DIKD 2 Flashcards
(54 cards)
1
Q
Pathogenesis of what?
- Interaction w/ tubular cell membrane
- increasing permeability & necrosis*
- Reduction in renal blood flow exacerbates ischemia*
A
Amphotericin B Nephrotoxicity
2
Q
Presentation of what?
- Nonoliguria (>500ml urine production/day)
- K, Na, Mg wasting*
- Impaired urinary concentration
- Dysfunction apparent in 1-2 weeks*
- Decrease in GFR / Rise in Scr and BUN*
- Damage may be irreversible*
A
Amphotericin B Nephrotoxicity
3
Q
What leads to wasting of Na, K, and Mg?
A
Direct damage of distal tubular membranes–>
Tubular glomerular feedback: further constriction of arterioles–>
Constriction of afferent arterioles leading to decreased glomerular filtration
4
Q
What “retains” calcium?
A
Hydrochlorithiazide
5
Q
Potassium needs to be around what # to be effective?***
A
4
6
Q
Risk Factors of what?
- CKD
- Large individual doses
- Large cumulative doses
- Short infusion times
- Volume depletion
- Hypokalemia
- Increased age
- Concomitant diuretics
- Concomitant nephrotoxins
A
Amphotericin B Nephrotoxicity
7
Q
How to prevent Amphotericin B Nephrotoxicity
(3 main things)
A
- Switching from liposomal form in high risk patients**
- Increase infusion time**
-
Alternative antifungal agents**
- Azoles
- Caspofungin
- Low threshold for stopping
- Limit cumulative dose
- Concomitant nephrotoxins
- Hydration
8
Q
Management of Amphotericin B Nephrotoxicity
(3 things)
A
- Discontinuation & Substitution
- Monitoring of renal function
- Correct electrolytes as needed
9
Q
Which drug?
- Toxicity is usually dose dependent
- It causes distal tubular dysfunction (a type 4 renal tubular acidosis) & severe vasoconstriction
- Regular blood level monitoring is important to prevent both acute & chronic nephrotoxicity
- Renal function usually improves after reducing the dose or stopping the drug
A
Cyclosporine
10
Q
With patients who are taking ______ to prevent kidney allograft rejection, kidney biopsy is often necessary to distinguish transplant rejection from _______ toxicity.
A
Cyclosporine / Cyclosporine
11
Q
Drug Induced Kidney Structural - Functional Alterations:
Hemodynamically Mediated Kidney Injury
What is the treatment?
A
- ACE-I**
- ARB**
- NSAIDs**
- Cyclosporine, tacrolimus
- OKT3-immunosuppresant (muromonab) (Anti-rejection drugs)
12
Q
Pathogenesis of what?
- Synthesis of angiotensin II is decreased
- Efferent arteriole remains dilated (mismatch)
- Reduces outflow resistance from the glomerulus
- Decreases hydrostatic pressure in the glomerular capillaries
- Becomes nephrotoxic particularly when renal blood flow is reduced!***
A
ACE-I and ARB nephrotoxicity
13
Q
Presentation of what?**
- Decrease in urine output
- Acutely reduces GFR, rise in Scr should be expected
- Scr rise up to 30% within 3-5 days
- desired pharmacologic effect
- Rise associated w/ preservation of renal function
- Stablilizes in 1-2 weeks
- Reversible upon stopping
A
ACE-I & ARB Nephrotoxicity
14
Q
What drug blocks prostaglandins?
A
NSAIDs
15
Q
- Are located in the stomach lining and kidney
- Involved in afferent blood flow
- NOT involved in efferent blood flow
A
Good prostaglandins
16
Q
What drug therapy?
- Synthesis of angiotensin II is decreased
- Preferential dilation of the efferent arteriole
- Reduces outflow resistance from the glomerulus & decreases hydrostatic pressure in the glomerular capillaries
- Alters Starling Forces across the glomerular capillaries to decrease intraglomerular pressure & GFR**
- Leads to nephrotoxicity**
- Particularly in the setting of reduced renal blood flow or effective arterial blood volume in pre-renal settings (CHF)
A
ACE-I
17
Q
What drug therapy?
