16 - Tubulointerstitial Renal Disease

Question 1

What is acute interstitial nephritis? What are some causes?

Answer 1

Inflammation of renal tubules and interstitium.

Causes:

• hypersensitivity rxn to drugs (msot common cause): PCN derivatives, NSAIDs, sulfonamides, and rifampin.
• Infections
• Autoimmune disesases: SLE, sjogrens

Question 2

How severe is acute interstitial nephritis?

Answer 2

Severity of clinical presentation can vary.

Drug-related cases are usually reversible.

Idiosyncratic, recurs with re-exposure, older pts particularly susceptible.

Question 3

What are features of hypersensitivity reaction causing acute interstitial nephritis? What does the urinalysis show and what is the gold standard for diagnosis?

Answer 3

• Feverm arthralgias, maculopapular rash.
• Peripheral blood eosinophilia
• Eosinophils in the urine

UA shows WBCs, WBC casts, and RBCs

Gold standard for diagnosis: renal biopsy

Question 4

What are the major indications for kidney biopsy? How does a kidney biopsy work?

Answer 4

1. Nephrotic syndrome: proteinuria (3g/dauy), low albumin
2. Nephritic syndrome: HTN, glomerular hematuria, azotemia
3. Unexplained acute kidney injury

Get two to three 10 mm x 2mm core samples and look at the LM, IF, and EM.

Question 5

How do you treat acute interstitial nephritis?

Answer 5

Most drug related cases resolve when offending drug is removed, corticosteroids sometimes used.

Treat associated infections.

Treat underlying cause in autoimmune disorders.

Question 6

What are morphologic features of acute interstitial nephritis?

Answer 6

• Inflammation and edema of interstitium with involvement of tubules (tubulitis) sparing glomeruli and vessels
• Lymphocytes, plasma cells, eosinophils
• May see granulomas

Question 7

What is acute pyelonephritis? What causes it?

Answer 7

Acute inflammation of hte kidney due to a bacterial infection; can be from the urinary route or the hematogenous route.

Typical urinary tract pathogens: usualy gram negative bacilli.

Question 8

What are predisposing conditions for pyelonephritis?

Answer 8

• Urinary obstruction - congenital or acquired
• Urinary tract instrumentation
• Vesicoureteral reflex
• Pregnancy
• Diabetes

Question 9

What are the gross and histological characteristics of pyelonephritis?

Answer 9

Can be deformed so much that it requires nephrectomy.

Histology: PMNs present. Looks similar to acute interstitial nephritis; you would need clinical picture to differentiate.

Question 10

How common is renal failure in multiple myeloma? What does the chronic renal failure result from?

Answer 10

Cancer of the plasma cells; light chains made by plasma cells are tubulotoxic.

Renal failure develops in 25% of pts.

Chronic renal failure results from:

• direct tubular toxicity of light chains
• tubular obstruction by casts
• interstitial inflammation

Question 11

What do the casts look like in multiple myeloma? What precipitates the cast formation?

Answer 11

Cast nephropathy due to excessive production and urinary excretion of light chains.

Presents as AKI

Favtors that favor intratubular precipitation and cast formation:

• hypercalcemia
• volume depletion
• nephrotoxins

Question 12

How does multiple myelome present? What is helpful to diagnose it?

Answer 12

• Older pts, usually over 40
• Renal insuff. and proteinuria
• Bone pain, frsctures
• Anemia
• Hypercalcemia
• Monoclonal light chains in blood or urine

Renal biopsy helpful

Question 13

What is seen on light microscopy, immunofluorescence, and electron microscopy in multiple myeloma?

Answer 13

LM: crystallin, fractured casts in tubules with associated cellular rxn

IF: May see light chain predominance (may be kappa or lambda)

EM: electron dense, fractured casts

Question 14

How do you treat multiple myeloma?

Answer 14

Acutely: hydration and urinary alkalization to prevent tubular obstruction by casts

Chemotherapy or stem cell transplant

Question 15

Acute interstitial nephritis is often caused by what? What is it characterized by?

Answer 15

Often caused by drugs.

Characterized by interstitial inflammation with eosinophil predominance, eosinophilia, and eosinophiluria.

Question 16

What is pyelonephritis usually caused by? What is it characterized by?

Answer 16

Ascending UTI.

Characterized by the presence of interstitial and tubular inflammation and the presence of bacteria on urine culture.

Question 17

What type of casts are seen in multiple myeloma? What are they characterized by?

Answer 17

Myeloma cast nephropathy.

Characterized by fractured tubular casts with either lambda or kappa light chain predominance.

Question 18

What is the difference between simple cysts and acquired cystic kidney disease?

Answer 18

Simple cysts are generally innocuous, 1-5 cm in diameter, translucent, and filled with clear liqued. They are usually confined to the cortex but massive ones can occur. They have smooth contours and are avascular.

