ckd Flashcards
CrCl =
[[140 - age(yr)]weight(kg)]/
[72serum Cr(mg/dL)]
1mg/dL = 88.4umol/L
x0.85 for women
ideal filtration markers are:
- freely filtered by the kidney
- not secreted, metabolised, or reabsorbed
- does not modify renal function
gold standard for estimating GFR
inulin (fructose polysaccharide, not naturally occurring in the human body):
- freely filtered, not secreted, not metabolised, not reabsorbed, not protein bound
SCr is a product of
metabolism of creatinine, which is produced by the muscle
- endogenously produced at a relatively constant rate
- freely filtered, some secretion at the renal tubule, small amt or reabsorption
limitations of using SCr in eqn estimating renal function
- variations in Cr production: vegetarian diet, creatinine supplements
- reduction in muscle mass: amputation, malnutrition, fraility
- when GFR is rapidly fluctuating eg. AKI, SCr takes some time to accumulate and reach a steady state
normal urine output >= 1200ml/day
non-oliguric: >500ml
oliguric: 50-500ml
anuric: <50ml
definition of AKI
- incr in SCr by >= 0.3mg/dL (26.5umol/L) within 48hrs
- incr in SCr to >= 1.5x baseline, which is known or presumed to have occurred within the prior 7 days
- urine vol <0.5ml/kg/h for 6hrs
risk factors for AKI
- advanced age
- pre-existing kidney impairment
- obstruction of urinary tract
- sepsis/infections
- rhabdomyolysis/ trauma/burns
- dehydration/vol depletion: vomiting, diarrhea, poor fluid intake, fever, diuretic use, intravascular vol depletion (congestive cardiac failure, liver disease with ascites)
- use of nephrotoxic agents/medications
causes of AKI
- pre-renal/functional
- intrinsic
- post-renal
causes of AKI: pre-renal/functional
hypoperfusion or decr glomerular hydrostatic pressure
- hemorrhage, vol depletion, CHF, renal artery stenosis, emboli
- med: ACEi, ARB, NSAID
causes of AKI: intrinsic
structural damage to kidneys:
- acute tubular necrosis, acute interstitial nephritis, acute glomerulonephritis, infections
- med: aminoglycosides, vancomycn
causes of AKI: post-renal
obstruction of urinary flow
- trauma, BPH, tumours
under normal physiologic conditions, to maintain glomerular hydrostatic pressure for filtration:
- afferent arterioles (PG): dilates, incr renal blood flow
- efferent arteriole (ATII): constricts, incr GFR
NSAIDs on AKI
inhibit PG > constriction of afferent arterioles > decr renal perfusion
ACEi an ARBs on AKI
antagonise effects of ATII > decr glomerular filtration pressure > decr GFR
diuretics on AKI
deplete plasma vol > decr renal blood flow
Aminoglycosides on AKI
ATN
- uptake through receptor expressed on epithelial cells along proximal convoluted tubule
> concentrated > induce myeloid body formation, impair protein synthesis, degrade mitochondrial function, culminate in apoptosis and eventual necrosis of the renal tubular epithelial cells
- direct glomerular injury can also occur
neomycin>gentamicin=tobramycin>amikacin>streptomycin
strategies to minimise AKI with AO
- in pt w pre-existing renal impairment or high risk of AKI, consider other abx choices
- avoid other nephrotoxins, avoid dehydration
- TDM
- single daily dosing whenever possible: lower risk of AKI compared to multiple daily dosing, using PAE
- use shortest duration possible
vancomycin on AKI
- may alter mitochondrial function and induce dose-dependent proliferation of proximal tubular cells
- oxidative stress may also be a potential mech of nephrotoxicity, esp involving the proximal tubule
ATN, AIN
most ep developed btw 4-17 days after initiation of therapy
strategies to min AKI with vancomycin
TDM:
- aim AUC/MIC 400-600mg.h/L, assuming MIC 1mg/L
- incr risk of AKI if vanco trough levels are maintained >15-20mg/L or if AUC/MIC exceeds 650-1300mg.h/L
- AUC/MIC method not validated in pt on dialysis
minimise concurrent use of nephrotoxins: concurrent use of vanco and piper-tazo incr risk of AKI, closer monitoring of renal function is warranted
