1
Q
CKD defined as ?
A
Abnormalities of kidney structure or function present for at least 3 months w/implications for health
2
Q
CKD classified based on cause, ____ and ___
A
GFR category
Albuminuria category
3
Q
Categorize the values and description for each GFR categorie
- G1
- G2
- G3a
- G3b
- G4
- G5
A
- Normal or high >= 90
- Mildly decr 60-89
- Mildly to mod decr 45-59
- Mildy to severely decr 30-44
- severely decr 15-29
- kidney failure <15
4
Q
Albuminuria categories
- A1
- A2
- A3
A
- Normal to mildly incr <30 mg/g or <3 mg/mmol
- mod incr –> 30-300 mg/g or 3-30 mg/mmol
- severely incr >300 mg/g or >30 mg/mmol
5
Q
What’s the most widely used endog marker for detection of kidney disease?
A
Creatinine
6
Q
Creatinine production
average for men and women?
A
- Men : 20-25 mg/kg
- women : 15-20 mg/kg (About 1 gram per day)
7
Q
Factors that affect Scr? (5)
A
Age
Muscle mass
strenuous exercise
high protein diet
creatine supplementation
8
Q
What happens to SCr of aa individuals?
A
GFR is 16% higher than white pt’s
9
Q
Measured Creatinine Clearance : Timed Collection
Useful in pt’s with?
How long is the collection?
What’s the equation?
A
- NON GFR determinants of creatinine bc u cant assume standard creatinine production rates
- 12 or 24 hr collection
- CLcr (mL/min) = ([Creatinine] urine * Volume of Urine ) / (1440 * [Creatinine] plasma)
10
Q
Urinalysis : State what the following indicate damage of
- Proteinuria
- Glucose in urine
- RBCs
- WBCS
- Leukocyte Esterases and nitrates
- Casts indicate ?
A
- glomerulus
- Diabetes or tubular injury
- glomerular injury
- infection or autoimmune disease
- confirm infection
- Damage in general (can be diff types)
11
Q
For each dipstick category , state the corresponding Albumin Concentration
Trace
1+
2+
3+
4+
A
15-30 mg/dL
30-100 mg/dL
100-300 mg/dL
300-1000 mg/dL
> 1000 mg/dL
12
Q
Proteinuria: For each classification, state the 24 hr urine collection value and Spot Urine Albumin : creatinine ratio
- Normal
- Mod incr
- Severely incr
A
- <30 mg , <30 mg/g
- 30-300 mg, 30-300 mg/g
- > 300 mg, > 300 mg/g
13
Q
What’s the highest etiology incidence of CKD?
A
Diabetes 44% followed by HTN 27%
14
Q
- Stage 1 Kidney Disease –> GFR is ____, but there’s evidence of ___
- Stage 2 ?
- Stages 3-5?
A
- Normal, kidney damage
- evidence of kidney damage AND a reduced GFR
- Reduction in GFR with OR WITHOUT evidence of damage to the kidneys
15
Q
For diabetes, how can it cause CKD?
What’s the first sign of damage to the kidney from diabetes?
A
excessive filtration of glucose increases osmotic pressure and thickening of the capillary basement membrane
protein spilling into the urine
16
Q
As kidney function declines… what does kidney do to the efferent and afferent arterioles?
What does this result in?
Causes progressive?
A
- constricts efferent and dilates afferent arterioles
- incr intraglomerular pressure to maintain GFR
- fibrosis, sclerosis, and nephron drop out
17
Q
What are the sx’s and signs of each CKD stage? (Note as we progress to each further stage, GFR decreases)
- CKD stage 1
- CKD stage 2
- CKD Stage 3
- CKD Stage 4
- CKD Stage 5
A
- Sx’s : Asymptomatic
Signs : HTN, abnormal urine test - SX’s : Usually none, or edema
Signs : HTN, abnormal urine test - SX’s : None to fatigue, edema, nocturia
Signs : Edema, anemia - SX’s :None to loss of appetite, dyspnea, worsening fatigue, edema, pruritus
Signs : MOD, electrolyte abnorms, onset of uremia - SX’s : Weight loss, dyspnea, fatigue, altered mental status
Signs : Severe HTN, Pulm edema, acidosis, hyperkalemia, encephalopathy
18
Q
Clinical Eval : Lab Work up for CKD
- Requires orders of ? (4)
- Serum creatinine is used to estimate ? Urinalysis used to estimate?
