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PHAR 255 Exam 1 > Renal 3 > Flashcards

Renal 3 Flashcards

1
Q

What are the complications of CKD?

A

Directly related to progressive inability of the kidney to perform its normal functions:

Regulate fluid, electrolyte, and acid-base balance
Remove metabolic waste products from blood
Removal of foreign chemicals from blood
Regulation of blood pressure
Secretion of hormones

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2
Q

When are the complications of CKD evident?

A

Can be evident as early as Stage G2

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3
Q

eGFRb and complication relationship

A

Likelihood of CKD complications increases as GFR decreases

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4
Q

When are lifestyle interventions such as….. required? Every pt?

A

Lifestyle, dietary, and pharmacological interventions required (Stage G3-5 CKD)

Complications might not occur at the same rate or to the same degree in patients within each CKD category

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5
Q

On average when do pts require tx for complications?

A

Stage 3

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6
Q

Sodium and Water Imbalance Cause, Sx, and Stage?

A

Progressive loss of ability of the kidneys to excrete excess water and sodium

Leads to weight gain, hypertension (RAAS activation), peripheral and pulmonary edema

Onset of symptoms usually Stage 4 CKD

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7
Q

TX of Na+ and H20 Imbalance

A

Sodium and water restriction

90mmol sodium (<2g) and 1-2L of fluid per day

Diuretics: Furosemide +/- metolazone

Stage 5: Dialysis

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8
Q

Diuretics for Na+ and H20 Imbalance

A

Thiazides less effective for diuresis once GFR < 30 ml/min (Can still have effect on blood pressure tho)

Furosemide preferred

40 mg PO daily (variable doses!)

Becomes less effective as kidney function declines – more frequent, high doses may be required (does not reach drug concentrations high enough in the kidney to have its effect)

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9
Q

FeNa Normal, Tzd, Loop

A

FeNa  Normally 1% in healthy individual
Thiazide  3-5%
Loop Diuretic  20-25% (excreted 4-5x more Na+ than thiazides)  More effective diuresis

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10
Q

Where does metolazone work?

A

Distal Convuluted Tubule

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11
Q

Limitation of Loop Diuretic

A

Patients can develop resistance to loop diuretics

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12
Q

Describe why loops are often combined with tzds?

A

Furosemide works on hoop of henle to block reabsorption of Na+ –> More Na+ in kidney, more urine production

  • There Can be a compensating mechanism in distal convulted tubule –> Increase Na+ uptake in distal tubule
  • Use thiazid elike diuretic like metolazone (blocks at distal tubule)
  • Effects are synergistic with one another –> Increase Na+ excretion and therefore H2O
  • Dietray Na+ restriction also beneficial here
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13
Q

When does furosemide resistance occur?

A

Will happen if dietary Na+ is high  Na+ restriction helps overcome resistance as well

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14
Q

What may be added to furosemide?

A

May add metolazone (or other thiazide)

Synergistic diuresis with furosemide due to natriuretic action at distal tubule

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15
Q

Monitoring of Diuretics.When?

A

Electrolytes (all but specifically K+)
Na+, K+, Cl-, HCO3, Mg, Ca

q1-2 weeks initially, every 3-6 months when stable

Clinical signs and symptoms of dehydration (volume depleted) –> Especially during acute illness (SADMANS)

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16
Q

Metabolic Acidosis Definition.Cause?

A

Characterized by a ↓ in the pH of the blood (acidemia) and a ↓ in serum bicarbonate levels (<22 mmol/L)
May be due to impaired excretion of acids and/or reabsorption of bicarbonate

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17
Q

Metabolic Acidosis in CKD mechanism

A

In CKD, can usually still acidify the urine (e.g., secrete H+), but the kidneys produce less ammonia to buffer the H+ –> leads to the retention of H+

Ammonia (NH3) + H+ –> Ammonium (NH4+) – excreted in urine

Exacerbated by hyperkalemia – further depresses NH3 production (correcting hyperK+ may helt correct acidosis to an extent)

Result: Reduction of bicarbonate levels in attempt to maintain blood pH –> As progresses, start to see acid being buffered by protein in mucle (muscle wasting), and by phosphates in bone –> brittle bones, fractures, etc.

