CKD & Associated Flashcards
define CKD and the classifications
CKD: chronic kidney disease
- abnromalizites in the structure or function > 3 months
Classifications based on …
- causes
- albuminuria
- GFR
Albuminuria
- A1 = < 30 (a mild increase or normal)
- A2 = 30-300 (moderate increase)
- A3 = > 300 (severe increase)
GFR (from 1 to 5; 5 is worst)
- > 90 = normal or high
- < 15 = kidney failure
Complications of CKD and their timing of onset
- CVD risk is the biggest: prevention begins early on
- anemia
- impaired sodium, water and potassium (electrolyte) balances
- secondary hyperparathyroidism
- bone and mineral disorders
- uremic bleeding
- metabolic acidosis
- pruritis
Normal role of Kidneys and their sodium/water homeostasis
what happnes in stage 4 & 5 CKD
Normally
- kidneys have the ability to regulate the sodium and water balance in the body via reabsorbtion and excretion
in CKD…
- there is a drop in the number of working nephrons
- therefore a drop in the GFR: rate of filteration
- therefore an increase in teh sodium and water that remains within teh body
- leads to HTN, edema, volum eoverload, increased intravascular volume and increased BP and kidney perfusion
in stage 4 & 5: there is an inadequate compensation; sodium retentiona leads to an increase in extracellular fluid and therefore HTN and edema
Treatment of the Sodium and Water retention in CKD pts.
Use IV Fluids cautiously
- those at risk of edema or with edema need to be infused at a much slower rate with constant monitoring
- can worsen the volume overload
use of Diuretics
- to prevent or to treat the volume overload in these pts, use of diuretics is helpful
- diuretic use can only be in pts. who are producing urine!!!
- loops, thiazides (only metolazone is good for GFR < 30) or a combo of both
- in those with stage 5 CKD or those who are anuric: you cannoy use diuretics: dialysis is warrented
Treatment of Sodium and Water Retention in CKD pts.
- role of ACE/ARBs and SGLT2i
ACE/ARB is preferred agent to help those with HTN and CKD
- for those with or without DM
- for those with severely or moderately increase albuminuria too (A2 and A3)
SGLT2 : decreases the progression of CKD and CVD
Names
- Dapagliflozin
- Cangliflozin: can ONLY be used in those with DM
- Empagagliflozin
- recommended use of SGLT2 with those with T2DM and CKD with GFR > 20 (off-label used for those witout T2DM)
MOA, DD interactions and ADE of SGLT2
MOA: work at the proximal covoluted tubule to decrease the sodium and gluocse reabsorpbtion by blocking the SGLT2transporters: therefore increasing the amoutn secreted
clearance decreases with decreased GFR: thus once GFR drops below 20 SGLT2 cannot be used
DD Interactions: can impact the role of antihypoglycemic agents
Side Effects
- fungal UTI: increase glucose in urine
- anaphlyxis
- dehydration: drop BP & volume status
- euglycemic ketoacidosis: bicarb and ABG used to monitor this
- AKI: due tothe osmotic duresis: pulls fluids with it: SCr and urine output to monitor this
- increase bone fx. risk
role of Finerenone in CKD pts.
MOA
ADE
contraindications
in addition to ACE/ARB, SGLT2 (or in replacement for SGLT2)…. finerenone can be used
for those with CKD + T2DM + albuminuria
MOA: selectively blocks MRA receptors–> mediating the sodium reabsorpbtion process and the activation ofthe epithelial cells (kdineys) and nonepithelial (blood vessles, heart)
ADRS
- hyperkalemia
- hyponatremia
- hypotension
Contraindications
- cannot be used with other strong CYP3A4 inhibitors this include grapefruit!
- cannot be used if K > 5 (becuase risk of kyperkalemia)
- cannot be used if breastfeeding
- cannot use with those who have adrenal insuff.
