Drugs and the Kidney Flashcards
What mediates the tubular reabsorption of peptide-like drugs such as β-lactam antibiotics and ACEIs?
Peptide transporters (PEPT1, PEPT2) expressed on the apical membrane of renal epithelial cells
keep in mind that must drugs enter the PT from the bloodstream on the BL and reabsorption is from the lumenal side is more rare
Describe the relationship between Pcr and GFR.
In healthy subjects, large declines in GFR are associated with relatively small increases in serum creatinine. Beyond drop of GFR of ~50%, further decrements are associated with larger increases in serum creatinine, which
makes the marker more sensitive to change.
Drugs are implicated in up to __% of acute kidney injury in hospitalized patients.
25%.
Why do drugs cause so much toxicity in the kidneys?
High bloodflow means kidney easily exposed to drugs
Reabsorption of water along loop of Henlé concentrates drug; this magnifies toxicity
When would creatinine be low even if the kidneys weren’t functioning well?
in those (typically females) with low muscle mass, low creatinine levels can exist even in the presence of significant renal insufficiency
How do NSAIDs affect GFR?
inhibit prostaglandin induced afferent vasodilation
What does chronic use of NSAIDs lead to?
Hyponatremia 2° to increased fluid retention (ADH effect)
Hyperkalemia & metabolic acidosis
Hyporeninemic hypoaldosteronism 2° to decreased RAAS activity
Hypertension
Why are aminoglycosides very nephrotoxic (10-25% of time)?
Their toxicity is directly related to charge (cationic). Proximal tubule accumulation results in cell death
How common is nephrotoxicity due to SMX-TMP?
~11%
What is seen in the kidneys with trimethoprim (TMP) administration?
increases measured serum creatinine w/o affecting GFR
inhibits epithelial N+ channels in DCT resulting in hyperkalemia
What is seen in the kidneys with SMX administration?
injury 2° to acute interstitial nephritis (AIN)
rarely, crystal nephropathy
How can you avoid the crystal nephropathy seen with SMX?
Hydrate and alkalinize urine
What are some other drugs causing AIN?
NSAIDs, including COX-2 inhibitors • Penicillins and cephalosporins • Rifampin • Diuretics, including furosemide and bumetanide, and thiazide-type diuretics • Ciprofloxacin • Cimetidine • Allopurinol • PPIs such as omeprazole and lansoprazole • Indinavir • 5-aminosalicylates (e.g., mesalamine)
When would AIN (typically) present after 1st exposure of a drug inducer?
10-14 days
When would AIN (typically) present after 1st exposure of a drug inducer?
3-5 days
How does AIN present?
Fever, rash (~50%), eosinophilia (>75%)
• Urinalysis
– WBC casts, hematuria, eosinophiluria, mild proteinuria, oliguria
Note on NSAID induced AIN
NSAIDs onset 2-3 m; NO eosinophilia/uria, fever or rash; proteinuria >3g/24 h
Are the effects of drug-induced AIN dose-related?
No, but definitely discontinue the offending agent
What are the three ‘parts’ of acute tubular necrosis (ATN)?
Initiation
Maintenance
Recovery
ATN is basically tubule damage/cell death result from acute ischemia
Where does the most intense ATN damage occur?
Most prominent damage in proximal tubules and in TALH
What happens during the ‘initiation’ stage of ATN?
– Hypo-perfusion plus casts and debris obstruct tubule lumen, causing back-leak of filtrate through the damaged epithelium
– Na+/K+ ATPase pumps and integrins relocate to apical
membrane
– ATP is depleted – pump function fails and cells swell,
accumulating Na+ and Ca2+
– Lipid peroxidation and free radical damage occurs
What happens during the ‘maintanence’ stage of ATN?
Low level GFR stabilizes over 1-2 weeks
What happens during the ‘recovery’ stage of ATN?
Tubular epithelial cells are regenerated
abnormal renal function may lead to salt/H2O loss and volume depletion
What drugs can cause ATN?
- Contrast media
- Aminoglycosides
- Vanco
- AmphoB
- cisplatin
- sulfa drugs
CAVACS
