CKD & Associated

Question 1

define CKD and the classifications

Answer 1

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

Question 2

Complications of CKD and their timing of onset

Answer 2

• 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

Question 3

Normal role of Kidneys and their sodium/water homeostasis

what happnes in stage 4 & 5 CKD

Answer 3

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

Question 4

Treatment of the Sodium and Water retention in CKD pts.

Answer 4

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

Question 5

Treatment of Sodium and Water Retention in CKD pts.
- role of ACE/ARBs and SGLT2i

Answer 5

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)

Question 6

MOA, DD interactions and ADE of SGLT2

Answer 6

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

Question 7

role of Finerenone in CKD pts.
MOA
ADE
contraindications

Answer 7

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

Question 8

role of a Dulaglutide in sodium, water homeostatis in CKD

Answer 8

Dulaglutide: a glucaogon-like peptide 1 antagonist
- can be used for those with T2DM, CKD to help reduce risk of CVD

Question 9

how does hyperkalemia occur in those with CKD
- at what GFR
- management

Answer 9

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

2. pharm management (patiromer or sodium zirconium)

eventaully dialysis will be needed if the above are not working

Question 10

Treatment of Chronic hyperkalemia in CKD

• patiromer
• sodium zirconium

MOA, ADE, etc.

Answer 10

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.

Question 11

Acute Hyperkalemia Management in CKD
- asymptomatic
- symptomatic

Answer 11

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

Question 12

Monitoring of acute and chronic hyperkalemia in CKD pts.

Answer 12

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)

Question 13

Anemia of CKD
two types
patho

when do you evaluate for anemia in a person with CKD

Answer 13

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

Question 14

Steps to Management of Anemia in CKD pts.

Answer 14

1. 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)
2. if they have anemia of chronic disease without iron deficency –> go right to ESA
   - no iron deficeny – give EPO

Question 15

Iron Supplementation
- oral
- IV

Answer 15

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

Question 16

Use of ESA in CKD
- indications
- names
- adverse reactions
- monitoring

Answer 16

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

Question 17

what types of bone and mineral disorders can arise as a result of CKD

Answer 17

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

Question 18

Key Aspects of Treatment for pts. with CKD and bone/mineral abnormalities

Answer 18

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

Question 19

explain the pathophysiology of CKD and bone/mineral abnormailites by way of phosphate and vit D3 precursor levels

Answer 19

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

Question 20

how is the diagnosis of CKD and MBD done

Answer 20

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

Question 21

Treatment of phosphorous abnormalities
- when does it appear
- overview

Dietary specifics

Answer 21

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

Question 22

Medications used to treat hyperphosphatemia in CKD BMD
Phosphate-binding agents
- Names
- preferred ones
- how they work
- adverse reactions

Answer 22

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)

Question 23

Sevelamer carbonate & sevelamer HCl
specifics
D-D interactions

Answer 23

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

Question 24

Lanthanum carbonate
specifics
Drug Interactions

Answer 24

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

Question 25

Iron-based Phosphorous Binders
- ferric citrate
- sucroferric oxyhydroxide

Answer 25

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
- $$$$$

Question 26

Calcium Containing medications for treating hyperphosphatemia
- Calcium acetate
- calcium carbonate

caution use why
who should not use
Drug interactions

Answer 26

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

Question 27

Last Line Phosphate Medications
- Aluminum Hydroxide & magnesium containing antacids

Answer 27

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

Question 28

Monitoring for those on Phosphate binding medications for CKD

Answer 28

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

Question 29

Vitamin D
- patho
- how it is effected in CKD

Answer 29

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

Question 30

Treatment of Vitamin D Deficiency in CKD
- assess what levels
- treatment with what
- goal levels

Answer 30

1. 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

Question 31

Treatment of Vit D deficiency in CKD
- for those stages 3-5 NOT on dialysis

Answer 31

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

Question 32

Treatment of Vit D deficiency in CKD
- for those CKD stage 5 AND on dialysis

Answer 32

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

Question 33

Calicitriol, & vitamin D analogs
- MOA
- ADE
- Drug Interactions

Answer 33

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

Question 34

Cinacalcet
- MOA
- ADE
- Drug inceratsion

Answer 34

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

Question 35

Monitoring of Vit D levels for those with CKD

Answer 35

• 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

Question 36

Chronic Metabolic Acidosis in CKD pts.
- patho
- management

Answer 36

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

Question 37

CKD and metabolic acidosis

Sodium Bicarbonate Tablets: ADEs

Bicitra and Shohls solution: ADEs

Answer 37

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

Question 38

Monitoring of metabolic acidosis and CKD

Answer 38

• 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!!

Question 39

Uremic Bleeding: CKD Complications
- patho
- management
- chronic management

Answer 39

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

Question 40

CKD: managing Puritis
- first line meds and management
- other optiosn

Answer 40

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

Question 41

CKD: management of vitamins

Answer 41

ESRD: hemodialysis
- will ahve higher levels of AEK fat soluable ones and less of water soluable ones (thiamine, folic acid, riboflavin,etc.)

Question 42

Drug Dosing in CKD pts.

when to dialyze

Answer 42

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