VPTH 123 | Kidney Function Tests

Elimination of metabolic waste
Fluid,electrolyte and acid balance
Conservation of nutrients (GLU & AA)
Endocrine function

Roles of kidney (4)

Erythropoietin

Produced by peritubular interstitial cells; stimulates the production of erythrocytes in response to hypoxia

Calcitriol (Vitamin D)

Produced in the proximal renal tubular epithelial cells upon stimulation of PTH

Prostaglandin

Intra-renal production of this hormone is very important for maintaining medullary blood flow

Renin

Produced by juxtaglomerular complex in afferent arterioles of the kidney. It is stimulated by renal hyperfusion (hypovolemia) and decreased chloride delivery.

Renal hyperfusion (hypovolemia)
Decreased chloride delivery

Main stimulation for renin secretion (2)

Aldosterone

Promotes sodium retention (& potassium excretion) in distal tubules of the kidneys, enhancing water retention

Protein catabolism

Most nitrogenous waste is formed through this mechanism

Urea

Readily filtered by glomerulus and resorbed by PCT. Increased flow rate (polyuria) will lead to the decrease of the concentration of this substance in the plasma by promoting excretion.

Increased BUN concentration

Blood level of BUN with decreased GFR, protein catabolism-fever, corticosteroids

Increased BUN concentration

Blood level of BUN when there is an increased protein digestion due to high dietary intake of protein or hemorrhage into the GIT

Creatinine

Produced in the muscle from creatine (produced in the liver). Freely filtered by glomerulus and not resorbed. High levels of this substance occur with GFR.

Sodium

Filtered and passively resorbed with water along a concentration gradient in the proximal convoluted tubule

Sodium

In the PCT, this electrolyte is co-transported with glucose, amino acids, and phosphate

Aldosterone

In the collecting tubules, Na resorption is controlled by _____, which increases Na absorption and promotes K excretion

Chloride

Resorption is both active and passive and both are indirectly linked to Na+ absorption

Chloride

Passively absorbed, with sodium, through leaky tight junctions in the later segments of the PCT along a concentration gradient

Two-thirds

Amount of filtered potassium (K+) is resorbed in the PCT

Potassium

In the DCT and collecting ducts, ____ is excreted passively. Meanwhile, in the collecting ducts, this substance is excreted actively by principal cells, under the influence of aldosterone.

Alodsterone
Tubular flow rate
Sodium delivery to the distal nephron

Factors that can affect excretion of potassium

Aldosterone

Enhances excretion of potassium in the collecting tubules by stimulating sodium absorption

Increased excretion of potassium

Increased tubular flow rate leads to (increased/decreased) excretion of potassium

Increasing lumen electronegativity and distal flow rates

Increased sodium delivery to the distal nephron increases excretion by _______

Calcium

Only the ionized form of this electrolyte is filtered

Calcium

Electrolyte mostly resorbed passively in the PCT (80-85%) following sodium and water resorption

Phosphate

Most of the filtered electrolyte (80-95%) is resorbed in the PCT with sodium

PTH
Glucocorticoids
Phosphatonins

Factors that influence low resorption of phosphate (3)

Vitamin D
Thyroxin
Growth hormone

Factors that influence high resorption of phosphate (3)

Magnesium

80% of this electrolyte (ionized only) is filtered, most of which is resorbed in the thick ascending limb of the loop of Henle (70%), with lesser amounts in the PCT (20-30%) and DCT (10%)

ADH
PTH
Glucagon
Calcitonin
Beta-adrenergics

Factors that influence resorption of magnesium (5)

Urine concentration

The formation of urine that is hyperosmotic to plasma (plasma has an osmolality of approximately 280-300 mOsm/kg), by resorption of water in excess of solute

Urine osmolality
Urine specific gravity

2 concepts that assess the ability of the kidney to CONCENTRATE or DILUTE urine

Urine speciic gravity

A measurement of the density of urine compared to pure water and is determined using a refractometer.

Urine osmolality

A direct measure of the number of molecules in urine and is not influenced by molecular weight or size.

Kidney

Organ essential in maintenance of acid-base balance and a stable pH

Changes in (1) renal hydrogen excretion or (2) bicarbonate retention

Important compensatory mechanisms for alterations in pH secondary to respiratory or metabolic causes (2)

Resorption of filtered bicarbonate
Excretion of the daily acid load produced by the body (tirtatable acidity)

Two steps involved in the renal control of pH

Acidemia (extracellular pH)

This promotes bicarbonate generation and hydrogen excretion in the tubules, both directly and indirectly by stimulating ammonia production in the PCT.

