Cardio/Renal - Final Exam Flashcards
1
Q
What is the difference between AKI and AKD?
A
AKI: acute kidney injury - abrupt decline in kidney function over 7 day or less
AKD: acute kidney disease - AKI between 7 to 90 days, precedes CKD diagnosis
2
Q
KDIGO staging of AKI
A
Stage 1: 1.5-1.9x baseline SCr OR 0.3+ mg/dL increase in SCr
Stage 2: 2.0-2.9x baseline SCr
Stage 3: 3x baseline SCr OR 4.0+ mg/dL increase in SCr OR initiating renal replacement therapy
3
Q
What are the traditional biomarkers of AKI? What are the novel biomarkers?
A
Traditional: SCr and BUN
Novel: NGAL, TIMP2 & IGFBP7, KIMI
4
Q
What is the most common trigger of AKI?
A
NSAID use
5
Q
What are 6 risk factors of AKI?
A
- Age > 65 years
- Black ethnicity
- Existing CKD
- DM
- Nephrotoxin use (ie. NSAIDs)
- Decreased circulatory volume (HF, cirrhosis, nephrotic syndrome, blood loss)
6
Q
What are 3 GENERAL prevention measures against AKI?
A
- Maintain euvolemia and normal electrolytes (balanced isotonic crystalloids)
- Maintain organ perfusion (MAP>65)
- Avoid nephrotoxins
7
Q
When would we use diuretics in an AKI patient?
A
Edema management, hyperkalemia/electrolyte abnormalities
Note: may cause hypovolemia, hypotension, or diuretic resistance (loop)
8
Q
T/F Dopamine and fenoldopam improve AKI outcomes
A
FALSE - increases arrhythmias and hypotension
9
Q
What medications should be temporarily held during hemodynamic AKI?
A
ACEi/ARBS, NSAIDs, SGLT2is, calcineurin inhibitors
10
Q
What meds should you temporarily hold for pre-renal AKI?
A
Loop diuretic, thiazide diuretic
11
Q
What diseases cause intrinsic AKI?
A
Glomerulonephritis, acute tubular nephritis, tubulointerstitial nephritis, vasculitis
12
Q
How do you treat pre-renal AKI?
A
Intravascular volume repletion
13
Q
How do you treat intrinsic AKI?
A
If caused by a medication, stop immediately and do not restart and list as allergy
If caused by disease state, treat that state accordingly (immunosuppression, supportive care, glucocorticoids)
14
Q
How do you treat post-renal AKI?
A
Relieve obstruction (acute - catheter, chronic - treat underlying cause)
15
Q
What is Kidney Replacement Therapy (KRT)? What are the two ways to conduct it?
A
Treatment for prolonged/severe AKI
1. Continuous Kidney Replacement Therapy (CKRT)
2. Intermittent Hemodialysis (IHD)
16
Q
What is the best marker of kidney function in AKI (hint: not GFR or SCr!)
A
Urine output
GFR and SCr are NOT RELIABLE! (fluctuate often depending on clinical context)
17
Q
eGFR and eCrCl (Cockcroft-Gault) are both used for kidney function assessment for drug dosing. How do you decide how to recommend a dose?
A
Since eGFR and eCrCl may cause 20-30% dosing disparities, use the method that was STUDIED during DEVELOPMENT.
Cockcroft-Gault is most often used!
BUT newer drugs are using eGFR
18
Q
If the drug dosed has a wide therapeutic index, is less than 30% renally excreted, and has inactive metabolites, then what changes need to be made in a patient with kidney dysfunction?
A
Nothing! These drugs need not be renally dosed.
19
Q
How does kidney dysfunction affect non-renal clearance?
A
Uremic toxins inhibit hepatic CYP enzymes and transporters in the gut/liver.
Altered first pass - less metabolism = more active drug
Reduced Phase I metabolism
20
Q
Drugs with toxic metabolites should be _________
Drugs with active metabolites should be _____ ____ ______
Drugs with inactive (but have) metabolites should be ________
A
Toxic = avoided
Active = used with caution
Inactive - monitored
21
Q
How does kidney dysfunction affect opioid PK/PD?
