Kidney

• Kidneys


  Paired, bean-shaped organs located retroperitoneally on either side of the spinal column
• Regions of the kidney

  • Cortex (outer region)
  • Medulla (inner region)
• Parts of the nephron (functional unit of the kidney)

  • Glomerulus
  • Proximal convoluted tubule
  • Loop of Henle
  • Distal convoluted tubule
  • Collecting duct
• Countercurrent multiplier mechanism


  Kidneys conserve fluid by building high sodium chloride gradients in the interstitial space between the descending and ascending limbs of loop of Henle
• Proximal convoluted tubule


  Responsible for the reabsorption of sodium, chloride, bicarbonate, other ions, glucose, amino acids, proteins, urea and uric acid
• About 25 liters of dilute urine is delivered to the ascending limb of Henle. Because the tubules from this point to the beginning of cortical collecting duct are water impermeable, the volume remains unchanged at 25 liters, but the osmolality decreases progressively to about 60-80 mOsm/L
• Collecting duct


  Final site for either concentrating or diluting urine
• Nonprotein nitrogenous compounds in plasma

  • Urea (45%)
  • Amino acid (20%)
  • Uric acid (20%)
  • Creatinine (5%)
  • Creatine (1-2%)
  • Ammonia (0.2%)
• Renal function panel


  • Glucose
  • BUN
  • Albumin
  • Creatinine
  • CO2
  • Phosphorus
  • Chloride
  • Calcium
  • Sodium
  • Potassium
• Functions of the kidneys

  • Elimination of waste products
  • Maintenance of blood volume
  • Maintenance of electrolyte balance
  • Maintenance of acid-base balance
  • Endocrine function (erythropoietin secretion)
• Glomerular filtration rate (GFR)


  Measure of the clearance of normal molecules that are not bound to protein and are freely filtered by the glomeruli and neither reabsorbed nor secreted by the tubules. It is the best overall indicator of the level of kidney function.
• 150 L of glomerular filtrate is produced daily
• GFR decreases by 1.0 mL/minute/year after age 20 to 30 years
• About 180 liters of water is filtered daily, 150 liters is reabsorbed in the proximal tubule, about 5 liters is reabsorbed in the descending limb of Henle of cortical nephrons
• Clearance


  Removal of a substance from plasma into urine over a fixed time. It represents the volume of plasma that would contribute all the solute excreted, expressed in mL/min.
• Inulin clearance


  Reference method for measuring GFR, requires continuous IV infusion and timed urine collections over many hours. Has higher values in males due to larger renal mass.
• Alternatives to inulin for measuring GFR


  • Radioactive markers 125l-iothalamate and 99mTc-DTPA
  • Iohexol and Chromium51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA)
  • Nonradiolabeled iothalamate
• Creatinine clearance


  Provides an estimate of the amount of plasma that must have flowed through the kidney glomeruli per minute. It is an excellent measure of renal function as creatinine is freely filtered by the glomeruli but not reabsorbed.
• Production and excretion of creatinine is related directly to muscle mass. When renal function is normal and stable, creatinine excretion is almost equal to its production, which depends primarily on muscle mass.
• The amount of creatinine generated from creatine turnover tends to remain constant for 24 hours. Excretion of creatinine is not routinely affected by diet (1.2-1.5 g creatinine excreted/day).
• Factors that increase creatinine clearance

  • High cardiac output
  • Pregnancy
  • Burns
  • Carbon monoxide poisoning
• Factors that decrease creatinine clearance

  • Impaired kidney function
  • Shock, dehydration
  • Hemorrhage
  • Congestive heart failure
• Urea clearance


  Can demonstrate progression of renal disease or response to therapy, but does not give reliable estimates of GFR since urea is freely filtered by the glomeruli but variably reabsorbed by the tubules.
• In the presence of normal renal function without volume depletion, urea clearance is about 50% of creatinine clearance (50% GFR), but in the presence of severe volume depletion, urea clearance could be as little as 10% of creatinine clearance.
• In advanced renal failure, urea clearance approaches unity with GFR, and is a better predictor of GFR than creatinine clearance.
• Volume depletion decreases creatinine clearance only by reduced filtration, but decreases urea clearance by both reduced filtration and increased reabsorption.
• Cystatin C


  A low molecular weight protease inhibitor produced at a constant rate by all nucleated cells. It is freely filtered at the glomerulus, not secreted by the renal tubules but reabsorbed and completely catabolized by the proximal convoluted tubule. Its serum level is an indirect estimate of GFR.
• Cystatin C increases more rapidly than creatinine in the early stages of GFR impairment.
• Beta trace protein


  A low molecular weight glycoprotein that belongs to the lipocalin protein family and functions as prostaglandin D synthase. It is freely filtered at the glomerulus, then reabsorbed completely and catabolized by the proximal tubule. Its increased levels indicate renal disease due to reduced filtration.
• Blood urea nitrogen (BUN)


  The major end product of protein (dietary) and amino acid catabolism, freely filtered at the glomerulus but substantially reabsorbed in the proximal convoluted tubule and inner medullary collecting duct. It is the first metabolite to elevate in kidney diseases and is easily removed by dialysis.
• About 25 g of urea is excreted daily in stable nitrogen balance.
• BUN to creatinine ratio

  10:1 to 20:1
• Methods for measuring BUN

  • Chemical method (direct method)
  • Enzymatic method (indirect method)
  • Isotope dilution mass spectrometry (reference method)
• Factors that increase BUN

  • Chronic renal disease
  • Stress
  • Burns
  • High protein diet
• Factors that decrease BUN

  • Decreased protein intake
  • Liver disease
  • Pregnancy
  • Hemodialysis
• Nitrogen content of urea

  Concentration of urea can be obtained from BUN (blood urea nitrogen)
• BUN:Creatinine ratio


  10:1 – 20:1
• Fasting sample is usually NOT required
• FLUORIDE OR CITRATE will both inhibit urease
• THIOSEMICARBAZIDE AND FERRIC IONS are added to enhance color development