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18
Q

When is acidosis the most prominent?

A

Most prominent in Stage 4-5 CKD

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19
Q

Treatment of Metabolic Acidosis

A

Sodium bicarbonate tablets

325-500mg PO BID-TID (variable dose)

(Baking soda dissolved in water)

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20
Q

Benefits of Sodium Bicarb and Cautions

A

Benefits: ↓ CKD progression, improved nutritional status
Concern: Possibility of sodium loading (not to same extent as NaCl)

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21
Q

Severe Acidosis Tx

A

Intravenous sodium bicarbonate
Severe acidosis in hospitalized patient
Dialysis (Stage 5 CKD)

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22
Q

HyperK+ Definition, Stage, and Cause

A

Inability to maintain a normal serum potassium of 3.5-5.0 mmol/L
Stage 4-5 CKD (v. mild in Stage 3)
Primarily due to decreased potassium excretion

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23
Q

Exacerbating factors of hyperK+

A
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24
Q

Describe the relationhsip between metabolic acidosis and hyperK+

A

Metabolic ACidosis –> excess H+ ions

Exchange at cellular level –> exchange K+ for H+ to improve pH of the blood

K+ ions in the blood that results in hyperkalmeia (more of it moved from the tissues into the the blood stream)

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25
Q

Many pt’s with hyperkalemia are…… Why?

A

Many patients are asymptomatic, especially with chronic hyperkalemia (adapt)

In response to continuously elevated K+ in CKD, the body finds ways to eliminate K+ (often the GI tract) –> Can maintain levels for a while through other mechanisms

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26
Q

Mild-Moderate HyperK+ range and sx

A

Mild to Moderate: (5.1 -7mmol/L)

Non specific sx such as Weakness, confusion, muscle & respiratory paralysis, ECG changes (6 - 7 mmol/L) such as peaked T-waves

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27
Q

Severe HyperK+ Range and Sx

A

Severe: (>7 mmol/L)

ECG changes (7-8 mmol/L) widened QRS complex, small amplitude P wave; (8-9 mmol/L) sinus waves; (>9 mmol/L) heart block, ventricular tachycardia, sudden cardiac death

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28
Q

HyperK+ 1st Line Tx

A

Identify/correct exacerbating factors
Drugs, diet

Most CKD patients with mild hyperkalemia (~5.5 mmol/L) can be managed with dietary potassium restriction

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29
Q

Mild HyperK+ Drug Tx

A

Mild acute or refractory chronic hyperkalemia potassium binders (remove K+ in GI tract)

Sodium polystyrene sulfonate (Kayexalate®, Solystat®)
Patiromer (Veltassa®)
Sodium zirconium cyclosilicate (Lokelma®)

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30
Q

Kayexylate MOA

A

Cation exchange resin: Removes K+ ions by exchanging it for Na2+ ions
Not absorbed by the GI tract

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31
Q

Kayxelate A/e

A

GI: Constipation, NVD

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32
Q

Kayexlate Formulation

A

Oral powder (15g = 4 level tsp) or liquid suspension
Can be given PO or as rectal enema
15-60g daily-QID

Oral route most common - lowest GI toxicity risk

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33
Q

Kayexylate Monitoring

A

Monitor for hypokalmeia

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34
Q

Compare K+ binders: MOA, Dose, Onset/Duration, Safety

A
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35
Q

Severe HyperK+ Tx

A

Severe hyperkalemia (>7 mmol/L or ECG changes) → Medical Emergency!