A
PK = opioids undergo phase II metabolism, so altered duration and peak concentration
PD = increased opioid receptor sensitivity, increased BBB permeability and CNS effects
22
Q
What 2 opioids are ok to use in renal dysfunction? What 3 are ok to use with caution? What 3 are contraindicated?
A
OK = fentanyl, methadone
Caution = hydromorphone, oxycodone, hydrocodone
AVOID = morphine, codeine, meperidine
23
Q
What is the loading dose formula? What is the most important variable?
A
LD = (desired change in concentration) x Vd
24
Q
What is the maintenance dosing equation? Which variable is most important?
A
MD = Css,desired x (CL x T) / F
Clearance is most important
25
What SEVEN antimicrobials DO NOT require renal dose adjustment? (MEMORIZE!)
*Clindamycin
*Azithromycin
*Linezolid
*Metronidazole
*Ceftriaxone
*Doxycycline
*Moxifloxacin
CALM CDM
26
How does volume of distribution change with edematous states in kidney dysfunction? With wasting/volume depletion?
Edematous = increased Vd
Wasting = decreased Vd
As renal function decreases, it decreases the ability to remove fluid
27
Phenytoin concentration is obscured by renal dysfunction due to alterations in ________ ________, Vd and free fraction. It also has a ______ therapeutic index and many DDIs.
Protein binding
Narrow
28
What is the target total [phenytoin]? What is the target *free* [phenytoin]?
Total target = 10 - 20 mcg/mL
Free target = 1 - 2 mcg/mL
29
What anticoagulants do NOT need renal dosing?
Warfarin, argatroban, heparin
30
What is the ranking of least to most renally cleared DOAC?
Least:
Apixaban
Rivaroxaban
Edoxaban
Dabigatran
Most:
31
What is the Cockcroft-Gault equation?
(140-Age) x IBW / (72 x SCr) [x 0.85 for women]
IBW = 50 [45.5 for women] + (2.3 x inches > 60)
32
______ diuretics and _____________ diuretics should be avoided is CrCl < 30 ml/min
Thiazides
Potassium-sparing
33
When dosing a loop diuretic, if the patient has a CrCl of:
25 - 50 ml/min = __ x the dose
<25 ml/min = __ x the dose
25 - 50 ml/min = 2x the dose
<25 ml/min = 4x the dose
34
What analgesics should absolutely be avoided in CKD?
NSAIDs
Use Tylenol instead
35
What is dialysis? What is CKD5?
Dialysis = removal of waste products/fluids from the body on the basis of particle differences passing through a membrane
CKD5 is when GFR<15
CKD5D is another name for “dialysis”
36
What are the qualifications for ESRD?
Dialysis required for >3 months
GFR<15 ml/min
37
What are some methods of drug removal in dialysis?
Diffusion (passive)
Convection (due to pressure, not concentration)
38
What are the 3 dialysis modalities?
Hemodialysis
Peritoneal dialysis
Continuous Kidney Replacement Therapy (CKRT)
39
What are the three ways to conduct hemodialysis from lowest risk to highest?
1. Arteriovenous fistula (preferred for long-term)
- where vein and artery are connected
2. Arteriovenous graft
- graft into nearby vein and artery
3. Central venous catheter
- tube into vena cava (last line)
40
What is peritoneal dialysis?
Infuse dialysate into peritoneal cavity, let it sit then remove (“dirty”)
Extracts urea
41
What is continuous kidney replacement therapy?
Aka “Slow hemodialysis”
For critically ill, Hemodynamically unstable patients
Includes CVVH (Continuous venovenous) and CVVHD (usually convection)
42
Hemodialysis mostly uses ______ clearance mechanism, while hemofiltration and hemodialfiltration mostly use ______ clearance.
1. Diffusion
2. Convection
43
What are the steps for HD drug concentration monitoring?