- These 2 important pieces of info allow u to do what 2 things?
- Fast progression of kidney disease is seen with?
A
- Serum chemistry, complete blood count, urinalysis, and urine chemistry for protein and creatinine
- The kidney function
- determine if there are injury markers such as proteinuria or
hematuria - stage the severity of
kidney disease using the GFR and determine how quickly the kidney disease will progress by
quantifying proteinuria - a greater amount of proteinuria
19
Q
HTN Management
- Only 11% of pt’s with CKD have __ controlled
- Goals of therapy for BP for CKD pt’s ?
- this is irrespective of ____ or ____ - More goals of therapy include reducing risk of ___ and slowing the progression of ___
- Goal for proteinuria is?
A
- BP
- BP should be <120/80 mmHg
-proteinuria, diabetes - CVD, CKD
- <1 gram/day
20
Q
Management of CKD
- Address _____of CKD –> if autoimmune disease like lupus nephritis… tx with __
- Slow progression of the CKD
-Use evidence based therapies such as ? (3) - Estimate and reduce ____
-Apply evidence based therapies such as ? (3) - Treat co-morbidities and complications of CKD! List them! (8)
A
- Underlying cause
- immunosuppression - RAAS agents, SGLT2 Inhibitors, finerenone
- CV risk
-RAAS, SGLT2I’s, statins - HTN, Diabetes, hyperlipidemia, anemia, bone disease, electrolyte abnorms, metabolic acidosis, smoking cessation
21
Q
Most
beneficial anti-hypertensives for patients with CKD and protein in the urine are ?
How do these drugs
slow the progression of CKD to end stage renal disease and slow the time to doubling of Scr?
Indicated for pt’s with proteinuria and these pt’s can be __ and __
A
- ACE’s and ARBS
- Dilate the efferent arteriole reducing intra-glomerular pressure and
reducing proteinuria.
-reduce intraglom pressure will initially decr GFR but will stabilize! –> reduction in albuminuria –> renal protection
diabetic, non-diabetic
22
Q
AE’s of ACEI’s and ARBS? (4)
A
-30% rise in Scr within the first two months of therapy
-Hyperkalemia
-Hypotension
-Worsening anemia and teratogenicity
23
Q
When can you titrate ur pt’s dose of ACEI’s or ARBS?
A
Monitor Scr and and K within 1-2 wks –> if Scr within 30% of baseline and potassium is normal, u can titrate dose
24
Q
DO NOT Initiate ACEIs and ARBS in CKD Stage ___ without ____?
A
5, consulting nephrology
25
CCB's in Proteinuric CKD
1. They are __ behind acei's or arbs
2. They dilate ____
3. Non DHP CCBs associated with ___. Name the 2 drugs
4. Don't use DHP CCB alone without ___ or ___ in proteinuric pt's bc they can ____
1. second line
2. afferent arteriole
3. anti-proteinuric effects. Diltiazem or verapamil.
4. ACEI , ARB , worsen proteinuria
26
Disadvantages of
CCBs ?
inhibit CYP 3A4 and interact with statins and calcineurin inhibitors used in
transplantation
27
Diabetes Management and CKD :
1. Goal of Blood sugar pre-prandial?
2. Goal of blood sugar post prandial?
3. A1C goal for early CKD Stages 2-3
4. A1C Goal for stage 4 or 5 CKD or pt's w/repeated hypoglycemia?
1. 90-130 mg/dL
2. <180 mg/dL
3. 6.5%
4. 8%
28
First line agent for patients with Diabetes and CKD?