- monitoring of renal function via repeating blood tests and monitoring urine output
contrast-induced nephrotoxicity `
- renal ischemia: systemic hypotension, osmotic diuresis/dehydration, renal vasoconstriction caused by the release of adenosine, endothelin, and other vasoconstrictors
- direct tubular toxicity caused by oxidative stress
presentation: SCr rises within 12-24hrs and peaks 2-5 days after procedure
esp in pt with ckd+dm, chf, adv age, concurrent adm of nephrotoxic drugs
strategies to min AKI with radiocontrasts
- use lowest possible dose of contrast medium in pt at risk
- use either iso-osmolar or low-osmolar iodinated contrast media, rather than high-osmolar iodinated contrast media in pt with incr risk of CIN
- iv vol expansion with either isotonic NaCl or sodium bicarbonate solutions 6-12hours before procedure
- oral N-acetylcysteine pre- and post-procedure
- discontinue current nephrotoxic agents and diuretics
clinical s/sx of ckd
fluid overload (SOB), HTN, uremic sx (nausea, anorexia, fatigue, LOA, itch, mental changes, uremic breath, asterixis, bleeding)
lab s/sx of ckd
azotemia, hyperP, hyperCa, hyperK, metabolic acidosis, anemia
stage 1 ckd
eGFR >=90, with risk factors
stage 2 ckd
60-89
stage 3 ckd
30-59
stage 4 ckd
15-29
- preparation for kidney replacement therapy
stage 5 ckd
<15, or dialysis
G3a
45-59
G3b
30-44
A1
<30mg/g
<3mg/mmol
A2
30-300mg/g
3-30mg/mmol
A3
> 300mg/g
30mg/mmol
causes of ckd
- dm
- htn
- glomerulonephritis
- autoimmune disease
- genetic disorders: polycystic kidney disease
- vascular diseases
- drugs
- infections
- urinary obstructions: kidney stones
- HIV-associated nephropathy
functions of kidney
- regulates fluid balance
- regulates electrolytes
- regulates pH
- removes waste/toxins
- produces erythropoietin
- activates vitD
complications of ckd
- regulates fluid balance > fluid overload, htn
- regulates electrolytes > electrolyte imbalance (K, P, Ca)
- regulates pH > metabolic acidosis
- removes waste/toxins > hyperuricemia, uraemia (contributes to LOA, anorexia, fatigue) > malnutrition
- produces erythropoietin > anemia
- activates vitD > secondary hyperparathyroidism, mineral bone disorders
PLUS ckd causes a systemic, chronic pro-inflammatory state contributing to vascular and myocardial remodeling processes > atherosclerotic lesions, vascular calcification > incr risk of cvd
s/sx of anemia
fatigue, sob, intolerance to cold weather, chest pain, tingling extremities, tachycardia, headaches, malaise
causes of anemia in ckd
- erythropoietin deficiency
- iron deficiency
- folate and b12 deficiency
- increased blood loss during dialysis
- reduced life span of erythrocytes
- inflammation
- infection
- bone marrow fibrosis secondary to hyperPTH
anemia diagnosis
Hb <13 for males, <12 for females
lab parameters for investigation of anemia
- Hb
- reticulocyte counts
- MCV, MCHC
- serum ferritin, TSAT
- serum b12 and folate levels
Hb target
10-11.5
give oral/IV iron if
- TSAT =< 30%
AND serum ferritin =< 500ng/mL
recommended daily dose of iron
200mg elemental iron
oral iron ddi
- calcium supplements
- tetracyclines
- FQ: bind to Fe, decr absorption of FQ
- thyroxine
- antacids
- H2RA, PPI: alters pH of gut, iron require acidic enough environment in gut for absorption, impaired absorption
ferrous sulphate Co Tab, contains ferrous sulphate anhydrous 200mg
32%, 65mg
ferrous gluconate Co cap (Sangobion), contains ferrous gloconate 250mg
12%, 30mg
iberet folate SR tab, contains ferrous sulphate 525mg
20%, 105mg
iron polymaltose drops 50mg/ml
50mg/ml (20 drops)
iron polymaltose 100mg tab/cap
100mg
ferrous fumarate, % elemental iron
33%
IV vs oral iron
- IV fe improves responsiveness to ESA therapy
- 100% bioavail
- reduction of pill burden
- reduction of ddi
- can also be used in PD and pre-dialysis pts where oral iron is insufficient
adr of iv fe
*Allergic reactions, hypotension, dizziness, dyspnoea, headache, flushing, nausea, injection/infusion site reactions
