CKD anc Complications Flashcards
Glomerular filtration rate classification G1 G2 G3a G3b G4 G5
G1 (normal or high): >=90 mL/min
G2 (mildly decreased): 60-89 mL/min
G3a (mildly to moderately decreased): 45-59 mL/min
G3b (moderately to severely decreased): 30-44 mL/min
G4 (severely decreased): 15-29 mL/min
G5 (kidney failure): <15 mL/min
Albuminuria classification
A1
A2
A3
A1 (normal): <30 mg/day
A2 (microalbuminuria): 30-300 mg/day
A3 (macroalbuminuria): > 30mg/day
Top four causes of CKD in US
Diabetes
Hypertension
Glomerulonephritis
Polycystic kidney disease
Risk factors of CKD progression
Both modifiable and non modifiable
Modifiable: Diabetes, HTN, Proteinuria, Hyperlipidemia, Tobacco use, Systemic inflammation, Environmental exposures (heavy metals)
Non modifiable: Older age, African-American or Native American ethnicity, Genetics (family history), Gender
A1C target in CKD for intensive blood glucose control
<= 7
What is the goal for CKD therapy? Choice - Increase kidney function - Stop the decline in kidney function - Slow the decline in kidney function How?
SLOW the slope of decline, not stop nor increase
Through intensive blood glucose control
First line agents for lowering BP in CKD patients?
ACE-I or ARB medications
ACEi: -pril
ARB: -sartan
What is the target BP for a patient with albuminuria and CKD? Without albuminuria?
<130/80 regardless
Non-dihydropyridine Calcium Channel Blockers Medication name: Effect: Side effect: Drug interaction:
- Medication name: verapamil, Diltiazem
- Effect: anti proteinuria effects (dilate afferent arteriolar), negative inotropes and chronotropes
- Side effects: negative inotropes and chronotropes
- Drug interaction: a lot, do not use with beta blockers
Dihydropyridine CCBS
- Medication name
- Effects
- Side effects
- Drug interaction
- Medication name: amlodipine, nifedipine
- Effect: no effect on proteinuria
- Side effects: risk of worsening edema
- Drug interaction
Antihypertensive Drug selection in CKD
- ACEi or ARB: titration to maximal dose for anti proteinuric effect
- Thiazides diuretics.
- If clinically evident edema — use loop diuretics
- Calcium channel blocker
- Non DHP (diltiazem) for additional anti proteinuric effects
- DHP for additional BP reduction
Non pharmacologic treatment for CKD patients?
Low sodium intake <2g/day
Moderate intensity exercise regimen
Weight loss to a BMI of 20-25 kg/m2
Limit alcohol intake to <= 2 drinks per day for males and <= 1 drink per day for females
Should we start statin in CKD pt with hyperlipidemia? In CKD dialysis? In CKD non dialysis? Dose adjustment?
Start statin in CKD non dialysis pt as it benefits for all causes mortality as well as cardiovascular events
Don’t start statin in CKD dialysis pt or might consider continue if pt is already on statin,
UNLESS the CKD dialysis pt also in acute coronary syndrome, then can use statin acutely (first 30-90 days)
There is no dose adjustment needed
Which is a first line antihypertensive drug for a patient with albuminuric CKD? Hydrochlorothiazide Diltiazem Enalapril Amlodipine
Hydrochlorothiazide — thiazides diuretics (second line of choice)
Diltiazem — non DHP CCBs for additional anti proteinuric effect
Enalapril — ACEi, first line of choice
Amlodipine — DHP CCBs for additional blood pressure reduction
A patient has an estimated GFR of 43ml/min/1.73m2 and a urinary albumin excretion of 225mg/g creatinine. What best categorizes their CKD? G3a, A2 G3a, A3 G3b, A2 G3b, A3
G3b, A2
What is the goal of albumin excretion in diabetic CKD management?
