PBL W3 Flashcards
What does a renal biopy show for acute drug induced interstitial nephritis?
- edema w/interstitial lymphoplasmocytic infiltrate
- no glomeruli involvement
- eosinophils prominent.
- edema w/mild tubulointerstitial fibrosis - lymphocytes and plasma cells present.
What are the side effects of furosemide?
- Ototoxicity
- HYPOkalemia
- Dehydration
- Allergy (sulfa)
- Nephritis (interstitial)
- Gout
What is the issue with using BOTH furosemide and ibuprofen (NSAIDs)?
- Furosemide normally stimulates PGE release for vasodilation. NSAIDs inhibit this and make them less effective.
- NSAIDs then constrict the afferent tubule reducing the flow. Could cause renal ischemia.
What is the spectrum of causes for acute interstitial nephritis?
- antibiotics
- NSAIDs
- diruetics
- anticonvulsants
- Bacteria
- Viruses
- Mycoplasma
- Sjogren’s
- Lupus
What is the mechanism for the peripheral edema with renal failure?
- Serum albumin is decreased due to loss through the glomerulus.
- Oncotic pressure of the vessel goes down.
- Less reabsorptive forces.
- P capillary increases - more filtration.
Why do we see eosinophils with acute interstitial nephritis?
- IL-5 and IgG lead to increased mast cells and eosinophil recruitment.
- NSAIDs creates more leuoktrienes, that leads to increased eosinohpil survival.
What are the symptoms of acute intersitital nephritis?
- fever
- Rash
- Joint pain
- Eosinophilia (increased serum IgE)
- MILD proteinuria
- hematuria
- pyuria - pus in the urine
Coud lead to acute renal failure
What are changes in the labs you see w/acute interstitial nephritis?
- increased creatinine
- granular and epithelial casts
What is the pathogensis of nephritis syndrome?
- T cells and cytokines cause podocytes to lose negative charge, in addition to damage.
What are the symptoms of nephritic syndrome?
- Proteinuria - >3 grams of protein lost per day in urine
- Hypoalbuminemia - serum albumin less than 3gm/dL
- Generalized pitting edema
- hyperlipidema & hypercholesterolemia
What causes hyperlipidemia with nephritic syndrome?
What do you see in the urine?
- LOW serum protein –> reactive hepatitis protein synthesis in the liver –> makes lipoproteins and decreaes catabolism –> increases serum cholesterol and LDL
- Can cause loss of HDL
-
urinanalysis - shows FATTY CASTS
- maltese interference pattern under UV light
What are the drugs that can cause acute interstitial nephritis?
use pneumonic.
- Please Note All Drugs That Can Possibly Scar Renals
- penicillin derivatives - methicillin
- NSAIDs
- Allopurinal
- Sulfa derived diuretics - thiazides, furosemides, acetazolamide
- Cephalosporins
- Proton pump inhibitors
- Sulfonamide antibiotics
- Rifampin
How should you treat drug-induced interstitial nephritis?
- REMOVE DRUG that is offending agent
- Treatment is supportive - hydration, symptom relief, removal of drugs
-
Corticosteroids if SEVERE
- 1mg/kg for 2-3 wks followed by tapering of PREDNISONE.
What is the urine albumin/creatinine used for?
How do you calculate it?
- used to determine if nephritic syndrome
- compare urine protein to urine creatinine
- patients was 100/50 = 2
- If > 2 - significant proteinuria - estimated 24 hour urine is 2 grams
- If <1 it isn’t significant
How do you determine if its nephritic syndrome?
Do a urine albumin/creatinine ratio
What is the FeNa used for?
- Pre-renal vs. renal disease
urineNa x plasmaCr x 100/ UrineCr x plasmaNa
- If FeNa < 1% = pre-renal
- If FeNa >1% = ATN
What is the Bun: Cr used for?
- determining pre-renal vs. renal disease
- Normal ratio is 15:1
- if greater than 15:1 it’s pre-renal
- Pre-renal has excessively increased BUN
What are 2 tests you can do to determine if pre-renal or renal disease?
- FeNa
- Bun:Cr
What are some of the renal toxicity of NSAIDs?
- Inhibit prostaglandins - decrease renal blood flow –> ischemic necrosis
- Increase Na reabsorption –> peripheral edema - really exacerbates the edema
- divert AA passage to produce leukotrienes –> increases vascular permeability in capillaires and glomerulus –> proteinuria + interstitial nephritis
What is a truncating variant? How does it relate to EMP2?
- truncating variant shortens the coding sequence of a gene
- should be 167 amino acids, however, it is Glu62 - stops at amino acid 62.
What are missense mutations?
- change in single nucleotide
-
Phe7leu
- Phe at amino acid 7 was changed to leucine
How do we know if the EMP2 protein sequences are conserved?
- compare with mouse at blast sequence - if over a bunch of sequences, the Phe7leu at amino acid never changes, it’s conserved evolutionarily
What is the potential protein that can be mutated with nephritis syndrome?
- EMP2
- epithelial membrane protein 2
How does EMP2 affect the kidney?
- acts on keviolin 1
- decreases podocytes & epithelial cells
- allows albumin to enter the urine through the glomerulus
- MORE CHILDHOOD CAUSE