1. Obtain drug concentration prior to HD
2. Estimate HD drug removal
3. Based on post HD estimates, adjust dose
44
What is the general schedule of hemodialysis?
HD = 3 times per week, each session is 3-4 hours long
45
Drug removal is ______ efficient with HD compared to peritoneal dialysis.
More
PD has much smaller pores
46
Name 6 complications of hemodialysis
Fatigue
Bleeding
Infection
Thrombosis
Cramping
Hypotension
F BITCH (lol)
47
What causes hypotension in hemodialysis?
Hypovolemia, excess fluid removal, antihypertensives before HD
48
What fluids/medication do we use to manage HD hypotension?
Small saline bolus
Decrease fluid removal
MIDORINE
- a-1 agonist = increased vasoconstriction (increases BP)
- 2.5 - 10 mg by mouth 30 minutes before HD
49
What causes cramping in hemodialysis? What drugs/fluids do you use to manage?
Causes: hypovolemia (less muscle perfusion)
Fluid treatment: small saline bolus
Drugs:
- Vitamin E (400 IU PO at bedtime)
- Quinine (324 mg PO daily) [not for leg cramping!]
50
What drugs should be used to manage thrombosis in hemodialysis?
Prevention: heparin with dialysis
Drugs: Alteplase 2 mg/mL instilled for 30-120 mins
51
What is the minimum vancomycin concentration for post-HD?
15-20 mg/L
52
What percent of vancomycin does hemodialysis usually remove?
30 - 70%
(We will use 40%)
53
What is the best measure of anemia? What is the cutoff for this measure of anemia in CKD?
Hemoglobin
Males: Hb < 13 g/dL
Females: Hb < 12 g/dL
54
What are the 4 goals of therapy for CKD anemia?
1. Increase oxygen-carrying capacity
2. Improve quality of life
3. Prevent symptoms and complications of anemia
4. Decrease need for blood transfusion
55
T/F: Decreased mortality is a goal of treatment
False!
56
When GFR is < ____ ml/min/1.73m2 anemia begins to develop
45
57
Which two labs are used to decide on treatment for anemia?
TSat (transferrin saturation)
Serum Ferritin
58
What does hepcidin do?
It allows for iron uptake
(If hepcidin is low, then iron cannot be taken into cells)
59
What is the most common cause of erythropoietin resistance?
Iron deficiency
60
How often should an iron panel be taken for ESRD patients?
Every 3 months
61
What is the goal of therapy for anemia in CKD?
TSat > 30%
Serum Ferritin > 500 ng/mL
62
What are some key points of oral iron therapy? (Absorption, AEs, adherence, price, speed of iron distribution)
- Poor absorption (10-15%)
-AEs: GI (nausea, constipation, dark stools)
- Bad adherence (<50%)
- Cheap
- Slow iron replenishment
63
What are some key points of parenteral/IV iron replacement therapy? (Absorption, AEs, adherence, price, speed of iron distribution)
- Good absorption
- AEs (infusion reactions/anaphylaxis)
AVOID IN INFECTION
- Adherence: usually inpatient only
- Expensive!!
- Quick replenishment
64
What is the most commonly used oral iron supplement?
Ferrous sulfate
65
What are the oral iron supplements?
Ferrous sulfate*
Ferrous fumarate
Ferrous gluconate
Polysaccharide iron
Ferric citrate
66
What is the dosing regimen of oral iron supplements?
Once daily or every other day
67
What are the IV formulations of iron replacement therapy? Which is the most common?
Iron Dextran (REQUIRES TEST DOSE! Anaphylaxis risk)
*Ferric Gluconate
*Iron Sucrose
Ferumoxytol
Ferric carboxymaltose
(These are more common outpatient, more expensive but require fewer doses)
68
If a patient is on dialysis, which type of iron replacement is preferred?
IV iron is preferred
69
What are erythropoesis-stimulating agents (ESAs)?
Type of colony-stimulating agent, promote differentiation of erythrocytes, reticulocytes are biomarkers
70
What are the 4 types ESAs?
