Nephrosis:

• It includes degenerative and inflammatory lesion, primarily affecting renal tubules, particularly proximal convoluted tubules.
• It is basically of 2 types; tubular injury caused by ischemia, called ischemic nephrosis and tubular injury caused by nephrotoxins, called toxic nephrosis
• It is the most common cause of acute kidney failure and often multiple animals are affected, if exposed to toxins, especially plant toxins
• Uremia may develop acutely or in terminal stages of chronic renal disease.

Ischemic nephrosis:

• Ischemia refers to reduced blood flow in any part of body. Ischemic nephrosis results from reduced blood flow through kidneys due to general circulatory failure.
• Ischemia may be acute or chronic in nature

Etiology:

Acute renal ischemia:

• General circulatory emergencies such as shock, dehydration, acute hemorrhagic anemia, acute heart failure, renal failure secondary to calf diarrhoea
• Embolism of renal artery, in horse
• Extreme ruminal distension in cattle

Pathogenesis:

In response to sudden fall in cardiac output, compensatory vasoconstriction of renal blood vessels, results in renal ischemia

Due to decreased blood flow to kidneys, glomerular filtration decreases and metabolites that are to be excreted, gets accumulated in bloodstream

Due to fall in glomerular filtration, tubular reabsorption increases, causing reduced urine flow

Upto certain stages, these changes are reversible, however acute ischemia of sufficient duration, results in acute renal failure. PCT are highly sensitive to ischemia as they are highly energetically mostly active cells in body.

Clinical Findings:

• Oliguria, azotemia
• Animal shows signs of acute renal failure:
  • Pruritus
  • Pallor
  • Dirty and evil smelling skin
  • Weakness, muscle twitching, convulsion, coma
  • Dry mouth, anorexia, vomiting
  • Polypnoea and recurrent attack of respiratory distress
  • Conjunctivitis and keratitis
  • Anemia, bleeding tendency
  • Osteoporosis, Osteomalacia, renal ricket
  • Retention of sodium and water leading to edema
  • Rubber jaw condition
  • Palpation shows enlarged kidney with hypersensitivity

Necropsy Findings:

• Renal cortex pale and swollen
• Cut surfaces of renal cortex bulges
• Medulla is pale or congested.
• Disruption of tubular basement membrane, called tubulorrhectic necrosis.

Diagnosis:

• On basis of history and clinical findings
• On basis of necropsy findings
• On basis of laboratory findings:
  • Proteinuria
  • Urine has low specific gravity
  • Increased level of BUN, creatinine, phosphorus and potassium level

Differential Diagnosis:

• Disease should be differentiated with toxic nephrosis, general circulatory failure
• Attempt should be made to differentiate early reversible prerenal stage from stage in which degeneration of renal parenchyma has occurred.

Treatment:

• Treatment should be aimed at correction of fluid, acid-base and electrolyte disturbances.
• Fluid therapy is indicated to correct fluid and electrolyte imbalances.
• Supportive therapy as in acute renal failure is indicated
• Diuresis may be induced by using mannitol @0.25-0.5 gm/kg, b.wt. through slow IV route to reduce edema
• Two parts of 5% dextrose and one part RL is suggested in maintenance of fluid balance
• Vasodilators should be used to improve renal circulation. Dopamine @ 2-3 mcg/kg/min in 0.9% NaCl constant IV drop along with furosemide drip @ 1mg/kg/hour
• Ampicillin should be used to control secondary infection
• Gastric protectants; Sucralfate @0.5-1.0 gm, PO may be given at 8 hours interval to correct vomition and protect gastric mucosa
• For acidosis, sodium bicarbonate @8-12 mg/kg, BID-TID may be tried. Dose should be adjusted based on urinary pH.
• Diet should contain less phosphorus. Intestinal phosphate binder like aluminium hydroxide, aluminium carbonate, calcium acetate should be given @ 30-90mg/kg/day
• For correction of anemia, anabolic steroid; testosterone propionate @10-15mg/day/dog or stanozol @ 25-50mg/l/m weekly in dogs and 0.5 and 2 mg orally at 12 hrs in cats
• Calcium supplement and vitamin D therapy should be adopted to correct hypocalcemia
• Water soluble B vitamins and vitamin C may be useful for correcting anorexia and bleeding tendency, respectively. Multivitamin containing Vit. A and Vit.D should be avoided.

