CKD Flashcards
Acute Kidney Injury
Sudden loss of kidney function due to non-renal conditions (drug).
Often reversible but can be permanent if precipitating factor is not corrected.
Common cause of AKI
Dehydration
Presentation of AKI
BUN: SCr ration greater than 20:1 plus
Decrease urine output
Dry mucus membranes
Tachycardia
Chronic Kidney Disease
A progressive loss of kidney function over months or years.
How is CKD severity measured?
Glomerular filtration rate (GFR)
Creatinine Clearance ( CrCl)
Albumin in the urine
End- Stage Renal Disease (ESRD)
Total and Permanent Kidney Failure
Fluid and waste accumulation
Dialysis or Transplant is needed
What are the most common causes Of CKD?
Diabetes
Hypertension
What is the function of the Nephron?
Control the concentration of sodium and water.
This regulate blood volume and in turn blood pressure.
What is the glomerulus ?
Large filtering unit that is located within the bowman capsule.
Afferent arteriole delivers blood into the glomerulus
Efferent arteriole unfiltered substance exit nephron here.
If the glomerulus is healthy?
Only substances less than 40,000 daltons including most drugs can pass through into the filtrate.
Large substance ( proteins and protein bound drugs) are not filtered and stayed in the blood.
If the glomerulus is damaged?
Some Albumin passes into the urine
Albumin + GFR assess CKD severity (nephropathy).
What is Proximal Tubule?
Entry point of nephron
Reabsorb filtered Na, Cl, Ca and water into bloodstream.
*Blood pH is regulated by the exchange of Hydrogen and Bicarbonate ions.
What is the Loop of Henle?
Descending limb (down): water is reabsorb
Ascending limb (up): Na and Cl ions are reabsorb
*If antidiuretic hormone (ADH) or Vasopressin is present water passes through the walls of the ascending limb and is reabsorbed into the blood; less water excreted in the urine (anti-diuresis)
Loop of Henle and Diuretics?
Loop diuretic inhibit the Na-K pump in the ascending limb ; less Na and Ca is reabsorb back into the blood.
Long term Ca depletion can decrease bone density.
Na concentration increase in filterate , less water is reabsorb and both are excreted in the urine.
What is the distal convoluted tubule?
The farthest point away from entry to nephron
Regulate K, Na, Ca and pH
Distal convoluted tubule and Diuretics?
Thiazide diuretic inhibit the Na-Cl pump
Thiazides( 5% Na reabsorb) is a weaker diuretic than loops (25% Na reabsorb).
Thiazides increases Ca reabsorption therefore long-term use has protective effect on bone.
What is the Collecting Duct?
Network of tubules and ducts that connects nephrons in each kidney to a ureter.
Involve with WATER and ELECTROLYTE balance affected by ADH and aldosterone
Urine Filtrate= Ureter to bladder then out the body via Urethra
Aldosterone role in distal convoluted tubule and collecting ducts?
Works in the tubule and duct to increase Na and water reabsorption but decrease K reabsorption.
Aldosterone Antagonist ( Spironolactone and Eplerenone) block aldosterone; more Na and water is excreted in the urine but serum K increases.
What is Drug Induced Kidney Disease (DIKD?
Linked to numerous medications
Acute and reversible; irreversible to CKD if drug is not stop.
Common in hospital setting and contributes to morbidity and mortality.
Drugs that cause kidney disease?
Aminoglycosides
Amphotericin B
Cisplatin
Cyclosporine
Loop diuretic
NSAIDS
Polymyxins
Radiographic Contrast Dye
Tacrolimus
Vancomycin
What are the two common laboratory markers use to estimate kidney functions and what do they measure?
BUN( blood urea nitrogen): measure amount of nitrogen in the blood that come from urea, a waste product of protein metabolism
SCr ( serum creatinine) : waste product of muscle metabolism
As kidney function declined BUN and SCr increases.
SCr Normal Range: 0.6 - 1.3 mg/dL
What common equation is use for CrCl?
