not all drugs are good drugs: Kidney

Question 1

Drug induced kidney disease risk factors

Answer 1

• 65+
• CKD
• Conmitant nephrotoxins
• Renin-dependent state
  
  • Low effective circulating volume
    
    • HF
    • Cirrhosis
• Known drug allergy
• Duration of therapy
• DM
• HTN

Question 2

Drug induced kidney disease general prevention

Answer 2

• Directly prevent the drugs MOA of kidney injury
• Avoid the drugs in high risk pts
• Maintain adequate kidney perfusiion
  
  • Hydration
  • IV isotonic crystalloids in pts at risk of AKI
    
    • Lacated ringers
    • Plasma-lyte A
    • 0.9% NaCl
• TDM if relevant

Question 3

Kidney function monitorinng

Answer 3

• SCr, BUN, eGFR, urinary output
• Novel biomarkers: are markers of damage;
• Traditional biomarkers: SCr and BUN are markers of function

Question 4

Drugs that cause hemodynamic mediated renal injury via reduction in glomerular pressure dt alterations in arteriole tone

Answer 4

• ACE/ARB
• NSAID
• SGLT2
• CNI (cyclosporine, tacrolimus)

Question 5

ACE/ARB mechanism of kidney injury

Answer 5

decrease angiotensin II → efferent arteriole dilation

Question 6

NSAID mechanism of kidney injury

Answer 6

decrease PGE2 production → afferent arteriole constriction

Question 7

Calcineurin inhibitor mechanism of kidney injury

Answer 7

afferent arteriole constriction

Question 8

hemodynamic mediated renal injury via reduction in glomerular pressure dt alterations in arteriole tone risk factors

Answer 8

• dehydration/low volume state + the culprit drugs → highest risk for AKI
• NSAID + ACE/ARB = loss of autoregulation → increased risk of decreased intraglomerular hydrostatic pressure → decreased GFR

Question 9

hemodynamic mediated renal injury via reduction in glomerular pressure dt alterations in arteriole tone prevention methods

Answer 9

• Adequate fluid intake
• Risk factor management
• Start with lowest dose in pts with highest risk
  - monitor SCR, BUN, K, wt Q2W until stable
  - hold diuretics during intiating/titrating
• Avoid NSAID + ACE/ARB combo in pts with CKD, HF, liver disease

Question 10

hemodynamic mediated renal injury via reduction in glomerular pressure dt alterations in arteriole tone treatment

Answer 10

• DC offending agent
• Provide sufficient fluids
  - typically 0.9% NaCl
• Monitor kidney function and electrolytes

Question 11

Drugs that cause pre-renal kidney injury via reduced blood flow in the kidney

Answer 11

diuretics; decreases effective circulatory volume if over-diuresis occurs

Question 12

Drugs that cause glomerulonephritis

Answer 12

• Gold
• Allopurinol

Question 13

Drugs that cause acute tubular necrosis (ATN)

Answer 13

• aminoglycosides
• amphotericin B (conventional has higher risk than liposomal)
• IV contrast media (iohexol, iodixanol)

Question 14

IV contrast media induced kidney injury risk factors

Answer 14

Agent specific
- Large volume
- High osmolal contrast
- Ionic contrast
- Short interval between contrast admin
Pt specific
- DM
- Age
- GFR < 60
- low ECV
- LVEF < 40%

Question 15

Aminoglycoside risk factor for kidney injury

Answer 15

• related to trough [ ] → TDM and PK individualization much important
• no difference in extennded and regluar interval dosing → but most places use extended

Question 16

Prevention method fo IV contrast media induced kidney injury

Answer 16

For contrast media: 0.9% NaCl give 1-1.5 ml/kg/hr 12 hours before and after
- can also add PO NAC 1200mg PO BID x 4 doses (limited evidence on efficacy but is well tolerated)

Question 17

Drug induced acute tubular nerosis treatment

Answer 17

• SUPPORTIVE CARE
• DC offending agent
• Hydration
• Electrolyte management
• Dialysis if severe (anuria, uremia, edema, K>7)

THIS IS ATN TREATMENT

Question 18

Drugs that cause acute interisitial nephritis

Answer 18

• Allopurinol
• Anti-epileptics
• Beta-lactams
• Diuretics
• *NSAIDs
  Penicillins
  PPIs
  Sulfa drugs**
• Vanco

Question 19

Mechanism of injury for acute interstitial nephritis (AIN)

Answer 19

Immune activation / hypersensitivity → leukocyte infiltration → inflammation → AIN

