Renal 3 Flashcards
(131 cards)
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
2
Q
When are the complications of CKD evident?
A
Can be evident as early as Stage G2
3
Q
eGFRb and complication relationship
A
Likelihood of CKD complications increases as GFR decreases
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
5
Q
On average when do pts require tx for complications?
A
Stage 3
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
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
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)
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
10
Q
Where does metolazone work?
A
Distal Convuluted Tubule
11
Q
Limitation of Loop Diuretic
A
Patients can develop resistance to loop diuretics
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
13
Q
When does furosemide resistance occur?
A
Will happen if dietary Na+ is high Na+ restriction helps overcome resistance as well
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
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)
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
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.
18
Q
When is acidosis the most prominent?
A
Most prominent in Stage 4-5 CKD
19
Q
Treatment of Metabolic Acidosis
A
Sodium bicarbonate tablets
325-500mg PO BID-TID (variable dose)
(Baking soda dissolved in water)
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)
21
Q
Severe Acidosis Tx
A
Intravenous sodium bicarbonate
Severe acidosis in hospitalized patient
Dialysis (Stage 5 CKD)
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
23
Q
Exacerbating factors of hyperK+
A
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)
25
Many pt's with hyperkalemia are...... Why?
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
26
Mild-Moderate HyperK+ range and sx
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
27
Severe HyperK+ Range and Sx
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
28
HyperK+ 1st Line Tx
Identify/correct exacerbating factors
Drugs, diet
Most CKD patients with mild hyperkalemia (~5.5 mmol/L) can be managed with dietary potassium restriction
29
Mild HyperK+ Drug Tx
Mild acute or refractory chronic hyperkalemia potassium binders (remove K+ in GI tract)
Sodium polystyrene sulfonate (Kayexalate®, Solystat®)
Patiromer (Veltassa®)
Sodium zirconium cyclosilicate (Lokelma®)
30
Kayexylate MOA
Cation exchange resin: Removes K+ ions by exchanging it for Na2+ ions
Not absorbed by the GI tract
31
Kayxelate A/e
GI: Constipation, NVD
32
Kayexlate Formulation
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
33
Kayexylate Monitoring
Monitor for hypokalmeia
34
Compare K+ binders: MOA, Dose, Onset/Duration, Safety
35
Severe HyperK+ Tx
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
36
Goal of tx for severe HyperK+
Prevent severe cardiac arrhythmia, death, correct potassium <5.5 mmol/L
37
CKD-BMD Definition
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
38
When does CKD-BMD occur? Outcomes?
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
39
CKD-BMD Mechanism
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
40
Describe the calcium-PTH-phosphorous pathway and CKD-BMD
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)
41
Diagnosis of CKD-BMD
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
42
Screening for CKD BMD Recommendation Canadian Society of Nephrology
Severe abnormalities in Ca, PO4 and PTH are uncommon in CKD G3
Recommend monitoring these parameters (and consequently initiating treatment) in CKD G4-G5
43
CKD-BMD Monitoring Summary
44
CKD-BMD Phosphate Risk
Phosphate (PO4)
Increasing serum concentrations associated with increased risk of all-cause mortality in CKD G3a-G5D
45
Prevantative Tx of Hyperphosphatemia
No benefit (and possible risk) in treatment to prevent hyperphosphatemia in patients with normal serum concentrations (only tx if high)
46
Goals of Phosphate in CKD-BMD
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)
47
Calcium Level Risks CKD-BMD
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
48
Tx of Hypocalcemia. Sx?
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)
49
Lab Tests for Calcium
Ionized calcium = “active” calcium
Total calcium = free (ionized) + calcium bound to albumin
Corrected calcium = calcium adjusted for albumin levels
50
PTH Risks CKD-BMD
Severe hyperparathyroidism (HPT) is associated with calciphylaxis, CVD, neuromuscular disturbances, and death in CKD stages 3-5D
51
Optimal PTH Levels
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)
52
PTH Treatment and Goals
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
53
Types of renal bone diseases
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
Hyperparathyroid Bone Dx Mechanism
55
Function of FGF-23 and PTH
Initially maintain serum Ca & PO4 levels
High levels lead to negative outcomes
56
FGF-23 Normal Role
Promotes PO4 excretion in kidneys
Stimulates PTH to ↑ PO4 renal excretion
Suppresses formation of calcitriol to ↓ PO4 absorption from GI tract
57
PTH Normal Role
↑ Ca reabsorption and PO4 excretion in the kidneys
↑ Ca mobilization from bone
58
Advance CKD and Hyperparathyroid Bone Disease Mechanism
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
What is calciphylaxis?
Calcification and occlusion of small blood vessels
Leads to ulceration, gangrene, secondary infection (sepsis), and is associated with a high mortality rate
60
Tx of Hyperparathyroid Bone Disease
Decrease Phosphate
Decrease PTH
61
Decrease Phosphate TX
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
Decrease PTH
Vitamin D
Calcitriol (Rocaltrol®)
Alfacalcidol (One-Alpha®)
Ergo or cholecalciferol
Calcimimetics
Cinacalcet
Parathyroidectomy
63
Restrict Dietary Phosphate
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
Phosphate BInders MOA.Counselling?
