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Tubulointerstitial diseases are a group of renal disorders characterized by primary abnormalities in the renal tubules or interstitium. There are four principal causes: infectious, toxic, metabolic, and immunologic.

The morphologic changes in tubulointerstitial disease include the following.

  1. Acute tubular necrosis (Table 49-1), which if widespread causes acute renal failure. The changes in all causes of acute tubular necrosis are similar and are discussed under renal changes associated with shock.

  2. Atrophy of tubules, with fibrosis of the interstitium, associated with nephron loss and chronic renal failure.

  3. Interstitial inflammation, either acute, with numerous neutrophils in the tubules and interstitium (acute interstitial nephritis); or chronic, with lymphocytes, plasma cells, macrophages, and fibroblasts (chronic interstitial nephritis).

  4. Tubular basement membrane thickening, as occurs in diabetes, amyloidosis, and transplant rejection.

  5. Deposition of abnormal substances such as calcium, amyloid, urate, myeloma proteins, and oxalate in the tubules and interstitium.

Table 49–1. Causes of Acute Tubular Necrosis.

Infectious Diseases

Acute Pyelonephritis


Acute pyelonephritis is extremely common—1more so in females than in males (10:1). Acute pyelonephritis occurs at all ages, with highest frequency during early sexual activity and during pregnancy.


Acute pyelonephritis is a bacterial infection, usually ascending from the lower urinary tract. Ascent of infection from the bladder is facilitated when vesicoureteral reflux is present. This is more important in children but occurs also in adults. Bacteria spread from the renal pelvis to the tubules by intrarenal reflux. Reflux from the pelvis into the tubules is common: Over 60% of normal kidneys have reflux into at least one papilla. Hematogenous infection of the kidney is uncommon. Factors important in etiology are as follows (Figure 49-1):

Figure 49–1.

Etiologic factors associated with acute pyelonephritis.

  1. A short urethra, as in females.

  2. Stasis of urine from any cause. The high incidence of urinary infections during pregnancy is believed to be the result of increased serum levels of progesterone, which decreases activity of the urinary tract smooth muscle, promoting stasis of urine.

  3. Structural abnormalities in the urinary tract that promote stasis of urine or establish a communication between the urinary tract and an infected site, such as fistulous tracts between the ...

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