Tubulointerstitial Diseases

Outline1. Acute tubular necrosis (ATN)2. Tubulointerstitial nephritis

a. Acute drug-induced interstitial nephritisb. Analgesic nephropathyc. NSAIDs nephropathy

3. Pyelonephritisa. Acuteb. Chronic

1. Acute tubular necrosis- MCC of Acute Renal Failure Classic Case: Fall in urine output and BUN and PCr (signifies GFR-renal function)

following major abdominal surgery that was complicated by episodes of hypotension. The differential diagnosis in this setting is prerenal disease versus ATN.

o Classic Finding= Muddy Brown Granular Casts in Urineo PT w/ ATN- Most of the tubules look more like distal tubules than proximal

tubules (should have lumens that are filled by vili/cytoplasm). They are dilated, and the epithelium is flattened(epithelial supplification). There is cellular debris in some of the lumina casts in urine. The interstitium is edematous.- No tubulitis b/c not inflammatory.

o Acute tubular necrosis (40X). Note the vacuolar degenerative changes in the tubular epithelium on the left. The tubular lumen on the right contains desquamated cells.

a. Acute phosphate nephropathy. Acute tubular necrosis with calcium phosphate deposits in tubular lumina. (H&E)

i. Acute tubular necrosis with calcium phosphate deposits in tubular lumina. (H&E)

2. Tubulointerstitial nephritisa. Acute drug-induced interstitial nephritis

i. Acute interstitial nephritis with diffuse inflammation and edema. Note uninvolved glomerulus (arrow). PASH

o Note “tubulitis” (arrows). PASH

o Acute interstitial nephritis. Note the granuloma on the right with a multinucleated giant cell (arrow). Even though this patient had tuberculosis, this granuloma is not due to that. In fact, the MCC of granulomatous interstitial nephritis is an allergic drug reaction. Note also that the glomerulus is uninvolved. H&E

o

b. Analgesic nephropathy (NSAIDS- Chronic interstitial nephritis that results from excessive consumption of mixtures containing phenacetin and aspirin

i. Papillary necrosis occurs first; secondary chronic interstitial nephritis.

ii. Papillary necrosis-The cut surface of the kidney shows yellow necrotic areas at the tips of the papillae. Note that the middle necrotic area is viewed from the inside of the calyceal system. The necrotic material can slough into the ureter and cause obstruction.

iii.

3. Pyelonephritis

a. Acute Pyelonephritis

i. More than 85% of cases are gram-negative bacilli that are normal inhabitants of the GI tract; E. coli is the most common

ii. Cortical surface shows grayish white areas of inflammation and abscess formation

iii. urinary bladder infectionvesicoureteral reflux intrarenal reflux. Requires Congenital deformity in Vsicouretral Jx- Vesicoureteral reflux demonstrated by a voiding cystourethrogram. Dye injected into the bladder refluxes into both dilated ureters, filling the pelvis and calyces.

c. 15% of time can be due to Hematogenous bacterial spread to kidneys (but much less common and patient needs to be Imunnocompromised.) Kidneys have many more abscess like shown.

d. Histologically- Ascending infect and Hematogenous spread look the same. - Acute pyelonephritis. The interstitium is edematous with

numerous neutrophils. Most of the tubules also contain neutrophils in the lumen. H&E

i.e. High power view of the inflammatory cells in the tubular lumen

(right side) and also in the interstitium between the two tubules. H&E

i.

CHRONIC PYELONEPHRITIS Chronic pyelonephritis. The surface is irregularly scarred. The cut section (right)

reveals characteristic dilatation and blunting of calyces. The ureter is dilated and thickened, a finding that is consistent with chronic vesicoureteral reflux

o Reflux nephropathy with chronic pyelonephritis and secondary FSGS . Low power LM

showing chronic cortical atrophy with “thyroidization” in the upper part, right two thirds of the slide. Notice the fibrotic and distorted papilla and chronic inflammation of the pelvic mucosa. The empty space in the lower left corner represents the lumen of the dilated pelvis.

o