Acquired cystic kidney disease occurs in ESRD; multiple cists present in cortex and medulla. Risk of renal neoplasms 100x greater than general pop.

Question 19

What helps dictate the severity of a renal cyst?

Answer 19

Bosniak classification system; based on how large they are, how septated they are, and how thick their walls are.

All of these properties indicate a higher probability of renal cell carcinoma.

Question 20

What occurs in autosomal dominant polycistic kidney disease (ADPKD)?

Answer 20

Multiple expending cysts affecting both kidneys.

Cysts destroy renal parenchyma.

1:500-1000

Question 21

What is the pathogenesis of aut dominant polycystic kidney disease (ADPKD)? Which is more severe?

Answer 21

PKD1 (90%) mutation on chrom 16 that encodes polycystin-1. Has a more severe clinical course.

PKD2 (10-15%) mutation on chrom 4 that encodes polycystin-2. LEss severe progression in kidney function.

Question 22

What are clinical features of aut dominant polycystic kidney disease? What is the prognosis?

Answer 22

Usually no symptoms before 4th decade of life.

Common symptoms: flank pain, palpation of abd. mass, gross hematuria, HTN (70%).

Ultimately progresses to ESRTD; avg age of ESRD is 50 but varies.

Question 23

What are the extrarenal manifestatios of autosomal dominant polycystic kidney disease (ADPKD)?

Answer 23

Saccular aneurysm of the circle of willis in 10-30% of pts: high incidence of subarachnoid hemorrhage (“thunderclap headache”)

• screen with MRI: fam hx of aneurysms, pt preference, “At risk” jobs (pilot, bus driver)

Polycystic liver disease >85%

• Liver function often PRESERVED (this differentiates it from aut recssive polycystic kidney disease)

Question 24

When do people get autosomal recessive polycystic kidney disease (ARPKD)? What causes it?

Answer 24

Childhood form, typically begins in utero.

1:20,000

Mutations in PKHD1 (encodes fibrocystin found in cilia - mechanism unknown)

Question 25

What are clinical features of aut recessive polycystic kidney disease (ARPKD)? How should it be treated?

Answer 25

• Numerous small cysts in the cortex and medulla (“spongelike”)
• Almost all cases: liver cysts and prolif of portal bile ducts
• Manifestations usually present at birth; pts who survive develop liver cirrhosis.

Combined kidney and liver transplant should be considered in causes of ESRD and extensive portal HTN.

Question 26

What is nephronophthisis (NPHP)? What is the pathology and prognosis?

Answer 26

RARE; progressive loss of nephrons. Formerly known as medullary cystic disease (Small cysts at corticomedullary junction)

Path: tubular BM abnormal, tubular atrophy with cysts, interstitial fibrosis.

Causes polyuria and enuresis (involuntary urination).

Poor prognosis, treatment is supportive, ESRD in childhood.

Question 27

What causes tuberous scleorsis? What are characteristics? How is it managed?

Answer 27

Aut dominant mutation in tumor suppressor gene - inactivating mutation of TSC1 (hamartin) or TCS2 (tuberin).

Tumor-like malformations, hamartomas in kidney, brain, heart, lung, skin.

Management: nephron sparing surgical resection of large cysts or renal cell carcinoma.

Question 28

What is Von Hippel Lindau and what is it caused by?

Answer 28

Aut dominant multi-system cancer predisposition syndrome.

Related to the VHL gene that makes a VHL protein that causes tumor supression.

Results in retinal hemangioblastomas, clear cell renal carcinomas, and pheocromocytomas.

• RCC typically bilateral and managed with resection

Question 29

What is medullary sponge kidney?

Answer 29

Dilated medullary and papillary collecting ducts.

Renal medulla develops spongy appearance; typically asymptomatic.

Associated with nephrocalcinosis (calcifications within kidney).

Question 30

Many of the cystic kidney diseases are slowly progressive. What is the exception to this?

Answer 30

Autosomal recessive polycystic kidney disease (ARPKD) which develops in utero and is seen in infancy.

Question 31

What is the most common cause of ESRD in population younger than 21 (40-50%)?

Answer 31

Congenital and developmental abnormalities.

Question 32

Who gets posterior urethral valves? What occurs? How is it managed?

Answer 32

Developmental defect in males resulting in subvesicular obstruction.

Mucosal folds in the urethra cause obstruction.

Obstruction causes distension of hte bladder, hydroureters, and hydronephrosis.

Management: transurethral resection of valves.

Question 33

What is a horshoe kidney? How common is it?

Answer 33

Kidneys joined at lower pole; during descent stopped by the inferior mesenteric artery (IMA).

1:400-800 births. More common in males.

Usually asymptomatic but can have problems with reflux, obstruction, or stones.