Chapter 18-19 Renal & Hepatic Diseases Flashcards
What is kidney disease?/ what are the common causes? What are the key roles of pharmacists in managing chronic kidney disease (CKD) patients, and how do they contribute to the prevention and treatment of related complications?
Approximately 30 million U.S. adults, more than one in seven, suffer from chronic kidney disease (CKD), with the highest risk observed among African-Americans, Hispanics, American Indians, and Asians. Common causes include diabetes and hypertension, with controlling blood glucose and pressure vital for preventing renal damage and delaying progression to end-stage renal disease (ESRD). Other less common causes encompass polycystic kidney disease, certain infections, renal artery stenosis, and drug-induced kidney disease due to nephrotoxic medications.
Pharmacists play a crucial role in assessing kidney impairment in CKD patients and ensuring safe medication dosage adjustments. They can also identify and recommend treatment for related disorders like anemia, hypertension, and electrolyte disturbances, alongside managing parathyroid hormone, phosphate, calcium, and vitamin D levels.
Renal/ Kidney Physiology
GLOMERULUS: What is it’s function?
The afferent arteriole supplies blood to the glomerulus, a key filtering unit within Bowman’s capsule. Substances with a molecular weight under 40,000 daltons, including most drugs, can pass through the glomerular capillaries into the filtrate and are eventually excreted in urine. Normally, larger substances such as proteins remain in the blood. However, if the glomerulus is damaged, some proteins like albumin may pass into the urine. Monitoring albumin levels in urine, along with the glomerular filtration rate (GFR), helps assess the severity of kidney disease.
Renal/ Kidney Physiology
PROXIMAL TUBULE: What is it’s function?
Proximal tubule, located nearest to Bowman’s capsule, reabsorbs sodium, chloride, calcium, and water initially filtered from blood. It regulates blood pH by exchanging hydrogen and bicarbonate ions. Medications targeting this area include SGLT2 inhibitors.
Renal/ Kidney Physiology
Loop of Henle: What is it’s function? and what medications can have an impact on it?
As filtrate descends through the loop of Henle, water is reabsorbed into the blood, increasing the concentration of sodium and chloride in the filtrate. As it ascends, sodium and chloride ions are reabsorbed, but not water, unless antidiuretic hormone (ADH) is present. ADH facilitates water reabsorption, leading to less urine production (anti-diuresis). Loop diuretics inhibit sodium reabsorption in the ascending limb, causing increased sodium concentration in the filtrate and reduced water reabsorption. This also leads to calcium depletion and potential long-term bone density decrease due to decreased calcium reabsorption.
Renal/ Kidney Physiology
DISTAL CONVOLUTED TUBULE: What is it’s function? and what medication effects this part of the kidney?
The distal convoluted tubule, located farthest from the nephron’s entry point, regulates potassium, sodium, calcium, and pH balance. Thiazide diuretics inhibit the Na-Cl pump here, resulting in weaker diuretic effects compared to loop diuretics. Thiazides also increase calcium reabsorption at the calcium pump in the distal convoluted tubule. Unlike loop diuretics, long-term use of thiazide diuretics has a protective effect on bones.
Renal/ Kidney Physiology
COLLECTING DUCT: What is it’s function? and what drugs work here?
The collecting duct connects nephrons to the ureter, facilitating the passage of urine filtrate into the bladder and out of the body through the urethra. It plays a role in water and electrolyte balance, influenced by levels of antidiuretic hormone (ADH) and aldosterone. Aldosterone acts in the distal convoluted tubule and collecting duct to increase sodium and water reabsorption while decreasing potassium reabsorption. Potassium sparing diuretics including Aldosterone antagonists like spironolactone or eplerenone inhibit aldosterone (distal and collecting duct), leading to increased sodium and water excretion in urine and elevated serum potassium levels
List of Drugs That Can Cause Kidney Disease
Aminoglycosides
NSAIDs
Amphotericin B
Polymyxins
Cisplatin
Cydosporine
Radiographic contrast dye
Loop diuretics
Tacrolimus
Vancomycin
What are the two common laboratory markers for estimating kidney function?
Two common laboratory markers for estimating kidney function are blood urea nitrogen (BUN) and serum creatinine (SCr).
.
BUN measures nitrogen in the blood from urea, a protein metabolism waste product. As kidney function worsens, BUN levels rise, although factors like dehydration can also elevate BUN.
.
Creatinine (Scr), a muscle metabolism waste product, is predominantly filtered by the glomerulus and is easily measurable. Its levels increase with declining kidney function, mirroring BUN trends. The normal SCr range is 0.6-1.3 mg/dL.
Creatinine Clearance VS. GFR
Creatinine clearance (CrCl) is commonly estimated using the Cockcroft-Gault equation for medication dosing. However, it may overestimate kidney function in frail elderly patients with low muscle mass. Factors like obesity and liver disease can also affect its accuracy. The formula isn’t ideal for very young children, end-stage renal disease (ESRD), or unstable renal function. While drug dosing typically relies on CrCl, certain medications use glomerular filtration rate (GFR) for adjustments, such as SGLT2 inhibitors and metformin.