- watch in those with hepatic impairment * with moderate CYP3A4 inhibitors
role of a Dulaglutide in sodium, water homeostatis in CKD
Dulaglutide: a glucaogon-like peptide 1 antagonist
- can be used for those with T2DM, CKD to help reduce risk of CVD
how does hyperkalemia occur in those with CKD
- at what GFR
- management
Hyperkalemia occurs due to the drop in GFR as the number of working nephrons decreases = decreased ability to excrete potassium in the distal tubule
- can also be a result of using ACE/ARB for HTN: but address and fix the hyperkalemia before taking the pt off the ACE/ARB
- this typically is occuring at GFR < 20 (when the GI tract can no longer compensate for the decreases ability of the kidneys)
Management
1. non-pharm manage
- via diet: decrease potssium to 50-80 meq/day
- via avoiding meds: NSAIDS, aldosterone antago. etc.
- diuretics can help offload potassium
- pharm management (patiromer or sodium zirconium)
eventaully dialysis will be needed if the above are not working
Treatment of Chronic hyperkalemia in CKD
- patiromer
- sodium zirconium
MOA, ADE, etc.
Chronic Hyperkalemia
Medications
Patiromer
- MOA: binds to potassium in GI tract to increase fecal exceretion (also does this with magnesium– Patiromer=pal)
- DD Interactions: administer 3 hrs before or after others
- ADRs: hypomagnesium and kalemia, constipation, dirrhea, flatuence
avoid in those with bwel obstruction/impaction, post-op, etc.
Sodium Zirconium Cyclosilicate
- MOA: binds potassium in GI tract to excrete into feces
- DD: administer 2 hours before or after foods
- ADRs: Edema, hypokalemia
edema: therfore do not give to thsoe at increased risk of edema- late stage CKD!!
do not give in post-op, bowel obsturction, etc.
Acute Hyperkalemia Management in CKD
- asymptomatic
- symptomatic
Asymptomatic
- those with K < 6
- use conservititve treatement: Furosemide (loop) to help increase amount of potassium being excreted via urine (can be good for CKD 4/5)
- sodium zirconium cyclosilate
- sodium polystyrene sulfonate: exchanges potassium for sodium to decrease potassium (PR (per rectum) can cause colonic necrosis and GI toxicities)
Symptomatic
- K > 6
- Cardiac abnormalities present!!: Peaked T waves, widened QRS or lost P wave
- first management is to stabilize the cardiac membrane via calcium gluconate IV STAT
- then manage with drugs to help decrease potassium within the bloodstream
- IV insulin (D5W if hypoglycemic)
- nebulized albuterol
Monitoring of acute and chronic hyperkalemia in CKD pts.
Chronic
- check the K every 1-2 weeks
Acute
- if K is > 5 = get EKG stat
- if cardiac changes= continuous ekg to monitor
- given insulin and dextrose = check K and glucose after 1 hours
- given albuterol = check K after 1 hours
- sodium polytyrene sulfonate = check K after 2-4 hours (given to the asymptomatic acute)
Anemia of CKD
two types
patho
when do you evaluate for anemia in a person with CKD
EPO: erythropoietin is produced in the kidneys & responsible for stimulation of RBS production
- drop in EPO with a drop in nephrons and therefore a drop in RBCs
- increased risk of CVD becuase less o2 carrying capacity
Uremic toxins decrease the lifespan of the RBC
iron deficiency aneami: blood loss occurs commonly due to the frequent blood draws and hemodyalsis & decreased baility of the GI to absorb
When To Evaluate
- symptoms of anemia
- stage 3,4 or 5 CKD
- hgb < 13 for men
- hgb < 12 women
get workout of CKD to stage progression ang get iron, folate and B12
Steps to Management of Anemia in CKD pts.