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
Calcium Based Binder Example
Calcium Carbonate
Not calcium citrate – increases aluminum absorption
66
First Line Tx Phosphate Binder
Calcium-based binders (calcium carbonate)
Usual first-line therapy (non-expensive, effective)
NOT calcium citrate – increases aluminum absorption
67
Dose Calcium based BInders
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
A/E calcium Based Binders
constipation, stomach cramps
hypercalcemia – especially if co-administered with calcitriol, high Ca dialysate (more concerning risk)
69
Aluminum or Magnesium Phosphate Binders
Marketed as OTC antacids
Not recommended for chronic use due to risk of accumulation and toxicity (NOT first line) - accumulate with kidney dysfx
70
Sevelamer Use
Useful in patients with hypercalcemia or when
not controlled with Ca-based binders
71
Sevelamer A/E and Limitation
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
Sevelamer Benefit
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
Lanathanum
Similar to sevelamer, but chewable tab
74
Sucroferric Oxyhydroxide
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
Why is vitamin D tx used?
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
Vitamin D tx risks
↑ risk of hypercalcemia & hyperphosphatemia
Causes an ↑ in FGF-23 levels
Uncertain if ↓ fractures or mortality
77
Vitamin D tx use in who
Should not be routinely used in patients not on dialysis – reserve for severe & progressive HPT on dialysis (>50) (some benefit but significant risk)
78
Vitamin D analogues examples
Calcitriol, alfacalcidiol pro-drug of calcitriol
79
Vitamin D analogue Formuylation, Dose adjustments, and A/e
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
Nutritional Vitamin D
Nutritional vitamin D (ergo- or cholecalciferol) – VIT D3
Can suppress PTH (esp. in CKD G3 (30-60) with less hyper-Ca/PO4
81
Vitamin D analogue Riskof PTH and Ca2 Levels
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
CalcimimeticsMOA?
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
Calciminetics Risk
Risk of hypocalcemia
Uncertain if ↓ fracture risk, cardiac events or mortality (studies fail to find)
84
Example of Calcimetic
Cincacelet
85
Cincalet use
Use: In dialysis patients +/- vit D therapy
($$$) – Not covered; not often used
86
Cincalet A/e.Monitoring?
nausea, vomiting, diarrhea (frequent), hypocalcemia (~75%) (acutely dangerous; QT prolongation, arrthymias, monitor Ca2+, PO4 and PTH levels)
87
Anti-resorptive examples
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
Anti-resorptive tx Use
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
Hyperparathyroid Bone Disease TX Monitoring
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
Parathyroidectomy
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
Adynamic Bone Dx
Low bone turnover disease
Lack of osteoblast/osteoclast stimulation → No bone remodeling
92
Adynamic Bone Dx Riskand where does it resulty from?
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
Tx Adynamic Bone Dx
Stop vitamin D supplementation
94
Osteomalacia.Causes, Outcomes?
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
Tx Osteomalcia
Stop aluminum-containing phosphate binders
96
Valvular calcificationseen when? How? Worry?
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
What lab value is normally looked at in CKD for evaluating anemia?
Transferrin Saturation (TSAT) – transfers iron to bone marrow (measure of the availability of iron to support erythropoiesis)
98
Main Type of Anemia in CKD and occurs when
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
Anemia Defined As....
Anemia = Hgb < 130 g/L in males and < 120 g/L in females
100
Why does anemia occur in CKD?
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
Iron Deficeinecy in What Stage and Why?
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
Typesof Iron Deficiency
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
Anemia Sx
Weakness, lethargy, malaise
Shortness of breath on exertion
Impaired memory and concentration
Feeling cold (quite bothersome and affect QOL)
104
Why tx anemia?
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
Pros and Cons of ESA
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
Goals for tx of anemia
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
Tx of anemia
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
Initiation of ESA Tx
Avoid initiating ESA therapy until all correctable causes of anemia (e.g., iron deficiency) have been addressed
109
Whatshould be initiated with ESA tx?
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
Iron Supplementation Formulation in CKD for....
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
Iron Formulations and Dose
Ferrous gluconate
Ferrous sulfate
Ferrous fumarate
Iron polysacchride (Feramax®)
~100-200mg elemental iron daily, in 2-3 divided doses
112
Iron A/e and D.I.
stomach cramping, constipation, nausea, vomiting, diarrhea, dark stools, heartburn, staining of teeth (liquid)
Drug interactions – calcium, etc.
113
When to use IV iron?
Intolerant, unresponsive, non-compliant to oral iron
Recommended 1st line in hemodialysis (HD) patients
114
IV Iron Dosing regimen
All are administered 1-3 times weekly until replete, then prn
115
A/e Injectable iron
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
EPO Function
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
ESA Tx Options
Epoetin alfa (Eprex®)
Resembles endogenous erythropoeitin
Shorter half-life
Darbepoetin alfa (Aranesp®)
Second-generation molecule
Longer half-life – less frequent dosing, advantage
118
ESA Formulation, Counselling, Coverage
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
Goals of ESA Tx
Reach Hgb target (~110 g/L) within 2 to 4 months, then maintain
Gradual ↑ Hgb by ~10 g/L every month, to target
120
Dose adjustments ESA
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
ESA Tx Monitoring
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
ESA A/e
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
ESA Main ISsue
Incomplete or lack of response to ESAat high doses
124
Causes of ESA Resistance
Iron deficiency
Vitamin deficiency (e.g., B12, folate)
Bleeding
Inflammation/infection
Aluminum toxicity
Inadequate dialysis
125
Tx of ESA resistance
Treat underlying cause if it can be corrected
Avoid ESA doses that are > 4x the initial dose
126
HIF-PHI MOA
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
HIF-PHI A/e
possible risk of malignancy due to its mechanism, long term risks not well studied
128
Tx of Neurological Complications
Dialysis or change dialysis prescription
129
Chronic Pruritis
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
Tx Chronic Pruritis
gabapentinoids, capsaicin, sertraline, sedating antihistamines, Uremol lotion
131
Difelikefalin
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%)