- Afferent & Efferent are affected
- Prostaglandin is NOT affected
- Increase in Scr of 30%
A
ACE-I
18
Q
Risk Factors of what toxicity?
-
Patient’s dependent on renal vasoconstriction to maintain BP and GFR*
- Renal Artery Stenosis*
-
Decreased arterial blood volume*
- CHF
- Volume depletion from excess diuresis
- Hepatic cirrhosis w/ ascites
- CKD
- Concurrent use of nephrotoxic drugs
A
ACE-I and ARB Nephrotoxicity
19
Q
How to prevent ACE-I and ARB Nephrotoxicity?
(2 things)
A
-
Choose shorter acting agent in patients at risk
- Captopril, enalapril > lisinopril, benazepril
-
Use low doses w/ gradual titrations
- 2-4 weeks
20
Q
ACE-I and ARBs can cause what?
A
Hyperkalemia
21
Q
Management of ACE-I and ARB Nephrotoxicity
A
- Discontinue if Scr increases >30% above baseline over 1-2 weeks
- Scr and hyperkalemia will resolve over several days
- Reinitiation can be attempted after correcting volume depletion
(be careful giving older pts NSAIDs bc/ their kidney function is dependent on prostaglandin…)
22
Q
Pathogenesis of what?
- Inhibit synthesis of vasodilatory prostaglandins**
- Alters normal response in reduced renal bood flow
- Unopposed renal vasoconstriction in afferent arteriole**
- Promotes renal ischemia & GFR reduction**
A
NSAIDs and COX-2 Selective Nephrotoxicity
23
Q
Presentation of what?**
- Occurs within days of volume loss or initiating therapy
- Diminished urine output
- Weight gain or edema
- Scr , BUN, potassium, and BP are elevated
A
NSAIDs and COX-2 Selective Nephrotoxicity
24
Q
Risk factors of NSAIDs and COX-2 Selective Nephrotoxicity
(a bunch and 1 main one*)
A
- **Age >60**
- CKD
- CHF
- Volume Depletion
- Concurrent diuretic therapy
- Hepatic disease w/ ascites
- Concurrent nephrotoxic drugs
25
**Management of what?\*\***
* Injury is rarely severe
* Recovery is usually rapid
NSAIDs & COX-2 Selective Nephrotoxicity
26
_Prevention of what toxicity?\*\*_
* **Avoid potent compounds in high risk groups**
* Indomethacin (used for gout)
* **Use analgesics w/ less PGE inhibition**
* APAP (acetaminophen)
* **Consider drugs w/ short half-lives**
* Sulindac
* **2 agents w/ similar effect**
* Meloxicam
* Celecoxib
NSAIDs and COX-2 Selective Nephrotoxicity
27
Drug-Induced Kidney Structural-Functional Alterations:
_Tubulointerstitial Disease_
* What is the condition we learned about in this category?
Acute Allergic Interstitial Nephritis
28
**What do these drugs cause?**
* Penicllins
* Ciprofloxacin
* NSAIDs
* Cyclooxygenase-2 inhibitors
* Proton pump inhibitors (omeprazole)
* Loop diuretics (furosemide)
Acute Allergic Interstitial Nephritis
| (Tubulointerstitial Disease)
29
2 drugs which cause Chronic Interstitial Nephritis
(Tubulointerstitial Disease)
* **Cyclosporine\*\***
* Lithium
30
What drug causes Papillary Necrosis
| (Tubulointerstitial Disease)
NSAIDs
31
3 types of Tubulointerstitial Diseases
* Acute allergic Interstitial Nephritis
* Chronic Interstitial Nephritis
* Papillary Necrosis
32
_Pathogenesis of what?_
* Allergic hypersensitivity response
* **Diffuse infiltrate of lymphocytes, eosinophils, and neutrophils**
* **Tubular necrosis is relatively common**
Methicillin - Induced Allergic Interstitial Nephritis (AIN)
33
_Presentation of what?\*\*\*_
* **Associated w/ all Beta-Lactam abx**
* **Presents 14 days after initiation of therapy (delayed presentation\*\*)**
* **Clinical signs:**
* fever
* macropapular rash
* eosinophilia
* arthralgia
* oliguria
Methicillin-Induced Allergic Interstitial Nephritis (AIN)
34
What are the risk factors and prevention of Methicillin-Induced Allergic Interstitial Nephritis (AIN)?
