Chronic kidney disease Flashcards

1
Q

Vitamin D activation

A

1) diet
2) activated in liver to calcidiol
3) converted in kidney to calcitriol

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2
Q

FGF-23

A

expressed in osteocytes
acts on FGF receptors with co-factor Klotho - tissue expression of Klotho determines tissue specificity of FGF-23
main site of action: kidneys
increase phosphate excretion
inhibits kidney activation of calcidiol –> triol

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3
Q

PTH effects

A

bone: increase calcium (need calcitriol) and phosphate resorption
kidney: increase Ca resorption, increase phosphate excretion increase calcitriol activation
Intestine: indirect effect through increased calcitriol

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4
Q

Calcitriol effects

A

Bone: increase calcium and phosphate resorption
Kidney: increase ca and phos resorption
intestine: increase Ca and phos absorption

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5
Q

FGF-23 effects

A

increase phosphate excretion
reduce calcitriol activation
intestine: indirect effect through reduced calcitriol activation

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6
Q

Modulators of PTH

A

stim: reduced serum Ca, increased serum phosphate
inhib: increased serum Ca and calcitriol

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7
Q

Modulators of Calcitriol

A

stim: increased PTH, reduced serum phosphate
inhib: increased FGF-23, increased serum phosphate

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8
Q

FGF-23 modulators

A

increased calcitriol, increased phosphate load

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9
Q

Consequences of hyperparathyroidism

A

increase calcitriol –> more intestinal absorption of PO4
increase PO4 resorption at bone
increase PO4 excretion at kidney (PTH effect on excretion overrides inhibition by calcitriol)

net effect = hypophosphatemia

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10
Q

CKD effect on minerals

A

hyper-PTHism
hypocalcemia
hyperphosphatemia
low calcitriol
increased PTH resistance to calcemic effect
- high Ca no longer able to suppress PTH release
- Ca set point changed, need higher level of Ca to suppress PTH release

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11
Q

Diffusion modulators

A

responsible for most solute clearance

1) concentration gradient
2) molecular weight of solute
3) resistance of membrane

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12
Q

Convection - dialysis

A

ultrafiltration

1) water pushed/pulled through membrane
- hydrostatic ultrafiltration: based on transmembrane pressure
- ultrafiltration coefficient (KUf): amount of fluid transferred across membrane/hr/mmHg gradient
- osmotic ultrafiltration: water diffuses down its concentration gradient - will drag solutes wiht it (transient)

2) solvent drag: solutes that pass easily through membrane are dragged along with water
loss of total mass of solutes but not change in plasma concentration

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13
Q

Clearance

A
volume plasma cleared of indicator per unit time
K = Cu x Q / Cb
Cu = concentration in urine
Cb = concentration in blood
Q = urine flow
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14
Q

Phosphate binders

A

dietary first - difficult

1) Ca-based: tums, first line, reduce in hypercalcemia
2) Sevelamer, Lanthanum, Magnesium (non-calcium): alternative when hypercalcemic, use when concern over adynamic bone disease, metastatic/vascular calcification
3) Al-based binders: only short courses, not first line (Al toxicity)

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15
Q

Ca supplementation

A

Ca-based binders
Calcitriol supplementation:useful when phosphate is controlled, avoid if PTH is suppressed
need to avoid hypercalcemia - prefer low-normal Ca

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16
Q

Hormonal replacements for CKD

A

Ergocalciferol - early CKD, treat vit D deficiency
Calcitriol - when evidence of elevated PTH, avoid with hypercalcemia/phosphatemia, reduce dose when PTH is within target range

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17
Q

Calcimimetics

A

increase ca-sensing receptors in PT gland
useful when treatment limited by hypercalcemia, hyperphosphatemia
useful for refractory hyper-PTH in patients on dialysis
expensive

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18
Q

Hemodialysis

A

bloodflow & dialysate flow opposite
blood flow rate almost linear relationship w/ clearance

