Renal Pharmacology

Question 1

What are four medical treatments associated with acute kidney injury?

Answer 1

Antibiotics, chemotherapy and radiocontrast dyes, thoracic surgery

Question 2

Chronic kidney diseases develops in __ - __% of acute kidney injury survivers?

Answer 2

20-30%

Question 3

What are some drugs on the market for treating acute kidney injury (AKI)?

Answer 3

there are none

Question 4

What can cause renal ischemia-reperfusion in AKI?

Answer 4

Arterial occlusion

Hypotension

Shock

Question 5

In AKI, renal iscemia-reperfusion can lead to…?

Answer 5

• Microvascular dysfunction
• Excess vasoconstriction
• Inflammation, oxidative stress
• Endothelial injury
• Endothelial-leukocyte interactions

Question 6

Acute Kidney Injury - emerging pharmacological agents

Anti apoptotic:

Anti-inflammatory:

Anti-Sepsis:

Growth factor:

Vasodilator:

Answer 6

Anti apoptotic: capsase inhibitors, minocycline

Anti-inflammatory: adenosine A2A agonist

Anti-Sepsis: Insulin

Growth factor: Recombinant erythropoietin

Vasodilator: Fenoldopam, ANP

Question 7

What are the two most common causes of CKD?

Answer 7

Diabetic Nephropathy and Hypertension

Question 8

What GFR is associated with each stage of CKD?

Stage 1:

Stage 2:

Stage 3:

Stage 4:

Stage 5:

Answer 8

Stage 1: ≥ 90

Stage 2: 60 - 89

Stage 3: 30-59

Stage 4: 15-29

Stage 5: <15

Question 9

What is the goal of treatment for CKD?

Answer 9

Inhibit the renin angiotensin system

Question 10

What function to ACEi and ARBs serve in CKD?

Answer 10

• Decrease progression of albuminuria
• Decrease progression of GFR decline
• Decrease risk of ESRD

Question 11

Why don’t you take NSAIDs with CKD?

Answer 11

Damage kidneys further

May interact with ACEi or ARB

Question 12

In CKD are ACEi and ARBs more effective together or separately?

Answer 12

Combination therapy tends to work better, but is still controversial

Question 13

What are the three management goals in diabetic nephropathy?

Answer 13

Good glycemic control (HbA1c < 7%)

Blood pressure control (< 140/90 mmHg)

Medications to minimize proteinuria (ACEi and ARB)

Question 14

What are two upcoming treatments to combat CKD?

Answer 14

Bardoxolone - halted due to safety concerns

EET analogs - pending approval

Question 15

Anema is most prevalent in which stages of CKD?

Answer 15

4-5

Question 16

What are the symptoms and causes of anemia in CKD?

Answer 16

Symptoms: fatigue and decreased cognition

Causes: decrease in release of erythropoietin

Question 17

1. What is Epoetin?
2. How is it administered?
3. What is it’s half life?

Answer 17

1. A human recombinant synthesized form of erythropoietin
2. IV (more rapid response) and SubQ (greater response)
3. 4-6 hour half life

Question 18

What are the unwanted side effects of Epoetin?

Answer 18

• Nausea, vomiting, diarrhea
• Headache
• Flu-like symptoms
• HTN
• Thrombosis of arteriovenous shunts (Increased RBCs)

Question 19

What are the physiological roles of calcium?

Answer 19

• Nerve conduction and regulation of cell membrane permeability
• Excitation and coupling of all types of muscles
• Secretion of endocrine and exocrine glands and release of neurotransmitters
• Intracellular messenger
• Impulse generation in the heart
• Coagulation of blood
• Bones and teeth

Question 20

What 3 hormones regulate plasma calcium?

Answer 20

Parathyroid hormone

Calcitonin

Calcitriol

Question 21

Of the calcium in the plasma, what percentage is bound to albumin?

Does hypoalbuminemia cause a decrease in calcium concentration?

Answer 21

40% (50% is free ionized and important form)

no decrease

Question 22

What form of plasma calcium is favored in acidosis?

