Renal papillary necrosis pathophysiology

Renal papillary necrosis is a significant kidney disorder, which is associated with ischemia of the inner renal medulla and papilla due to chronic conditions such as diabetes, sickle cell disease, urinary tract obstruction, urinary tract infection and long term use of analgesics. Decreased prostaglandin synthesis and subsequent reduced renal blood flow is an important mechanism for developing renal papillary necrosis.

• The exact pathogenesis of renal papillary necrosis is not fully understood.
• It is thought that Renal papillary necrosis is the result of damage to interstitial medullary and papillary cells due to direct effect of diseases such as diabetes, sickle cell disease, urinary tract obstruction, renal vein thrombosis, upper urinary tract infection, tuberculosis, vasculitis, renal transplant rejection and long term analgesics use such as acetaminophen and NSAIDS. ^[1][2][3]

• Renal medullary and papillary cells are susceptible to ischemia. ^[5]
• Medullary cells usually produce prostaglandins and proteoglycans. ^[1]
  • Damage of medullary cells leads to changes in renal matrix and vessels due to decreased production of prostaglandins that causes vasoconstriction, reduced renal perfusion, ischemia and necrosis. ^[1][6]
• Another mechanism is inhibiting cyclooxygenase enzymes; COX I and COX II, which play a major role in the prostaglandins synthesis, following NSAIDS use. ^[7]
  • Multiple NSAIDS taking and hypovolemic condition could facilitate development of renal papillary necrosis. ^{[1] [2]}

• Accumulation of sickle-shaped RBCs in patients with sickle cell disease can lead to intravascular obstruction, blood stasis and thrombosis that results in ischemic necrosis of renal papillary and medullary cells.^[8]

• The most important characteristics of renal papillary necrosis on gross pathology are irregular round shaped necrosis of renal papillary and medullary area. ^{[9] [3]}

• On microscopic histopathological analysis, the characteristic findings of renal papillary necrosis include^[9][10][11]:
  • Coagulative necrosis of papillary area
  • swelling and sloughing of papilla
  • partial necrosis of medullary area
  • mild inflammation at necrotic area
  • microcalcifications at necrotic area
• Other renal histological findings include^[9][12]:
  • diabetic nephropathy:
    • diffuse nodular mesangial sclerosis
  • analgesic nephropathy:
    • interstitial fibrosis
    • cytoplasmic edema
    • dilation of organelles
    • increased production of proteoglycan
    • tubular atrophy
    • endothelial cell injury
      • capillary sclerosis
    • damage to loops of Henle
    • Platelet thrombus
  • sickle cell nephropathy:
    • intravascular obstruction
    • intravascular thrombosis