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Tubulointerstitial Renal Diseases

Updated on June 19, 2013

Macroscopy of acute tubular necrosis

Microscopy of acute tubular necrosis

Tubulointerstitial renal diseases are diseases which affect the renal interstitium and tubules primarily. This is a heterogeneous group of disorders. Glomerular involvement, if present, usually a secondary event in these diseases. Usually the glomerular involvement is mild and occurs in the advanced stages.

The diseases covered are:

  • Acute tubular necrosis
  • Acute and chronic pyelonephritis
  • Toxic tubulointerstitial nephritis – drug induced, heavy metal
  • Chronic renal disease


Acute tubulointerstitial nephritis:

In acute tubulointerstitial nephritis there is interstitial edema, focal tubular necrosis, inflammatory infiltration predominantly composed of neutrophils.

Chronic tubulointerstitial nephritis:

In chronic tubulointerstitial nephritis there is interstitial fibrosis, tubular atrophy, inflammatory infiltration predominantly composed of lymphocytes and plasma cells.

Secondary tubulointerstitial diseases:

Secondary involvement of the interstitium is due to primary glomerular diseases, vasculitic conditions, diabetes mellitus, hypertension etc. In these conditions tubular interstitial involvement plays a role in progression of the disease.



Acute tubular necrosis
Acute renal failure associated with tubular epithelial injury. Acute tubular epithelial injury could be due to:

  • Ischemic injury
  • Toxic injury

Ischemic injury
Ischemic injuries of the kidney are commonly due to acute hypoperfusion to the kidney caused by hypotension. Hypotension could be due to:

  • acute loss of body fluids causing shock – extensive hemorrhage following trauma, extensive burns, dehydration following severe diarrhea.
  • septic shock
  • pancreatitis

Nephrotoxins
Acute or chronic damage to the parenchyma of the kidney could be due to wide variety of substances such as:

  • Organic solvents – carbon tetrachloride, ethylene glycol.
  • Heavy metals – mercury, lead.
  • Antibiotics – amphotericin B, Gentamycin.
  • Chemotherapeutic agents – methotrxate, cisplatin.
  • Endogenous toxins like myoglobin (in severe skeletal muscle injury such as extensive crush injury, snake venom) or Hemoglobin (in severe intravascular hemolysis).

Kidney macroscopy in acute tubular necrosis:
The kidney is pale and swollen. The cortex is pale and swollen, the medullar is congested. These macroscopic features are typically seen in acute tubular necrosis following shock.

Kidney microscopy in acute tubular necrosis:
There is necrosis of tubular epithelial cells. Tubular lumina contain desquamated necrotic epithelial cells. Interstitial edema and mononuclear inflammatory infiltration can be seen.


Clinical features of acute tubular necrosis:

  • Rapidly increasing serum creatinine levels.
  • Oilguria or anuria.
  • Urine analysis: degenerated epithelial cells and granular casts.


Pyelonephritis
Pyelonephritis is the commonest form of tubulointerstitial renal diseases. Here there is tubulointerstitial inflammation due to infectious causes. The infectious agent is commonly a bacterium which causes infection in the lower urinary tract (cystitis). Acute infection of the renal parenchyma with these organisms causes acute pyelonephritis and repeated infections can later lead to chronic pyelonephritis.

Routes of bacterial entry:
1.Ascending infection from the lower urinary tract – this is the most common route of bacterial entry.
2.Hematogenous spread - usually following septicemia (usually causes acute pyelonephritis).

Some extra facts regarding ascending infection
Commonly involved bacteria are those that cause urethritis and cystitis (usually derived from the normal fecal flora):
E. coli, proteus, klebsiella and enterobactor.

The most important phenomenon which facilitate ascend of bacteria from the bladder to the kidney is vesicoureteral reflux. This could be due to incompetence of the vesicoureteral valve, urinary tract obstruction or persistent bladder atony due to spinal cord injury. Intrarenal reflux propel bacteria into the renal pelvis and parenchyma.

Risk factors for ascending infections

  • Urinary tract obstruction.
  • Instrumentation of the urinary tract – catheterization ( facilitate ascend of lower urethral flora into the bladder).
  • Vesicoureteral reflux.
  • Pregnancy – bacteriuria is relatively common during pregnancy.
  • Preexisting renal lesions.
  • Diabetes mellitus.
  • Immunodeficiency.


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