Kidney Function
Kidney disease
• the presence of functional or structural abnormalities in one or both kidneys
• loss of 2/3 or more of functional nephrons is associated with loss of adequate urine concentrating ability,
• loss of 3/4 or more of functional nephrons results in azotemia.
Azotemia
• An abnormal concentration of urea, creatinine, and other nonprotein nitrogenous substances in blood, plasma, or serum.
• Because nonprotein nitrogenous compounds (including urea and creatinine) are endogenous substances, abnormally elevated serum concentrations may be caused by an
• increased rate of production (by the liver for urea; by muscles for creatinine)
• by a decreased rate of clearance (primarily by the kidneys).
Creatinine
• Creatinine is a nonenzymatic breakdown product of phosphocreatine in muscle, and daily creatinine production is determined largely by individual muscle mass.
• In dogs and cats, creatinine excretion is accomplished almost
exclusively by glomerular filtration, and the creatinine concentration is inversely related to GFR.
• Small quantities of creatinine may be absorbed when diets contain muscle. Intra-individual variations in serum creatinine concentrations are partially due to diet (i.e., amount of meat consumed).
• A rather constant amount of creatine is converted to creatinine daily;
creatinine is not reutilized.
• Serum creatinine concentrations should be evaluated on at least two occasions when the patient is well-hydrated.
An estimate of the GFR can be calculated from the creatinine content of a 24-hour urine collection, and the plasma concentration within this period.
The volume of urine is measured, urine flow rate is calculated (ml/min) and the assay for creatinine is performed on plasma and urine to obtain the concentration in mg per dl or per ml.
Creatinine clearance
Limitations of Creatinine Measurment
• Factors affecting creatinine production such as muscle mass and cachexia.
• Young animals have lower creatinine concentrations,
• Males and well-muscled animals have higher concentrations.
• Greyhounds have slightly higher serum creatinine concentrations than do non-greyhounds
• High serum bilirubin concentrations (3 mg/dl) can falsely lower creatinine concentrations
• Three-fourths of renal function must be lost before abnormalities in creatinine concentration can be discerned.
Urea
• Urea production and excretion do not occur at a constant rate. While renal dysfunction can cause increased BUN concentration, nonrenal causes also often result in increased BUN concentration.
• Small quantities of urea are ingested and absorbed from the large intestine.
• The majority of urea in plasma is synthesized by the liver. Specifically, the hepatic urea cycle synthesizes urea from ammonia that is a waste product of protein catabolism.
• Once urea enters the vascular system, it passively diffuses throughout the total body water compartment. Approximately 90 minutes are required for equilibrium to be established.
• Gastrointestinal (GI) hemorrhage may also increase BUN
concentrations because blood is an endogenous protein source.
• BUN concentrations may decline in patients with portosystemic shunts or hepatic failure and those receiving low-protein diets
Interpretation of increased BUN concentration
• Prerenal: renal hypoperfusion, Increased protein catabolism, high-protein diets
• Renal: when approximately three-fourths of the nephrons are nonfunctional.
• Postrenal: obstruction of urinary flow or postrenal leakage
Causes of decreased BUN concentration
• Low BUN values may be seen in hepatic insufficiency, low protein diets, and following the administration of anabolic steroids.
• Possible mechanisms resulting in a decreased BUN concentration include decreased production of urea via decreased hepatic urea cycle function or reduced protein catabolism and availability of ammonia for urea synthesis.
• Young animals may have low BUN values from increased fluid intake, increased urine output, and a high anabolic state of rapid growth.
Calcium
• Calcium metabolism is regulated by
• parathyroid hormone (PTH),
• calcitriol (1,25-dihydroxycholecalciferol),
• and calcitonin.
• The major organs involved in its regulation are the kidneys, the small intestine, and bone.
• The total calcium concentration is composed of three fractions:
• protein-bound calcium (35%),
• ionized calcium (50%),
• and complexed calcium (15%).
• Ionized calcium is the biologically active form.
• Calcium disturbances in patients with CKD are a result of decreased vitamin D metabolism through multiple mechanisms.
• In CKD, the loss of functional renal mass
• leads to decreased production of 1-alpha-hydroxylase
• an enzyme that converts calcidiol to calcitriol (the active form of vitamin D).
PHOSPHORUS
• Phosphorus metabolism is regulated by the same hormones as calcium: PTH, calcitriol, and calcitonin.
• It is absorbed primarily in the duodenum, and absorption is increased by the influence of calcitriol.
• Phosphorus is primarily excreted by the kidneys. Most (80% to 90%) of the filtered load is reabsorbed by the proximal tubules.
• PTH decreases phosphorus reabsorption and is the most important regulator of renal phosphate transport.
• Hyperphosphatemia is commonly seen in patients with acute and chronic kidney disease because of decreased renal excretion.
• Other causes of hyperphosphatemia is increased intestinal absorption
• vitamin D toxicosis,
• increased dietary phosphorus intake
Miscellaneous alterations occurring in renal disease
• Nonregenerative anemia occurs
• Decreased erythropoietin secretion because of decreased functional renal
• Hyperkalemia occurs when oliguria or anuria is associated with acidosis in renal failure
• Hypermagnesemia
• Metabolic acidosis. The anion gap is increased due to uremic acids
• Hyponatremia and hypochloridemia may occur with renal disease, due to tubular failure and sodium is lost into the urine.
• Hyperamylasemia and hyperlipasemia can be associated with renal failure in the dogs as these enzymes are degraded and excreted by the kidney