- first address the iron deficiency (if present) due to iron, b12 or folate
- if the anemia persists after repletion of these, add an ESA (erythropoetin stimulation agent) - if they have anemia of chronic disease without iron deficency –> go right to ESA
- no iron deficeny – give EPO
Iron Supplementation
- oral
- IV
oral iron is preferred as long as they are not on dialysis (they wont absorb it)
Names/preparations
- ferrous sulfate
- ferrous fumarate
- ferrous gluconate
- polysaccharide iron
- heme iron polypeptide
Instructions of Oral Iron
- food will decrease absorbtion: take on empty stomach
- citrus (absorbic acid) increases the absorbtion
SIde Effects
- constipation, nausea, cramping
- taking with food can help lessen these
IV Iron
- indicated if oral isnt effective or if they are on dialysis
Names (all equally effective)
- iron sucrose
- ferumoxytol
- iron dextran (LAST LINE: anaphlyaxis risk, myalgias,etc.)
ADE
Happen during infusion
- hypotension, flushing, nausea, injection site reaction
slow infusion rate = less effect of these
longer term
- dyspnea
- HA
- low back pain
- arthralgias, arthritis
- syncope
- anaphylaxis with dextran
Use of ESA in CKD
- indications
- names
- adverse reactions
- monitoring
ESA: erythropoetin stimulation agent (induce over 10-60 days)
Indications
- pts. NOT on dialysis with Hgb < 10 and have no iron, B12 or folate deficiency
- pts. On dialysis with Hgb < 9-10 and have no iron, B12 or folate deficiency
- pts. on iron and ESA are usually on iron to prevent IDA
subcu. injection preferred becuase its more predicable
Names
- epoetin alfa (most common)
- darbopoetin alfa (risk of stroke– less used)
ADE
- HTN is most common side effect : therefore avoid in these pts. and manage the HTN in those who it may develop
- seizures
- vascular access thrombosis
- thrombosis (DVT, PE and stroke risk)
Monitoring
- check Hgb weekly at first ; once stable then cehck every 1-2 weeks
- then once they get to hgb < 11.5 STOP ESA
- iron stroes: check every month for those not getting iron, cehck every 3 if they are also getting iron
what types of bone and mineral disorders can arise as a result of CKD
abnormalities in bone turnover, mineralization, volume growth and strength & calcifications of arteries
common in CKD 3, 4 and 5
Osteitis fiberosa cystic: high bone turnover disease (most common)
osteomalacia: low bone turnover disease
adynamic bone disease
these bone diseases increase mortality in pts. and increase risk of fracture rates & bone pain
Key Aspects of Treatment for pts. with CKD and bone/mineral abnormalities
The key is to prevent it early on!!! once symptoms develop–> it is not easily treated
Treating the Calcifications
- no none way to treat the formation of the calcifications in the soft tissue and the vasculature
- the only prevention is to avoid the pt. getting into hypercalcemia; ultimately when they get to this stage the risk of mortaity is increased significantly
explain the pathophysiology of CKD and bone/mineral abnormailites by way of phosphate and vit D3 precursor levels
progressive kidney disease =
- leads to a decrease in the ability to excrete phosphate through the kidneys – leading to an increase in the amount of phosphate within the body (phosphate retention due to decreased secretion)
- leads to a decrease in the kidneys ability to produce the precursor for vitamin D, (calcitriol), thus less active vitamin D
Vitamin D= helps absorb calcium from teh GI tract; without it, decreased calcium absorbtion
Phosphate within the body= binds to calcium adn therefore drops the amount of free calcium in the body
two mechanisms which decrease the amount of calcium in the body = hypocalcemia
hypocalcemia triggers the parathyroid hormone to signal to the pararthyroid gland that it needs to release calcium from the stores — aka the bones
this decreases the bone function & leads to the disorders
but also need to watch becuease too much calcium will lead to further cacification in the vessels and soft tissues
how is the diagnosis of CKD and MBD done
early!! need to identify the changes in lab values prior to the changes within the bone structure – fractures and bone pain – want to catch prior to calcifications occuring within the vasculature too!
