azotaemia occurs when there is decreased GFR due to acute or chronic renal disease. There is decreased renal clearance of both urea and creatinine.
• Post-renal azotaemia occurs when there is an obstruction of the urinary tract distal to the kidneys. GFR will decrease, serum urea and creatinine will increase
• Increased synthesis of urea is a rare cause of azotaemia e.g. due to intestinal haemorrhage, high protein diet or protein catabolism. Creatinine will not increase concurrently.
• Non-renal pathologies of uraemia include epithelial lesions, cardiovascular effects, pulmonary effects and lesions associated with altered calcium and phosphorus metabolism.
• Epithelial lesion from uraemia tend to occur on the oral mucosa, the tongue (especially the underside and lateral borders), the gastric mucosa (ulcerative and haemorrhagic gastritis), and the colon (ulcerative and haemorrhagic colitis). There is degeneration and necrosis of endothelial cells resulting in vasculitis, then thrombosis and infarction
• Epithelial lesions of uraemia occur because urea is increased in the saliva and intestines. This is acted on by bacteria, forming ammonia. There is then caustic injury to the epithelium.

  Ulcerative necrotic stomatitis is common in dogs, producing brown mucoid material adherent to the oral mucosa, most commonly under the tongue.
• Haemorrhages and ulcers in the gastric mucosa are common secondary to renal disease. This leads to gastritis in dogs and cats, and may be associated with mucosal mineralisation; Results in signs such as vomiting, melaena and anorexia. In cattle and horses there can be ulcerative and haemorrhagic colitis.
• Cardiovascular lesions of uraemic origin include necrosis of the wall of the left auricle, proximal aorta and pulmonary trunk. Erosion of the wall may be associated with thrombus formation.

  Renal disease can lead to hypertension, causing cardiac hypertrophy (esp LHS), medial hypertrophy of arterioles and fibrinoid degeneration of small artery muscle coats. Especially important in cats.

  Fibrinous pericarditis secondary to renal failure is deposition of fibrin on the visceral pericardial surface.
• A normocytic, normochronic or moderate anaemia is often seen secondary to chronic renal failure in the dog. This is multifactorial, due to increased RBC fragility and lack of erythropoietin production.
• The juxtaglomerular apparatus regulates renal blood flow via the afferent arteriole and DCT of the same nephron. Reduced renal blood flow causes renin release from the JGA, converting angiotensinogen to angiotensin 1. ACE converts this to angiotensin 2, causing aldosterone release and increased vascular resistance .’. increased blood pressure.
• Hypertension causes cardiac hypertrophy, hypertrophy of the tunca media of small arteries and fibrinoid degeneration of small arteries, hence in a small number of cases, hypertension itself can lead to progressive decline in renal function.
• Uraemia can cause vasculitis and concurrent increased vascular permeability. This can lead to pulmonary oedema. Mineral is deposited into the walls of alveolar ducts and arterioles, and neutrophils and macrophages invade -> uraemic pneumonitis.
• Altered serum phosphate metabolism occurs in renal disease as there is decreased renal clearance of inorganic PO4 (increased in pre-r, renal, and post-r disease). Seum calcium can be low, normal or high in renal disease but is often low in dogs and cats. Less calcitriol is produced by the kidney  so less calcium is absorbed in the intestines or reabsorbed from bone. Parathyroid hormone increases, leading to bone demineralisation.
• Alterations in phosphate and calcium metabolism secondary to renal disease can cause:

  • Parathyroid hyperplasia (renal secondary hyperparathyroidism)
  • Soft tissue mineralisation (calcium deposition in subpleural connective tissue of intercostal spaces, stomach wall, lungs and kidneys)
  • Osteodystrophy as bone is demineralised. Causes thickened maxilla, fibrous tissue at tooth roots in growing dogs and softening of bone in older dogs
• Serum potassium is often high in renal failure when there is oliguria (low urine output) as renal excretion is decreased.

  Metabolic acidosis may also occur due to decreased renal excretion of hydrogen.
• The main fatures of developmental disease in the kidney are:

  • Renal aplasia (agenesis )
  • Renal hypoplasia
  • Ectopic kidney
  • Dysplasia
  • Cysts
• Renal aplasia (agenesis) is rare but seen in some familial groups of Dobermans and beagles. Renal hypoplasia is also rare- there is incomplete renal development, with clinical manifestations depending on extent of deficit.
• Ectopic kidneys are a developmental disease seen most commonly in pigs and dogs, where the kidney is usually in the pelvic or inguinal region. Consequences include incontinence, hydronephrosis, and pyelonephritis. Fused kidneys may be seen due to abnormal nephrogenesis leading to one large kidney with two ureters.
• Kidney dysplasia is a developmental disease which occurs due to disorganised development of the renal parenchyma. Affected kidneys are usually small (so may look like hypoplasia). May be congenital,  acquired  neonatally or secondary to infection or ureteral obstruction.
• Kidney cysts are a developmental condition which may be acquired or congenital.