Question 20

Vanco AKI risk factors

Answer 20

• high trough >20 mg/L
• AUC >600
• TDD >4g
• LOT >7D
• wt >101.4kg

Question 21

Prevention methods for vanco induced kidney injury

Answer 21

avoid concomitant use with aminoglycosides, amphotericin, and contrast

Question 22

drug indcued acute interstitial nephritis treatment

Answer 22

• Stop offending drug
• Avoid cross-reacting drugs
• Supportive care
• Steroids: early aggressive steroid may improve long-term renal outcome
  > give large bolus, then taper
  MePn 250-500mg IV QD x 3-5 days
  Then Pred 1 mg/kg/d tapered x 8-12 weeks

Question 23

Drugs that cause vasculitis

Answer 23

• PTU
• Allopurinol
• Phenytoin
• Cocaine

Question 24

Drugs that cause nephrolithiasis

Answer 24

• Acyclovir
• Allopurinol
• Furosemide
• Sulfonamides
• Topiramate

Question 25

**Prevention** methods for drug indcued nephrolithaisis

Answer 25

- Adequate hydration - goal urine output >2.5 L/day - TZD diuretic if high urinary Ca → decrease the amount of Ca that can precipitate into stones

Question 26

Drug indudced nephrolithiasis treatment

Answer 26

- Hydration - Pain management - Lithotripsy: shockwave disintegration of stone

Question 27

Drugs that cause rhabdomyolysis intra-tubular obstruction

Answer 27

- statins/statin-fibrate combos

Question 28

Statin induced kidney injury MOA

Answer 28

Statins → rhabdomyolysis → muscle breakdown → precipitation of myoglobin in kidneys

Question 29

drug induced rhabdomyolysis intra-tubular obstruction **treatment**

Answer 29

- DC offending agent - Aggressive IV fluid -> treats the intra-tubular myoglobin obstruction) - may require urinary alkanization if urine pH < 6.5 - alternate between IV NaCl and sodium bicarb to fix - Target UOP ~ 3ml/hr

Question 30

Lithium indcued CKD risk factors

Answer 30

cumulative lithium dose and other common sense things

Question 31

lithium induced CKD prevention methods

Answer 31

* Lithium TDM * Stay hydrated * Renal monitoring * Avoid DDI (e.g. HCTZ)

Question 32

lithium induced CKD treatment

Answer 32

- damage is IRREVERSIBLE - DC lithium - Hydrate - Amiloride 5-20mg QD if polydipsia/polyuria and especially if nephrogenic diabetes insipidus) - Avoid other nephrotoxic drugs - Monitor renal function

Question 33

#1 cause of CKD

Answer 33

diabetes

Question 34

number 2 cause of CKD

Answer 34

HTN

Question 35

A patient is considered high risk for drug induced kidney disease if:

Answer 35

Renin dependent disease states - late stage CKD - HF - liver disease - pronounced albuminuria @ baseline On many nephrotoxic drugs

Question 36

24 hour trough goal for EIAD

Answer 36

undetectable EIAD = extended interval aminoglycoside dosing

Question 37

CIN agent: Iohexol [Omnipaque 450]

Answer 37

nonionic lower osmolality

Question 38

CIN agent: Iodixanol [Visipaque 320]

Answer 38

* nonionic * iso-osmolar * preferred contrast media

Question 39

Monitoring for CIN (contrast media)

Answer 39

Renal fx - SCr, BUN Q12H x 2 days, then Q24H x 5-7 days inpatient UOP - strict in/out x 4 days Med review Electrolytes - only if renal injury develops

Question 40

When monitoring for CIN, we regularly monitor for electrolytes: True/False?

Answer 40

False Electrolytes only checked if kidney injury develops - does not tell you about RISK or the presence of injury

Question 41

IBW

Answer 41

F: 45.5 + 2.3 (inches over 60) M: 50 + 2.3 (inches over 60)

Question 41

Cockcroft gault

Answer 41

[(140 - age ) x IBW] **/** (72xSCr) - if female x 0.85

Question 42

ATN presentation

Answer 42

* Acute progression - rapid recovery * ↑SCr, BUN * ↓GFR, UO (non-oligu/olig ) * Proteinuria * Muddy brown casts, granular * +/- acidosis, hyperkalemia * FeNa >1% (pre-renal AKI would have FeNa<1%)

Question 43

AIN presentation

Answer 43

* Type 4 hypersensitivity * Fever, rash, eosinophilia * WBC casts