SGLT2I's
29
Technically, SGLT2I's have shown benefit in which group of pt's?
What are the drugs able to do?
Both diabetic and non diabetic CKD stages 2-4
for reducing proteinuria, GFR decline, and CV death
30
In early stages of diabetic nephropathy what happens?
Hyperfiltration bc of upreg of SGLT2 receptors to absorb glucose and Na+ resulting in Afferent arteriole vasodilation and incr GFR
-bc of decr Na+ delivery to macula densa, u have impaired tubuloglomerulo feedback --> blunts afferent tone
SGLT2I's --> restore TGF, allow for incr Na+ delivery to macula densa --> AA constriction --> normalization of GFR
31
Eligible pt's for SGLT2I's with CKD :
1. eGFR ?
2. High priority features? (2)
3. Potential CI's? (4)
4. Which SGLT2I's have proven benefits? (3)
1. egfr >= 20 mL/min/1.73 m^2
2. ACR >= 200 mg/g or >= 20 mg/mmol
3. Genital infection risk
diabetic ketoacidosis
foot ulcers
immunosupression
4. Canagliflo --> 100 mg
Dapagliflo --> 10 mg
Empagliflo --> 10 mg
32
SGLT2I Dosing in CKD
1. DAPA
-dose?
-eGFR by which dosing is approved?
2. EMPA
-Dose?
-eGFR by which dosing is approved for pt's with T2D + ASCVD for glucose control and for HF?
3. CANA
-Dose?
-eGFR by which dosing is approved?
1. 10 mg daily
- >=25
2. 10 mg daily. can incr to 25 mg daily prn for glucose control!
>= 30 for T2D and ASCVD for gluc control
>= 20 for HF
3. 100 mg daily (high dose of 300 mg not rec for CKD)
>=30
33
What Additional med for TX of Diabetes for pt's with CKD (After metformin and SGLT2 INHIBITOR) would you add on?
GLP1 agonist
34
GLP1RA Dosing in CKD : State dosing and CKD adjustment for each drug
1. Dulaglutide
2. Exenatide
3. Exenatide ER
4. Liraglutide
5. Lixisenatide
6. Semaglutide Injection
7.Semag Oral
1.
A. 0.75 mg and 1.5 mg once weekly
B. No dose adj. Use with eGFR > 15
2.
A. 10 microgram BID
B. Use with CrCl > 30 mL/min
3.
A. 2 mg once weekly
B. eGFR >45
4.
A. 1.2 mg and 1.8 mg once daily
B. No dose adj
5.
A. 10 microg and 20 microg once daily
B. No dose adj. Not recc with eGFR < 15
6.
A. 0.5 mg and 1 mg once weekly
B. N/A
7.
A. 3mg, 7mg, or 14 mg daily
B. N/A
35
Metformin is an excellent tx of diabetes in CKD but is CI if egfr< ___ due to risk of?
If GFR 30-44... WHAT do u do to the metformin dose?
30
lactic acidosis
Initiate at half the dose and titrate upwards to half of the max recc dose
36
Third Tier Therapy for CKD Diabetes ?
It's useful in CKD especially advanced CKD stage 5 when you cannot use an
SGLT2 inhibitor why?
Which one doesnt need dose adjustment for CKD pt's?
DPP 4 Inhibs
Lack of hypoglycemia and neutral weight effects
Linagliptin
37
Dyslipidemia and CKD
CKD is considered a ______
-Most pt's w/dyslipidemia and CKD require a?
-DOC?