  • Congenital cysts are a common incidental finding in pigs and calves. They are usually solitary. Not to be confused with polycystic kidney disease where there are many cysts and progressive renal compromise (Persian cats and Cairn terriers)
  • Acquired cysts are usually small, occurring as a sequel to interstitial fibrosis, where tubules become obstructed by scar tissue. Perinephric psuedocysts have a similar cause, but these develop between the capsule and renal reflection of the peritoneum.
• Gross haemorrhage in the kidney e.g. subcapsular or intrarenal, can lead to complete renal failure. These are often caused due to trauma.

  Petechial haemorrhages are common in septicaemic disease  e.g. strep infections

  Renal cortical ecchymotic haemorrhages are a significant lesion in neonatal herpes virus infection of puppies.
• Renal infarcts occur due to a vascular occlusion, usually following thrombosis or embolism. There is stasis and congestion, followed by swelling of the parenchyma, necrosis and then repair by fibrosis. Consequences depend on the occluded vessel:

  • Renal artery: total or sub-total renal necrosis
  • Arcuate artery: wedge shaped necrosis of the cortex and medulla
  • Interlobular vessel: cortical necrosis
• An acute infarct will appear swollen with haemorrhage. Within 2-3 days the area becomes pale, with a surrounding zone of hyperaemia. A chronic renal infarct will appear shrunken and fibrotic with a distortion of the surface.
• circulatory disturbances of the kidney:

  • Hyperaemia/ congestion – active/ passive or hypostatic
  • Haemorrhage
  • Infarcts
  • Renal cortical necrosis – results from widespread thrombosis e.g. in sgram negative septicaemia, endotoxaemia, DIC. Destroys tubules and glomeruli
  • Renal papillary necrosis – result of reduced medullary blood flow or as a primary disease following NSAID therapy
  • Hydronephrosis – ischaemic lesions develop as pressure backs up and GF persists -> pressure atrophy.
• The primary function of the glomerulus is ultrafiltration of plasma. Damage to the glomerulus results in the leakage of protein -> proteinuria. Causative diseases are called protein losing nephropathies which can contribute to nephrotic syndrome (characterised by proteinuria, hypalbuminaemia, hypercholesterolaemia and oedema.)

   

  Hypercholesterolaemia is caused by increased hepatic production and defective metabolism of the VLDL fraction of lipoproteins.  
• Oncotic pressure pushes to keep fluids in vessels, hydrostatic pressure is pushing out
• The urine protein to creatinine ratio is used to quantify urinary protein loss (although not the cause). Generally, the higher the number, the more likely it is that glomerulonephropathy is present.  

   

  Pre-glomerular proteinuria can be caused by excretion of Bence-Jones proteins in myeloma

  Causes of post-glomerular proteinuria include pyelonephritis and lower urinary tract infections.
• Glomerular diseases include familial renal disease, glomerulonephritis, amyloidosis and glomerulitis.

   

  Familial renal disease affects the glomerulus, often splitting the collagens and structural proteins of the basement membrane, compromising function. This tends to manifest in younger animals as PU/PD, mild azotaemia and proteinuria.
• Glomerulonephritis is an immune mediated disease which may precede end-stage kidney disease and renal failure. Two forms:

  • Immune complex: deposition of antigen-antibody complexes in the glomerulus, attracting complement fixation and neutrophil chemotaxis. Has been associated with persistent bacterial or viral infection, autoimmune disease and neoplasia.
  • Autoimmune antibodies against the glomerular basement membrane.
• In acute glomerulonephritis, the kidney appears grossly swollen and tense. Individual glomeruli may be prominent as pinpoint ped dots on the surface of the cortex.

  In chronic glomerulonephritis, the gross changes resemble those of chronic interstitial nephritis with shrinking and pitting of the capsule, cortical thinning and fibrosis.
• The histopathology of glomerulonephritis shows changes including increased cellularity in glomerular tufts, thickening of the basement membrane, adhesions between glomeruli and bowman’s capsule and haemorrhage into the urinary space.
• Severe, prolonged glomerular damage causes glomerulosclerosis: glomeruli are hypocellular and non-functional, with fibrosis and shrinkage.