Calcium gluconate IV (to stabilize myocardium)
Glucose plus human regular insulin
Sodium bicarbonate IV (*only if metabolic acidosis)
Salbutamol via nebulizer
Kayexalate® 30-60g PO q4h until K+ normalized

Dialysis (Stage 5 CKD or severe acute hyperkalemi

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36
Q

Goal of tx for severe HyperK+

A

Prevent severe cardiac arrhythmia, death, correct potassium <5.5 mmol/L

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37
Q

CKD-BMD Definition

A

A systemic disorder of mineral and bone metabolism due to CKD manifested by either one, or a combination of, the following:

Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism (i.e., minerals)

Abnormalities in bone turnover, mineralization, volume, linear growth, or strength (i.e., bone metabolism)

Vascular or other soft tissue calcification

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38
Q

When does CKD-BMD occur? Outcomes?

A

Changes in bone and mineral metabolism begin in stage 3 CKD (GFR <60 ml/min) and progress

Bone abnormalities present in nearly all dialysis patients

Outcomes: bone pain, fractures, CVD, death

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39
Q

CKD-BMD Mechanism

A

Increased serum phosphate (PO4) due to decreased kidney excretion
–> Calcium binds to excess phosphate in the blood

Decreased serum calcium (Ca) due to decreased GI absorption due to decreased Vitamin D (also due to binding with phosphate)
–> Why? Because the final synthesis step to active calcitriol occurs in the kidney

Negative feedback between serum Ca2+ and parathyroid galnd/PTH

Negative feedback leads to increased parathyroid hormone (PTH) which ultimately depletes Ca2+ from the bone

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40
Q

Describe the calcium-PTH-phosphorous pathway and CKD-BMD

A

Because we a reduction in calcitriol production with impaired kidney production, less Ca2+ reabsorbed from the gut –:> Increase activation of PTH and ultimately deplet Ca2+ from the bone (why it is a bone dx in the end)

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41
Q

Diagnosis of CKD-BMD

A

Biochemical abnormalities
–> Serum calcium, phosphorus, PTH, alkaline phosphatase (ALP)
–> Help predict underlying bone turnover

Bone abnormalities

-Definitive diagnosis requires a bone biopsy (not routinely used)
- Bone Mineral Density (BMD or DXA) (predict fracture risk and osteoporosis)
–> Does not predict the type of renal osteodystrophy (not routinely done in those with CKD)

Vascular calcification (increasingly worried about in regards to mortality of CKD pt’s)
E.g., echocardiogram to identify valvular calcification

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42
Q

Screening for CKD BMD Recommendation Canadian Society of Nephrology

A

Severe abnormalities in Ca, PO4 and PTH are uncommon in CKD G3

Recommend monitoring these parameters (and consequently initiating treatment) in CKD G4-G5

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43
Q

CKD-BMD Monitoring Summary

A
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44
Q

CKD-BMD Phosphate Risk

A

Phosphate (PO4)

Increasing serum concentrations associated with increased risk of all-cause mortality in CKD G3a-G5D

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45
Q

Prevantative Tx of Hyperphosphatemia

A

No benefit (and possible risk) in treatment to prevent hyperphosphatemia in patients with normal serum concentrations (only tx if high)

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46
Q

Goals of Phosphate in CKD-BMD

A

Lower levels toward normal range (0.81-1.45 mmol/L) in patients with overt hyperphosphatemia

Goals:
ND-CKD > 1.49 mmol/L
HD/PD-CKD > 1.78 mmol/L (dialysis; all will require tx)

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47
Q

Calcium Level Risks CKD-BMD

A

Low levels contribute to secondary hyperparathyroidism and renal osteodystrophy, and prolong the QT interval

Elevated serum concentrations associated with higher mortality and risk of CV events in CKD patients

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48
Q

Tx of Hypocalcemia. Sx?

