Kidney Disorders 3 Flashcards
CKD complications
1
Q
What are the complications of CKD related to?
A
the progressive inability of the kidney to perform its functions
-fluid, electrolyte, acid-based balance
-remove metabolic waste products
-remove foreign chemicals
-regulate blood pressure
-secrete hormones
2
Q
What are the complications of CKD?
A
fluid and electrolyte abnormalities
-sodium and water imbalance
-metabolic acidosis
-hyperkalemia
mineral bone disease
anemia
other: CV, GI, neurological
3
Q
What increases the likelihood of CKD complications?
A
decreasing GFR
-can be evident as early as stage 2
4
Q
How does sodium and water imbalance arise in CKD?
A
progressive loss of ability of kidneys to excrete excess water and sodium
5
Q
What does sodium and water imbalance lead to in CKD?
A
weight gain
hypertension
peripheral and pulmonary edema
6
Q
When do you typically see the onset of symptoms due to water and sodium imbalance in CKD?
A
stage 4
7
Q
What is the treatment of sodium and water imbalance in CKD?
A
sodium and water restriction
- < 2g of sodium, 1-2L of fluid/day
-diuretics: furosemide +/- metolazone
-stage 5: dialysis
8
Q
Why is furosemide preferred for sodium and water retention in CKD?
A
thiazides are less effective for diuresis once GFR < 30ml/min
9
Q
When would you consider adding metolazone for sodium and water retention in CKD?
A
loop diuretic resistance
-synergistic with loops due to natriuretic action at distal tubule
10
Q
Describe proper diuretic monitoring.
A
electrolytes
-Na+, K+, Cl-, HCO3, Mg, Ca
-q1-2 weeks initially, q3-6 months when stable
signs and symptoms of dehydration
-especially acute illness (SADMANS)
11
Q
What is metabolic acidosis?
A
decrease in pH of the blood and a decrease in sodium bicarbonate (< 22mmol/L)
12
Q
Describe metabolic acidosis in CKD.
A
impaired excretion of acids and/or reabsorption of bicarb
-can still acidify the urine but kidneys produce less ammonia to buffer H+=retention of H+
-exacerbated by hyperkalemia (depresses NH3 production)
result: retained acid is buffered by bicarb, protein in muscle, and phosphate in bone
most prominent in stage 4-5
13
Q
What is the treatment of metabolic acidosis in CKD?
A
sodium bicarbonate tablets
-325-500mg po BID-TID
14
Q
What are the benefits of sodium bicarbonate treatment for metabolic acidosis in CKD?
A
delays CKD progression
improves nutritional status
15
Q
What is the concern with sodium bicarbonate treatment for metabolic acidosis in CKD?
A
sodium loading
16
Q
What is hyperkalemia?
A
inability to maintain normal serum potassium of 3.5-5.0mmol/L
-due to decreased excretion
17
Q
What are the exacerbating factors for hyperkalemia in CKD?
A
metabolic acidosis
excessive dietary intake
potassium sparing diuretics
ACEI/ARB
NSAIDs
18
Q
True or false: many patients with hyperkalemia are symptomatic
A
false
19
Q
What is the treatment of hyperkalemia in CKD?
A
identify/correct exacerbating factors
most CKD patients with mild hyperkalemia can be managed with dietary restrictions
mild acute or refractory chronic hyperkalemia–> binders
-sodium polystyrene sulfonate
-patiromer
-sodium zirconium cyclosilicate
20
Q
What is the MOA of Kayexalate?
A
cation exchange resin
-removes K+ ions by exchanging it
not absorbed by GI tract
21
Q
What are the adverse effects of Kayexalate?
A
GI: constipation, NVD
22
Q
Differentiate between the different binders based on MOA.
A
sodium polystyrene sulfonate
-nonspecific cation binding (Na+ for K+)
sodium zirconium cyclosilicate
-selective K+ binding (Na+ for K+)
patiromer
-nonspecific cation binding (Ca2+ for K+)
23
Q
Which binder has the fastest onset of action?
A
sodium zirconium cyclosilicate
24
Q
Which binder can be administered rectally?