None
35
Management of Methicillin-Induced Allergic Interstitial Nephritis (AIN)?
* **Corticosteroids should be initiated immediately\*\*\*** + stop the drug!!
* Discontinue offending agent
* Full recovery if prompt discontinuation
36
Drug-Induced Kidney Structural-Functional Alterations:
_Obstructive Nephropathy_ (post-renal)
* What are the 3 types?
* **Crystal Nephropathy\*\***
* **Nephrolithiasis\*\***
* Nephrocalcinosis
37
**5 drugs which cause Crystal Nephropathy**
(Obstructive Nephropathy) post renal
* **Acyclovir\*\***
* **Sulfonamides\*\***
* _Methotrexate_
* Indinavir
* Foscarnet
38
**3 drugs which cause Nephrolithiasis**
| (Obstructive Nephropathy)
* **Sulfonamides\*\* (Bactrim DS, take w/ large volume of water)**
* Triamterene
* Indinavir
39
_Obstructive Nephropathy:_
* **Precipitation of drug crystals in tubular lumen\*\***
* **Hyperuricemia\*\***
* adequate hydration
* allopurinol
* **Rhabdomyolysis**
* precipitation of myoglobin
Crystal Nephropathy
40
What 2 types of drugs cause Rhabdomyolysis associated w/ Crystal Nephropathy?
* **HMG-CoA reductase inhibitors\*\***
* Simvastatin
* Lovastatin
* **Risk is increased w/ concurrent CYP3A4 drugs\*\***
* Gemfibrozil
* Niacin
* Erythromycin
41
_Obstructive Nephropathy_
* **Formation of renal calculi or kidney stones\*\***
* GFR not usually decreased
* Presentation:
* pain, hematuria
* infection, urinary tract obstruction
Nephrolithiasis
42
3 drugs are implicated for Nephrolithiasis
* **Ciprofloxacin\*\***
* **Amoxicillin\*\***
* **Nitrofurantoin\*\***
43
What 2 drugs cause Renal **Vasculitis\*** and **thrombosis\*?**
* Hydralazine
* Methamphetamines
44
Most drug induced cases of vasculitis result in the development of what?
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis
45
**Presentation of what?**
* hematuria
* proteinuria
* oliguria
* red cell casts
* fever
* malaise
* myalgias
* arthralgias
Drug Induced Renal Vasculitis and thrombosis
46
**Tx** of drug induced renal vasculitis and thrombosis?
* Withdraw offending drug
* Administer **corticosteroids** or other immunosuppressive therapy
(leads to resolution of sxs within **weeks to months**) = _takes a long time to resolve_
47
What 2 drugs cause Cholesterol Emboli?
* Warfarin --\> purple toes
* Thrombolytic agents
48
Warfarin and other thrombolytic agents act to remove / prevent thrombus formation over ulcerative plaques or may induce hemorrhage within clots, thereby causing showers of _______ that lodge in small diameter arteries of the kidney (renal arterioles and glomerular capillaries)
Cholesterol crystals
49
\_\_\_\_\_\_ induce an endothelial inflammatory response which leads to complete obstruction, ischemia, and necrosis of affected vessels within weeks to months after initiation of therapy
Cholesterol crystal emboli
50
Purple discoloration of the toes and ____ over the legs are important clinical clues of what?
mottled skin
| (Warfarin causing cholesterol emboli)
51
**Tx** of cholesterol emboli?
Supportive in nature, since the kidney injury is generally irreversible
52
DIKD: _Glomerular Disease_
What is the hallmark sign of glomerular injury?
Proteinuria (nephrotic range \>3.5g/day) with or without a decline in GFR
53
3 types of Glomerular Disease
* Minimal Change Disease
* Membranous Disease
* Focal Segmental Glomerulosclerosis
54
What medications are implicated for glomerular disease?
(2 main ones)
* **NSAIDs\*\***
* **Cyclooxygenase inhibitors\*\***
* Lithium
* Pamidronate
* Interferon alpha and beta
* anabolic steroids