-Need to check ___
-DDI's with ___
-High dose ___ associated with ___
-AVOID ___ due to INCR risk of ____
Cardiovascular risk equivalent
- Mod intensity statin
- HMG COA Reduct Inhib
-Renal dosing
-CCB's Diltiazem and amlodipine
-Rosuvastatin , worsening proteinuria
-Fibrates. Myopathies
38
ANEMIA and CKD
1. What kind of anemia develops?
2. Goals of therapy for HgB, TSAT and Ferritin?
3. Ferritin goal for dialysis and nondialysis pt's?
1. normocytic, normochromic anemia
2. 9.5-11 g/dL, rate of rise 1-2 g/dL per month
TSAT 20-50% and Ferritin
100-500 ng/mL
3. >200
>100
39
ANEMIA : Oral Iron
1. Dosing range?
2. AE's? (4)
3. DDI's? (4)
1. 200 mg elemental iron /day
2. constipation, nausea, abd cramping, food decr oral abs
3. Antacids, H2 antags, PPI's, quinolone antibiotics
40
For each Oral Iron Product state the elemental iron and then the doses per day to reach the 200mg elemental iron requirement
1. Ferr Sulfate
2. Ferr Fumarate
3. Ferr Gluc
4. Polysach Iron (Niferex)
5. Ferr Citrate (Auryxia)
1. 65 mg per 325 mg
tab. 3
2. 99 mg per 300 mg
tab. 2
3. 36 mg per 325 mg
tab. 6
4. 150 mg per 150
mg. 1
5. 210 mg per 1 gram . 3
41
When do you switch to IV Iron therapy?
If tx doesnt work after 3-6 months
42
IV Iron
1. Iron dextran has small risk of?
-requires test dose of?
2. Iron sucr or Gluc in sucrose release free iron much more ___ than ___. BUT They can cause ___ and large doses cannot be given by ___
3. Ferumoxytol can be given in a ___ as IV push, convenient for ___
4. Iron therapy associated with worsening of ___
1. Anaphylaxis
-25 mg to be administered
2. rapidly, iron dextran.
-Hypotension
-IV push
3. Large dose (510 mg)
- outpt admin
4. infections
43
Kim : Refer to Outline for full dosing for each IV agent
1. Total course of IV IRON should be ? (Loading Dose)
2. For dialysis dep pt's what's the Iron gluconate in sucrose dose?
-Iron sucrose/iron dextran?
3. For non dialysis pt's
what's the Iron Sucrose Dose?
Ferumoxytol dose?
4. DONT RE CHECK IRON INDICES FOR AT LEAST?
1. 1 gram
2. 125 mg IV push w/each dialysis session for 8 doses
- 100 mg IV push w/dialysis session for 10 doses
3. 500 mg over 3.5 hrs for 2 consec doses
510 mg IV push or intermittent infusion for 2 doses
4. 2 weeks
44
ESA Therapy
1. 2 products?
2. Which has longer half life and less freq dosing?
3. For dialysis pt's whats the dosing scheme?
4. For non dialysis pt's what's dosing?
1. EPO ALFA AND DARBEPOETIN
2. Darbepoetin.
3. Epo alfa 3x weekly w/each dialysis session
4. Epo alfa SQ once monthly initially and adjusted to Hgb target (Can incr freq to once weekly depending on kidney function and rate of rise in Hgb)
45
Most pt's in CKD stage __ require ESA
ESA therapy is usually initiated if the Hgb
drops below?
ESA should be admined SQ why?
4
9.5 g/dL.
30% reduction in dose compared to IV admin
46
AE/BBW for ESA?
AE : flu like symptoms, increased risk of malignancy in
patients with active cancers and worsening hypertension
BW : Mortality , serious cardio and thromboembolic events, INCR risk of tumor progression or recurrence
47
Epo Alfa Dosing
1. Hemodialysis
2. CKD
Darbo Dosing
1. CKD?
In both cases, hold when HgB gets to more than ?
1. 100 units/kg SC three
times weekly
2. 10,000 units SC qmonth
3. 40-60 mcg SC q month
4. 11
48
As CKD progresses, what happens to urinary excretion of phosphorous?
What happens as serum phosphorous incr?
Decreased activation of 25-OH vitamin D leads to?
It diminishes --> increased serum
phosphorus.
It serves as a stimulus for PTH secretion, resulting in increased
PTH
It leads to decreased gut absorption of calcium and hypocalcemia. This also stimulates PTH secretion
49
High PTH causes?