Lab abnormalities
- phosphorous
- vitamin D
- PTH
- calcium
- fiberoblas growth factor-23
Treatment of phosphorous abnormalities
- when does it appear
- overview
Dietary specifics
hyperphosphatemia occurs first in those with CKD: usually need to begin screening for this aroound stage 3
Overview
- dietary phophate restriction
- minimize aluminum
- meicidaons
- dialysis (if unsuccessful)
- parathyroidectomy is last result
Dietary
- considered first line intervention for those with stage 3, 4, 5 CKD + ULN phosphorous or elevated iPTH
- aim for 800-1000 mg/day only
- avoiding high phosphrous foods: meats, cheese, beans, nuts, soda, beer and peanut butter
- get dietary involved to help with adequate protein consumption
Minimize Aluminum
- such as antacds which have aluminum
Dialysis
- not sufficient alone to lower the goals, but in combo with meds and dietary changes can be effective
PArathyroidectomy
- last line for those who do not respond to medication
Medications used to treat hyperphosphatemia in CKD BMD
Phosphate-binding agents
- Names
- preferred ones
- how they work
- adverse reactions
Phosphate-Binding Agents
MOA: form insoluable compounds with phosphate to excrete in feces and therefore reduce the amount that can be taken up into the serum
ADE
- constipation
- N/V/D
- abd. pain
titrate based on the their phosphate and calcium trends
phosphate-binders MUST be taken with meals and 3x daily with each meal!!!!!!
Names preferred agents are wihtout calcium
- sevelamer HCl
- sevelamer carbonate
- lanthanum preferred agents
- calcium carbonate
- cacium acetate
- ferric citrate
- sucroferric oxyhydroxide
last line meds: aliuminum hydroxide, carbonate and magnesium containing antacids (want to avoid aluminum)
Sevelamer carbonate & sevelamer HCl
specifics
D-D interactions
Specifics
- nonabsborbale non-elemental hydrogel
- no calcium
- the carbonate is preferred over the HCl for risk of metabolic acidosis
Drug-Drug Interactions
- think about binding mechanisms; as thats how they work to bind to phosphate and excrete it
- cyclosporins, tacromlimus
- caicitriol!!!!
- levothyroxine
- quinolones
seperate timing of meds given to avoid the binding
Lanthanum carbonate
specifics
Drug Interactions
Specifics
- another phosphrous binder - but this is elemental in that it disassociates in the gastric environment (if on a PPi– wont work becuase not acidic enough)
- MUST BE CHEWED for effectiveness
Drug Interactions
- antacids
- statins
- quinolones
- tetracyclines
- levothyroxine
Iron-based Phosphorous Binders
- ferric citrate
- sucroferric oxyhydroxide
Ferric Citrate
- lowers phosphorous & treats iron deficiency !!
Sucroferric Oxyhydroxide
- lowers phophate
- but does not work on IDA; still can increase iron studies and lower the need for IV iron or ESA use
Precautions of these meds
- discoloration of stool (bcuz iron)
- drug interactions due to the iron
- $$$$$
Calcium Containing medications for treating hyperphosphatemia
- Calcium acetate
- calcium carbonate
caution use why
who should not use
Drug interactions
Calcium Acetate (preferred agent of the two - Acetate= A+)
- more effective thatn carbonate
- decreases phosphroud but increases calcium (watch thier orignial calcium levels!!! before giving)
- more soluable and better absorbed at an alkaline pH
Calcium Carbonate
- decreases phosphrous, increases calcium
- cheap, OTC
- better in an acidic environment to absorb
Caution Use
- chronic use of calcium containing phosphate binders cane lead to an increase in calcifications in the vasculature and soft tissures = inc. CVD risk!!
- titrate doses Q2-3 weeks
do not use calcium containig meds if…
- high calcium levels (ULN)
- aterial calcifications
- adynamic bone disease
Drug-Drug INteractions
- interfers with iron, zince and quinolone abx. separate meds by 1-3 hours
Last Line Phosphate Medications
- Aluminum Hydroxide & magnesium containing antacids
Aluminum Hydroxide
- last line: only short term therapy (4 weeks or less) if they are unresponsive to other oral treatments
- CNS toxicity with this
- aluminum is renally eliminated = but kidneys arent working…..
