Renal / Hepatic Flashcards
Kidneys:
1. What is the main function of nephrons?
- First, the ________(afferent/efferent) arteriole delivers blood into the glomerulus where the Bowman’s capsule lies. Substrates with a MW <40,000 will pass through, which are typically what kinds of substances?
- If substance does NOT pass through the Bowman’s capsule, it will exit the kidney back into the blood via the _______(afferent/efferent) arteriole.
- How is glomerular filtrate rate (GFR) assessed?
- Regulate Na and water which regulates blood volume, blood pressure, and pH
- Afferent;
-Substances w/ MW <40,000: most drugs, water, electrolytes (what does NOT pass: proteins, protein-bound drugs) - Efferent
- When kidneys are damaged, some albumin can pass through the glomerulus –> amount of albumin in urine is used to estimate GFR
Kidneys:
1. Once substances are filtered through the glomerulus, they enter the proximal tubule which does what?
- Next the substance can enter the Loop of Henle. Explain the functions of the descending loop and ascending loop.
- Next the substance can enter of the distal convoluted tubule which regulates what?
- Finally, where does urine go?
1.
-Major source of initial filtering of Na, Cl, Ca, and water to reabsorb back into the blood along
-Regulates blood pH through exchanges of hydrogen and bicarbonate molcules
-Main point of absorption in general –> can absorb many other substances (ex. glucose, amino acids, vitamins, urea, choline)
2.
-Descending loop: reabsorbs water into blood (NOT Na and Cl which increases their concentration in the filtrate)
-Ascending loop: Na and Cl ions reabsorbed into blood (NOT water UNLESS antidiuretic hormone = ADH or vasopressin is present –> anti-diuresis effects if present)
- Regulates K, Na, Ca, and pH (less reabsorption than initial parts of nephron)
- Through the collecting duct which can make any final adjustments of electrolytes and aldosterone acts on to increase Na and water reabsorption (increases BP, blood volume) –> ureter –> bladder –> urethra
Drug-induced nephrotoxicity
1. What are risk factors to renal toxicity?
- What drugs are specifically associated with renal toxicity?
Risk factors:
-Decreased renal blood flow (dehydration, hypotension, heart failure)
-Preexisting kidney disease
-Increased age
-Multiple concurrent nephrotoxic medications (especially at frequent and/or large doses)
Nephrotoxic Medications:
-Anti-infectives: amionglycosides, amphotericin B, polymyxins, vancomycin
-Others: cisplatin, cyclosporine, tacrolimus, loop diuretics*, radiographic contrast dye/constrast media, NSAIDs
- Associated w/ AKI due to excessive volume loss
Explain how BUN, SCr, and CrCl can reflect kidney function
Blood Urea Nitrogen (BUN) - the amount of nitrogen in the blood that comes from urea, a waste product of protein metabolized that is excreted by the kidneys
-As BUN increases, kidney function decreases –> OTHER things can increase too (ex. dehydration)
Serum Creatinine (SCr): water product of muscle metabolism mostly filtered from the glomerulus
-As SCr increases, kidney function decreases
-Normal Range: 0.6-1.3 mg/dL
Creatinine Clearance (CrCl): estimates kidney function with SCr, but may change on muscle mass (ex. frail pts with low muscle mass may have decreased SCr leading to overestimation and wrong dosing)
-NOT preferable in: young children, kidney failure, or unstable renal function that fluctuates
Define AKI, CKD, and ESRD along with potential causes
Acute Kidney Injury (AKI): sudden, temporary loss of kidney function
-Precipitating factors: drugs, dehydration (reflected by BUN:SCR > 20:1)
Chronic Kidney Disease (CKD): progressive loss of function over time measured by GFR or CrCl and degree of albuminuria
-Most common causes: HTN and DM
-Other causes: polycystic kidney disease, infections (ex. HIV, HepB, HepC), renal artery stenosis, nephrotoxic medications
End-Stage Renal Disease (ESRD): total, permanent kidney failure where fluid and waste accumulate and dialysis or transplant will be needed
CKD is confirmed when a pt has either a eGFR <____mL/min/1.73m2 OR albuminuria equivalent to a urine albumin excretion rate (AER) >/= _______mg/24 hours or urine albumin-to-creatinine ratio (UAC) >/= ______mg/g.
How long must these values have been occurring for to be considered CKD as opposed to AKI?