Answer 22

Free ionized form

Question 23

How does Kidney failure affect calcium levels?

Answer 23

In kidney failure there is decreased renal excretion of phosphate and diminished production of calcitrol leading to decrease in plasma calcium

Question 24

How does Kidney failure lead to metabolic bone disease and soft tissue calcifications?

Answer 24

Increased phorphate and reduced calcium feeeback can lead to Secondary Hyperparathyroidism which leads to metabolic bone disease and soft tissue calcifications

Question 25

What are the major factors leading to an increase in PTH and secondary hyperparathyroidism?

Answer 25

Decreased production of Vitamin D3 (calcitriol) Decreased serum calcium Increased serum phosphorous

Question 26

What modifications are made in each generation of Vitamin D analogs?

Answer 26

1st gen: Synthetic form of endogenous Vitamin D 2nd gen: Side chain modifications 3rd gen: A-ring modifications (paricalcitol)

Question 27

What is the MOA of Vitamin D analogs?

Answer 27

* Enhancement of absorption of calcium and phosphate from intestine * Enhances recruitment and differentiation of osteoclast precursor for remodeling-resorption of calcium and phosphate from bone * Enhances renal tubular reabsorption of calcium

Question 28

Which Vitamin D analog requires kidney 1-α hydroxylation?

Answer 28

Ergocalciferol

Question 29

What Vitamin D analogs are used in kidney disease? What is their half life?

Answer 29

Hydroxylated active forms of alfacalcidol or calcitrol (short half lives - 3 hours)

Question 30

Which vitamin D analog requires IV injections?

Answer 30

Paricalcitol

Question 31

What are the signs of vitamin D deficiency? At what stages of CKD are vitamin D analogs indicated?

Answer 31

* Fractures * Hyperparathyroidism Indicated at stage 3 if Ca \< 9.5 and P \<4.6 Always indicated at stage 4

Question 32

What are the phosphate binders and how do they work?

Answer 32

Calcium carbonate, calcium acetate, lanthanum carbonate Decrease phosphate absorption by reacting with phosphate to form an insoluble compound

Question 33

What are side effects of phosphate binders?

Answer 33

GI side effects hypercalcemia

Question 34

How can renal transplant cause hypercalcemia?

Answer 34

Patients already have high levels of PTH due to previous renal failure so addition of functioning kidney leads to extremely high plasma calcium levels

Question 35

What is the function of bisphosphonates in hypercalcemia? Which is the most long lasting?

Answer 35

Pyrophosphate analogs that bind to hydroxyapatite crystals in bone matrix to inhibit bone resorption Zoledondrate can suppress bone resorption for up to a year after a single dose

Question 36

What are the three generations of Bisphosphonates?

Answer 36

* First gen: * Etidronate * Tiludronate * 2nd gen: * Pamidronate * Aledronate * Ibadronate * 3rd gen: * Risedronate * **Zoledronate**

Question 37

What is the function of calcitonin?

Answer 37

Produced by parafollicular cells of thyroid gland Secreted when plasma calcium rises Lowers plasma calcium by limiting bone resorption and increasing phosphate excretion in the urine

Question 38

What are some unwanted side effects of calcitonin?

Answer 38

Facial flushing Headache GI Taste disturbance

Question 39

How do you treat hyperuricemia and gout in kidney disease?

Answer 39

Colchicine Allopurinol Febuxostat Rasburicase

Question 40

Colchicine: onset of action? Side effects?

Answer 40

Onset: pain relief begins at about 18 hours and is maximal by 48 hours SE: GI, Rash

Question 41

What are the SE of the Xanthine Oxidase Inhibitors (Allopurinol and Febuxostat)?

Answer 41

* GI Upset * Risk of acute gout * Hypersensitivity (Allopurinol) * Drug interactions

Question 42

How does rasburicase work? What are its SE?

Answer 42

* Recombinant version of enzyme urate oxidase * Promotes uric acid conversion to allantoin * Metabolized by peptide hydrolysis in plasma * Used primarily as prophylaxis during chemotherapy SE: Fever, nausea, vomiting, hypersensitivity, hemolysis