Magnesium containing antacds
- effective, but diarrhea! and watch potassium levels
Monitoring for those on Phosphate binding medications for CKD
At initiation of treatment: watch phosphrous every 1-4 weeks
when stable: watch phosphrous and calcium every 1-3 months
can monitor PTH too
want to focus on the tredsn of thier corrected calcium, phosphrous and PTH levels
Vitamin D
- patho
- how it is effected in CKD
patho
- vit d comes from the sun, from food and supplements
- it is biologically inactive then converted to calcidiol form in the liver, then converted to active form in the kidneys
- active form = calcitriol (1, 25 dihydroxyvitamin D)
- the conversion to the active form can also happen outside the kidneys
CKD
- all pts. with CKD: stages 1-5 are at risk for vitamin D deficiency
- left untreated = leads to increase PTH levels and subsequent issues
Treatment of Vitamin D Deficiency in CKD
- assess what levels
- treatment with what
- goal levels
- assess vitamin D levels (calcidiol)
- insufficient = 30-49
- deficiency = less than 30
ensure the calcium and phosphate levels are normal or almost normal before supplementing the vit d (becuase those issues can precipiate a vit D deficiency)
Treatment
- supplement with oral ergocalciferol (vit D2) or cholecaciferol (vit D3)
- normal goal: want calcidiol levels > 50
the reason we can treat these people with inactive VitD is becuase although their kidnye function is not great, vit D synthesis can happen extra-renally thus the conversion process can still happen if they have only low VitD and not PTH
Treatment of Vit D deficiency in CKD
- for those stages 3-5 NOT on dialysis
if calcidiol levels NORMAL, but PTH is elevated they need the active form of Vit D ; they cannot convert anymore
Meds
- calcitriol (biologicallt active form of Vit D)
- Vitamin d analog (doxercalciferol, paricalcitol)
always ensure the calcium and phosphate levels are normal or close to normal before starting vit D treatment
Treatment of Vit D deficiency in CKD
- for those CKD stage 5 AND on dialysis
if on dialysis, AND PTH levels 2-9 times ULN = need to lower the PTH levels
lowering PTH via giving active vit D (calcitriol, doxercalciferol, dapicalcitol, cinacelcelt)
for those with…
- elevated PTH
- normal calcium and phosphrous
give calcitriol, doxercalciferol or paricalcitol
for those with…
- elevated PTH
- elevated calcium
- elevated phosphrous
give cinacalcet
Calicitriol, & vitamin D analogs
- MOA
- ADE
- Drug Interactions
MOA
- these are biologicall ACTIVE forms of Vit D
- they bind to the vit D receptor on the parathyroid gland, intestine, bones and kidneys
- this inhibits the suprresion of PTH (therefore stopping the signal that we need to conserve vit D)
- this then allows greater absorbtion of clacium and phosphate from the GI tract & downregulation the PTH
ADE
- hypercalcemia
- hyperphosphetemia
- oversupressed PTH
- adynamic bone disease
- all of these more likely to occur with calcitriol than the other anologs; the anologs bind better th PTH not the GI so less of the SE
Drug Interactions
- Doxercalciferol: pro-hormone: needs CYP3A4!! cant use with inhibitors of CYP3A4
- paricalcitol: MAJOR CYP3A4 SUBSTRATE: watch with inducers and inhibitors
- calcitriol and doxercalciferol: minor substrates at cyp3a4
Cinacalcet
- MOA
- ADE
- Drug inceratsion
Cinacalcet: used in CKD 5; dialysis with elevaetd PTH, calcium and phosphate (too much of everything!!)