1. Epoetin alfa [Epogen] (SQ preferred)
2. Darbepoetin alfa (200x more potent than epo alfa)
3. Methoxy polyethylene glycol epoetin beta (longest acting)
4. Epoetin alfa epbx [Retacrit] (cheaper, biosimilar of Epogen)
71
What is the Hb goal for ESA treatments?
Hb: 10-11 (do not exceed 11.5, BBW for >11)
72
What are some adverse effects of using ESAs?
Hypertension
Increased thrombosis (DVT, PE, MI, **CVA**)
Headache, edema, fatigue
PRBCA: Pure red blood cell aplasia (dangerous!)
73
While we try to avoid blood transfusions as much as possible, when would you want to use one?
Administer packed red blood cells in SEVERE ANEMIA (Hb <7 g/dL)
74
As GFR declines, MBD worsens. What are some symptoms MBD?
USUALLY ASYMPTOMATIC
Identified through routine lab testing
75
What 3 parameters should be monitored in CKD-MBD?
1. Calcium + Phosphorus
2. iPTH
3. 25-OH Vitamin D
76
What is the corrected calcium equation?
Correct Ca+2 = measured Ca + 0.8 x (4 - albumin)
77
What are 3 consequences of CKD-MBD?
CV disease
Bone disease
Calciphylaxis (CUA)
78
What are the goals of treatment of CKD-MBD?
- prevent CV disease and calcification
- prevent secondary hyperparathyroidism and renal osteodystrophy
- maintain critical parameters (calcium, phosphate, PTH)
- Prevent mortality (but no treatments help w mortality)
79
What are the three steps in treatment of CKD-MBD?
1. Phosphate binders
2. Activated vitamin D
3. Calcimimetic
80
In CKD-MBD, when using PHOSPHATE BINDERS you use _________ if calcium is *normal or high* and ________ if calcium is low.
Normal-high: non-calcium based binder
Low: calcium based binder
81
Name the 4 major calcium-based binders (phosphate binders) and when each would be preferrred
1. Sevelamer carbonate (Renvela) = 1st line
2. Lanthanum (Fosrenol) = chewable
3. Ferric citrate (Auryxia) = if iodine deficiency (mild), $ and 6 tabs QD
4. Sucroferric oxyhydroxide (Velphoro) = good if pill burden is high
82
What are the two main calcium-based binders (phosphate binders)? Which is 1st line?
1. Calcium acetate (1st line) = more $, but less Ca = lower hypercalcemia risk
2. Calcium carbonate = cheaper, high Ca may risk hypercalcemia
83
In CKD-MBD, when using PTH LOWERING AGENTS you use _________ if calcium is *high* and ________ if calcium is *low*.
High = Calcimimetic
Low = Activated vitamin D + analogs
84
What are the two calcimimetics to know? Which is PO and which is IV?
PO: Cinacalcet (Sensipar)
IV: Etelcalcitide (Parsabiv)
Calcimimetics pretend to be Ca, causes downregulation calcium synthesis
85
What are the three Vitamin Ds? Which one is endogenous/active and which two are not?
Calcitriol = endogenous and active!
Non-endogenous:
Paricalcitol
Doxcalciferol
(Contain less calcium and phosphate)
86
Goals for treatment of secondary hyperparathyroidism are: (4)
1. Avoid hypercalcemia from overcorrection
2. Get phosphorus into normal range
3. Ca x Phos <55 (not recommended to use this)
4. iPTH < 2 - 9x ULN for assay
87
Phosphate binders should ALWAYS be taken _______ _______
With food!
88
What are some adverse effects of calcium-based phosphate binders?
Abdominal pain/GI discomfort and Nephrolithiasis
“Bones got Stones and abdominal groans”
Also calciphylaxis
89
What drugs have DDIs with calcium-based phosphate binders? (3) How long is the required windows between administrations?
DDIs:
Fluoroquinolone
Levothyroxine
Iron
Separate by ~2 hours
90
What is the dosing for non-calcium based binder Sevelamer?