CKD Criteria
The KDIGO guidelines advise using glomerular filtration rate (GFR), degree of albuminuria, and the cause of chronic kidney disease (CKD) to assess renal impairment severity/stage.
.
The criterias include:
- eGFR < 60 (less than half of the expected value)
- Albuminuria (marker of kidney damage): AER > 30, or UACR > 30.
- Decreased eGFR or albuminuria has occurred for greater than 3 months
GFR Categories
Degree of Albuminuria and Categories
Delaying Progression of CKD: HTN
KDIGO recommends SBP <120 (this is less than the <130/80 recommended by AHA/ACC). An ACEi or ARB is the first line for patients with CKD and HTN.
.
When initiating ACEi or ARB, baseline serum creatinine (SCr) may increase by up to 30%, which is normal and shouldn’t warrant treatment cessation! However, if SCr rises by more than 30%, discontinuing treatment is recommended.
Delaying Progression of CKD: Diabetes
The KDIGO recommends SGLT2i (if eGFR is >20). SGLT2i (esp. cana, empa,dapa) has been shown to reduce cardiovas event and CKD progression
Common medication-related scenarios in kidney disease include:
- Adjusting dosage or intervals for drugs cleared by kidneys to prevent accumulation and side effects.
- Identifying nephrotoxic drugs that can cause or worsen kidney disease.
- Recognizing drugs less effective with declining kidney function, like thiazide diuretics.
- Contraindicating drugs at certain kidney impairment levels due to safety concerns or worsening kidney damage, such as NSAIDs or aldosterone receptor antagonists.
SELECT DRUGS THAT REQUIRE
DECREASE DOSE OR DECREASE IN CKD: Just know the key drugs
DRUGS THAT ARE C/I IN CKD
CKD Mineral and Bone Disorder
CKD mineral and bone disorder (CKD-MBD) is prevalent in renal impairment and nearly universal in dialysis patients. It’s linked to fractures, cardiovascular issues, and higher mortality rates. Advanced kidney disease necessitates monitoring of parathyroid hormone (PTH), phosphorus (phosphate), calcium, and vitamin D levels.
CKD Mineral and Bone Disorder
Hyperphosphatemia
Hyperphosphatemia, linked to chronically elevated PTH levels (secondary hyperparathyroidism), requires treatment to prevent bone disease and fractures. Initially, dietary phosphate restriction is recommended, avoiding foods like dairy products, cola, chocolate, and nuts. As CKD advances, phosphate binders are often necessary. These binders prevent dietary phosphate absorption by binding to it in the intestine, taken just before each meal. If a dose is missed, the binder should be skipped, with normal dosing resumed at the next meal or snack. Phosphate binders come in 3 types: aluminum-based, calcium-based, and aluminum-free, calcium-free drugs
Explore the relationship between PO4, Ca+, vitamin D, and anemia in CKD
Phosphate Binders
Calcium Based (First Line): List the drugs, dosing, SEs, notes
Drugs
Calcium Acetate and Calcium Carbonate (Tums) - both are dose TID with meals
.
SEs: Constipation, Hypercalcemia
.
Notes: Hypercalcemia may be problematic with concomitant use of Vitamin D (d/t increased calcium absorption!)
Phosphate Binder
Aluminum Based: What’s the issue with it?, Drugs, Dosing, SEs
Aluminum based phosphate binder is potent! But rarelt used d/t risk of aluminum accumulation (which can cause nervous system and bone toxicity. TX duration is 4wks!
.
Drug: Aluminum Hydroxide -dosed TID with meals
.
SEs: Aluminum toxicity, Dialysis Dementia
Phosphate Binder
Aluminum-Free & Calcium-Free: no aluminum accumulation and no hypercalcemia BUT IT’S MORE $$$… Name the Drugs, general dosing, warnings, SEs
- Sucroferric oxyhydroxide (TID with meal)
- Ferric citrate (TID with meal)
- Lanthanum carbonate (TID with meals - chew throughly to reduce GI issues like N/V/D)
.
Warnings for the iron based ones (1 and 2): Iron absorbption occurs with #2 - Ferric Citrate. Both can cause iron related SEs = D/Consitpation and black stool
Phosphate Binder
Sevelamer: non-aluminum, non-calcium that is NOT systemically absorbed. Name the drugs, general dosing, warnings/ SEs, notes
Drugs: Sevelamer Carbonate (Renvela) and Sevelamer Hydrochloride (Renagel) - 800-1600 mg PO TID with meals
.
Warnings: can reduce absorption of vitamin D, E, K, and folic acid - so consider vitamin/mineral supp. SEs = n/v/d
.
Note: can lower total cholesterol and LDL!
Phosphate Binder Drug Interactions: general
Important ro seperate phosphate binders from levothyroxine, quinolones, and tetracyclines
Vitamin D Deficiency & Secondary Hyperparathyroidism: Talk about it and how to manage it?
