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Flashcards in Chronic kidney disease Deck (51):
1

Vitamin D activation

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

2

FGF-23

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

3

PTH effects

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

4

Calcitriol effects

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

5

FGF-23 effects

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

6

Modulators of PTH

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

7

Modulators of Calcitriol

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

8

FGF-23 modulators

increased calcitriol, increased phosphate load

9

Consequences of hyperparathyroidism

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

10

CKD effect on minerals

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

11

Diffusion modulators

responsible for most solute clearance
1) concentration gradient
2) molecular weight of solute
3) resistance of membrane

12

Convection - dialysis

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

13

Clearance

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

14

Phosphate binders

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)

15

Ca supplementation

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

16

Hormonal replacements for CKD

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

17

Calcimimetics

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

18

Hemodialysis

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

Net clearance = diffusive + convective transport

19

Hemodialysis -pros

quick
relieve uremia
works for most blood vessels

20

Hemodialysis - cons

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

21

Indications for acute hemodialysis

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

22

Peritoneal dialysis

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

Convective transport in perit, dialysis

20% of solute removal, more significant than hemodialysis
use osmotic agents to induce fluid movement

24

Ideal osmotic agent

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

Glucose - osmotic agent

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

26

AAs as osmotic agent

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

Icodextrin as osmotic agent

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

Chronic renal failure definition

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

Causes of CKD

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

30

Risk factors for progression of CKD

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

Screen for CKD

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

GFR thresholds

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

Stages of CKD - Sx

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

34

BP control for CKD

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

Uremia symptoms

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

Uremic toxins

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

GFR equation (pressures)

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

Normal GFR

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

GFR equation (clearance)

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

40

Ideal GFR marker

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

Inulin clearance

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

42

Serum creatinine for GFR - pros

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

43

SCr for GFR - cons

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

relationship btw GFR and SCr

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

45

Creatinine clearance

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

Nuclear medicine glomerular filtration

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

GFR prediction equations

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

Cockroft-Gault equation

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

MDRD study equation

estimates GFR

50

CKD-EPI

eGFR
more accurate in people with normally/mildly reduced renal function

51

Serum cystatin C

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