A

Mild and asymptomatic hypocalcemia may not require treatment

Severe or symptomatic hypocalcemia (e.g., numbness, tingling, myalgia) should be corrected BUT avoid hypercalcemia (risks are acute)

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49
Q

Lab Tests for Calcium

A

Ionized calcium = “active” calcium

Total calcium = free (ionized) + calcium bound to albumin

Corrected calcium = calcium adjusted for albumin levels

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50
Q

PTH Risks CKD-BMD

A

Severe hyperparathyroidism (HPT) is associated with calciphylaxis, CVD, neuromuscular disturbances, and death in CKD stages 3-5D

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51
Q

Optimal PTH Levels

A

Optimal PTH level is unknown in CKD patients not on dialysis

Modest increases may be an appropriate response to worsening kidney function (to overcome PTH resistance and to ↓ PO4)

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52
Q

PTH Treatment and Goals

A

PTH should be progressively rising or persistently high in order to initiate treatment (specifically in pt’s not on dialysis)

Target in CKD G5D: PTH 2-9x upper limit of normal (in dialysis)

Upper limit of normal is around 8; do not treat until around 50 or higher; significantly higher levels

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53
Q

Types of renal bone diseases

A

Hyperparathyroid bone disease (high bone turnover disease) Most Common of the 3
↑ bone turnover, ↑ PTH levels (secondary HPT)

Adynamic bone disease (low bone turnover disease)
↓ bone turnover, normal or ↓ PTH levels

Osteomalacia
↓ vitamin D activity

54
Q

Hyperparathyroid Bone Dx Mechanism

A
55
Q

Function of FGF-23 and PTH

A

Initially maintain serum Ca & PO4 levels

High levels lead to negative outcomes

56
Q

FGF-23 Normal Role

A

Promotes PO4 excretion in kidneys
Stimulates PTH to ↑ PO4 renal excretion
Suppresses formation of calcitriol to ↓ PO4 absorption from GI tract

57
Q

PTH Normal Role

A

↑ Ca reabsorption and PO4 excretion in the kidneys
↑ Ca mobilization from bone

58
Q

Advance CKD and Hyperparathyroid Bone Disease Mechanism

A

In advanced CKD, the kidneys fail to respond to FGF-23 and PTH

Ca and PO4 abnormalities worsen
Sustained HPT leads to:

1) Persistent calcium resorption from bone (i.e., high bone turnover) leads to osteitis fibrosis cystica
–> Bone pain and fragility
–> Bone marrow fibrosis (can lead to EPO resistance)
–> Also, refractory pruritis

2) Parathyroid gland hyperplasia & resistance to exogenous calcitriol therapy

59
Q

What is calciphylaxis?

A

Calcification and occlusion of small blood vessels

Leads to ulceration, gangrene, secondary infection (sepsis), and is associated with a high mortality rate

60
Q

Tx of Hyperparathyroid Bone Disease

A

Decrease Phosphate

Decrease PTH

61
Q

Decrease Phosphate TX

A

Restrict dietary phosphate

Phosphate binders
–> Calcium products
–> Aluminum or magnesium binders
–> Sevelamer (Renagel®)
–>: Lanthanum (Fosrenol®)
–> Sucroferric oxyhydroxide (Velphoro®)

Intensified dialysis schedules (will also eliminate phosphate but not to the extent needed)

62
Q

Decrease PTH

A

Vitamin D
Calcitriol (Rocaltrol®)
Alfacalcidol (One-Alpha®)
Ergo or cholecalciferol
Calcimimetics

Cinacalcet

Parathyroidectomy

63
Q

Restrict Dietary Phosphate

A

Natural phosphates are less bioavailable and may impact serum PO4 levels less vs. packaged sources

Aggressive PO4 restriction can lead to inadequate intake of other nutrients – especially protein. Requires involvement of a dietician

64
Q

Phosphate BInders MOA.Counselling?