Reduce proteinuria to minimum possible; 30-50% reduction
Benazepril
Brand name: Lotensin Starting dose: 5mg daily Maximum dose: 80 mg daily FDA indications: HTN Duration of action: 24 hours Elimination: 60% renal, 40% biliary
Captopril
Brand name: Capoten Starting dose: 12mg TID Maximum dose: 150mg TID FDA indications: HTN, HFrEF, LV dysfunction Duration of action: 6-10 hours Elimination: 50% renal, 50% hepatic
Enalapril
Brand name: Vasotec Starting dose: 2.5mg daily Maximum dose: 10mg BID or 20mg daily FDA indications: HTN, HRrEF, LV dysfunction Duration of action: 12-24 hours Elimination: 94% renal
Fosinopril
Brand name: Monopril Starting dose: 10mg daily Maximum dose: 40mg daily FDA indications: HTN, HFrEF Duration of action: 24 hours Elimination: 50% renal, 50% biliary
Lisinopril
Brand name: Zestril, Prinivil Starting dose: 5mg daily Maximum dose: 80mg daily FDA indications: HTN, HFrEF Duration of action: 24 hours Elimination: 100% renal
Moexipril
Brand name: Univasc Starting dose: 3.75 mg daily Maximum dose: 30 mg daily FDA indications: HTN Duration of action: 24 hours Elimination: 7% urine, 52% feces
Quinapril
Brand name: Accupril Starting dose: 5mg daily Maximum dose: 80mg daily FDA indications: HTN, HFrEF Duration of action: 24 hours Elimination: 96% renal
Ramipril
Brand name: Altace Starting dose: 1.25mg daily Maximum dose: 20mg daily FDA indications: HTN, HFrEF Duration of action: 24 hours Elimination: 60% renal, 40% feces
Trandolopril
Brand name: Mavik Starting dose: 1mg daily Maximum dose: 4mg daily FDA indications: HTN, LV dysfunction Duration of action: 24 hours Elimination: 33% urine, 66% feces
Azilsartan
Brand name: Edarbi Starting dose: 40mg daily Maximum dose: 80mg daily FDA indications: HTN Duration of action: 24 hours Elimination: 55% feces, 42% urine
Candesartan
Brand name: Atacand Starting dose: 4-8mg daily Maximum dose: 32mg daily FDA indications: HTN, HFrEF Duration of action: 24 hours Elimination: 65% hepatic, 35% renal
Eprosartan
Brand name: Teveten Starting dose: 600mg daily Maximum dose: 800mg daily FDA indications: HTN Duration of action: 12-24 hours Elimination: 90% feces, 7% urine
Irbesartan
Brand name: Avapro Starting dose: 75-150mg daily Maximum dose: 300mg daily FDA indications: HTN, Diabetic nephropathy Duration of action: 24 hours Elimination: 80% hepatic, 20% renal
Lorsartan
Brand name: Coozar Starting dose: 25-50 mg daily Maximum dose: 100-150mg daily FDA indications: HTN, LVH, Diabetic nephropathy Duration of action: 24 hours Elimination: 60% feces, 40% urine
Olmesartan
Brand name: Benicar Starting dose: 20mg daily Maximum dose: 50mg daily FDA indications: HTN Duration of action: 24 hours Elimination: 50% feces, 50% urine
Telmisartan
Brand name: Micardis Starting dose: 20mg daily Maximum dose: 80mg daily FDA indications: HTN, CV risk reduction Duration of action: 24 hours Elimination: 97% feces
Valsartan
Brand name: Diovan Starting dose: 1.25mg daily Maximum dose: 20mg daily FDA indications: HTN, HFrEF, LV dysfunction Duration of action: 24 hours Elimination: 83% feces, 13% urine
Aliskiren
- Brand name
- MOA
- Efficacy
- Contraindications
Brand name: Tekturna MOA: Direct renin inhibitor Dosing: 150-300mg PO once daily Efficacy: Reduces proteinuria and BP Contraindications: pregnancy, combination with ACEi or ARB
Goals of RAAS Inhibitors
- BP < 130/80 mmHg
- Reduction in albuminuria by 30-50%
- Slow progression of CKD
- Adhere to daily dose of medication with minimal AEs
RAAS Inhibitor Contraindications
ABSOLUTE Contraindications
Use with caution
Absolute Contraindications:
- Pregnancy
- Bilateral renal artery stenosis
- History of ACE/ARB related angioedema
Use with caution:
- Unilateral renal artery stenosis
- Hyperkalemia
- Dehydration / hypovolemia
- Hypotension
- Kidney dysfunction (SCr>3.0mg/dL, eGFR<30mL/min/1.73m2)
Monitoring of RAAS Inhibitors
Side effects:
Hyperkalemia and decrease GFR
- Closely monitor the SCr and serum potassium
- As long as the decline in GFR doesn’t go above 30%
Orthostatis, Angioedema, Cough
Adverse effects:
- Hypotension/ orthostasis/ dizziness
- Cough
- Hyperkalemia
- Angioedema
What is the main goal of an ACE inhibitor when being used to treat CKD?