It increases ____ and causes impaired ____
bone resorption and an increased risk of fractures
osteoclastic activity, mineralization of bone
-
50
For patients, you must assess the following aspects? (6)
serum calcium, calculate the corrected calcium if pt is hypoalbuminemic, assess serum
phosphorus, alkaline phosphatase, PTH and 25-OH vitamin D concentrations
51
What's the corrected calcium equation?
Corrected Ca = ((4-serum albumin)*0.8) + serum calcium
52
Treatment of bone disease always targets what first?
TX algorithm :
1. Control phosphorous using ? (2)
2. Replace Vitamin D
-Check ___ level and replete vitamin ___ as necessary
-If iPTH elevated, trend first and look at other markers such as ___ to determine if pt needs ___
Phosphorous control
1. Dietary restriction (no dairy, dark colored soda, nuts, beans, chocolate) and BINDERS
2. 25OH , D2
- alkaline phosphatase
-active Vitamin D replacement
53
KIM : Print out Phosphorous Binders Table
1. WHat is the first line binder?
Sevelamer
54
1. Sevelamer
-What's not systemically absorbed?
-It also lowers?
Polymer resin
Total cholesterol and LDL
55
2. Lanthanum carb
-How does it bind phosphorus?
-Lack of?
Dissociates into trivalent cation which binds phos
long term safety data
56
3. Calcium based binders
-No longer ___
-What binds more phos for same amount of calcium as compared to calc carb?
first line for hyperphos
calcium acetate
57
4. Aluminum Hydroxide
-Most ___ phos binder
-Use is limited by?
-Limit therapy to?
potent
accumulation and AE's : encephalopathy, anemia, and bone disease
4 weeks
58
Newer Phos Binders
1. Ferric citrate (Auryxia)
-Both a ___ and ___
-Similar efficacy to __ and ___
-AE's ? (5)
-Mg and dosage?
2. Sucroferric Oxyhydroxide (Velphoro)
-Same as?
-Similar efficacy to?
-___ binder
AE's ? (3)
-Mg and dosage?
phos binder + iron replacement therapy
sevelamer + calc carb
N/V/D, constipation, ABD pain
210 mg tabs, 1-2 tabs po TID with meals
2. iron sucrose
sevelamer
phosphate
N,D,stool discoloration
500 mg chew tabs, 1 tab PO TID w/meals
59
Phosphate Binder Counseling
1. Take at ___ of meal
2. Carry a small pill box in case of?
3.___ is a problem
1. Start
2. unplanned snacks or small meals where u'll need extra tabs
3. adherence
60
Routine use of Vitamin D analogs is not recommended in CKD stage ___
Vitamin D analogs should be reserved for ?
3-5 not on dialysis
CKD stage 4-5 w/severe and progressive hyperparathyroidism
61
What are the 3 Vitamin D analogs?
How does Calcitriol work?
Calcitriol is associated with?
Calcitriol, paricalcitol, doxercalciferol
Interacts with Vitamin D receptors in gut to increase intestinal absorption of calcium and correct hypocalcemia
Greater incidence of hypercalcemia compared to other agents
62
KIM : print/look at vit D analogs on outline
What are the AE's of Vit D analogs?
Drug interactions?
HYPER calcemia, phosphatemia, adynamic bone disease
Cholestyramine (decr absorption)
Paricalcitol (with 3A4 inhibs)
63
DOSING
1. Calcitriol
2. Doxercalciferol or paricalcitol
3. pulse dosing 3 times weekly associated with?
4. To reduce risk of hypercalcemia, admin oral vit D analogs on __
1. 0.25 mcg po daily to 3 times weekly
2. 1 mcg po daily to three times weekly
3. Less hypercalcemia than daily dosing
4. empty stomach
64
Calcimimetics -Cinacalcet
MOA?
Used when?
Calcium sensing receptor on surface of parathyroid gland
-mimics extracellular ionized Ca
Feedback between serum calcium concentration and parathyroid gland is disrupted (i.e hypercalcemia and high PTH)
Therapeutics
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