16 - Tubulointerstitial Renal Disease Flashcards
What is acute interstitial nephritis? What are some causes?
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
How severe is acute interstitial nephritis?
Severity of clinical presentation can vary.
Drug-related cases are usually reversible.
Idiosyncratic, recurs with re-exposure, older pts particularly susceptible.
What are features of hypersensitivity reaction causing acute interstitial nephritis? What does the urinalysis show and what is the gold standard for diagnosis?
- Feverm arthralgias, maculopapular rash.
- Peripheral blood eosinophilia
- Eosinophils in the urine
UA shows WBCs, WBC casts, and RBCs
Gold standard for diagnosis: renal biopsy
What are the major indications for kidney biopsy? How does a kidney biopsy work?
- Nephrotic syndrome: proteinuria (3g/dauy), low albumin
- Nephritic syndrome: HTN, glomerular hematuria, azotemia
- Unexplained acute kidney injury
Get two to three 10 mm x 2mm core samples and look at the LM, IF, and EM.
How do you treat acute interstitial nephritis?
Most drug related cases resolve when offending drug is removed, corticosteroids sometimes used.
Treat associated infections.
Treat underlying cause in autoimmune disorders.
What are morphologic features of acute interstitial nephritis?
- Inflammation and edema of interstitium with involvement of tubules (tubulitis) sparing glomeruli and vessels
- Lymphocytes, plasma cells, eosinophils
- May see granulomas
What is acute pyelonephritis? What causes it?
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.
What are predisposing conditions for pyelonephritis?
- Urinary obstruction - congenital or acquired
- Urinary tract instrumentation
- Vesicoureteral reflex
- Pregnancy
- Diabetes
What are the gross and histological characteristics of pyelonephritis?
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.
How common is renal failure in multiple myeloma? What does the chronic renal failure result from?
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
What do the casts look like in multiple myeloma? What precipitates the cast formation?
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
How does multiple myelome present? What is helpful to diagnose it?
- Older pts, usually over 40
- Renal insuff. and proteinuria
- Bone pain, frsctures
- Anemia
- Hypercalcemia
- Monoclonal light chains in blood or urine
Renal biopsy helpful
What is seen on light microscopy, immunofluorescence, and electron microscopy in multiple myeloma?
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
How do you treat multiple myeloma?
Acutely: hydration and urinary alkalization to prevent tubular obstruction by casts
Chemotherapy or stem cell transplant
Acute interstitial nephritis is often caused by what? What is it characterized by?
Often caused by drugs.
Characterized by interstitial inflammation with eosinophil predominance, eosinophilia, and eosinophiluria.
What is pyelonephritis usually caused by? What is it characterized by?
Ascending UTI.
Characterized by the presence of interstitial and tubular inflammation and the presence of bacteria on urine culture.
What type of casts are seen in multiple myeloma? What are they characterized by?
Myeloma cast nephropathy.
Characterized by fractured tubular casts with either lambda or kappa light chain predominance.
What is the difference between simple cysts and acquired cystic kidney disease?
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.
What helps dictate the severity of a renal cyst?
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.
What occurs in autosomal dominant polycistic kidney disease (ADPKD)?
Multiple expending cysts affecting both kidneys.
Cysts destroy renal parenchyma.
1:500-1000
What is the pathogenesis of aut dominant polycystic kidney disease (ADPKD)? Which is more severe?
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.
What are clinical features of aut dominant polycystic kidney disease? What is the prognosis?
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.
What are the extrarenal manifestatios of autosomal dominant polycystic kidney disease (ADPKD)?
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)
When do people get autosomal recessive polycystic kidney disease (ARPKD)? What causes it?
Childhood form, typically begins in utero.
1:20,000
Mutations in PKHD1 (encodes fibrocystin found in cilia - mechanism unknown)
What are clinical features of aut recessive polycystic kidney disease (ARPKD)? How should it be treated?
- 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.
What is nephronophthisis (NPHP)? What is the pathology and prognosis?
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.
What causes tuberous scleorsis? What are characteristics? How is it managed?
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.
What is Von Hippel Lindau and what is it caused by?
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
What is medullary sponge kidney?
Dilated medullary and papillary collecting ducts.
Renal medulla develops spongy appearance; typically asymptomatic.
Associated with nephrocalcinosis (calcifications within kidney).
Many of the cystic kidney diseases are slowly progressive. What is the exception to this?
Autosomal recessive polycystic kidney disease (ARPKD) which develops in utero and is seen in infancy.
What is the most common cause of ESRD in population younger than 21 (40-50%)?
Congenital and developmental abnormalities.
Who gets posterior urethral valves? What occurs? How is it managed?
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.
What is a horshoe kidney? How common is it?
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.