A
sodium polystyrene sulfonate
25
Differentiate the binders based on their different adverse effects.
sodium polystyrene sulfonate
-GI (intestinal necrosis)
sodium zirconium cyclosilicate
-edema
patiromer
-constipation
26
What is the treatment of severe hyperkalemia?
calcium gluconate IV (stabilize myocardium)
glucose + regular insulin
if metabolic acidosis: sodium bicarb IV
salbutamol via nebulizer
kayexalate 30-60g po q4h until K+ normalized
dialysis if stage 5 or acute severe hyperkalemia
27
What is the goal of therapy for severe hyperkalemia?
prevent severe cardiac arrhythmia, death, correct K+ < 5.5mmol/L
28
What is CKD-MBD?
systemic disorder of mineral and bone metabolism due to CKD manifested by either one, or a combo of the following:
-abnormalities of calcium, phosphorus, PTH or vit D metabolism
-abnormalities in bone turnover, mineralization volume, linear growth, strength (bone metabolism)
-vascular or other soft tissue calcification
29
When do changes in bone and mineral metabolism begin?
stage 3 and progresses
-bone abnormalities present in nearly all dialysis patients
30
What are the mechanisms of CKD-MBD?
increased serum phosphate due to decreased exceretion
decreased serum calcium due to decreased GI absorption due to decreased vitamin D
negative feedback leads to increased PTH
31
How is CKD-MBD diagnosed?
biochemical abnormalities
-serum Ca, PO4, PTH, ALP
bone abnormalities
-biopsy or BMD
vascular calcification
32
At what stage of CKD do we recommend monitoring Ca, PO4, and PTH?
CKD G4-G5
33
What is the risk of increased serum phosphate in CKD G3a-5?
increased risk of all-cause mortality
34
Is there a benefit in treating CKD patients to prevent hyperphosphatemia with normal serum concentrations?
no benefit
-possible risk
35
What do low levels of calcium contribute to in CKD?
secondary hyperparathyroidism
renal osteodystrophy
prolonged QT interval
36
What do elevated levels of calcium contribute to in CKD?
higher mortality and risk of CV events
37
Which severity of hypocalcemia is typically treated in CKD?
severe or symptomatic (numbness, tingling, myalgia)
-avoid hypercalcemia (risks are acute)
-mild and asymptomatic may not require tx
38
What are the risks of severe hyperparathyroidism in CKD?
calciphylaxis
CVD
neuromuscular disturbances
death
*stages 3-5*
39
What is the optimal PTH level in CKD?
unknown in CKD patients NOT on dialysis
-G5: 2-9x upper limit of normal
*levels should be progressively rising or persistently high in order to initiate treatment*
40
What are the types of renal osteodystrophy?
hyperparathyroid bone disease
-increased bone turnover, increased PTH levels
adynamic bone disease
-decreased bone turnover, normal or low PTH levels
osteomalacia
-decreased vitamin D activity
41
What is the role of FGF-23?
promote PO4 excretion
stimulates PTH to increase PO4 excretion
suppresses formation of calcitriol to decrease PO4 absorption in GI tract
42
What is the role of PTH?
increases Ca reabsorption and PO4 excretion
increases Ca mobilization from bone
43
What happens to FGF-23 and PTH response in advanced CKD?
kidneys fail to respond
=Ca and PO4 abnormalities worsen
44
What does persistent hyperparathyroidism lead to?
persistent calcium resorption from bone
-bone pain and fragility
-bone marrow fibrosis
-refractory pruritis
parathyroid gland hyperplasia and resistance to exogenous calcitriol
45
What is calciphylaxis?
calcification and occlusion of small blood vessels
-leads to ulceration, gangrene, sepsis, high mortality rate
46
What is the general overview of the treatment of hyperparathyroid bone disease?
to decrease phosphate:
-restrict dietary phosphate
-binders (Ca products, Al/Mg products, sevelamer, lanthanum, sucroferric oxyhydroxide)
-intensified dialysis schedules
to suppress PTH
-vitamin D (calcitriol, alfacalcidiol, ergo or cholecalciferol)
-calcimimetics
-parathyroidectomy
47
Why should a dietician be involved in regulating dietary phosphate of a CKD patient?
aggressive PO4 restriction can lead to inadequate intake of other nutrients like protein
48
How do all phosphate binders work?
binding dietary PO4 in GI tract-->eliminated in feces
49
How should all phosphate binders be taken?
within the first few bites of a meal
-multiple times per day with meals
-still requires dietary PO4 restriction
50
Which phosphate binders are first line therapy for hyperphosphatemia in CKD?
calcium-based binders (calcium carbonate)
-not calcium citrate
51
What is the usual dose of calcium carbonate in CKD?