- Reduce cardiovascular events
- Reduce albuminuria by 30-50%
- Reduce albuminuria go <130 mg/g creatinine
- Stop the decline in GFR
Reduce albuminuria by 30-50%
Goal is to slow the decline in GFR, surrogate markers of decreased albuminuria (by 30-50%) and blood pressure <130/80 are used to achieve this
What is an absolute Contraindications to quinapril?
- Unilateral renal artery stenosis
- Serum creatinine of 2.5 mg/mL
- Pregnancy
- Blood pressure of 126/78 mmHg
Pregnancy
Quinapril is an ACEi
A patient with CKD starts lisinopril 10mg PO daily. At baseline their eGFR is 60ml/min/1.73m2 and serum potassium is 4.0 mEq/L. Two weeks after initiation their eGFR is 48mL/min/1.73m2 and serum potassium is 4.5mEq/L. What should be done at this point given these new labs?
- Continue current lisinopril dose; re-check labs in 2-4 weeks
- Increase lisinopril dose to 20mg PO daily; re-check labs in 1-2 months
- Decrease lisinopril dose to 5mg PO daily; re-check labs in 1-2 days
- Hold lisinopril; re-check labs in 1 weeks
Continue current lisinopril dose; re-check labs in 2-4 weeks
eGFR declined by ~20%, which does not meet the 30% threshold for action. Would re-check labs to ensure the eGFR doesn’t drop further. This is an expected change in eGFR when starting an ACEi or ARB. Potassium remains WNL so no intervention needed there.
What are the benefit of SGLT2 inhibitors? And what is it used for?
What are the adverse effects?
- gliflozin
Slows progression of kidney disease in patients with or without diabetes, reduce cardiovascular morbidity and mortality
Used as a second line treatment option for T2DM and CKD
Adverse effects:
- Acute kidney injury
- Euglycemic diabetic ketoacidosis
- Urinary tract infections/ genital mycotic infections
- Lower limb amputations
Allopurinol and Febuxostat
Used:
Goal:
- Decreased uric acid generation
- Goal uric acid in CKD <7mg/dL
- Allopurinol has been shown to slow CKD progression and improved cardiovascular outcomes
- Allopurinol Hypersensitivity syndrome
- Systemic hypersensitivity, including Stevens-Johnson Syndrome, renal and hepatic injury
- Dosing: 1.5 mg x eGFR
Alkali Therapy: Sodium Bicarbonate
- Used
- Goal
Use sodium bicarbonate to manage chronic metabolic acidosis, may also slow regenerating of CKD (but not much evidence on this)
- Target serum bicarbonate is 20. When it’s below 20, start sodium bicarbonate or sodium citrate. When it’s above 20 (goal), can start to decreasing the dose, but likely need some chronic bicarbonate supplementation because the kidney is not regenerating like it does normally
SGLT2 inhibitors slow progression of CKD in both diabetic and non-diabetics
True
False
True
- DAPA CKD trial showed better renal outcomes in DM and non-DM populations
What non-pharmacologic intervention is recommended to slow CKD progression? High protein diet Low potassium diet Achieve a healthy BMI (20-25kg/m2) No more than 3 alcoholic drinks per day
Achieve a healthy BMI (20-25 kg/m2)
Other include:
- Reduce dietary proteins as CKD worsens (<=0.8 g/kg/day)
- Na< 2g/day, NaCl <5 g/day
- Limited alcohol intake (female 1 drink per day, male 2 drinks per day)
- Smoking cessation
- Goal BMI <25 kg/m2 (weight loss strategy includes exercise — 4 to 5 days a week for 30 minutes a session)
Definition of Anemia in CKD
HGB<13 g/dL in males
HGB<12 g/dL in females
Goals of therapy of Anemia of CKD
- Increase oxygen carrying capacity
- Improve quality of life
- Prevent / alleviate symptoms and complications of anemia
- Decrease need for blood transfusions
The goal does not include mortality rate
Target HGB (hemoglobin) range in Anemia
10-11 g/dL
-Oxygen carrying capacity of RBCs
Serum Ferritin target range in Anemia? What does it do?