Net clearance = diffusive + convective transport

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19
Q

Hemodialysis -pros

A

quick
relieve uremia
works for most blood vessels

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20
Q

Hemodialysis - cons

A
4-8 h, 3x/wk
meds, diets, fluid restriction
need needle access
travel
sepsis, hypotension
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21
Q

Indications for acute hemodialysis

A
volume excess (respiratory failure, respiratory HTN)
metabolic (severe metabolic acidosis, hyperkalemia)
clinical (uremic encephalopathy, uremic pericarditis)
Drug overdoses (ASA, methanol, ethylene glycol, lithium)
22
Q

Peritoneal dialysis

A

peritoneum: monolayer of mesothelium + CT
-covers abdominal wall & viscera
- secretes surfactant
- microvilli
normally ~100ml of peritoneal fluid

continuous
peritoneal access
change dialysate 4-5x /day
can be done independently
proteins cleared - malnutrition
23
Q

Convective transport in perit, dialysis

A

20% of solute removal, more significant than hemodialysis

use osmotic agents to induce fluid movement

24
Q

Ideal osmotic agent

A
good solute clearance and UF capacity
supplied by nutrition
normal pH, buffered at physiological pH
minimal absorption and non-toxic
antibacterial/antifungal
biocompatible with membrane
inexpensive
25
Q

Glucose - osmotic agent

A

cheap, easy, non-toxic
Bad: small, rapidly absorbed, metabolized (caloric load)
induces fibrosis & inflammation of peritoneal membrane

26
Q

AAs as osmotic agent

A

Good: higher osmotic effect (charged), equivalent to glucose in solute drag and ultrafiltration equivalent, absorbed
Bad: appetite suppression, metabolic acidosis, urea increases, effects on membrane

haven’t shown to be very effective

27
Q

Icodextrin as osmotic agent

A

glucose polymer, induce colloid osmotic effect
Good: only slightly absorbed (10-20% over 8 hours), prolonged ultrafiltration, colloid osmosis, equivalent solute clearance, lower caloric load
Bad: unsure about effects of high maltose

28
Q

Chronic renal failure definition

A

persistent (>3mth) abnormal kidney function due to intrinsic disease of kidneys
OR
normal function but persistent structural/functional abnormality of kidneys with markers for kidney damage (proteinuria, hematuria)

29
Q

Causes of CKD

A
diabetes
HTN
ischemic/vascular
Glomerular (nephrotic, nephritic)
PCKD
drug-induced
pyelonephritis
Reflux
30
Q

Risk factors for progression of CKD

A
persistence of underlying disease
HTN
hemodynamic injury to kidney
proteinuria
nephrotoxic injury
male
degree of scarring on renal biopsy
prior AKI
Refer to nephrologist:
 GFR<30
acute renal failure
progressive loss of GFR by 10ml/min/yr
persistent significant proteinuria
31
Q

Screen for CKD

A
diabetes
HTN
atherosclerosis, vascular disease
FHx
high risk ethnicity: first nations, S. asian, pacific inlander
Other: age, unexplained anemia, CHF

Consider reversible factors (vol depletion, obs, NSAIDs, illness)
Need to do repeat measurements, once confirmed:
PE, urinanalysis/urine protein, renal US

32
Q

GFR thresholds

A

Stage 5 - kidney failure, GFR < 15
severe 4 - 15-29
moderate 3 - 30-59

Recently: include albuminuria

macroalbuminuria: male > 25, female >35
microalbuminuria: male 2.5-25, female 3.5-35

macroalbuminuria = very high risk for complications

33
Q

Stages of CKD - Sx

A

see HTN at all stages, CVD most stages
Anemia start to see at <30 , 30-59 mild
Neuropathy/malnutrition at later stages

