Tubulointerstitial disease

Question 1

According to KDIGO, acute kidney injury is defined by any of the following:

Answer 1

Increase in serum creatinine by ≥ 0.3mg/dLwithin 48 hours; or
Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days; or
Urine volume less than .5 mL/kg/h for six hours

Question 2

Causes of Acute Kidney Injury (acute renal failure)

Answer 2

ATN – 45 percent
Prerenal disease – 21 percent

Acute on chronic renal failure – 13 percent (mostly due to ATN or prerenal disease)
Urinary tract obstruction – 10 percent
Glomerulonephritis or vasculitis – 4 percent
Acute interstitial nephritis – 2 percent
Atheroemboli – 1 percent

Question 3

Can divide kidney diseases into those that affect the basic morphologic components:

Answer 3

Blood vessels
Tubules
Interstitium
Glomeruli

Question 4

most common cause acute kidney injury

Answer 4

Acute tubular injury is the most common cause acute kidney injury (acute renal failure)

clinical outcome is determined by the magnitude and duration of acute tubular injury.

Question 5

Acute tubular injury (ATI) Major causes

Answer 5

Ischemia

Nephrotoxic:
- Endogenous toxins
myoglobin, hemoglobin, monoclonal light chain, bilirubin

• Exogenous toxins
  drugs, radio-contrast dyes, heavy metals, solvents

Question 6

Patterns of Tubular Damage

in Acute Kidney Injury

Answer 6

Ischemic
- Patchy necrosis

Toxic
- Mixed patchy and Continuous necrosis

Casts
- Distal tubules and collecting ducts

Question 7

Acute Kidney Injury (AKI)Clinical Course

Answer 7

Initiating phase: Lasts ~ 24-36 hrs from injury
Progressive azotemia (increased BUN, Creatinine)
Progressive oliguria (decreased GFR)

Maintenance phase: Oliguria (40 – 400 ml/24 hours) 
Azotemia (high)
Metabolic acidosis and hyperkalemia
May be highly transient 
	Not clinically evident 50% cases

Recovery phase
Polyuria (tubules still injured so water & ion loss persists)
Hypokalemia
Decreasing Azotemia (as tubule function recovers)

Question 8

Acute Kidney Injury (AKI) Prognosis

Answer 8

Prognosis Relates to Underlying Etiology

Remove underlying cause or brief insult (nephrotoxic):
95% Recovery

Prolonged shock 2o to extensive burns, sepsis… (ischemia):
50% Recovery

Question 9

Renal Tubular EpitheliumToxins

Answer 9

Antiviral agents
NSAIDs
Antibiotics
Immunomodulatory agents
Antineoplastic agents
Radiologic contrast media
Narcotics
Anesthetics
Herbal medications

Question 10

Proximal tubular epithelial cells have exceptionally high energy requirements and are thus quite susceptible to

Answer 10

ischemia

Question 11

Tubulointerstitial Nephritis- defn and types

Answer 11

• kidney diseases that involve structures in the kidney outside the glomerulus.

two common clinical presentations:
acute and chronic

Primary- limited to the tubules and the interstitium

Secondary- associated with a primary glomerular, vascular or systemic disease

Question 12

Tubulointerstitial nephritis

Causative factors

Answer 12

Drugs 75%

Infection 5%

Question 13

Now AIN is most often associated with

Answer 13

drugs 75-90% (antibiotics, NSAIDs)

rare in children

an uncommon cause of acute kidney injury

Question 14

most common causes of acute tubulointerstitial nephritis

Answer 14

Hypersensitivity reaction to drugs or infectious agents

present with rash, fever, eosinophilia

Question 15

Acute tubulointerstitial nephritis

Answer 15

causes a decline in creatinine clearance and is characterized by an inflammatory infiltrate in the kidney interstitium.

often reversible

Symptoms usually develop days to a few weeks after drug is started

Pathologic hallmark : inflammatory infiltrates within the interstitium usually sparing glomeruli and blood vessels

Rarely show immune deposits

Question 16

Drug-induced Acute Tubulointerstitial Nephritis Prognosis and Management

Answer 16

Withdrawal of drug –> Recover normal or near normal renal function within weeks (12% do not recover renal function)
Worst prognosis with increasing age, renal failure lasting longer than three weeks

Question 17

Chronic tubulointerstitial nephr

Answer 17

Characterized by progressive scarring

Progression of primary glomerular diseases –> chronic glomerulonephritis –> Chronic tubulointerstitial nephritis –> ESRD

Question 18

Primary Chronic Interstitial Nephritis Causative Factors

Answer 18

Analgesic nephropathy (rare since the withdrawal of phenacitin)
NSAIDs
Balkan endemic

(Lithium, 5-aminosalicylic acid, chinese herb nephropathy, heavy metals, radiation nephropathy)

Question 19

Balkan nephropathy (chronic interstitial nephritis)

Answer 19

Endemic kidney disease confined to Balkan geographic area (Croatia, Romania, Serbia, Albania…)
Results from contamination of wheat flour with aristolochia acids from endemic plant.

