Part 1 Drug Induced Kidney Disease

Question 1

Drug Induced Kidney Disease Diagnosis

Answer 1

Elevated SCr and BUN

Question 2

DIKD Renal Insufficiency

Answer 2

Often reversible upon discontinuation but may lead to ESRD

Question 3

DIKD + hospital admissions

Answer 3

20%

Question 4

Drug induced AKI + hospital

Answer 4

60%

Question 5

Drugs frequently involved

Answer 5

AG
Radiocontrast media
NSAIDs
COX2 inhibitors
Amp B
ACEI

Question 6

Nephrotoxicity evidenced

Answer 6

Early sign of renal tubular function without loss of GFR and as markers of proximal tubular injury

Question 7

Outpaint Setting Nephrotoxicity

Answer 7

NSAIDs = most common and best defined

Question 8

NSAIDs

Answer 8

Prescribed and OTX therapy has be associated with a 4-fold increased risk of acute RF

Question 9

NSAID RF

Answer 9

Male greater than 65
HD drugs
CVD
Recent hospitalization for non-renal
In combo with nephrotoxic drugs

Question 10

NSAIDs + >70 y.o.

Answer 10

2 fold increased risk for hospitalization

Question 11

Hemodynamically mediated Acute renal failure

Answer 11

Due to NSAIDs and ACEi
RF: Preexisting insufficiency
Decreased RBF due to volume depletion
HF
Liver disease

Question 12

Glomerular Filtration

Answer 12

Monitor SCr and BUN

Measure urine output (esp with radiographic contrast media, NSAIDs and ACEi)

Question 13

Outpatient setting, nephrotoxicity is recognized with

Answer 13

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

Question 14

What may quantify the loss of glomerular filtration?

Answer 14

SCr or BUN + urine collection

Question 15

Renal Tubular function can be altered without

Answer 15

Loss of glomerular filtration

Question 16

General indicators of proximal tubular injury are

Answer 16

Metabolic acidosis with bicarbonatura
Glycosuria without hyperglycemia
Hypophosphatemia and hypouricemia due to increased urine loss

Question 17

Indicators of distal tubular injury are

Answer 17

Polyuria (inability to concentrate urine)
Metabolic acidosis
Hyperkalemia (can’t excrete K)

Question 18

KIM-1

Answer 18

Used for early detection of AKI

Upregulated in the urine within 12 hours of ischemic acute tubular necrosis

Question 19

NGAL

Answer 19

May be detected in the urine within 3 hours of ischemic injury

Question 20

Drug Induced Nephrotoxicity

Answer 20

Highly heterogeneous with respect to the drugs involved and the lesions produced

Question 21

Renal Susceptibility

Answer 21

Kidneys are more sensitive to drug toxicity compared to other organs
Both immunological and non mechanisms can contribute

Question 22

High blood flow

Answer 22

Enhanced kidney’s exposure to circulating drugs

Question 23

Within each nephron

Answer 23

BF and prssure are regulated by glomerular afferent and efferent arterioles

Question 24

Specialized BF regulated by interrelations

Answer 24

Between renal, PGs, atrial natruiretic factors, sympathetic nervous system, RAG, and the macula densa response to distal tubular solute delivery

Question 25

BB and NSAIDs

Answer 25

decrease total RBF

Question 26

Radiographic contrast media

Answer 26

May shut intrarenal BF away from superficial nephron

Question 27

ACEi

Answer 27

Dilate glomerular efferent arterioles leading to decrease glomerular filtration pressure in the presence of ischemic RVD

Question 28

Dietary salt restriction

Answer 28

Activate neurohumoral renal hemodynamic control systems that increase renal susceptibility to drug nephrotoxicities

Question 29

Drugs or metabolites can accumulate

Answer 29

In areas of active tubular secretion and reabsorption (proximal tubule)

Question 30

What plays a role in the eliminatio of drugs

Answer 30

OCT1 OAT1 P-gp

Question 31

AG and cyclosporines

Answer 31

Appear to mediate nephrotoxicity through intracellular accumulation

Question 32

Gentamycin

Answer 32

Increases intracellular and superoxide ion, H2O2, and hydroxyl radicals

Question 33

Cyclosporine

Answer 33

Increase H2O2 which contributes to oxidative stress and nephrotoxicity

Question 34

Methoxyfluorane

Answer 34

Metabolized to fluoride which acts in the ascending limb of the loop of Henle and collecting ducts

Question 35

High energy requirements by renal tubular cells

Answer 35

Medullary tubular epithelial cells are sensitive to drugs that exacerbate the already hypoxic environment by decrease energy production or oxygen delivery

Question 36

AmpB

Answer 36

Damge due to imbalance between increased cellular energy requirements and inadequate O2 delivery

Question 37

Concentration of solute in the tubular lumen

Answer 37

Luminal surface of the proximal tubular is exposed to high concentrations of drugs due to increase water reabsorption

Question 38

Urine acidication

Answer 38

Solutes can precipitate and obstruct the tubular lumen at a pH of 4.5

Question 39

Age + Renal =

Answer 39

Age-related decline in renal function

Question 40

Prevention of drug nephrotoxicity

Answer 40

Avoid nephrotoxic agents