Vitamin D deficiency results from the kidney’s inability to convert vitamin D to its active form, worsening bone disease, compromising immunity, and increasing cardiovascular disease risk. Vitamin D exists as D3 aka cholecalciferol (from sunlight exposure) and D2 aka ergocalciferol (from dietary sources). Vitamin D analogs like calcitriol are used in later CKD stages or ESRD to enhance calcium absorption, raise serum calcium levels, and lower PTH secretion. Newer analogs such as paricalcitol and doxercalciferol cause less hypercalcemia. Cinacalcet, a calcimimetic, reduces PTH secretion by increasing calcium receptor sensitivity and is reserved for dialysis patients.
Drugs for the Treatment of Secondary Hyperparathyroidism
Vitamin D Analogs: MOA, drug names, warnings/SEs, note
- MOA: Increase intestinal absorption of Ca, which provides negative feedback to the parathyroid gland.
- Drugs: Calcitriol, Calcifediol
- Warnings: Digitalis toxicity (d/t hypercalcemia)
- Note: Take with food to decrease GI issues
Drugs for the Treatment of Secondary Hyperparathyroidism
Calcimimetic: MOA, name, SEs
- MOA: Increases sensitivity of the calcium -sensing receptor on the parathyroid gland, which causes decrease in Ca/ PTH/ PO4
- Name: Clnacalcet (Senslpar): 30-180 mg PO with food QD
- SEs: hypocalcemia, use caution in patietn with hx of sz
ANEMIA OF CKD: Discuss pathophysilogy. How does anemia occur in CKD?
Anemia, defined by a hemoglobin level below 13 g/dL, is common in CKD due to several factors. A key issue is the reduced production of erythropoietin (EPO), typically generated by the kidneys to stimulate red blood cell (RBC) production in the bone marrow. With declining kidney function, EPO production diminishes, leading to lower hemoglobin levels and anemia symptoms like fatigue and pale skin. CKD exacerbates this condition through inflammation, further reducing EPO production.
ANEMIA OF CKD: What drug/ agent is typically used for help with anemia in patients with CKD?
Erythropoiesis-stimulating agents (ESAs), like epoetin alfa and darbepoetin alfa, can help avoid the need for blood transfusions in anemia treatment. However, they carry risks such as increased blood pressure and clotting. ESAs should only be used when hemoglobin is below 10 g/dL, and their dosage should be adjusted or stopped if hemoglobin exceeds 11 g/dL due to heightened risk of thromboembolic events. Adequate iron is crucial for ESA effectiveness, so assessing iron levels (iron, ferritin, and transferrin saturation) and providing supplementation is vital to prevent iron deficiency. In end-stage renal disease (ESRD), iron levels may be low due to reduced absorption and blood loss during dialysis. Intravenous iron supplementation is administered at dialysis centers.
Steps for Treating Severe Hyperkalemia: Stabilize, Move it, Remove it
Just know the general drug/ what they are used for
.
General note:
- Sodium polystyrene sulfonate (SPS, Kayexalate): can bind to other medications so check DDI
- Patiromer (Veltassa): can cause hypomag, can bind to other drugs so seperate it by at least 3 hours, can also cuase constipation
DRUG TREATMENT FOR HEPATITIS C: List the drugs, the duration
Hepatitis C virus (HCV) has six genotypes (1-6) and various subtypes. Treatment choices and duration depend on genotype, cirrhosis presence, and previous treatment. Recommended therapies typically include 2-3 direct-acting antivirals (DAAs) with different mechanisms, usually for 8-12 weeks. Certain combinations may include ritonavir, not active for HCV but used to enhance levels of HCV protease inhibitors.
.
Remember to take PI with food!
DAA
List the name/generic of the common DAAs, SEs, Notes, how are each medications used
List the name/generic of the common Ritonivir based DAAs, C/I, warnings
HBV NRTIs: Preferred Agents Only
- Tenofovir disoproxil fumarate (TDF) (Viread)
- Tenofovir alafenamlde (TAF) (TAF) (Vemlidy)
- Entecavir (Baraclude)
General dosing, Warning, SEs, Notes
Cirrhosis is deflnitively diagnosed with a liver biopsy, but certain labs can suggest cirrhosis or liver damage.. what are these labs (acute vs. chronic)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are liver enzymes, with a normal range of 10 - 40 units/L. Elevated levels typically indicate more active liver disease. Albumin and PT/INR are indicators of liver synthetic function, often affected in chronic liver disease, especially cirrhosis.
DRUG-INDUCED LIVER INJURY: What to do? and what are the common drugs that can cause hepatic injury? What considerations are important when using acetaminophen and NSAIDs in patients with cirrhosis?”
Stop hepatotoxic drugs when liver function tests (LFTs) exceed 3x the upper limit of normal (ALT or AST > 150 units/L), but clinical judgment is crucial. Rechallenge may be considered if necessary. Acetaminophen is hepatotoxic and should be used cautiously in cirrhosis patients, at lower doses and for limited periods.NSAIDs should be avoided in cirrhosis due to potential decompensation, including bleeding.