Cockcroft Gault Equation
CrCl (mL/min) = (140-age)/(72*Scr) ×weight x 0.85 (female)
What weight to use to calculate CrCl?
Use Actual Body weight if less than calculate Ideal Body Weight
Use Ideal Body Weight if BMI is in normal range
Use Adjusted Body Weight if BMI is in overweight range
IBW = ( 45.5 or 50 kg) + 2.3kg (inches over 5ft)
AdjBW= IBW + 0.4(TBW - IBW)
What’s calculate CrCl use for?
To determine dosing adjustments and medication contraindications.
Calculate CrCl accuracy is decreased?
When a patient has very low muscle mass (frail elderly patients)
Low muscle mass = low Scr
Overestimate CrCl
Calculate crockcroft gault CrCl can be inaccurate in patients with ?
Obesity
Liver disease
Pregnancy
High muscle mass
Very young children (crockcroft gault not preferable)
ESRD or unstable kidney function (crockcroft gault not preferable)
Drug dosing is usually base on CrCl but sometimes is base on GFR.
Which drug dosing can be base on GFR?
SGLT2 inhibitor
Metformin
How is GFR Calculated?
Calculated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
What is albumin in relation to CKD?
The primary protein that is measured in the urine to assess kidney disease.
Known as Albuminuria or Proteinuria
What is KDOQI guidelines recommendations?
Use GFR and degree of ALBUMINURIA (levels in urine) along with cause of CKD to Determine the degree/ stage of renal impairment.
Which levels of GFR and/or Albumin suggests a patient have CKD?
GFR less than 60 mL/ min/1.73m3
Albuminuria greater than or equal to 30 mg/mmol
ACE and ARBs role in CKD?
ACE and ARBs are FIRST- LINE drugs to prevent progression of disease in patients with CKD, Diabetes, and/or HTN if Albuminuria is present.
Works by inhibiting RAAS causing efferent arteriolar dilation.
Reduce pressure in the glomerulus, decrease Albuminuria and provide cardiovascular protection.
What to expect in SCr when starting treatment with ACE inhibitor or ARBs?
Scr can increase up to 30%
If more than 30% increase D/C medication and referred patient to nephrologist.
What should be monitored when on ACE Inhibitor and ARBs?
Scr and K. 1 to 2 weeks after initiating
NEVER use both class together
They increase Potassium (K)
Advice pt to avoid K supplement and salt substitutes (KCl)
MAXIMIZED Dose for Renal protection
What is KDIGO Guidelines Recommended BP goal for CKD patient?
No Proteinuria: Less than 140/90 mmHg
Proteinuria: Less than 130/80 mmHg
Reasons to MODIFY DRUG THERAPY in CKD
Drug is Eliminated through the Kidneys: modify to avoid accumulation and SE/toxicity; Reduce dose and/or extend interval
The drug can cause or worsen kidney disease( Nephrotoxic)
Drug become less effective as kidney function declines (ex. Thiazide, and Nitrofurantoin)
Drug is CONTRAINDICATIONED at a specific level of kidney impairment because accumulation is unsafe. (Ex. Bleeding risk with anticoagulants)
Drug can cause further kidney damage ( ex. NSAIDS)
Drug can cause more harmful effects than usual when kidney function is reduced (ex. Hyperkalemia with aldosterone antagonist)
Dose Adjustments may be required or necessary when:
CrCl is less than 60 mL/min (1/2 of normal)
CrCl is less than 30 mL/min (1/4 of normal; additional adjustments may be needed or drug may be CONTRAINDICATED)
Related disorders associated with CKD
Anemia
Hypertension
Acid-Base and ELECTROLYTE disturbances
Bone mineral metabolism disorder ( management of PTH, PO4, Ca and Vit D levels)
What is CKD Mineral and Bone Disorder (CKD-MBD)?
Common in renal impairment pt and almost in all pt receiving dialysis.
Associated with fractures, cardiovascular disease and increase mortality.