500mg elemental calcium po TID with meals
-total recommended dose unknown
52
What are the adverse effects of calcium carbonate?
GI: constipation, cramps
hypercalcemia (esp if co-administered with calcitriol)
53
What is the use of aluminum or magnesium phosphate binders for hyperphosphatemia in CKD?
short-term use only
-not recommended for chronic use due to risk of accumulation and toxicity=NOT FIRST LINE
54
Describe sevelamer.
phosphate binder
useful in pts with hypercalcemia or when not controlled with Ca-based binders
AE: ++ GI tolerability
expensive (EDS)
55
Describe lanthanum.
similar to sevelamer
chewable tab
56
Describe sucroferric oxyhydroxide.
newest calcium-free binder
iron-based but negligible contribution to iron intake
AE: black stools and nausea
EDS
57
What are impacts of vitamin D therapy on PTH, Ca, and PO4 levels?
supress PTH levels
-stimulates absorption of Ca in GIT
-directly acts on parathyroid gland to suppress PTH
increased risk of hypercalcemia & hyperphosphatemia
-increase in FGF-23 levels
58
What are the impacts of vitamin D therapy on fractures and mortality?
uncertain if it decreases fractures or mortality
59
In which CKD population should we initiate vitamin D therapy?
severe & progressive HPT
-should NOT be routinely used if not on dialysis
60
What are examples of vitamin D analogues?
calcitriol
alfacalcidol
61
What are the usual doses of vitamin D analogues?
usual: 0.25-1mcg po OD
IV: 3x weekly with dialysis
*adjust doses based on serum Ca, PO4, PTH levels*
*serum Ca and PO4 should be in range prior to initiating therapy*
62
What is the benefit of nutritional vitamin D therapy in HPT?
can suppress PTH (esp. G3) with less hyper-Ca/PO4
63
What is the MOA of calcimimetics?
increase sensitivity of parathyroid gland to calcium
lowers PTH concentrations without increasing serum Ca or PO4 (useful in hypercalcemia)
64
Are the benefits of calcimimetics certain/well proven?
uncertain if they decrease fracture risk, CV events or mortality
65
What is an example of a calcimimetic?
cinacalcet
66
What is the use of cinacalcet?
dialysis patients +/- vit D therapy
67
What are the adverse effects of cinacalcet?
N/V/D
hypocalcemia
68
What is the role of antiresorptive therapy in CKD-MBD?
may increase BMD and decrease fracture risk
might use in CKD-MBD if low BMD and/or fragility fracture
-particularly if GFR >30ml/min, CKD G3a-b
CSN 2020 recommends against routine use in G4-5
69
What are examples of antiresorptive therapy?
denosumab
-poses risk of hypocalcemia
bisphosphonates
-may induce/exacerbate low bone turnover
-use with caution at CrCl < 35ml/min
70
What are the proper monitoring parameters for HPT?
serum Ca, PO4, and PTH levels at least MONTHLY
many drug interactions to be watch for
71
When is a parathyroidectomy used in CKD-MBD?
parathyroidectomy=partial removal of parathyroid gland
when PTH, Ca, PO4 abnormalities not medically correctable
-usually stage 5
72
What is a post-op concern with parathyroidectomy?
hungry bones syndrome
73
Describe adynamic bone disease.
low bone turnover
-lack of osteoblast/osteoclast stimulation
associated with more fractures and calcification
results from Ca and vit D supplementation and over suppression of PTH (overtreated PTH)
74
What is the treatment of adynamic bone disease?
stop vitamin D supplementation
75
Describe osteomalacia.
inadequate mineralization of Ca and PO4
-due to reduced production and action of calcitriol
can also result from aluminum deposition in bone
results in: fractures, myopathy, neurological deficits, dementia, seizures
76
What is the treatment of osteomalacia?
stop aluminum-containing phosphate binders
77
Describe vascular calcification.
vascular smooth muscle cells change into osteoblast-like cell
-seen in high and low bone turnover disease
-increased prevalence of CV calcification in CKD
78
Provide a brief review of the labs used for anemia.
hemoglobin
-iron based protein in RBC that transports O2
hematocrit
-volume % of RBC in blood
reticulocyte count
-immature RBCs (indicates production from bone marrow)
total iron binding capacity (TIBC)
-amount of iron that can be bound to transferrin
serum iron
-amount of circulating iron bound to transferrin
transferrin saturation (TSAT)
-transfers iron to bone marrow
ferritin
-stored iron
79
What are expected labs of anemia in CKD?
