Pathology of tubulointerstitial and cystic renal disease

Question 1

Renal tubulointerstitial disease

Answer 1

• Abnormalities of renal tubules and interstitium w/ sparing of the glomeruli
• May be due to injury, infection, reaction to substances, ischemia

Question 2

Acute pyelonephritis 1

Answer 2

• Inflammation of the kidney and its pelvis, affecting the tubules and interstitium
• Pts have costovertebral tenderness
• Acute pyelonephritis (APN) is usually associated w/ UTIs (usually E coli/enteric bacteria)
• Most common mechanism is ascending infection from bladder, which is promoted by urine stasis (obstructive uropathy, reflux)
• Pregnancy increases risk, as does immunosuppression
• Diabetes predisposes for UTI: nephrogenic bladder, urine stasis, decrease WBC function, vascular problems

Question 3

Acute pyelonephritis 2

Answer 3

• Lab data: pyuria (pus in urine), WBC casts, organisms in blood
• Pathology: grossly the kidney is enlarged w/ yellow streaks and inflamed calyces and pelvis
• Microscopically there is infiltration of PMNs into the interstitium and tubules w/ micro-abscesses
• There is lots of space btwn tubules, but this space is filled w/ PMNs
• Complications: septicemia and shock, preterm labor, papillary necrosis (in DM pts), pyonephrosis (pus obstruction causing hydronephrosis), perinephric abscess

Question 4

Chronic pyelonephritis (CPN) 1

Answer 4

• Chronic tubulointerstitial inflammation and renal scarring w/ involvement of calyces and pelvis
• Calyceal involvement (blunting of calyces) distinguishes CNP from other tubulointerstitial diseases
• Combination of etiologies, most important being bacterial infection but also reflux and obstruction play a role
• There is scarring of the renal parenchyma and distortion of the renal calyces and pelvis (dilation of pelvis and calyces)

Question 5

Chronic pyelonephritis (CPN) 2

Answer 5

• Grossly there is lots of fibrosis, microscopically there is patchy atrophic tubules and surviving tubules that may be hypertrophic and dilated w/ colloid casts (thyroidization- since it looks like thyroid tissue)
• There is interstitial fibrosis but the glomeruli are spared initially
• Calyces and pelvis develop fibrous thickening and show chronic inflammation (mononuclear cells)
• Clinical manifestations: often insidious onset and is not recognized until renal failure
• Pt has bacteriuria, pyuria, proteinuria, and elevated BUN/Cr
• Can’t progress to renal cell CA

Question 6

Xanthogranulomatous pyelonephritis

Answer 6

• A form of CNP in which there are foamy macs mixed w/ plasma cells, lymphocytes and PMNs w/ occasional giant cells
• Associated w/ proteus infections and often superimposed obstruction (calceal stag horn calculi)
• Looks similar to renal cell CA, but can’t progress to renal cell CA

Question 7

Interstitial nephritis

Answer 7

• Caused by drugs, analgesics, radiation
• Drugs includes penicillins, rifampin and cause a hypersensitivity rxn (1 or 4) or have a directly toxic effect
• These drugs produce AIN, characterized by abundant eos, PMNs, lymphocytes, macs in interstitium but gloms are normal
• Analgesic nephropathy is usually due to excessive use of phenacetin and presents as papillary changes w/ patchy/diffuse necrosis of epithelial cells w/ interstitial fibrosis
• Its a chronic interstitial nephritis due to decreased RBF
• Radiation nephritis is often from CA Rx and it causes glomerular hyalinization

Question 8

Ischemic ATN

Answer 8

• The medulla is particularly susceptible to ischemia due to its high O2 consumption
• Lack of renal perfusion leads to vasoconstriction and a reduced GFR/oliguria
• Most frequently seen after an episode of shock (sepsis, burns, trauma, hemolytic anemias)
• If blood flow to kidneys is restored in time the tubules will regenerate (glomeruli/DT normal)
• Microscopically there are short segments of focal tubular necrosis at multiple points along the nephron (different necrosis pattern than toxic-induced necrosis)
• In ischemic ATN there are parts of the PT affected, but its mostly the thin ascending limb thats affected
• Can see brown granular muddy casts in urine sed + Tamm Horsfall protein (granular casts)

Question 9

Toxic ATN

Answer 9

• Usually due to aminoglycosides (gentamycin), amphotericin, contrast
• This has a different necrosis pattern than ischemic ATN
• Toxic ATN affects close to all of the PT, as well as the thin ascending limb
• Necrosis in the PT is extensive and continuous (broken up and focal in ischemic ATN)

Question 10

Autosomal dominant polycystic kidney disease (ADPKD)

Answer 10

• Dominant form of PKD is seen in adults (less severe), whereas the recessive form is seen in infants (very severe)
• In ADPKD there are expanding cysts that eventually destroy the renal parenchyma and cause renal failure
• These cysts are not present at birth
• Micro: variably-sized cysts lined by simple epithelium w/ normal intervening parenchyma present
• Associated abnormalities: liver/pancreatic cysts, cerebral aneurysms/rupture, ao regurg/valve anomalies
• Causes of death: uremia
• Complications: MI, CHF, ICH, ruptured berry aneurysm

Question 11

Autosomal recessive polycystic kidney disease (ARPKD)

Answer 11

• Seen in infants, not normally compatible w/ life
• Cysts are more uniform in size/shape than in adult form
• Associated congenital abnormalities: cystic liver disease and biliary dysgenesis w/ hepatic fibrosis leading to portal HTN
• Death due to rapid renal failure

Question 12

Medullary sponge kidney vs uremic medullary cystic disease

Answer 12

• MSK and UMCD are identical in almost every way, except that UMCD pts have Sx and MSK pts do not have Sx
• Both have kidneys w/ small cysts mostly in medulla/corticomedullary junction
• Sx in UMCD: polyuria/polydipsia (due to tubular defect in concentrating ability), Na wasting and tubular acidosis
• Other forms of cystic diseases: simple renal cysts (no clinical significance) and dialysis cystic disease (from chronic dialysis)