A

All work by binding to dietary PO4 in the GI tract –> eliminated in feces

Must be taken at the beginning of a meal (within the first few bites)

Typically have to be taken multiple times per day with meals (and potentially also snacks)

Patients still require dietary PO4 restriction

65
Q

Calcium Based Binder Example

A

Calcium Carbonate
Not calcium citrate – increases aluminum absorption

66
Q

First Line Tx Phosphate Binder

A

Calcium-based binders (calcium carbonate)
Usual first-line therapy (non-expensive, effective)
NOT calcium citrate – increases aluminum absorption

67
Q

Dose Calcium based BInders

A

KDIGO 2017: Limit the dose of calcium-based binders (unspecified), even in patients without hypercalcemia or other risk factors

KDOQI 2020: Max 800-1000mg elemental/day from all sources (incl. diet)

68
Q

A/E calcium Based Binders

A

constipation, stomach cramps
hypercalcemia – especially if co-administered with calcitriol, high Ca dialysate (more concerning risk)

69
Q

Aluminum or Magnesium Phosphate Binders

A

Marketed as OTC antacids

Not recommended for chronic use due to risk of accumulation and toxicity (NOT first line) - accumulate with kidney dysfx

70
Q

Sevelamer Use

A

Useful in patients with hypercalcemia or when
not controlled with Ca-based binders

71
Q

Sevelamer A/E and Limitation

A

Adverse effects: ++ GI tolerability problems (worse GI effects)
Expensive, EDS only for ESRD where Ca or Al
binders are inappropriate or not tolerated (dialysis or not receiving dialysis can get coverage)

72
Q

Sevelamer Benefit

A

Less likely to attribute to hypercalcemia; hoped it would improve CV endpoints as not supplementing Ca2+ (Trials: Has not panned out to show their is a demonstrate in reducing these endpoints (vasculaer calcification) compared to Ca2+)

73
Q

Lanathanum

A

Similar to sevelamer, but chewable tab

74
Q

Sucroferric Oxyhydroxide

A

Newest calcium-free binder
Iron-based, but has negligible contribution to iron intake
Adverse effects: Can cause black stools and nausea (due to the iron)
EDS for ESRD

75
Q

Why is vitamin D tx used?

A

Helps suppress PTH levels
Stimulates absorption of Ca in the GI tract (neg. feedback to ↓ PTH)
Directly acts on parathyroid gland to suppress PTH synthesis

76
Q

Vitamin D tx risks

A

↑ risk of hypercalcemia & hyperphosphatemia
Causes an ↑ in FGF-23 levels
Uncertain if ↓ fractures or mortality

77
Q

Vitamin D tx use in who

A

Should not be routinely used in patients not on dialysis – reserve for severe & progressive HPT on dialysis (>50) (some benefit but significant risk)

78
Q

Vitamin D analogues examples

A

Calcitriol, alfacalcidiol pro-drug of calcitriol

79
Q

Vitamin D analogue Formuylation, Dose adjustments, and A/e

A

IV option available: given 3x weekly with dialysis (pulse therapy)

Dose adjustments based on serum Ca, PO4, PTH levels

Adverse effects: Hypercalcemia, hyperphosphatemia

Serum Ca and PO4 levels should be in range prior to initiating therapy (add a phosphate binder first before calcitriol tx)

80
Q

Nutritional Vitamin D

A

Nutritional vitamin D (ergo- or cholecalciferol) – VIT D3
Can suppress PTH (esp. in CKD G3 (30-60) with less hyper-Ca/PO4

81
Q

Vitamin D analogue Riskof PTH and Ca2 Levels

A

Elevated PTH levels are less acutely dangerous than acute high or lows of calcium -

If dvelop hypercalcemia, stop calcitriol  Do not care if PTH rises acutely (more worried about chronic rise)

Quite symptomatic with hypercalcemia
Sacrifice PTH at the expense of controlling Ca2+ levels

If only phosphate increased and not Ca2+, more likely to make changes to diet or binders

82
Q

CalcimimeticsMOA?

A

Increase sensitivity of the parathyroid gland to already circulating calcium in the body
Directly lowers PTH concentrations without increasing serum Ca or PO4 (useful in hypercalcemia) – Do not increase absorption of Ca2+ and PO4

83
Q

Calciminetics Risk

A

Risk of hypocalcemia

Uncertain if ↓ fracture risk, cardiac events or mortality (studies fail to find)

84
Q

Example of Calcimetic

A

Cincacelet

85
Q

Cincalet use

A

Use: In dialysis patients +/- vit D therapy
($$$) – Not covered; not often used

86
Q

Cincalet A/e.Monitoring?