*Rare but serious: anaphylaxis
*Iron overload
*Increased risk for infections
*Withhold during acute infections, restart after infection resolves (usually after the end of the abxcourse)
*May consider switching to oral iron
evaluate iron status (TSAT and ferritin) at least every
3 months during ESA therapy, including decision to start or continue iron therapy
- but more frequently ie. monthly when: initiating or increasing ESA dose, blood loss, monitoring response after a course of IV iron
short-acting ESA
Eprex, Recormon
long-acting ESA
Darbepoietin alpha (Nesp), Methoxy polyethylene-glycol-epoietin beta (Mircera)
moa of ESA
stimulate erythropoiesis either directly or indirectly by acting on the EPO receptor
starting dose of eprex
IV 50-100u/kg, 3x/wk
starting dose of recormon
SC 20u/kg 3x/wk
or IV 40u/kg 3x/wk
starting dose of nesp
SC/IV 0.45mcg/kg once a week
starting dose of MIrcera
SC/IV 0.6mcg/kg Q2weeks
adr of ESA
generally well-tolerated:
- pure red cell aplasia
- HTN: not a c/i unless uncontrolled or urgency
- vascular access thrombosis
- seizuresL prior hx of seizure not a c/i
- flu-like sx
- use in caution in malignancy or hx of malignancy
time to steady state of ESA
takes apporx 10 days for erythrocyte progenitor cells to mature and release into circulation
finerenone
non-steroidal MRA
- shown to have potent anti-inflammatory and anti-fibrotic effects than steroidal MRA (spironolactone, eplerenone)
- used for HTN in CKD if ACEi/ARB does not achieve good control of BP
preferred DM agents
SGLT2i
GLP-1 RA
DPP4-i
absolute Fe deficiency
low TSAT, low ferritin
functional Fe deficiency
low TSAT, high ferritin
microcytic, hypochromic RBA
iron deficiency anemia
macrocytic
b12 or folate deficiency
normocytic, normochromic anemia
anemia of chronic disease
iron panel for iron deficiency
MCV: microcytic
iron: low
ferritin: low
TIBC: high
transferrin: high
TSAT: low
iron panel for inflammatory anemia
MCV: normal
iron: low
ferritin: high
TIBC: low
transferrin: low
TSAT: low
iron panel for iron overload
MCV: normal
iron: high
ferritin: high
TIBC: low
transferrin: low
TSAT: high
protein req
0.8g/kg/day, due to inability to excrete nitrogenous waste (urea)
- for dialysis pt: 1-1.2g/kg/day due to protein loss
what adjust vit not recommended
vit A and E, risk for toxicity in ESRD pt
- vit C alos
- folic acid, L-carnitine, pentoxifylline not recommended as well
metabolic acidosis
- decr H+ excretion > drop in pH and serum bicarbonate levels
- decr excretion of NH3 (mech to remove excess H+)
- decr excretion of PO4 (mech to remove excess acid)
compensatory fall in pCO2 result in less decr in arterial pH
clinical presentation: anorexia, nausea, lethargy
bicarbonate deficit formula
0.4 x weight (kg) x (24-bicarb level)
serum bicarb goal
> 22mmol/L
mgmt of metabolic acidosis
use of alkalinising salts to replenish bicarb stores:
- sodium bicarb
- citrate/citiric acid reparations (but re liver metabolism to bicarb, co2, water)
dose of sodium bicarb
1g BD-TDS
which is more selective: lokelma or resonium
lokelma (SZC)
agents that reverse ECG effects (by hyperK)
calcium
agents that allow urinary K loss
frusemide
agents that redistributes K
insulin w glucose
sodium bicarb
b2 agonist
agents that incr K elimination
SZC, SPS, patiromer (Veltessa), Hd
corrected calc mg/dL
(0.8 * (Normal Albumin - Pt’s Albumin)) + Serum Ca
goals of therapy for ckd-mbd
*Maintain normal levels of serum Calcium, Phosphate, PTH
*Prevent or reduce parathyroid gland hyperplasia
*Maintain normal skeletal function
*Prevent extra-skeletal and vascular calcification
*Reduce cardiovascular morbidity and mortality
77
adr of sodium bicarb
sodium or fluid overload, gi intolerance eg stomach discomfort or bloatedness, nausea
what is a classic feature of hyperphosphatemia
pruritis
limit dietary phosphate intake
800-1000mg/day
- difficult since P found in most foods rich in protein, might compromise nutrition!