In relation to CKD-MBD patient with advanced kidney disease require monitoring for
Parathyroid Hormone (PTH)
Phosphorus (PO4)
Calcium (Ca)
Vitamin D levels
Explain the interaction of Ca, PO4, Vitamin D and EPO in CKD
PO4 increase bc kidneys cannot eliminate
Vitamin D cannot be activated by kidney causing Calcium absorption to decrease
High PO4 and low Ca cause increase release of PTH (usually increase Ca reabsorption via feedback)
PTH pull Ca from bone causing demineralization and increase fracture
High PO4 levels( hyperphosphatemia) continued to stimulate PTH (secondary hyperparathyroidism) and hypercalcemia persist causing calcification and cardiovascular disease
Kidney produce less erythropoietin (EPO) resulting in decrease RBC production in the bone marrow which causes anemia.
Hyperphosphatemia must be treated to prevent bone disease and fractures. Treatment is focused on;
Restricting dietary phosphate
Avoid dairy products, cola,chocolate and nuts
What is the MOA of Phosphate Binder?
Block absorption of dietary PO4 by binding to it in the intestine.
Missed dose ( food is absorb) = Skipped till next meal or snack
3 types: Aluminum-based, Calcium-based and
Aluminum and Calcium free drug
Aluminum based Phosphate Binders:
*Potent but Rarely Use due to Aluminum accumulation/ toxicity
Aluminum Hydroxide Suspension
300-600 mg TID
SE : *Dialysis Dementia
Aluminum toxicity due to accumulation cause nervous system and bone toxicity
Osteomalacia
Constipation
Nausea
MONITOR: Ca, PO4 , PTH, S/SX ALUM.TOX
Calcium base Phosphate Binders:
*FIRST LINE
Calcium Acetate (Phos-lyra, Phos-lo): bind more
Calcium Carbonate (Tums)
Daily Calcium less than 2000 mg
SE: *Hypercalcemia (especially with concomitant use of Vit D due to increased calcium absorption )
Constipation
Nausea
MONITOR: Ca*, PO4, PTH
Alu/Ca Free Phosphate Binders:
Sucroferric Oxyhyroxide (Velp-Horo) Ferric Citrate (Aury-Xia) Lanthanum Carbonate ( Fos-Renol)
*MORE Expensive; *Less hypercalcemia; *No Aluminum accumulation
- Sucroferric Oxyhyroxide (Velp-Horo)
- Ferric Citrate (Aury-Xia)
WARNING: *Iron absorption occurs with ferric citrate ( reduce IV iron dose; store out of reach of children)
SE: Diarrhea, Constipation, discolored black feces
MONITOR: Iron, ferritin, Tstat (ferric citrate), PO4, PTH
- Lan-tha-num Carbonate ( Fosrenol)
- Chew tab thoroughly to reduce severe GI adverse effects.
CONTRAINDICATIONS: GI obstruction, fecal impaction, illeus
WARNING: GI perforation
SE:* NVD, Constipation, Abdominal pain
MONITOR: Ca, PO4, PTH
Alu/Ca Free Phosphate binder:
Sevelamer Carbonate (Ren-vela) Sevelamer Hydrochloride (Ren-agel)
- No Hypercalcemia; No Aluminum
- Not systemically Absorbed
Sevelamer Carbonate (Renvela)
Sevelamer Hydrochloride (Renagel)
CONTRAINDICATIONS: Bowel obstruction
WARNING: reduce dietary absorption of vit DEK and folic acid; give with vit supplement
SE: *NVD (GREATER THAN 20%), Dyspepsia, Constipation, Abdominal Pain, Flatulence
MONITOR: Ca, PO4, HCO3,Cl, PTH
Note: * lower CHOLESTEROL and LDL by 15-30%.
Sevelamer Carbonate maintain bicarbonate concentration.