RBCs: normochromic, normocytic (stages 3-5)
HgB: < 130g/L (males), < 120g/L (females)
decreased reticulocytes
*nearly universal in ESRD*
80
What is the primary reason for anemia in CKD?
loss of erythropoietin generation by the kidneys
-also decreased RBC t1/2 in uremia, blood loss, bone marrow fibrosis, or iron, folate, vit B12 deficiency
81
Describe iron deficiency in anemia due to CKD.
common in stages 4-5 due to decreased GI absorption, inflammation, blood tests, blood loss in HD
-iron demands increase with ESA therapy
absolute iron deficiency:
-decreased TSAT, ferritin
-total iron stores in body are low
functional iron deficiency:
-decreased TSAT, normal or increased ferritin
-might be anemia of chronic disease, adding iron may not help
82
What are the signs and symptoms of anemia in CKD?
weakness, lethargy, malaise
shortness of breath on exertion
impaired memory and concentration
feeling cold
83
Why do we treat anemia in CKD?
improve QOL
risk factor for adverse outcomes (ex: LVH, CVD)
84
What are the pros of treatment with ESAs?
eliminate need for blood transfusions
decreased fatigue, symptoms of anemia (QOL)
85
What are the cons of treatment with ESAs?
failed to improve CV outcomes
associated with increased risk of stroke and other thromboembolic events
86
What are the goals of treatment for anemia in CKD?
hemoglobin:
-target: 100-110g/L (initiate ESA when < 90g/L)
-optimal HgB is unknown
-risks with higher targets
TSAT:
-maintain > 20% (avoid iron overload)
serum ferritin:
-> 100mcg/L (non-dialysis and PD), > 200mcg/L (HD)
normal serum B12 and folic acid levels
87
Provide an overview of the management of anemia in CKD.
correct blood loss
replace vitamin, iron deficiencies
ESA therapy
dialysis to correct uremia (as applicable)
blood transfusions if required (last resort)
88
What should be done before initiating ESA therapy for anemia in CKD?
avoid initiating ESA therapy until all correctable causes of anemia (ex: iron deficiency) have been addressed
89
What is the correlation between iron supplementation and ESA therapy for anemia in CKD?
iron supplementation may correct anemia without the need for ESA therapy if iron deficiency present
most patients receiving ESA therapy need iron therapy
90
What is the benefit of iron supplementation in functional iron deficiency?
questionable benefit
91
Which route of admin is recommended for initial therapy of anemia in CKD?
oral iron for 1-3 months prior to initiating IV therapy
-in HD patients, IV is required
92
What is the dose of oral iron for anemia in CKD?
100-200mg elemental iron daily
-2 to 3 divided doses
93
What are the adverse effects of oral iron?
black stools
N/V/D
cramping
constipation
heartburn
staining of teeth (liquid)
94
When do we use IV iron for anemia in CKD?
intolerant, unresponsive, non-compliant to oral iron
-1st line in HD patients
95
What are the injectable formulations of iron?
iron dextran (dc)
iron sucrose
iron sodium ferric gluconate
iron isomaltoside
96
What are the adverse effects of IV iron?
*generally well tolerated*
hypersensitivity reactions
hypotension
infection
97
Describe erythropoietin.
hormone produced by kidney when they sense decreased blood oxygenation
stimulates development and maturation of RBCs
-increase O2-carrying capacity of blood
-restore tissue oxygenation
*production becomes deficient as CKD progresses*
98
Differentiate between epoetin alfa and darbepoetin alfa.
epoetin alfa:
-resembles endogenous EPO
-shorter t1/2
darbepoetin alfa:
-2nd gen molecule
-longer t1/2
99
What are the doses of epoetin alfa and darbepoetin alfa?
epoetin alfa: 50-100 units/kg IV or SC 2-3x/week
darbepoetin alfa: 0.45mcg/kg weekly IV or SC
100
What is the goal with ESA therapy?