phosphate binders: calcium salts
MOA: combines with dietary P to form insoluble calcium-phosphate - not absorbed systemically, cleared through feaces
calcium carbonate
40% elemental Ca
1 tab TDS w meals
SE: n/v, constipation, hyperCa, LOA, urolithiasis
calcium actate
25% elemental Ca, 667mg = 167mg elemental Ca
1-2 tabs TDS with meals
SE: n/v, constipation, hyperCa, LOA
limit ____g of elemental Ca per day
2
- 1.5g from Ca-based binders: up to 3 tabs of calcium carbonate per day or 9 tabs of calcium acetate per day
MOA of sevelamer
non-absorbable polymer that inhibits intestinal phosphate absorption
dosing of sevelamer
800-1600mg TDS with meals
SE of sevelamer
constipation, diarrhea, flatulence, indigestion, n/v, metabolic acidosis
Renvela
sevelamer CO3
Renagel
sevelamer HCl
which sevelamer salt has lower risk of metabolic acidosis?
renvela, co3
adv of sevelamer
- does not contain Ca or Al; does not contribute to Ca load, no risk for hyperCa or Al-induced toxicities, allowing higher doses of vit D
- lipid lowering effects
disadv of sevelamer
- pill burden: swallow whole, cannot chew
- expensive
MOA of lanthanum
rare earth element, inhibits absorption of dietary phosphate by forming highly insoluble lanthanum phosphate complexes in gut
Fosrenol
lanthanum carboante
lanthanum dosing
500-1000mg TDS w meals, chewed
Al-based P binder: MOA
binds with phosphorus in GIT
- al hydroxide 600mg tab, mixture
SE of al-based P binder
GI: constipation, diarrhoea, gi obstruction
phosphate depletion: weakness, mental status changes
al toxicity: dementia, encephalopathy, worsening anemia, osteomalacia, adynamic bone disease (esp w concurrent use of citrate salts)
when are al-based P binders used?
severe hyperP (>2.2mmol/L) uncontrolled by other binders
- not for lt use, due to risk of toxicity
- not recommended for use > 4 weeks
Velphoro
sucroferric oxyhydroxide
- novel polynuclear iron(II)-oxyhydroxide P binder
sucroferric oxyhydroxide dose
2.5g chewable tablet = 500mg elemental Fe
- 500mg TDS, incr to 1g TDS based on response
- minimal iron absorption
velphoro vs sevelamer
as effective, but loewr pill count
3 vs 9 tabs per day
velphoro SE
high incidence of GI se: nausea, diarrhea, abnormal stool colour (black)
phosphate binder ddi
quinolones, thyroxine, digoxin, warfarin, antiepileptics
native/nutritional vit D
ergocalciferol (D2) - less effective, 50000IU
cholecalciferol (D3) - 1000IU
when is vit D and its analogues used?
reserved for ckd stage 4-5 pt with severe and progressive hyperPTH
vit D analogues
active form
- alfacalcidol
- paricalcitol
MOA of vit D and its analogues
- incr absorption of Ca and P
- decr PTH secretion and synthesis
PO dose of calcitriol and alfacalcidol
0.25mcg, 3x/wk
IV dose of calcitriol and alfacalcidol
1mcg/wk
limitations of of calcitriol and alfacalcidol
incr GI absorption of Ca and P > resulting in hyperCa and hyperP (dose-limiting SE)
alfacalcidol requires
hepatic function for conversion to active form
paricalcitol adv over calcitriol and alfacalcidol
less hyperCa or hyperP
- selective actiation of vit D receptors in PTH glands inhibiting PTH synthesis and secretion
MOA of calcimimetics
binds and modifies calcium sensing receptors on parathyroid glands, causing incr sensitivity to extracellular ca hence reducing pth levels
Regpara
PO cinacalcet 25mg tab
- 25mg 3x/wk, uptitrated to 100mg OD at 3-wk intervals
what to monitor for with hypoCa
seizures
Parsabiv
IV etelcalcitide
2.5-15mg 3x/wk, with dose adj every 4 weeks
switching from cinacalcet to etelcalcitide
discont cinacalcet for at least 7 days prior to starting etelcalcitide
switching from etelcacitide to cinacalcet
discont etelcalcitide for at least 4 days prior to starting cinacalcet
acoid fleet enemas in renal failure due to
high phosphate content
PD peritonitis should be diagnosed when at least 2 of the following are resent
1.Clinical features consistent with peritonitis, that is, abdominal pain and/or cloudy dialysis effluent;
2.Dialysis effluent white cell count > 100/μL or > 0.1 ×109/L (after a dwell time of at least 2 h), with > 50% polymorphonuclearleukocytes (PMN);
3.Positive dialysis effluent culture