Phosphate binder interactions
*Separate administration from levothyroxine and antibiotics that chelate (quinolones, tetracycline)
Key Anti-infectives drugs that require lower dose or increase interval in CKD
Aminoglycosides (increase dosing interval primarily)
Beta-lactam antibiotics (most)
Fluconazole
Quinolones (except Moxifloxacin)
Vancomycin
Key Cardiovascular drugs that require lower dose or increase interval in CKD
LMWHs (enoxaparin)
Rivaroxaban (for AFib)
Key Gastrointestinal drugs that require lower dose or increase interval in CKD
H2RAs (famotidine, ranitidine)
Metoclopramide
Key Other drugs that require lower dose or increase interval in CKD
Bisphosphonates
Lithium
Other Anti-infectives drugs that require lower dose or increase interval in CKD
Amphotericin B
Anti-tuberculosis meds ( ethambutol, pyrazinamide)
Antivirals ( Acyclovir, Valacyclovir, Ganciclovir, Valganciclovir, Oseltamivir)
Aztreonam
NRTIs, including tenofovir
Polymyxins
Sulfamethoxazole / Trimethoprim
Other cardiovascular drugs that require lower dose or increase interval in CKD
Antiarrhythmics (digoxin, disopyramide, dofetilide, procainamide, sotalol)
Apixaban ( for Afib)
Dabigatran (for Afib)
Statins (most)
Other Pain/Gout drugs that require lower dose or increase interval in CKD
Allopurinol
Colchicine
Gabapentin, Pregabalin
Morphine and Codeine
Tramadol ER
Other drugs that require lower dose or increase interval in CKD
Cyclosporine
Tacrolimus
Topiramate
Select drugs that are contraindicated in CKD
CrCl less than 60 mL/min
Nitrofurantoin
Select drugs that are contraindicated in CKD
CrCl less than 50 mL/min
Tenofovir Disoproxil Fumarate containing products (Ex. Stribild, Complera, Atripla, Symfi, Symfi Lo)
Voriconazole IV ( due to the vehicle)
Select drugs that are contraindicated in CKD
CrCl less than 30 mL/min
Tenofovir Alafenamide containing products ( ex. Genvoya, Biktarvy, Descovy, Odefsey, Symtuza)
NSAIDs
Dabigatran *(DVT/PE)
Rivaroxaban* (DVT/PE)
Select drugs that are contraindicated in CKD
GFR less than 30 mL/min/1.73m3
SGLT2 Inhibitor (Canagliflozin, Dapagliflozin, Empagliflozin)
Metformin
Other:
Meperidine. ***Not specific
Other drugs that are contraindicated in CKD
CrCl less than 30 mL/min
Avanafil
Bisphosphonates
Duloxetine
Fondaparinux
Potassium Sparing Diuretics
Tadalafil*
Tramadol ER
Others not specific recommendations:
Dofetilide
Edoxaban
Glyburide
Sotalol (Betapace AF)
*indication specific
After controlling hyperphosphatemia, ELEVATED PTH are treated primarily with….
Vitamin D
What cause Vit D deficiency in CKD?
Kidney is unable to Hydroxylate Vit D to its final ACTIVE FORM ;
1,25 - Dihydroxy Vit D
Vitamin D deficiency can lead to ?
Worsen Bones Disease
Impair Immunity
Increased ris of CARDIOVASCULAR Disease
What are the 2 forms of Vitamin D?
- Vitamin D3 (CHOLECALCIFEROL) ; synthesize in skin after exposure to ultraviolet light from the sun
- Vitamin D2 (ERGOCALCIFEROL); produce from plant steriod; dietary source of Vit D
Oral supplements of both may be necessary for pt with early CKD (stage 3&4)
What are Vitamin D analog used for?
Use in later stage of CKD or ESRD to
INCREASE Ca Absorption from the gut;
Raise Ca concentration ; and
Inhibit PTH Secretion
What’s Vitamin D Analog MOA?