60; 30; 30
Must occur for 3 months at least
CKD recommendations in HTN
-What is the BP goal?
-What drugs are considered first line and when are they recommended?
-What should be monitored?
SBP < 120mmHg if tolerated (lower than the general ACC/AHA <130/80mmHg target)
Drugs: ACEI or ARB due to inhibition of renal-angionetensin-aldosterone system (RAAS) causing efferent arteriolar dilation
-Ultimately reduces glomerular pressure, decreases albuminuria, and delays progression to ESRD by reducing kidney workload
-Recommended when albuminuria present in pt
Monitoring: SCr and K 2-4 weeks after intiation and maximize dose if K is normal
-Normal SCr increase of up to 30% (if increases further, D/C)
-ACEIs and ARBs should NEVER be used together due to similar MOA which will increase hyperkalemia risk
-Avoid K supplements and salt substitutes with KCl
CKD Recommendations in DM: What drugs are helpful?
Sodium-glucose cotransporter 2 (SGLT2) inhibitors if eGFR >20
-Demonstrated a reduction in CV events and/or CKD progression
-If unable to use medication or requires additional glycemic control: GLP-1 receptor agonist
Finerenone: non-steroidal mineralcorticoid receptor antagonist that can decrease CKD progression and CV risk as well which can be added to SGLT2i and max-tolerated ACEI or ARB in eGFR >25, albuminuria, and normal K levels
CKD: drugs that may require decreased dose or increased dosing interval
-Anti-infectives
-CV drugs
-GI drugs
-Others
Anti-infectives:
-Aminoglycosides (increase dosing interval primarily, due to nephrotoxicity)
-Beta-lactams ABXs (exceptions: nafacillin, oxacillin, ceftriaxone) - seizure risk
-Fluconazole
-Quionolones (except: moxifloxacin) - seizure risk
-Vancomycin
CV Drugs: LMWHs (enoxaparin), rivaroxaban, apixiban, dabigatran - bleeding risk
GI drugs: H2RAs (CNS risk), metoclopramide (EPS risk)
Others: bisphosphonates, lithium (NTI that is almost 100% renally cleared), cyclosporine, tacrolimus
CKD: drugs that are CI in CKD when:
-CrCl <60mL/min
-CrCL <50mL/min
-CrCl <30mL/min
-eGFR <30mL/min
-Others that have no CrCl specified cutoff
CrCl <60mL/min: nitrofurantoin (NOT effective)
CrCl <50mL/min:
-Tenofovir disoproxil fumarate containing products (Complera, Delstrigo, Stribild**, Symfi),
-Voriconazole IV (NOT from drug, but due to VEHICLE)
CrCl <30mL/min:
-Tenofovir alafenamide-containing products (Biktarvy, Descovy, Genvoya, Odefsey, Symtuza)
-NSAIDs
-Dabigatran* (for DVT/PE)
-Rivaroxaban*
eGFR <30mL/min: SGLT2 inhibitors, metformin**
Others: meperidine (seizure risk)
*Medication has indication-specific recommendations
**For treated patients, do NOT start TX if CrCl <70mL/min
***For treated patients, do NOT start TX if eGFR </=45
What are complications of CKD and why?
Increased PO4 - kidneys do NOT excrete as well
Decreased vitamin D and Ca - kidneys do NOT activate vitamin D which helps with Ca absorption
–> BOTH send signals to increase parathyroid hormone (PTH) which signals to reabsorb Ca++ (in chronic: Ca+ reabsorbed from bones which can cause bone fractures)
Hypercalcemia can be caused from chronic PTH levels, which can lead to calcium deposits in the eyes, lungs, heart, or blood vessels increasing risk of stroke
Decreased erythropoietin: produced by kidneys that signals to bone marrow to produce RBCs (anemia from chronic CKD)
Hyperphosphatemia in CKD: General Treatment
-What are DDIs with the treatmenet options?