Does it affect any other condition (dyslipidemia)?
If SPhos is:
5.5 - 7.5 mg/dL = 800 mg TID
7.5 - 9 mg/dL = 1200 - 1600 mg TID
>9 mg/dL = 1600 mg TID
Also helps lower LDL and increase HDL!
91
What is the dosing for Lanthanum carbonate?
Initial dose = 500 mg TID
**MUST CHEW**
A little more potent than sevelamer
92
What is the dosing for ferric citrate? (As a Phosphate binder)
What are some AEs? What is it’s benefit?
420 mg (two 210 mg tabs) TID
AEs: GI, diarrhea, iron overload, stool discoloration
Benefit = moderate TSat and ferritin increase (8.6%, 114 ng/mL)
93
Aluminum based phosphate binders exist and bind to phosphate extremely effectively. Why don’t we use them?
They are last line because there are serious AEs (GI, CNS toxicity, aluminum toxicity, microcytic anemia)
94
For ESRD patients, every 1 mg/dL increase in PHOSPHORUS above normal increases mortality risky by ____%!
18
95
Vitamin D2 = ______
Vitamin D3 = ________
1,25-OH D3 = ___________
D2 = Ergocalciferol
D3 = Cholecalciferol
1,25-OH D3 = calcitriol (active)
96
When should calcitriol NOT be used to stabilize secondary hyperparathyroidism?
When the patient has hypercalcemia or hyperphosphatemia (use calcimimetics)
97
Ergocalciferol and cholecalciferol are _______ forms of vitamin D. They are available OTC and are (cheap/expensive). Recommended for vitamin D deficiency.
Inactive, cheap
98
What is calcifediol?
A prohormone of calcidiol
Approved in CKD stages 3 and 4 (not ESRD!)
Available as ER capsule
AEs: hypercalcemia/hyperphosphatemia
SCa < 9.8, SPhos < 5.5
99
What is the MOA of calcitriol?
Suppresses PTH by increasing calcium concentrations = direct stimulation of parathyroid VDR and suppression of PTH release
100
Vitamin D analogs have what advantages?
Less hypercalcemia
Less hyperphosphatemia
Highly effective
101
What is cinacalcet dosing? What is the time frame for titration up?
Dose: 30 mg/day PO
Titration up over 2 - 4 weeks
102
Cinacalcet is metabolized by ________ and has a (large/small) Vd. It is (not highly/highly) protein bound.
CYP3A4
Large
Highly
103
What are major AEs and DDIs of cinacalcet?
GI = N/V in ~50%
Hypocalcemia (bc Calcimimetic)
QTc prolongation
Potent CYP2D6 inhibition
CYP3A4 inhibitors increase cinacalcet concentration
104
What is Etelcalcitide and what are it’s adverse effects?
IV Calcimimetic (as opposed to cinacalcet) and is dosed at hemodialysis
Less GI effects, still some N/V
105
When classifying CKD, what are the GFR stages and cutoffs?
G1: >90
G2: 60-89 (mild)
G3a: 45-59 (mild/mod)
G3b: 30-44 (mod/severe)
G4: 15-29 (severe)
G5: <15 (failure)
106
When classifying CKD, what are the albuminuria cutoffs?
A1: <30 mg/g (mild)
A2: 30-300 mg/g (moderate)
A3: >300 mg/g (severe)
107
What is the “CGA” that dictates CKD classification?
Cause
GFR
Albuminuria category
108
What is the intact nephron hypothesis? (From patho)
When there is moderate nephron loss, the remaining nephrons work harder to filter urine, causing kidneys to appear “healthy”. Nephron loss is replaced by fibrotic tissue.
109
What 4 major conditions cause CKD?
1. Diabetes
2. Hypertension
3. Glomerulonephritis
4. Polycystic kidney disease
110
What is the first sign of diabetic nephropathy?
Elevated albumin
111
What are modifiable risk factors for CKD?
- Diabetes
- HTN
- protenuria
- hyperlipidemia
- tobacco use
112
What is the MOST important predictor of CKD progression?