Increased intestinal absorption of Ca which provides negative feedback to the parathyroid gland
Vitamin D Analog
Treatment of Secondary Hyperthyroidism
Pari and Doxer cause less hypercalcemia
Calci-triol (ROCAL-TROL) : active form of Vit D3; take with food
Calci-fediol (RAYAL-DEE) : prodrug of calcitriol; 25 hydrox toxicity
Doxer-calci-ferol (HECTO-ROL)
Pari-calci-tol (ZEM-PLAR)
CONTRAINDICATIONS: Hypercalcemia; Vit D Toxicity
WARNING: Digitalis toxicity by hypercalcemia
SE: *Hypercalcemia, Hyperphosphatemia, NVD ( GREATER THAN 10%)
MONITOR: *Ca, PO4, 25 hyroxy vit D (Calcifediol)
What are CALCIMIMETIC Used for?
Mimic the action of Calcium on the parathyroid gland and reduce PTH
It is only used in dialysis patients
What the MOA of CALCIMIMETIC?
INCREASED SENSITIVITY of the calcium-sensing receptors on the parathyroid gland, which causes DECREASE PTH, Ca , PO4.
CALCIMIMETIC Drugs
Treatment of Secondary Hyperthyroidism
-Cina-calcet (SENSI-PAR)
CONTRAINDICATIONS: Hypocalcemia
WARNING: caution in pt with hx of seizures
SE: *Hypocalcemia, NVD, Paresthesia, HA, Fatigue, Depression, Constipation, UTI, muscle pain and weakness, fracture
MONITOR: Ca, PTH, PO4
-Etel-calce-tide (PAR- SABIV)
WARNING: *Hypocalcemia, worsening HF, GI bleeding, decreased bone turnover
SE: *Muscle Spasms, Paresthesia, NVD
MONITOR: Ca, PTH, PO4
What is hemoglobin level is consider Anemia?
Hemoglobin less than 13 g/dL
Why is Anemia common in CKD?
One of the causes of Anemia is LACK OF ERYTHROPOIETIN(EPO), which is normally PRODUCED by the KIDNEY.
EPO goes to the bone marrow to Stimulate the production of red blood cells (RBCs).
RBCs (contains hemoglobin) and they transport oxygen to the blood.
Anemia in CKD is treated with what?
- Erythropoiesis Stimulating Agents (ESAs)
- Iron
Erythropoiesis Stimulating Agents (ESAs)
INDICATION: Anemia in CKD to prevent the need of blood transfusion.
EFFECTIVE: If adequate IRON is Available. Check ferritin and Tstat.
WHEN TO USE: hemoglobin less than 10 g/dL
WHEN TO D/C: Hemoglobin greater than 11 g/dL due to risk of thromboembolic disease (DVT, PE, MI, STROKE)
Risk: Elevated Blood Pressure and Thrombosis
TYPES:
E-poetin Alfa (PROCRIT, EPOGEN, RETACRIT)
Darbe-poetin Alfa (ARANESP) : long lasting formulation
Why is iron levels low in ESRD and what is the solution?
Low level can be due reduce GI absorption and blood loss from dialysis treatment.
Solution: IV IRON is given at dialysis center.
What is Hyperkalemia?
Normal Potassium: 3.5 to 5
Potassium Levels greater than 5.3 or 5.5
Clinical Concerns: levels greater than 5
Most Common Cause: DECREASED RENAL EXCRETION due to KIDNEY FAILURE.
SYMPTOMS:
Muscle Weakness
Bradycardia (monitor with ECG)
Fatal Arrhythmias ( (monitor with ECG))
What is potassium?
Most abundant INTRACELLULAR CATION essential for life.
Normal daily intake: 1mEq/kg/day
Food: meats, beans and fruits
How is potassium Eliminated?
via KIDNEY and partially by GUT
Renal potassium excretion is increased by:
Aldosterone hormone
Diuretics ( loops is greater than thiazides)
High urine flow ( osmotic diuresis)
Negatively charge ion in the distal tubule (bicarbonate)
Potassium in normal kidney function?
High level potassium DOESNOT cause HYPERKALEMIA in normal kidney.
High level are offset by release of INSULIN,
which causes potassium to shift into the cells.
Why are Diabetic patients at high risk of hyperkalemia?
Insulin deficiency reduce the ability to shift potassium into the cell.
Many patients with diabetes take ACE inhibitors or ARBs.
Key Drugs that Raise Potassium Levels?