Decreased bicarbonate filtration
Activation of renin-angiotensin-aldosterone system

Reasons why bicarbonate may be retained (generated) in volume depletion (2) (Extracellular volume) (increased retention)

Metabolic alkalosis

Chloride depletion produces this (metabolic alkalosis/acidosis)

Hypokalemia

With _____, the kidneys try to conserve K+ in exchange for hydrogen, thus promoting acid excretion.

Potassium

K+ depletion will also stimulate the production of this substance by the tubules.

Acute renal disease
Chronic renal disease

2 classification of renal disease

Renal disease

Leads to loss of ability to concentrate or dilute tubular filtrate, to eliminate nitrogenous wastes and maintain acid-base balance

Acute renal injury

Characterized by deterioration in renal function over hours to days, resulting in failure of the kidney to excrete nitrogenous wastes and maintain fluid, electrolyte and acid base status

Chronic renal disease

Type of renal disease due to slowly progressive, chronic deterioration of kidney function and may be preceded by acute renal injury in some (but not all) cases.

Stage 1 – Decreased renal reserve
Stage 2 – Chronic renal insufficiency
Stage 3 – Chronic renal failure
Stage 4 – End-stage renal disease

Four stages of chronic kidney disease

Glomerulonephritis

Most common cause of chronic renal failure in large animals

Glomerulonephritis
Amyloidosis

Causes of chronic renal failure in small animals (2)

Proteinuria

First sign of renal disease in breeds with inherited renal disease

Azotemia
Hyperphosphatemia
Metabolic acidosis with a high anion gap

Similar laboratory features of both acute and chronic renal failure

Azotemia

Defined as an increase in urea nitrogen and creatinine

Uremia

Term for the clinical syndrome of renal failure with azotemia and multisystemic problems

Prerenal azotemia
Renal azotemia
post-renal azotemia

3 types of azotemia

Urinalysis (esp assessment of USG)
Evaluation of clinical signs
Results of other diagnostic tests (radiographic evidence of UT obstruction)

Procedures for differentiation of the causes of azotemia (3)

Pre-renal azotemia

Due to a decrease in glomerular filtration rate (GFR) from circulatory disturbances causing decreased renal perfusion (hypovolemia, cardiac disease, renal vasoconstriction)

Decreased

Urine specific gravity may be ____ (despite a prerenal azotemia) if there are other factors reducing concentrating ability.

Renal azotemia

Results from decreased GFR when more than 3⁄4 of the nephrons are non- functional

1. Primary intrinsic renal disease (glomerulonephritis, ethylene glycol toxicity)

2. Secondary to renal ischemia from prerenal causes or from kidney damage from urinary tract obstruction (post-renal azotemia)

Possible causes of renal azotemia (2)

Isosthenuric urine

Loss of 3⁄4 of kidney function usually follows concentrating defects (requires loss of 2/3 of the kidney), therefore ________ urine (USG 1.008-1.012) is common in renal azotemia

Increased serum phosphate (due to decreased GFR)
Increased potassium (due to reduced urinary elimination)

Concentration of phosphate and potassium in azotemia

Decreased sodium chloride is seen, with decreases in chloride being most consistent (associated with concurrent metabolic alkalosis)

Concentration of sodium chloride in bovine

Often see a decrease in sodium chloride (especially chloride)

Concentration of sodium chloride in equine

ACUTE: total calcium is often low and phosphate is high (especially in young horses)
CHRONIC: hypercalcemia (total calcium) and hypophosphatemia occur (not in all cases)

Acute renal failure vs chronic renal failure in equine

High anion gap metabolic acidosis

Anion gap common in all species with renal failure

Decreased renal elimination of “uremic acids”, such as phosphates, sulfates, and citrates, that are normally excreted by the kidneys.

Cause of high anion gap metabolic acidosis

Post-renal azotemia

Azotemia that results from obstruction (urolithiasis) or rupture (uroabdomen) of urinary outflow tracts

Clinical signs (e.g. frequent attempts to urinate without success or presence of peritoneal fluid due to uroabdomen)
Ancillary diagnostic tests (e.g. inability to pass a urinary catheter).

Diagnosis of post-renal azotemia (2)

Markedly increased potassium (hyperkalemia)
Markedly increased magnesium (hypermagnesemic)

Concentration of potassium and magnesium in animals with post-renal azotemia

Uroperitoneium

Can be confirmed by comparing the concentration of creatinine in the fluid to that in serum or plasma

Higher creatinine in fluid than in serum

Indication of leakage of urine in uroperitoneium (concentration of creatinine)

Urea

Synthesized by hepatocytes from ammonia generated by catabolism of amino acids derived either from digestion of proteins in the intestines or from endogenous tissue proteins

Kidneys
Intestine (high in horses)
Saliva
Sweat

Organs or bodily fluids that excretes urea

Decreased glomerular filtration rate (GFR)

Measurement of urea concentration in serum is mainly to screen for ______

Severe lipemia: decreased urea
Severe hemolysis: increased urea
Severe icterus: increased urea

Effect of severe lipemia, severe hemolysis, severe icterus on urea concentration

Endogenous NH4 ions

These ions in the urine may interfere with measurement of urea concentration, with elevated concentrations occurring in acidic conditions (acidosis)

• Increased protein catabolism: Fever, burns, corticosteroid administration,

  starvation, exercise.

