Nephrotoxicity

• The main roles of the kidney are excretion and detoxification
• The kidney mainly excretes metabolic waste
• The renal cortex receives the most blood flow so is the target for toxicants
• The medulla and papillary are exposed to toxicants for the longest time
• The kidney contains endothelium and podocytes
• The proximal tubule has 3 segments
• P1 is involved in sodium transpotation
• Proximal tubule reabsorbs 60-80% of water and solutes
• The proximal tubule absorbs low molecular weight proteins
• A key clinical sign of damage to the proximal tubule is small proteins in urine
• The loop of Henle has a thin descending limb which is water permeable
• Thick ascending limb absorbs actively transports Na+ and Cl-
• The loop of henle has a high oxygen demand and ATPase activity so target for hypotoxicity
• Distal tubule has a main role in feedback
• An increased solute delivery leads to constriction to prevent fluid loss
• Increase in pores means more concentrated urine
• Acute kidney injury leads to a decreases GFR
• The GFR is the volume filtered in the glomerulus per unit time
• GFR is calculated using creatine clearance
• Creatine cannot be reabsorbed so a good measure for GFR
• NSAID lead to nephrotoxicity

  • Cause vasoconstriction of afferent arterioles
  • Causes hypoxia
  • Causes acute tubular necrosis
  • Can lead to acute interstitial nephritis
• ATP dependent mechanisms means they are vulnerable to hypoxia
• • Cadmium bind to detoxifying transport protein
  • Accumulates in proximal tubule
  • Increase ROS causing cellular damage
  • Decrease in GFR
• Cadmium toxicity can be diagnosed by proteins in the urine
• Urate is the end product of purine metabolism
• Urate is a scavenger for free radicals
• Toxicants can inhibit reuptake of urate by basolateral transporters and can a build up of urate in the blood
• A build up or urate in the blood can cause gout
• Aminoglycosides are only toxic at frequent lower doses as transporters are open
• Aminoglycosides given at single high concentrates are non-toxic as the transporters become saturated
• High molecular weight proteins in the urine indicates a damaged glomerular damage
• Collagen and cystatin are both glomerular markers
• Microglobulin and microalbumin are proximal markers