34
Q

BP control for CKD

A
lifestyle
target: 140/90 non-diabetic, 130/80 diabetic
1st line: ACEi OR ARB (NO COMBINATION)
2nd: diuretic
- thiazide if GFR > 30
- loop if GFR < 30
- spironolactone - effective but risk of hyperkalemia
3rd: long-acting CCB (DHP/non-DHP)

better outcome with ACEi + CCB rather than ACEi + diuretic

35
Q

Uremia symptoms

A
fatigue
cold intolerance
nausea
anorexia
pruritus
restless legs, leg cramps
constipation
edema
SOB
pulmonary edema
reduced urine output
reduced sexual drive
ED
change in mental status
36
Q

Uremic toxins

A

small, non-N compounds: phosphate, cresol, phenylacetic acid
small N compounds: guanidines, spermidine, indoxyl sulphate, homocysteine
Middle molecules: beta-2 microglobulin, cytokines, complement factor D, advanced glycation end products, advanced oxidation protein products

37
Q

GFR equation (pressures)

A

Lp x SA x [(Pgc - Pbs) - s(pigc - pibs)]
Lp = permeability of capillary wall
SA = surf area available for filtration
s = reflection coefficient for proteins across capillary wall (0- completely permeable; 1 = completely impermeable)

38
Q

Normal GFR

A

neonates ~40
2-12 yrs ~130
13-21: ~140 (male), ~120 (female)
after 20-30, normal GFR decreases 0.5-1 ml/min/1.73m2 per yr

39
Q

GFR equation (clearance)

A
GFR = UxV/(PxT)
U = [urine] of indicator
V = urinary volume
P = [plasma] of indicator
T = time
40
Q

Ideal GFR marker

A
constant production
readily diffuses through EC space
freely filtered, not protein-bound
no tubular reabsorption
no tubular secretion
no extrarenal elimination/degradation
does not influence GFR
cheap, convenient, easily measured

Inulin - gold standard, not easily measured

41
Q

Inulin clearance

A

rarely performed
requires iv infusion of inulin
not available in most laboratories
needs iv infusion of inulin

42
Q

Serum creatinine for GFR - pros

A
produced endogenously
proportional to muscle mass
constant throughout day
freely filtered at glomerulus
convenient and inexpensive
43
Q

SCr for GFR - cons

A

widely used yet inaccurate
variability between individuals
muscle mass can change
can be altered by increased creatine and creatinine consumption
extra renal elimination: intestinal bacteria - significant in renal dysfunction
secreted by tubules - increases with declining kidney function, overestimation of kidney function

44
Q

relationship btw GFR and SCr

A

non-linear
when nephrons are lost, compensatory hyperfiltration of other nephrons
as GFR falls, increase in tubular secretion of creatinine

45
Q

Creatinine clearance

A

24 hr urine, measure volume and [creatinine], and blood [creatinine]
Pros: don’t worry about muscle mass and extrarenal creatinine elimination
Cons: not the same as true GFR - still tubular secretion
- cumbersome collection process

Uses: no often used for assessment of renal function
assess proteinuria
assess electrolyte excretion

46
Q

Nuclear medicine glomerular filtration

A

Radiolabelled indicator filtered at glomerulus
-5-10% bound by protein, slight underestimation of GFR
-20% cleared with each pass through kidney
Serial imagining of kidneys with gamma ray counter

cons: inconvenient
used when accurate measurement of GFR is essential (transplant)

47
Q

GFR prediction equations

A

use demographic & clinical info to predict GFR
Pros: preferred method of GFR estimation. more variables, not dependent on urine collection

Cons: rely on individual being at steady state, not always at avg state in population, still affected by tubular secretion/extrarenal elimination

48
Q

Cockroft-Gault equation

A

estimation of creatinine clearance (overestimate GFR)
Cr clearance = [(140-age) x weight] / (serum creatinine x 50)
x0.85 women
x 60 for ml/min
creatinine = umol/L
weight kg

49
Q

MDRD study equation

A

estimates GFR

50
Q

CKD-EPI

A

eGFR

more accurate in people with normally/mildly reduced renal function

51
Q

Serum cystatin C

A

LMW protein freely filtered at glomeruli but metabolized by renal tubules
maybe more accurate in certain populations