ACE Inhibitors
ARBs
Aldosterone Receptor Antagonists
Aliskiren
Canagliflozin
Drospirenone containing COCs
Sulfamethoxazole/ Trimethoprim
Transplant Drugs (Cyclosporine, Everolimus, Tacrolimus)
Other Drugs:
Glycopyrrolate
Heparin
NSAIDs
Potassium containing IV fluids (parenteral nutrition)
Potassium Supplements
Pentamidine
Treatment of Severe Hyperkalemia?
D/C potassium source
Stabilize the Heart: Stabilize myocardial cells ( prevent arrhythmias)
Move it: rapidly shift potassium intracellularly
Remove it: induce elimination from the body.
Drugs use to treat HYPERKALEMIA?
They work quickly but DONOT LOWER total body potassium
See Chart on pg 299 & 300
Drugs use to Stabilize the Heart in severe Hyperkalemia?
Calcium Gluconate
Route : IV
Onset: 1 to 2 mins
Indication: Stabilize myocardial cell and prevent arrhythmias.
Drugs use to SHIFT EXCESS K INTRACELLULAR LY severe Hyperkalemia?
Regular Insulin: IV, 30 min; with glucose&dext
Dextrose: IV, 30 stimulate insulin; not alone
Sodium Bicarbonate: IV, 30; use when metabolic acidosis is present
Albuterol: neb, 30 min; monitor tachy and chest pain
Drugs use to REMOVE K in severe Hyperkalemia?
Furosemide: IV, 5 min; K in Urine
Sodium Polystyrene: Oral & Rectal, 1 hr; bind K in GI; use rectal in acute
Patiromer: Oral; 7 hr; bind K in GI; notfor acute/ emergency
Sodium Ziconium Cyclosilicate: oral,1hr; bind K in GI ; not for acute/ emergency
Hemodialysis: Remove K from Blood; too long to set up/ complete
Drugs for Treatment of Hyperkalemia?
Sodium Polystyrene Sulfonate (Kayexalate, Kionex): Rectal dose use in Emergency
Patiromer (Vel-tassa):* Not for Emergency; refrigerate powder and used 3 month at room temp
Sodium Zirconium Cyclosilicate (Lo-kel-ma): *Not for Emergency; store at room
SE: N/D, *Constipation ,Vomiting (Kionex), peripheral Edema (Lokelma)
WARNING: *bind to other oral medication (Separate by 3 for Veltassa and 2 hrs for Lokelma)
Can worsen GI motility (Veltassa and Lokelma)
Electrolyte Disturbances
Hyper-Na, Hypo-Mg,K,Ca, fecal impaction and GI necrosis: increase risk with sorbitol not to be use together (Kionex)
*Hypo-Mg( Veltassa)
MONITOR: K, Mg ( Na, Ca for Kionex)
Metabolic Acidosis in CKD
CAUSE: KIDNEYS ability to reabsorb bicarbonate DECREASE as CKD Progress.
Metabolic Acidosis in CKD Treatment
INITIATED: Serum Bicarbonate less than 22 mEq/L
TREATMENT: Replace Bicarb
- Sodium Bicarbonate (Neut)
- Sodium Citrate/Citric acid solution (Cytra-2, Oracit, Shohl Solution); metabolized in the liver; may not be effective in liver failure.
MONITOR: *sodium level; caution in HTN and Cardiovascular disease.
When is Dialysis required?
If CKD progress to Failure ( STAGE 5) and pt who did not receive KIDNEY TRANSPLANT.
Primary TYPE of Dialysis ?
Hemodialysis Dialysis (HD); Dialysis Machine 3 to 4 hrs/3 time per week
Peritoneal Dialysis (PD); Dialysis solutions pump into peritoneal cavity repeated though out the day, everyday
Factors that affect drug removal during Dialysis
DRUG CHARACTERISTIC:
Molecular weight/size: smaller
VD: small vd
Protein-Binding: low protein bound
DIALYSIS FACTORS:
Membrane; high( large pore)
Blood Flow Rate; high flow rate
