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What is the most common manifestation in Drug induced kidney injury?
Decline in glomerular filtration rate (GFR) which results in rise of Scr and BUN
Initial diagnosis of DIKD is delayed because what?
Bc it is based on detection of elevated Scr and BUN for which there is a temporal relationship between kidney injury and exposure to nephrotoxic drug
What causes hemodynamically mediated kidney injury? How do we prevent this?
ACEI and ARBs
NSAIDs and Selective COX2 inhibitors
Calcineurin inhibitors (Tacro and Cyclosporine)
How do ACEI cause kidney injury?
ACEI inhibit synthesis of angiotensin II which dilate the efferent arteriole → reduce outflow resistance and decrease GFR
How do NSAIDs cause kidney injury?
Constrict the AFFERENT ARTERIOLE → decrease GFR
Instead of NSAIDs and COX-2 inhibitors, what can you use?
AVOID indomethacin (potent)
Use APAP, nonacetylates salicylates, aspirin, and even nabumetone when anti inflammation needed
Tramadol (nonnarcotic analgesic) can be useful but do not provide anti-inflammatory activity
How do calcineurin inhibitors cause kidney injury?
Afferent vasoconstriction with reduced GFR
Aminoglycoside associated ATN is due to accumulation of high drug concentrations within what?
Within proximal tubular epithelial cells and subsequent generation of reactive oxygen species that produce mitochondrial injury → cellular apoptosis
What causes acute tubular necrosis in aminoglycosides?
Number of cationic groups (-NH2)
Neomycin, gentamycin, tobramycin, amikacin
The number of cationic groups on the drug appears to correlate to nephrotoxicity → Neomycin is most toxic because it has the most NH2 groups
How does radiographic contrast media cause nephrotoxicity? What are risk factors?
Renal ischemia results from systemic hypotension and nephrptoxiity and simultaneous acute vasoconstriction caused by disruption of normal prostaglandin synthesis
Cellular toxicity is also related to duration of tubular cell exposure to contrast
Risk factors: GFR <60, concurrent use of NSAIDs, ACEI, aminoglycosides
How does Cisplatin cause nephrotoxicity?
Tubular cell injury and death via necrosis and/or apoptosis
Accumulation in proximal tubular epithelial cells
If you have cisplatin nephrotoxicity, what can you do for prevention?
Dose reduction and decreased frequency of administration
Use of hypertonic saline (3% saline) to reduce tubular cisplatin uptake
Amifostine, an organic thiophosphate that is converted to active metabolite can reduce the Cisplatin nephrotoxicity
What is the pathogenesis of amphotericin B neprhotoxicity?
Direct tubular epithelial cell toxicity → interaction of amphotericin B with ergosterol in cell membrane → necrosis of proximal tubular cells
Exacerbated by ischemic injury which is result of reduction in renal blood flow and GFR bc vasoconstriction
What is characteristic of glomerular disease?
Proteinuria, particularly nephritic range PROTEINURIA (urine protein greater than 3.5 g/day per 1.73 m²) with or without a decline in the GFR is hallmark
In tubulointerstitial disease, what drug can cause chronic interstitial nephritis?
Lithium
What is the pathogenesis of lithium?
Lithium induced nephrogenic diabetes insipidus: lithium reduces the kidney’s ability to concentrate urine → lithium down regulates aquaprin 2 water channel expression
For tubulointersititial disease, what is the pathogenesis of aristolochic acid?
Aristolochic acid is metabolized to mutagenic compounds called aristolactam 1 and II → from aristolochic acid DNA adducts in humans → DNA damage and apotosis
In tubulointersititial disease, what is papillary necrosis?
Necrosis of renal papillae → collecting ducts enter renal pelvis which leads to progressive kidney disease
In Obstructive nephropathy, what is intratubular obstruction? (Direct)
Direct means precipitation of the drug itself
Acyclovir, Foscarnet complexation with CALCIUM ION
Indinavir, Sulfadiazine, methotrexate may precipitate in acidic urine
In Obstructive nephropathy, what is intratubular obstruction? (Indirect)
Antineoplastic drugs: intratubular precipitation of uric acid crystals
HMG-CoA reductase inhibitors or statins: intratubular precipitation of myoglobin (drug induced rhabdo)
Warfarin: RBCs
What is the pathogenesis in nephrocalcinosis for obstructive neprhopathy?
extensive tubulointerstitial precipitation and deposition of calcium phosphate crystals leading to marked tubular calcification. associated with hypercalcemia and hypercalciuria