Drug-Induced Kidney Disease Pt 1

Question 1

initial diagnosis of DIKD

Answer 1

often involves elevated SCr and BUN

**renal insufficiency is often reversible upon D/C of therapy but may eventually lead to ESRD

Question 2

epidemiology of DIKD

Answer 2

Pts taking drugs outside of the hospital setting make up about 20% of hospital admissions for kidney injury and in-hospital drug use takes up about 60%

Question 3

what are some drugs that can cause DIKD?

Answer 3

aminoglycosides, radiocontrast media, NSAIDS, COX-2 inhibitors, amphotericin B, ACE-I

Question 4

what is the most common and least defined drug-induced nephrotoxicity in the outpatient setting?

Answer 4

NSAID nephrotox
4X increased risk of hospitalization for acute renal failure
2X increased risk for hospitalization >70 years old

Question 5

predominant risk factors for NSAID DIKD

Answer 5

males >65 yo, high dose, CV disease, recent hospitalization for nonrenal, and concomitant use of potentially nephrotoxic drugs

Question 6

risk factors for hemodynamically mediated acute renal failure (NSAIDS, ACE-I, etc)

Answer 6

preexisting renal insufficiency, decreased effective RBF due to vol depletion, heart failure, liver disease

Question 7

what may be used to quantify the loss of GFR?

Answer 7

SCr, BUN conc, and urine collection (urine output)

Question 8

how is nephrotox recognized in the outpatient setting?

Answer 8

uremia (malaise, anorexia, and vomiting) or volume overload (edema)

Question 9

what are general indicators of proximal tubule injury?

Answer 9

1. ) metabolic acidosis w/bicarbonaturia
2. ) glycosuria w/o hyperglycemia
3. ) hypophosphatemia and hypouricemia due to increased loss of phos and uric acid

Question 10

what are general indicators of distal tubule injury?

Answer 10

1. ) polyuria
2. ) metabolic acidosis from impaired urinary acidification
3. ) hyperkalemia from impaired K+ excretion

Question 11

markers for early detection of acute kidney injury

Answer 11

KIM-1, n-acetyl-B-D-gucoamidase, NGAL, IL-18

Question 12

KIM-1

Answer 12

upregulated in urine w/in 12 hours of ischemic acute tubular necrosis

Question 13

NGAL

Answer 13

may be detected in the urine w/in 3 hours of ischemic injury

Question 14

renal susceptibility to drug toxicity

Answer 14

kidneys are more sensitive to drug tox compared to other organs
both immune and non-immune mechanisms contribute to tox

Question 15

what enhances the kidney’s exposure to circulating drugs?

Answer 15

high blood flow and specialized hemodynamics (20% of cardiac output)

Question 16

what is renal blood flow regulated by?

Answer 16

interrelations b/w renal prostaglandins, atrial natriuretic factor, symp NS, RAG, and macula densa response

Question 17

beta-blockers and NSAIDS

Answer 17

may decrease total RBF

Question 18

radiographic contrast media

Answer 18

may shut intrarenal blood flow away from superficial nephrons

Question 19

ACE-I

Answer 19

may dilate glomerular efferent arterioles leading to decreased glomerular filtration pressure in the presence of ischemic renal vascular disease

Question 20

dietary salt restriction

Answer 20

can activate neurohumoral renal hemodynamic control systems that increase renal susceptibility to drug nephrotox

Question 21

tubular epithelial cell absorptive and secretory functions

Answer 21

drugs or metabolites can accumulate in areas active in tubular secretion and reabsorption (esp proximal tubule)

Question 22

tubular transport systems within the nephron

Answer 22

organic cation transporter (OCT1), organic anion transporter (OAT1), P-GP

Question 23

OAT1 in elimination of drugs

Answer 23

OAT1 assoc with antivirals (adefovir and cidofovir) and some ceph abx
administration of an OAT1 inhibitor (probenacid) reduces cytotoxicity of these agents

Question 24

aminoglycosides and cyclosporine

Answer 24

mediate nephrotox through intracellular accumulation

Question 25

gentamycin

Answer 25

increase intracellular conc of superoxide ion, hydrogen peroxide → oxidative stress and nephrotox

Question 26

drug metabolism to toxic species (P450 and MFOs)

Answer 26

mostly in proximal tubular epithelial cells
formation of toxic metabolites are generally electrophiles and free radicals which can react with macromolecules
Ex. methoxyfluorane

Question 27

high energy requirement by renal tubular cells

Answer 27

Anything that can cause cellular energy reduction can cause kidney injury in cells
Ex. Amphotericin B= causes imbalance b/w increased cellular energy requirements and inadequate oxygen delivery

Question 28

Concentration of solute in the tubular lumen

Answer 28

water reabsorption conc solutes and toxins esp in the proximal tubule
luminal surfaces can be exposed to high conc of drug due to increased water reabsorption
Ex. enhanced aminoglycoside tox due to systemic vol depletion

Question 29

urine acidification

Answer 29

urine pH decreases to 4.5 with max H+ secretion and solutes precipitate (certain solutes can precipitate and obstruct the tubular lumen at this acidic pH)
Ex. methotrexate during high dose chemo can precipitate in urine if it is too acidic

Question 30

adaptive mechanism of nephrons

Answer 30

surviving nephrons have hyperfiltering glomeruli and hyperfunctioning tubules