A

nausea, vomiting, diarrhea (frequent), hypocalcemia (~75%) (acutely dangerous; QT prolongation, arrthymias, monitor Ca2+, PO4 and PTH levels)

87
Q

Anti-resorptive examples

A

Denosumab (Prolia®)
Poses risk of hypocalcemia – requires monitoring

Bisphosphonates (e.g., alendronate)
May induce/exacerbate low bone turnover (or adynamic bone disease)
Use with caution at CrCl <35 mL/min (rarely nephrotoxic)
Have not been studied at lower kidney function; do have theoretical risk of AKI

88
Q

Anti-resorptive tx Use

A

May ↑ BMD and ↓ fracture risk

Might use in CKD-MBD if low BMD and/or fragility fracture (particularly if GFR >30 mL/min, CKD G3a-b)

CSN 2020 recommends against routine use in G4-5

89
Q

Hyperparathyroid Bone Disease TX Monitoring

A

Monitoring is important

With all treatments, monitor serum calcium, phosphorus, and PTH levels at least monthly (more frequent at the beginning)

Many drug interactions with iron, etc. (particularly with binders, iron in anemia)

90
Q

Parathyroidectomy

A

Partial removal of parathyroid gland

Reserved for patients where PTH, calcium, phosphate abnormalities not medically correctable (usually Stage 5 CKD)

Post-op: “hungry bones syndrome” – the building of bone increases drastically after removal; uses up Ca2+, PO4, Mg2+ and result in hypocalcemia and hypophosphatemia

91
Q

Adynamic Bone Dx

A

Low bone turnover disease
Lack of osteoblast/osteoclast stimulation → No bone remodeling

92
Q

Adynamic Bone Dx Riskand where does it resulty from?

A

Associated with more fractures and calcification (when serum Ca2+ if not taken up by bone, deposits elsewhere, can go to heart valves)

Results from calcium and vitamin D supplementation and oversuppression of PTH (likely an overtreatment of 2° hyperparathyroidism) – MAIN CAUSE

93
Q

Tx Adynamic Bone Dx

A

Stop vitamin D supplementation

94
Q

Osteomalacia.Causes, Outcomes?

A

Inadequate mineralization of calcium and phosphate
“Softening” of bone

Due to reduced production and action of calcitriol

Can also result from aluminum deposition in bone
- Aluminum phosphate binders
- Aluminum replacing Ca2+ in bone structure, reduced by no longer aluminum based binders

Can result in fractures, myopathy, neurological deficits, dementia, seizures (aluminum also in serum)

95
Q

Tx Osteomalcia

A

Stop aluminum-containing phosphate binders

96
Q

Valvular calcificationseen when? How? Worry?

A

Seen in high and low bone turnover disease (not taken up in bone, can go elsewhere)

Vascular smooth muscle cells change into an osteoblast-like cell

Increased prevalence of cardiovascular calcification in patients with CKD

Coronary arteries, heart valves

Not yet used as reliable surrogate for CV outcomes

97
Q

What lab value is normally looked at in CKD for evaluating anemia?

A

Transferrin Saturation (TSAT) – transfers iron to bone marrow (measure of the availability of iron to support erythropoiesis)

98
Q

Main Type of Anemia in CKD and occurs when

A

Normochromic (normal red color), normocytic (normal cell size) anemia occurring in Stage 3-5 CKD

Hypo-proliferative (inadequate production) - ↓ reticulocytes (due to lack of EPO production)

Nearly universal in end-stage renal disease (ESRD)

99
Q

Anemia Defined As….

A

Anemia = Hgb < 130 g/L in males and < 120 g/L in females

100
Q

Why does anemia occur in CKD?

A

Results primarily from loss of erythropoeitin generation by the kidneys

Also due to ↓ RBC half-life in uremia (120 days to 60), blood losses (lab tests, dialysis, GI bleeding), bone marrow fibrosis (where RBC’s are made) (due to HPT), or iron, folate, vit B12 deficiencies

101
Q

Iron Deficeinecy in What Stage and Why?