reach target HgB (~110g/L) within 2-4mo (then maintain)
-gradual increase in HgB by ~10g/L q month, to target
101
Describe the dose adjustments for ESAs.
if HgB rise is inadequate (<10g/L) after 4 weeks, increase dose by 25%
if HgB rise is excessive (>10g/L) in 2 weeks, decrease dose by 25%
*do not adjust dose more than q1-2 months because of delay in changes in HgB levels (2-6 weeks)*
102
Describe the proper monitoring for ESA.
serum iron, TIBC, iron sat, ferritin:
-q1-3 months
HgB:
-q1-2 weeks initially, then monthly
-HgB >100g/L (non-HD) or >110g/L (HD): hold/decrease dose
103
What are the adverse effects of ESA?
*well-tolerated*
hypertension (dose-dependent)
flu-like (transient)
thrombosis
MI, stroke, death (avoid >110g/L)
PRCA
104
What is erythropoietin resistance?
incomplete or lack of response to ESA
-epoetin alfa > 300U/kg/wk
-darbepoetin alfa > 1.5mcg/kg/wk
105
What are the causes of erythropoietin resistance?
iron deficiency (most common)
vitamin deficiency
bleeding
inflammation/infection
aluminum toxicity
inadequate dialysis
106
How do we manage erythropoietin resistance?
treat underlying cause if it can be corrected
avoid ESA doses > 4x the initial dose
107
What is the MOA of HIF-PHIs?
inhibit enzyme that degrades hypoxia-inducible factor
-improves iron mobilization into serum
-increased EPO production which increases HgB (without causing a spike in EPO)
108
What is an example of a HIF-PHI?
daprodustat
109
What are the cardiovascular complications of CKD?
hypertension
LVH
heart failure
hyperlipidemia
pericarditis
110
Describe hypertension as a complication of CKD.
can be both a cause and consequence of CKD
causes progression of stage 1-4
~90% of patients have hypertension by stage 5
*contributes to CV morbidity/mortality*
111
What are the contributing factors to hypertension in CKD?
water and salt retention
RAAS activation
ESA therapy
HPT
renal vascular disease
112
Do we see typical dosing of hypertension drugs in hemodialysis patients?
may see unusual dosing
113
What is the most common structural cardiac abnormality in CKD?
LVH
114
What are the risk factors for LVH in CKD?
HTN
fluid retention
anemia
DM
age
Ca/PO4 abnormalities
uremia
115
What are the symptoms of LVH in CKD?
generally asymptomatic in early stages
leads to: decreased diastolic compliance, IHD, HF
116
What is the treatment of LVH in CKD?
manage HTN and fluid overload
treat anemia
manage Ca, PO4, and PTH abnormalities
117
What are the precipitating factors for HF in CKD?
anemia
HTN
fluid overload
LVH
CAD
118
What is the treatment of HF in CKD?
correct underlying factors
treat as per HF guidelines
119
What are the neurological complications of CKD?
peripheral neuropathy
uremic encephalopathy
uremic polyneuropathy
-restless legs
-leg cramps
-numbness/tingling/paraesthesias
-carpal tunnel
-myopathy
120
What is the treatment for the neurological complications of CKD?
dialysis or change dialysis prescription
121
How common is chronic pruritis in CKD?
~40% of patients with ESRD
122
What are the complications of chronic pruritis?
ulcers, infection, QOL, sleep
123
Which part of the body is affected by chronic pruritis in CKD?
can affect parts of or whole body
124
What is the cause of chronic pruritis in CKD?
no clear cause
-makes treatment a challenge
125
What are the treatment options for chronic pruritis in CKD?
gabapentinoids
capsaicin
sertraline
antihistamines
Uremol lotion
126
What is the new option that has been approved for pruritis in CKD?
difelikefalin
-MOA: peripheral kappa opioid receptor agonist
-approved by HC for mod-severe pruritis associated with HD in CKD
-dose: IV 3x/wk following HD
-clinically significant decrease in itch
-AE: dizziness, somnolence, mental status change
127
What are normal phosphate levels?
0.81-1.45mmol/L
lower levels to normal range in pts with overt hyperphosphatemia
-ND CKD: > 1.49mmol/L
-HD/PD CKD: > 1.78mmol/L
