Tubulointerstitial disease Flashcards
According to KDIGO, acute kidney injury is defined by any of the following:
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
Causes of Acute Kidney Injury (acute renal failure)
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
Can divide kidney diseases into those that affect the basic morphologic components:
Blood vessels
Tubules
Interstitium
Glomeruli
most common cause acute kidney injury
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.
Acute tubular injury (ATI) Major causes
Ischemia
Nephrotoxic:
- Endogenous toxins
myoglobin, hemoglobin, monoclonal light chain, bilirubin
- Exogenous toxins
drugs, radio-contrast dyes, heavy metals, solvents
Patterns of Tubular Damage
in Acute Kidney Injury
Ischemic
- Patchy necrosis
Toxic
- Mixed patchy and Continuous necrosis
Casts
- Distal tubules and collecting ducts
Acute Kidney Injury (AKI)Clinical Course
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)
Acute Kidney Injury (AKI) Prognosis
Prognosis Relates to Underlying Etiology
Remove underlying cause or brief insult (nephrotoxic):
95% Recovery
Prolonged shock 2o to extensive burns, sepsis… (ischemia):
50% Recovery
Renal Tubular EpitheliumToxins
Antiviral agents NSAIDs Antibiotics Immunomodulatory agents Antineoplastic agents Radiologic contrast media Narcotics Anesthetics Herbal medications
Proximal tubular epithelial cells have exceptionally high energy requirements and are thus quite susceptible to
ischemia
Tubulointerstitial Nephritis- defn and types
- 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
Tubulointerstitial nephritis
Causative factors
Drugs 75%
Infection 5%
Now AIN is most often associated with
drugs 75-90% (antibiotics, NSAIDs)
rare in children
an uncommon cause of acute kidney injury
most common causes of acute tubulointerstitial nephritis
Hypersensitivity reaction to drugs or infectious agents
present with rash, fever, eosinophilia
Acute tubulointerstitial nephritis
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
Drug-induced Acute Tubulointerstitial Nephritis Prognosis and Management
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
Chronic tubulointerstitial nephr
Characterized by progressive scarring
Progression of primary glomerular diseases –> chronic glomerulonephritis –> Chronic tubulointerstitial nephritis –> ESRD
Primary Chronic Interstitial Nephritis Causative Factors
Analgesic nephropathy (rare since the withdrawal of phenacitin)
NSAIDs
Balkan endemic
(Lithium, 5-aminosalicylic acid, chinese herb nephropathy, heavy metals, radiation nephropathy)
Balkan nephropathy (chronic interstitial nephritis)
Endemic kidney disease confined to Balkan geographic area (Croatia, Romania, Serbia, Albania…)
Results from contamination of wheat flour with aristolochia acids from endemic plant.
Primary Chronic Interstitial Nephritis Clinical Manifestations
indidious onset, tubular dysfunction (renal tubular acidosis, increased urine frequencey), anemia (loss of erythropoietin producing interstitial cells)
Acute Pyelonephritis
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
UTI commonly causd by
E. coli (80-85%)
also catheter-associated infections
Chronic pyelonephritis
Vesicoureteral reflux and/or obstruction –> Recurrent pyelonephritis
Pathways of renal infection
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)
Most common cause of reflux
Congenital- partial or complete lack of oblique entry/angle of the intravesical portion of the ureter
acute pyelonephritis: predisposing medical conditions
Diabetes Pregnancy Immunosuppression Instrumentation Obstruction to urinary outflow
Acute pyelonephritis clinical findings and histologic hallmarks
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
what pattern of acute pyelonephritis is most typical of hematogenous dissemination?
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
Acute Pyelonephritis Involving Kidney Allografts
(Polyomavirus Nephropathy)
need to decrease immunosuppressive drugs.
–> allograft failure in up to 5%
Urinary Tract Defense Mechanisms
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
Complications of Acute Pyelonephritis
Papillary necrosis (esp. in diabetics and complete urinary tract obstruction)
Pyonephosis- exudate cannot drain
Perinephric abscess
Early stages of renal papillary necrosis
involve the tip of the renal papilla.
loss of cellular definition, loss of staining affinity in the area of the papillary tip
Chronic pyelonephritis can be divided into two forms:
Reflux nephropathy (most common form) Chronic obstructive pyelonephritis
name staghorn calculus.
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
Morphologic hallmarks of chronic pyelonephritis
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
Pyelonephritis key concepts
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
Systemic Diseases Associated with Tubulointerstitial Nephritis
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
Urate Nephropathy
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
Light Chain Nephropathy
(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