• Increased protein digestion: Hemorrhage into the gastrointestinal system, high protein diets.

• Decreased GFR: Due to prerenal, renal, or postrenal causes

Pathophysiologic interpretation of increased urea concentration (3)

Ammonia contamination

Artifact that could possible cause increased urea concentration

• Increased production of urea, e.g. protein catabolism.

• Early prerenal azotemia (most causes of a high UN in horses and ruminants are due to prerenal causes).

• Artifactual depression of creatinine, e.g. severe icterus.

Following situations that could cause INCREASED urea w/ NORMAL creatinine (3)

• Decreased protein intake or protein anabolism: Dietary restriction of protein, young animals (high anabolic rate).

• Increased excretion: Any cause of polyuria, e.g. hyperadrenocorticism, diabetes mellitus.

• Decreased production: Liver disease.

Pathophysiologic interpretation of decreased urea concentration (3)

Hepatic urea production
Renal tubular flow rate

2 factors that influence urea concentration

high flow rate: 40%, low flow rate: 60%

At high flow rates, approximately ___ of filtered urea is reabsorbed. At low flow rates, as happens in hypovolemic individuals, approximately ___ of filtered urea is reabsorbed and added back to the blood urea concentration

Creatinine

Produced as the result of normal muscle metabolism

Phosphocreatine

An energy-storing molecule in muscle, that undergoes spontaneous cyclization to form creatine and inorganic phosphorous

Creatinine

Produced when creatine decomposes

Creatinine

Substance filtered freely through the glomerulus and is not reabsorbed in the tubules

Severe hemolysis: increased creatinine
Severe icterus: decreased creatinine

Effect on creatinine concentration of severe hemolysis and severe icterus

Glucose

Can act as a chromogen in the picric-acid reaction, falsely elevating creatinine concentration results.

1. Cephalosporin

2. Cefoxitin

In serum and plasma samples, therapeutic levels of antibiotics containing ___(1)___ result in significantly false-positive values of creatinine concentrations. __(2)___ causes spuriously high results.

Foals and heavily muscled horses
Ingestion of a recent meat meal

Physiologic causes of increased creatinine concentrations (2)

• Decreased GFR: Due to prerenal, renal or post-renal causes

• Release from muscle: Studies have shown that acute myositis does not consistently increase creatinine. Increases in creatinine more likely due to a renal azotemia from myoglobinuric nephrosis as a consequence of myoglobin release from severe myositis or myopathy.

Pathophysiologic causes of increased creatinine concentrations (2)

Creatinine

Best indicator of GFR in ruminants and horses

Myoglobinuric nephrosis

Studies have shown that acute myositis does not consistently increase creatinine. Increases in creatinine more likely due to a renal azotemia from _______ ______ as a consequence of myoglobin release from severe myositis or myopathy.

• Decreased muscle mass: Young animals (reported in puppies)

• Increased GFR: occurs during pregnancy (due to increased cardiac output)

Physiologic causes of decreased creatinine activity or concentration (2)

• Decreased production: Loss of muscle mass from starvation or cachexia. Severe liver disease from cirrhosis = decreased creatine production.

• Increased GFR: Animals with portosystemic shunts. Decreased liver synthesis of urea.

Pathophysiologic causes of decreased creatinine activity or concentration (2)

1. Early prerenal azotemia Normal glomerular filtration rate (GFR) with ↑ urea nitrogen

2. High protein diet, upper gastrointestinal (GI) bleed

3. ↓ GFR with ↓ creatinine

4. Decreased muscle mass (cachexia)

Interpretation of increased urea nitrogen levels and normal or decreased creatinine concentration (4)

1. ↓ GFR with ↓ urea nitrogen

2. Hepatic failure, polyuria-polydipsia (in absence of chronic kidney disease), low protein diet, metabolism of urea nitrogen by GI flora (horses and cattle)

3. Normal GFR with ↑ creatinine

4. A normal finding in Greyhounds (increased muscle mass)

Interpretation of normal or decreased urea nitrogen levels and increased creatinine concentration

Cystatin C

A small (13 kD) protein that is used as a marker of glomerular filtration rate (GFR) or kidney function, particularly in chronic renal disease (CKD).

Chronic renal disease (CKD)

Cystatin C is a marker of GFR or kidney function, particular in this disease

Cysteine proteases

Cystatin C is produced by all cells in the body at a constant rate and functions as an inhibitor of ______ ________