A

Iron deficiency

Common in stage 4-5 CKD due to ↓ GI absorption, inflammation by urea, frequent blood tests, blood loss in HD

↑ iron demands with ESA therapy

102
Q

Typesof Iron Deficiency

A

Absolute iron deficiency - ↓ TSAT, ↓ ferritin
Total iron stores in the body are low

Functional iron deficiency - ↓ TSAT, normal or ↑ ferritin
- Might be anemia of chronic disease, and adding iron may not always help
- More helpful to correct the underlying cause (e.g. dialysis of significant uremia)

103
Q

Anemia Sx

A

Weakness, lethargy, malaise
Shortness of breath on exertion
Impaired memory and concentration
Feeling cold (quite bothersome and affect QOL)

104
Q

Why tx anemia?

A

Decreases patient quality of life (improve QOL)
A known risk factor for adverse outcomes (e.g., LVH, CVD)

Reduced O2 carrying capacity chronically, it causes tachycardia and changes to heart

105
Q

Pros and Cons of ESA

A

Pros:
Practically eliminated need for blood transfusions
↓ fatigue, improves symptoms of anemia (QofL)

Cons:
Failed to improve CV outcomes
Associated with increased risk of stroke and other thromboembolic events
Especially if treated to higher Hgb target values

106
Q

Goals for tx of anemia

A

Hemoglobin
Target: 100-110 g/L (usually initiate ESA when <90g/L)

TSAT
Maintain > 20%
Avoid iron overload

Serum Ferritin
>100mcg/L (non-dialysis CKD and PD) and >200mcg/L (HD)

Normal serum Vitamin B12 and folic acid levels (also causes of anemia)

107
Q

Tx of anemia

A

Correct blood loss (e.g., treat GI bleeding)

Replace vitamin, iron deficiencies

Erythropoiesis-Stimulating Agent (ESA) Therapy

Dialysis to correct uremia (as applicable) – contributes to inflammation and inhibits erythropoiesis to an extent

Blood transfusions if required – LAST RESORT (ESRD many on transplant; antibodies that introduced in blood transfusions make them not eligible for transplant)

108
Q

Initiation of ESA Tx

A

Avoid initiating ESA therapy until all correctable causes of anemia (e.g., iron deficiency) have been addressed

109
Q

Whatshould be initiated with ESA tx?

A

May correct anemia without the need for ESA therapy if iron deficiency is present

Most patients receiving ESA therapy will require iron supplementation (increased production)

Iron supplementation may further ↑ Hgb or allow a ↓ in the ESA dose (even when TSAT and ferritin are already at target) – trial even if iron levels in range

Questionable benefit in functional iron deficiency

110
Q

Iron Supplementation Formulation in CKD for….

A

For CKD patients not on dialysis or using PD:

a trial of oral iron is suggested for 1 to 3 months prior to initiating IV therapy (not on dialysis)

A lot of Pt’s are successful and do fine with po tx

In HD patients (and many PD patients), IV route is required

111
Q

Iron Formulations and Dose

A

Ferrous gluconate
Ferrous sulfate
Ferrous fumarate
Iron polysacchride (Feramax®)

~100-200mg elemental iron daily, in 2-3 divided doses

112
Q

Iron A/e and D.I.

A

stomach cramping, constipation, nausea, vomiting, diarrhea, dark stools, heartburn, staining of teeth (liquid)

Drug interactions – calcium, etc.

113
Q

When to use IV iron?