> 100 ng/mL CKD 1-4
500 ng/mL ESRD
- Storage form of iron
- Normal Range: >10-20 ng/mL
Transferrin Saturation target range in Anemia, and what does it do?
Transferrin Saturation (Tsat) >30%
- Reflects iron available for immediate erythroposiesis
- Normal Range: (M) 15-50%, (F) 12-45%
The most common causes of Erythropoietin resistance
- What is this
- Therapeutic response
- Goal
Iron deficiency
- Must correct this first
- Iron panel should be monitored every 3 months in an ESRD pt or anyone receiving erythropoietin for anemia
- Therapeutic response
- Increased Reticulocyte count within 7-14 days
- Increased HGB and HCT within 3-4 weeks
- The goal is to obtain Tsat >30% and serum ferritin >500 ng/mL
Oral vs Parenteral Iron Therapy
Oral: Poor absorption (10% -15% bioavailability), GI complications (nausea, cramping, constipation), poor adherence, slow replenishment of iron stores
- Side effects include GI upset and dark stool
Parenteral: Better absorption, rapid replenishment of iron stores, risk of iron overload, infusion reactions, anaphylactic reactions, avoid IM use (variable absorption, painful, bleeding risk)
- Side effects include dyspnea/ wheezing, itching, myalgias, hypotension, flushing, edema, chest pain, cardiac arrest, injection site reactions, anaphylactic and anaphylactic reactions, infections
What is the goal transferrin saturation for a hemodialysis patient?
10-11g/dL
30-50%
500-1200ng/mL
2-9 times the upper limit of normal for the assay
30-50%
What is a contraindication to intravenous iron therapy? Active malignancy Hypertension Systemic infection Use of a proton pump inhibitors
Systemic infection
Complications of oral iron therapy includes (SATA) Poor oral absorption Constipation Dark colored stool Intestinal necrosis
Poor oral absorption
Constipation
Dark colored stool
KDIGO and FDA Guidelines for Initiation of ESAs and Hemoglobin Targets in Non dialysis CKD patients and dialysis patient (ESRD)
Initiation of ESA in ND-CKD - KDIGO: Hb < 10 g/dL - FDA: Hb < 10 g/dL Initiation of ESA in ESRD - KDIGO: Hb 9-10 g/dL - FDA: If < 10 g/dL
Target Hb for ND-CKD - KDIGO: Do not exceed 11.5 - FDA: 10 avoid transfusion Target Hb for ESRD - KDIGO: Do not exceed 11.5 - FDA: 10-11 avoid transfusion
Erythropoiesis Stimulating Agents (ESA) Dosing
Goal change in HGB: 1-2 g/dL/month
- Dosing adjustments at 4 weeks (steady state)
- Reduce ESA dose by >=25% as the patient’s HGB approaches 12g/dL or if HGB increases >1g/dL in 2 weeks or less
- Increase ESA dose by 25% if HGB is below target after 4 weeks of treatment
What is ESA resistance? What causes it?
ESA resistance is failure to achieve a target HGB at a dose of >500 units/kg/week (around 5 times higher than normal)
Causes: Iron deficiency ACE inhibitors Hyperparathyroidism Aluminum toxicity Folate and/or Vitamin B12 deficiency Infection Malignancy Trauma Inflammation
Adverse effects of ESA
Hypertension Hypercoagulability — increased risk of thrombosis (ex: DVT, PE, MI, CVA, etc) Hypersensitivity reactions PRBCA (pure red blood cell aplasia) Headache, fatigue, edema Progression of malignancy
Do not use ESA if:
Active malignancy
High risk of CVA
HGB > 11 g/dL
Compared to epoetin alfa, darbepoetin alfa: Has a longer half life Is dosed more often Has a lower risk of stroke Can be used in several hypertension
Has a longer half life
- All do the ESAs have risks of stroke/HTN, there are Novell declineatd differences between the agents in terms of these outcomes the major differences are duration of action and therefore dosing interval
According to the FDA, a patients with non dialysis CKD should be treated with an ESA to a hemoglobin target of: 10-11 g/dL 10 g/dL 10-11.5 g/dL >7 g/dL
10 g/dL
What is an absolute contraindication to the use of an ESA?