MOA: calcimimetic
- increases how sensitive the calcium sensing receptors on the Parathyroid gland is: thus they sense the calcium and are about to reduce the secretion of PTH
- they do not increase calcium and phophate absorbtion in the GI tract: a goo thing becuase there is already too much
- they actually can reduce calcium and phosphate levels: because they increase PTH receptors then stop the reabsorbtion of calcium and phosphate in the seurm
ADE
- avoid in pts: low calcium and phosphate and those with seizure risk
- N/V
- hypocalcemia: paresthesias, myalgias, carmping, tetany, seizures
Druge Intercations
many DD interactions
- major CYP2D6 substrate and inhibitor
Monitoring of Vit D levels for those with CKD
- monitor PTH levels: avoid oversuprresion as that can lead to adynamic bone disease
- monitor PTH every month until stable, then every 3months
phosphorous and calcium levels
- get prior to starting meds
- get within 1st week
- then get everytime you get a PTH level
Chronic Metabolic Acidosis in CKD pts.
- patho
- management
Patho
- there is a decrease in renally elimiated H+ and thereofer a build u = acidosis
- accumulation of phosphate and anions lead to an elevated anion gap
at a pH < 7.35..
- bone metabolism altered
- decrease vit D effectiveness
- protein catabolism (breakdown) occurs
at pH , 7.2
- supressed heart contractiliy
- caridaic arrythmias
- hemodialysis needs to be started
Management
- treat underlying disorder
- give orla alkalinzing salt to replensih bicarb stores which are gone
salts
- sodium bicarb tablets
- bicitra & Shohl solution (sodium citrate and citric acid)
- avoid citrates that contain potassium for risk of hyperkalemia
CKD and metabolic acidosis
Sodium Bicarbonate Tablets: ADEs
Bicitra and Shohls solution: ADEs
ADE: sodium bicarb tablets
- volume overload: due to the sodium retention
- exacerbation of heart faiure and HTN
- gas, gastric disturbeances due to CO2 production when dissolivng
- hypernatermia
- metabolic alkalosis (if too aggressive with treatment)
ADEs: Bicitra and Shohls solution
- better tolerated than sodium bicarbs, less flatuence and overload risk
- hypernatermia and alkalosis still possible
Monitoring of metabolic acidosis and CKD
- dose dependent administration of medications based on weight & base deficit
- administer loading dose, then maintenance dose
Monitor
- pH
- bicarb
- sodium (daily in inpt, weekly with dialysis in outpt.)
DDI: wathc with citrate-containing products: can ehnace aluminum absoption!!
Uremic Bleeding: CKD Complications
- patho
- management
- chronic management
Patho
- uremia = alters the ability of clotting factors = leads to hemorrhage risk
- specifically alters platelet function and ability to aggregate (alters thromboxane production)
- decreased vonwillbrad production, inability for platlets and the vessel wall to interact to clot properly
- this issue is made worse by anemia in CKD and medications that are preventing clotting
Management- Acute
Desmopression DDAVP
- increases the release of actor VIII (vonwills friend)
- 1 hour onset of action, works for 8 hours
- risk of tachyphlyaixis, flushing dizzy and HA
- cryoprecipitate (blood products)
- take 1 hour to work but risk of infection
Management - Chronic
- IV or PO estrogen (IV onset of action is quicker, lasts longer)
- wathc hot flashes, fluid retention and HTN
CKD: managing Puritis
- first line meds and management
- other optiosn
First line:
- dialysis = attempt to remove the uremic toxings causing the itch
- manage phopsphate and protein intake
Meds
- antihistamines (hydroxyzine and diphenhydramine)
Other Options
- oils and emollients
- oral charcol to bind to uremic toxins
- gabapentin
- zofran
- naloxone
- topical capsaicin
- photothearpy
CKD: management of vitamins
ESRD: hemodialysis
- will ahve higher levels of AEK fat soluable ones and less of water soluable ones (thiamine, folic acid, riboflavin,etc.)
Drug Dosing in CKD pts.
when to dialyze
stages of CKD, mainly 3, 4, 5 and those on dialysis
Dialysis
- drug dosing dependent on the type of dialysis they are on and requires close monitoring of response to
when to Dilyze
- symptoms and signs due to kidney failure (serositis, acid-base issures, itchy)
- inability to control volme or BP
- deterioration in nutrtion
- cognitive impairment
- often beteen GFR 5-10