Question 20

Primary Chronic Interstitial Nephritis Clinical Manifestations

Answer 20

indidious onset, tubular dysfunction (renal tubular acidosis, increased urine frequencey), anemia (loss of erythropoietin producing interstitial cells)

Question 21

Acute Pyelonephritis

Answer 21

suppurative inflammation of the kidney, reaches by hematogenous spread or MORE COMMONLY through the ureters in association with vesicoureteral reflux

more common in females than males

Question 22

UTI commonly causd by

Answer 22

E. coli (80-85%)

also catheter-associated infections

Question 23

Chronic pyelonephritis

Answer 23

Vesicoureteral reflux and/or obstruction –> Recurrent pyelonephritis

Question 24

Pathways of renal infection

Answer 24

Acute pyelonephritis is almost always the result of ascending cystitis infection.

Defective Vesicoureteral Junction (50% children with UTIs have reflux)

Bladder Outlet Obstruction
(older males with prostatic hypertrophy)

Question 25

Most common cause of reflux

Answer 25

Congenital- partial or complete lack of oblique entry/angle of the intravesical portion of the ureter

Question 26

acute pyelonephritis: predisposing medical conditions

Answer 26

Diabetes
Pregnancy
Immunosuppression
Instrumentation
Obstruction to urinary outflow

Question 27

Acute pyelonephritis clinical findings and histologic hallmarks

Answer 27

Clinical findings of acute pyelonephritis
Fever, malaise, and flank pain.
Costovertebral angle tenderness may be observed on physical examination

Histologic hallmarks acute pyelonephritis
Patchy interstitial suppurative inflammation
Intratubular aggregates of neutrophils
Neutrophilic tubulitis
Tubular necrosis

Question 28

what pattern of acute pyelonephritis is most typical of hematogenous dissemination?

Answer 28

microabscesses (cortical)

Abscesses are apparent on the cut surface of the cortex, and there are straight yellow streaks and hyperemia in the medulla. The pelvic mucosa is congested, granular, and dull

Question 29

Acute Pyelonephritis Involving Kidney Allografts

Answer 29

(Polyomavirus Nephropathy)

need to decrease immunosuppressive drugs.

–> allograft failure in up to 5%

Question 30

Urinary Tract Defense Mechanisms

Answer 30

Extrinsic bladder mechanisms:
Endogenous bacteria protect by lowering local pH (lactobacillus), steric hindrance and competition for receptor sites
Surface mucosal antibodies

Intrinsic bladder mechanisms:
Relatively low pH of urine, high urine osmolality and high urea content suppress bacterial growth
Glycosaminoglycans line the urothelium
Tamm-Horsfall proteins bind type I fimbriae preventing bacterial attachment

Question 31

Complications of Acute Pyelonephritis

Answer 31

Papillary necrosis (esp. in diabetics and complete urinary tract obstruction)

Pyonephosis- exudate cannot drain

Perinephric abscess

Question 32

Early stages of renal papillary necrosis

Answer 32

involve the tip of the renal papilla.

loss of cellular definition, loss of staining affinity in the area of the papillary tip

Question 33

Chronic pyelonephritis can be divided into two forms:

Answer 33

Reflux nephropathy (most common form)
Chronic obstructive pyelonephritis

Question 34

name staghorn calculus.

Answer 34

Sometimes a very large calculus nearly fills the calyceal system, with extensions into calyces that give the appearance of a stag’s (deer) horns—hence

Question 35

Morphologic hallmarks of chronic pyelonephritis

Answer 35

Medullary scars
deformed calyces
***plasma cells (most characteristic) and lymphocytes –> interstitial fibrosis and scarring
tubular atrophy with proteinaceous casts (thyroidization) –> interstitial fibrosis and sclerosis of glomeruli

Question 36

Pyelonephritis key concepts

Answer 36

caused by infection via the ascending (more common) or hematogenous route. Obstructive lesions = predisposing factors

Bacteria are the most common infectious agent

Chronic pyelonephritis ensues when anatomic anomalies result in urine reflux or urine outflow obstruction

Question 37

Systemic Diseases Associated with Tubulointerstitial Nephritis

Answer 37

Sarcoidosis
Systemic lupus erythematosus
Usually associated with some glomerular abnormalities
Sjogren’s syndrome
Urate Nephropathy
Post chemotherapy for lymphoma/leukemia
Hyperuricemia (gout)
Hypercalcemia  Extensive calcinosis
Light chain nephropathy (Myeloma kidney)
Hepatorenal syndrome

Question 38

Urate Nephropathy

Answer 38

Acute caused by precipitation of uric acid crystals in renal tubules (chemotherapy for hematologic malignancies)

Chronic associated protracted hyperuricemia, tubule crystal deposits and inflammatory reaction

Uric acid stones and urinary tract obstruction

Question 39

Light Chain Nephropathy

Answer 39

(multiple myeloma)
Usually chronic kidney disease develops insidiously and progresses slowly
Bence-Jones proteinuria directly toxic to tubular cells and forms tubular casts
Associated with amyloidosis
Light chain deposition disease in glomerular basement membrane and mesangium
Hypercalcemia and hyperuricemia