History of hypertension, current blood pressure 138/78 mmHg
History of myocardial infarction 5 years ago
Systemic infection
Active malignancy with anticipated cure
Active malignancy with anticipated cure
Calcium calculation
Corrected calcium = measured calcium + 0.8 (4 - albumin)
Goal of treatment of CKD-MBD
- Prevent consequences of cardiovascular and extra vascular calcification
- Prevent the development of secondary hyperparathyroidism and renal osteodystrophy
- Maintain critical biochemical parameters (calcium, phosphate, and iPTH) within target ranges
- Prevent mortality
List two calcium based binder
Calcium acetate (PhosLo) — preferred Calcium carbonate
List 4 non calcium based binder
Sevelamer carbonate (Renvela) — first line
- Causes diarrhea
Lanthanum carbonate (Fosrenol) — chewable
Ferric citrate (Auryxia) — iron deficiency anemia
Sucroferric oxyhydroxide (Velphoro) — pill burdenList 4 ways to lower parathyroid hormone
Normal to low serum calcium
Normal to high serum calcium
Activated Vitamin D and Analogs:
- Calcirtriol (Rocaltrol) — Endogenous
- Paricalcitol (Zemplar); Doxercalciferol (Hectorol) — Less hyperkalemia and less hyperphosphatemia
Calcimimetic
- Cinacalcet (Sensipar)
- Etelcalcitide (Parsabiv)
Goal for CKD-MBD
- Goal serum Calcium: avoid hyperkcalcemia; asymptomatic hypocalcemia is acceptable
- Goal serum phosphate: towards the normal range (3.5 - 5.5 mg/dL)
- Goal iPTH: 2-9 x ULN (~ 150-600 pg/mL)
Calcium based phosphate binders drug interactions
Fluroquinolones
Levothyroxine
Iron
Separate administration by ~2 hours
What is the goal serum phosphorous concentration in a CKD patient?
Avoid hyperphosphatemia, asymptomatic hypophosphatemia is acceptable
Toward the normal range (2.7-4.6mg/dL or 3.5-5.5mg/dL are acceptable)
2-9 times the upper limit of normal for the assay
10-11mg/dL
Toward the normal range (2.7-4.6mg/dL or 3.5-5.5mg/dL are acceptable)
A patient with CKD MBD has a serum calcium of 7.7mg/dL, phosphorous of 6.2mg/dL, and albumin of 3.3g/dL. Which phosphate binder should be used? Calcium acetate Sevelamer carbonate Aluminum hydroxide Sucroferric oxyhydroxide
Calcium acetate
- Low correct serum calcium — use calcium based binders first
When is sucroferric oxyhydroxide most useful? Iron deficiency anemia To decrease pill burden When cost is a barrier to adherence When the patient is also hypocalcemic
To decrease pill burden
A unique side effect of sevelamer is GI upset/ nausea Diarrhea Dark stools Kidney stones
Diarrhea
Role of Vitamin D in a CKD-MBD patient
Should be used in …
- Elevated iPTH despite calcium and phosphate at goal
- Persistent hypocalcemia with hyperparathroidism
Should not be used in…
- Hypefcalcemia and/or hyperphosphatemia
Dosing for Cinacalcet (Sensipar)
Extracellular calcium sensing receptors on the parathyroid gland to enhance affinity for extracellular calcium and suppress PTH secretion for treatment of secondary hyperparathyroidism
Dose: 30mg/day orally and titration up every 2-4 weeks to MDD (180mg)
- Based on GI side effects and PTH suppression
Can cause hypoglycemia, treat Ca if <8.4 mg/dL
Compared to paricalcitol, calcitriol Causes more hypocalcemia Is more expensive Is more potent to suppress PTH Requires hepatic activation
Causes more hypercalcemica
An ESKD patient has a corrected serum calcium of 10.9mg/dL, phosphate of 4.2mg/dL, and iPTH of 800pg/mL. What medication should be used to treat their MBD? Calcitriol Doxercalciferol Calciferol Cinacalcet
Cinacalcet
- Correct calcium is slightly high, would want to use a calcimimetic which will actually lower serum calcium. Any vitamin D product will increase serum calcium and worsen their hypercalcemia