Toxic nephrosis:

• This type of nephrosis occurs due to effect of nephrotoxins.
• Kidneys are susceptible to endogenous and exogenous toxin, as they receive 20% cardiac output and also substances get concentrated in kidney for excretion.

Etiology:

• Metals; mercury, arsenic, cadmium, selenium and organic copper compounds.
• Antimicrobials such as aminoglycosides and overdosing with neomycin and gentamicin in treatment of calves, repeated daily dosing with long-acting oxytetracycline, sulphonamides
• Horse treated with vitamin K₃ through IV or IM, treated with vitamin D_2­ and D₃
• Treatment of horse with NSAID; phenylbutazone, flunixin meglumine
• Monensin in ruminants, low-level Aldrin poisoning in goats
• Highly chlorinated naphthalenes
• Oxalates in plants, oxalates in fungi, oxalates in ethylene glycol or ascorbic acid
• Tannins in foliage of oak trees and acorns.
• Mycotoxins such as ochratoxins, citrinins, fumonisins in ruminant
• Unidentified toxin in Amaranthus retroflexus in pigs, cattle, and lambs, in Narthecium asiaticum fed to cattle and Isotropis forrestii in ruminants
• Ingestion of Lophyrotoma interrupta (sawfly) larvae by cattle
• Cantharidin in horses following ingestion of dead blister beetles in alfalfa hay and hay products

Pathogenesis:

In acute nephrosis there is obstruction to the flow of glomerular filtrate through the tubules caused by interstitial edema and intraluminal casts. If there is sufficient tubular damage, there may be back leakage of glomerular filtrate into the interstitium. There may also be a direct toxic effect on glomeruli, which decreases glomerular filtration. The combined effect is oliguria and uremia. In sub-acute cases, impaired tubular resorption of solutes and fluids may lead to polyuria.

Clinical Findings:

• Clinical signs may not be related to urinary system
• Horses injected with vitamin K₃ shows signs of colic and stranguria.
• Depression, dehydration, anorexia
• Hypothermia, slow or elevated heart rate
• Weak pulse
• Diarrhoea is severe enough to cause dehydration
• In severe nephrosis, cattle exhibit exudative diathesis
• Polyuria is present in chronic case.
• Continuous mild hypocalcemia in cattle which responds to calcium therapy

Necropsy Findings:

• Kidney is swollen and wet on cut surface
• Edema, especially of perirenal tissues
• Hyaline casts are present in dilated tubules, when examined microscopically
• Ulcers in all or most part of alimentary tract from mouth to colon, in case of phenylbutazone toxicity.

Diagnosis:

• On basis of history and clinical findings
• On basis of necropsy findings
• On basis of laboratory findings:
  • Increased urea and creatinine concentration in plasma or serum
  • Proteinuria, glucosuria, enzymuria, and hematuria are initial changes on urinalysis in experimental toxic nephrosis
  • Hypoproteinemia
  • In acute renal disease of horses, hypercalcemia and hypophosphatemia can be present

Differential Diagnosis:

• Disease should be differentiated from diabetes mellitus
• Cushing’s syndrome in horse
• Diarrhoea in terminal stages may be confused with other acute cause of diarrhoea

Treatment:

• General supportive care as required in acute renal failure is suggested.
• Toxin, if identified should be removed immediately.
• Hemodialysis should be used in cases of drug toxicity to remove drugs and filters blood to assist kidney function
• Fluid therapy should be administered to correct fluid and electrolyte imbalances.
• Ampicillin should be used to control secondary infection
• Gastric protectants; Sucralfate @0.5-1.0 gm, PO may be given at 8 hours’ interval to correct vomition and protect gastric mucosa
• Calcium supplement and vitamin D therapy should be adopted to correct hypocalcemia
• Water soluble B vitamins and vitamin C may be useful for correcting anorexia and bleeding tendency, respectively. Multivitamin containing Vit. A and Vit.D should be avoided.