Treatment:
-Nonpharm: restrict diet (dairy products, chocolate, soda, nuts)
-Phosphate binders: binds phosphate to the intestine to have less absorbed into blood
Phosphate binder types:
1. Aluminum based - aluminum hydroxide (LAST line: due to potency and toxicity, used no longer than 4 weeks and often in hospital setting)
2. Calcium-based - considered first line (calcium acetate > calcium carbonate)
3. Aluminum- and calcium-free: can be more expensive)
-Iron-based: sucroferric oxyhydroxide, ferric citrate
-Lanthanum carbonate
-Sevelamer carbonate (dialysis or not) and sevelamer hydrochloride (dialysis only)
DDIs: levothyroxine, quinolones, tetracyclines, oral bisphosphonates –> SEPARATE
Aluminum hydroxide:
-MOA
-ROA
-Administration
-AVEs
-Monitoring
MOA: phosphate binder for hyperphosphatemia
ROA: suspension
Administration: take WITH MEALS (if meal missed, skip)
AVEs: ALUMINUM INTOXICATION (CNS and bone toxicity: confusion, seizures, osteomalacia), constipation, nausea
Monitoring: treatment duration limited to 4 weeks due to toxicities
-Ca, PO4, PTH, s/sx of aluminum toxicity
Calcium-based phosphate binders:
-Drugs/Brands
-Administration
-AVEs
-Monitoring
Drugs: calcium acetate (Calphron, Phoslyra - D/C), calcium carbonate (Tums)
Administration: take WITH MEALS (if meal skipped, skip)
AVEs: HYPERCALCEMIA (especially with Vitamin D supplementation), CONSTIPATION, nausea
Monitoring: Ca, PO4, PTH
-Calcium acetate binds more dietary phosphorus than calcium carbonate
Iron-based phosphate binders
-Drugs/Brands
-Administration
-AVEs
-Warnings
-Monitoring
Drugs: sucroferric oxhydroxide (Velphoro), ferric citrate (Auryxia)
Administration: take with MEALS (if meal skipped, skip)
AVEs: diarrhea, discolored (black) fecers, constipation (ferric citrate)
Warnings: iron absorption with ferric citrate (dosage reduction of IV iron may be needed), store out of reach with children to prevent accidental overdose
Monitoring: PO4, PTH
-Ferric citrate: iron, ferritin, TSAT
Lanthanum carbonate
-Brand
-MOA
-Administration
-AVEs
-Warnings/CIs
-Monitoring
Brand: Fosrenol
Administration: take WITH MEALS (if meal skipped, skip); comes as chewable tablet –> CHEW THOROUGHLY (reduces risk of GI AVEs, but also increases surface area to help with phosphate binding)
AVEs: N/V/D, constipation, abdominal pain
Warnings/CIs:
-Warnings: GI perforation
-CIs: GI obstruction, fecal impaction, ileus
Monitoring: Ca, PO4, PTH
Sevelamer carbonate and Sevelamer hydrochloride:
-Brand
-Administration
-Differences between the salts
-AVEs
-Warnings
-CIs
-Monitoring
Brands: sevelamer carbonate (Renvela), sevelamer hydrochloride (Renagel)
Administration: take WITH MEALS (if meal skipped, skip)
Salts:
-Carbonate: can be used in dialysis pts or not
-Hydrochloride: dialysis only
AVEs: N/V/D (20%), dyspepsia, constipation, abdominal pain, flatulence, meetabolic acidosis (with sevelamer hydrochloride)
Warnings:
-Reduced absorption of vitamin D, E, and K and folic acid
-Tablets can cause dysphagia and get stuck in esophagus –> consider powder if difficulty swallowing
-Metabolic acidosis in sevelamer HYDROCHLORIDE (Cl may decrease bicarbonate levels)
CIs: bowel obstruction
Monitoring: Ca, PO4, HCO3, Cl, PTH
-Both can lower total cholesterol and LDL by 15-30%
CKD: Vitamin D deficiency and secondary hyperparathyroidism
-Pathophysiology
-General TX
Kidneys are unable to hydroxlyate vitamin D into active form 1,25-dihydroxy vitamin D which hypocalcemia stimulates PTH release
-Vitamin D3 (cholecalciferol): synthesized in skin after UV light expsoure
-Vitamin D2 (ergocalciferol): from dietary sources
Treatment:
-Earlier stages may be able to take vitamin D supplements (D3, but still need to be activated)
-Vitamin D analogs reserved foe later stages of CKD (4 and 5) with progressive hyperparathyroidism which increase Ca absorption from gut, increasing Ca and lowering PTH