A

Intolerant, unresponsive, non-compliant to oral iron
Recommended 1st line in hemodialysis (HD) patients

114
Q

IV Iron Dosing regimen

A

All are administered 1-3 times weekly until replete, then prn

115
Q

A/e Injectable iron

A

Generally well-tolerated (no GI tolerability issues)

Hypersensitivity reactions → anaphylaxis, shock
Primarily an issue with iron dextran (core that surround sthe iron, 1/100 pt’s – close monitoring – dc)

Hypotension (can be minimized by decreasing the rate of infusion) – Long period of time
Infection

116
Q

EPO Function

A

Hormone produced by kidney cells when they sense decreased blood oxygenation

Stimulates the development and maturation of red blood cells

Increase oxygen-carrying capacity of the blood

Restore tissue oxygenation

Production becomes deficient as CKD progresses

117
Q

ESA Tx Options

A

Epoetin alfa (Eprex®)
Resembles endogenous erythropoeitin
Shorter half-life

Darbepoetin alfa (Aranesp®)
Second-generation molecule
Longer half-life – less frequent dosing, advantage

118
Q

ESA Formulation, Counselling, Coverage

A

Available as single use pre-filled syringes
Refrigerate
Covered by SK drug plan (EDS) for CKD pre-dialysis and by SAIL for all dialysis patients

119
Q

Goals of ESA Tx

A

Reach Hgb target (~110 g/L) within 2 to 4 months, then maintain
Gradual ↑ Hgb by ~10 g/L every month, to target

120
Q

Dose adjustments ESA

A

If Hgb rise is inadequate (<10 g/L) after 4 weeks ↑ dose by ~25%

If Hgb rise is excessive (>10g/L) in 2 weeks ↓ dose by ~25%

Do not adjust dose more than every 1 to 2 months, because of delay in changes to Hgb levels (takes 2-6 weeks)

Lag until we notice the benefit; so don’t change dose too quickly

121
Q

ESA Tx Monitoring

A

Serum iron, total iron binding capacity, iron saturation, ferritin: every 1-3 months

Hemoglobin: every 1-2 week initially, then monthly

Hgb > 100 g/L (non-HD) or > 110 g/L (HD) : hold or ↓ dose

122
Q

ESA A/e

A

Well-tolerate
Hypertension (5-24%) – dose-dependent
Flu-like symptoms (transient)
Thrombosis – HD access site, VTE (5-10%)
STROKE, MI, death –> avoid Hgb >110g/L
Pure Red Cell Aplasia (PRCA) (<1%) – where the bodies form antibodies against endogenous EPO; life threatening

123
Q

ESA Main ISsue

A

Incomplete or lack of response to ESAat high doses

124
Q

Causes of ESA Resistance

A

Iron deficiency
Vitamin deficiency (e.g., B12, folate)
Bleeding
Inflammation/infection
Aluminum toxicity
Inadequate dialysis

125
Q

Tx of ESA resistance

A

Treat underlying cause if it can be corrected
Avoid ESA doses that are > 4x the initial dose

126
Q

HIF-PHI MOA

A

Inhibit enzyme that degrades hypoxia-inducible factor = Improves iron mobilization into serum, ↑ endogenous EPO production, which ↑ Hgb (without causing a spike in EPO)

Daprodustat - tx of anemia for pt’s recieving dialysis

127
Q

HIF-PHI A/e

A

possible risk of malignancy due to its mechanism, long term risks not well studied

128
Q

Tx of Neurological Complications

A

Dialysis or change dialysis prescription

129
Q

Chronic Pruritis

A

Affects ~40% of patients with ESRD

Generalized, and can affect parts of or whole body

Complications: ulcers, infection, QofL, sleep

No clear cause, making treatment a challenge
(Attributed to: High PTH PO4 levels, high urea levels)

130
Q

Tx Chronic Pruritis

A

gabapentinoids, capsaicin, sertraline, sedating antihistamines, Uremol lotion

131
Q

Difelikefalin

A

Peripheral kappa opioid receptor agonist

Approved by Health Canada (Feb ‘23) for tx of moderate to severe pruritis associated with HD in adults with CKD

RCT: clinically significant ↓ in itch, 52% vs. 31% with placebo

A/E: dizziness (6.8% vs. 3.8%), somnolence (4.2% vs. 2.4%), mental status change (3.3% vs. 1.4%)

PHAR 255 Exam 1 (8 decks)

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