Management of underlying causes of CKD
113
What are the first, second and third line agents for diabetics with CKD?
1. SGLT-2i and Metformin
2. GLP1-RA (weight loss benefits, no renal benefits)
3. Other diabetic drugs
114
What are the first, second (2), and third line agents to treat CKD in patients with HTN?
1. ACE/ARBs
2. Finerinone (non-steroid MCRA)
OR
2. DHP CCB [diltiazem, verapamil]
3. Steroidal MCRA (spironolactone)
115
What are the first and second line agents to treat CKD in patients with hyperlipidemia?
1. Moderate-high intensity statin
2. Antiplatelet agents (P2Y12s, aspirin)
OR
2. Ezetimibe, PCSK9i, icosapentyl ethyl
116
What is the BP goal of KDIGO?
Systole < 120 mmHg (aggressive!)
117
What are some non-pharmacological treatments for HTN in CKD patients according to KDIGO?
Limit Na intake to <2g a day
Moderate intensity exercise
Weight loss to 20-25 BMI
Limit alcohol to 1-2 drinks daily
118
Are statin drugs renally eliminated? Would this make it more or less likely to be used in treatment of hyperlipidemia with CKD?
They are NOT significantly renally eliminated. It’s first line for hyperlipidemia with CKD.
119
Should we initiate statins for CKD stage 5 patients on dialysis?
Do NOT initiate!
120
For general CKD management/slowing progression, what is the first-second-third line treatments?
1st = ACE/ARBs
2nd = SGLT2is
3rd = Finerinone
121
We target proteinuria reduction of ____ to ____ % on CKD patients
30-50%
122
What drugs are best at reduction proteinuria in CKD patients?
ACEis/ARBS
123
Which ACEis are short acting?
Captopril
Enalapril
124
Which ARBs** are short acting?
Trick question! They’re all relatively long acting compared to short-acting ACEis
125
Should we initiate dual RAAS inhibition?
In most cases, NO! ACEi + ARB can be dangerous (hypotension). Instead combine one ACEi/ARB with Finerinone
126
What is Aliskiren?
A direct renin inhibitor (RAAS), dosed at 150-300 mg PO daily
CI in preganancy or combination with ACEi/ARB
Not as commonly used
127
What are ABSOLUTE CONTRAINDICATIONS of RAAS inhibition in CKD?
Pregnancy
Bilateral** renal artery stenosis
History of ACEi/ARB angioedema
128
What are conditions to USE CAUTION when using RAAS inhibitors in CKD?
Unilateral* renal artery stenosis
Hyperkalemia
Dehydration/hypovolemia
Hypotension
Kidney dysfunction (SCr>3)
129
What labs would you monitor for RAAS inhibitor use in CKD and when?
K+ and SCr within 1-2 weeks if high risk, or 4 weeks if normal
130
What are some AEs that come with RAAS drugs?
Hypotension
Orthostasis
Dizziness
Cough
Hyperkalemia
131
Quinapril (an ACEi) contains magnesium. What two drug classes should be avoided?
Fluoroquinolones, tetracyclines
132
T/F: SGLT2is should only be administered if a CKD patient is diabetic
False! Second line regardless of diabetes status!
133
Who should AVOID SGLT2is of the CKD patients?
THose with Type I diabetes! May cause euglycemic diabetic ketoacidosis
134
What is the dosing for Finerinone?
10-20 mg PO daily
135
What are some potential AEs of Finerinone?
Hyperkalemia (often potassium sparing)
Hypotension (MCRAs are used in HTN)
136
What drug (also used to decrease uric acid) can be used to slow CKD? [technically KDIGO says there is insufficient evidence]
Allopurinol
137
What drug may slow metabolic acidosis in CKD patients?
Sodium bicarbonate
138
What are some consequences of secondary hyperparathyroidism? (7)
ESA resistance
LV hypertrophy
Parathyroid hyperplasia
Myocardial fibrosis
Immune dysfunction
Lipid metabolism
Renal Osteodystrophy