-Calcitriol: active form of vitamin D3
-Paricalcitriol and doxercalciferol: newer vitamn D analogs that cause less hypercalcemia than calicitriol
-Cinacacalcet: mimics the actions of Ca on parathyroid gland which increases sensitivity of Ca receptors reducing PTH (used in dialysis ONLY)
Vitamin D Analogs:
-Drugs/Brands
-MOA
-Administration
-TX
-AVEs
-Warnings/Cis
-Monitoring
Drugs: calcitriol (Rocaltrol), calcifediol (Rayaldee), doxercalciferol (Hectorol), paricalcitol (Zemplar)
MOA: vitamin D analogs that increase Ca absorption in the gut, increasing serum Ca and lowering PTH
-Calcifediol: prodrug of calcitriol
Administration: take with food or shortly after meal to decrease GI upset (calcitriol)
TX: CKD later stages (3-5), dailysis
AVEs: hyperphosphatemia, N/V/D
Warnings/Cis: HYPERCALCEMIA (newer analogs: doxercalciferol and paricalcitol cause this less), vitamin D toxicity
Monitoring: Ca, PO4, PTH, 25-hydroxy vitamin D (calcifediol)
Cinacalcet:
-Brand
-MOA
-TX
-AVEs
-Warnings
-CIs
-Monitoring
Brand: Sensipar
MOA: mimics actions of Ca on parathyroid hormone to increase sensitivity of receptors to decrease PTH production
TX: dialysis pts
AVEs: N/V/D, HA, anorexia, constipation, weakness, myalgia, URTIs
Warnings: HYPOCALCEMIA (caution in hx of seizures, QT prolongation), GI bleeding, decreased bone turnover
CI: HYPOCALCEMIA
Monitoring: Ca, PO4, PTH
Etelcalcetide:
-Brand
-MOA
-TX
-AVEs
-Warnings
-Monitoring
Brand: Parsabiv
MOA: mimics actions of Ca on parathyroid hormone to increase sensitivity of receptors to decrease PTH production
TX: dialysis pts
AVEs: MUSCLE SPASMS, PARESTHESIA, N/V/D
Warnings: HYPOCALCEMIA, worsening HF, GI bleeding, decreased bone turnover
Monitoring: Ca, PO4, PTH
CKD: Anemia
-Pathophysiology
-General TX (see anemia flashcards for in-depth)
Kidneys do NOT produce erythropoietin (EPO) as much which stimulates RBCs from bone marrow and inflammatory state
Treatment:
-Erythropoiesis-stimulating agentes (ESAs): act like EPO to produce more RBCs (epoetin alfa, darbepoetin alfa), but have RISKS (elevated BP and thrombosis) –> only when Hgb <10 g/dL (D/C or hold if Hgb exceeds 11g/dL)
-ESAs only effective with adequate iron stores (assess iron, ferritin, and TSAT levels) –> may need to give IV iron at dialysis center
-Daprodustat (Jesduvroq): ORAL ESA indicaeted for CKD pts who have been receiving dailysis for at least four months
CKD: Hyperkalemia
-Pathophysiology
-Other contributing factors
-Symptoms
Potassium is NOT excreted as well through kidneys (primarily excreted through gut and kidneys)
Contributing factors:
-Medications (ACEIs/ARBs; K-sparing diuretics, aliskiren, canagliflozin, drosperinone-containing COCs, K-containing IV fluids, K supplements, Bactrim, cyclosporine, tacrolimus, everolimus)
-High urine flow
-Negatively charged ions in distal tubule (bicarbonate)
-Insulin deficiency in DM
**Diet does NOT usually affect because offset by insulin
Symptoms: often asymptomatic, but can cause muscle weakness, bradycardia, and fatal arrhythmias
CKD: Hyperkalemia TX
- Stabilize the heart: calcium gluconate (preferred) > calcium carbonate
-does NOT decrease K, but stabilized myocardial cells to prevent arrythmias
-IV route, onset: 1-2 minutes - Move K intracellularly: onset of 30 minutes
-Regular insulin IV: given w/ dextrose to prevent hypoglycemia, but can be used alone if BG >/=250
-Sodium bicarbonate IV: when metabolic acidosis present
-Albuterol, nebulized: monitor for tachycardia and chest pain - Remove K
-Loop diuretics (typically furosemide): IV onset of 5 minutes; eliminates K IN URINE
-Hemodialysis: immediate once started, but takes several hours to setup/complete; other methods usually used in conjunction
-Potassium binders (sodium polystrene sulfonate, patiromer, or sodium zirconium cyclosilicate)
**Always D/C potassium source as well
