Dosing in renal impairment — MCQs

10 questions

A 25-year-old college student is diagnosed with acute myelogenous leukemia after presenting with a 3-week history of fever, malaise, and fatigue. He has a history of type 1 diabetes mellitus, multiple middle ear infections as a child, and infectious mononucleosis in high school. He currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and denies any illicit drug use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 87/min, and respiratory rate 17/min. On physical examination, his pulses are bounding; his complexion is pale, but breath sounds remain clear. A rapidly progressive form of leukemia is identified, and the patient is scheduled to start intravenous chemotherapy. Which of the following treatments should be given to this patient to prevent or decrease the likelihood of developing acute renal failure during treatment?

A 54-year-old African American man presents to the clinic for his first annual well-check. He was unemployed for years but recently received health insurance from a new job. He reports feeling healthy and has no complaints. His blood pressure is 157/90 mmHg, pulse is 86/min, and respirations are 12/min. Routine urinalysis demonstrated a mild increase in albumin and creatinine. What medication is indicated at this time?

A 65-year-old female patient with a past medical history of diabetes mellitus and an allergy to penicillin develops an infected abscess positive for MRSA on the third day of her hospital stay. She is started on an IV infusion of vancomycin at a dose of 1000 mg every 12 hours. Vancomycin is eliminated by first-order kinetics and has a half life of 6 hours. The volume of distribution of vancomycin is 0.5 L/kg. Assuming no loading dose is given, how long will it take for the drug to reach 94% of its plasma steady state concentration?

A patient is receiving daily administrations of Compound X. Compound X is freely filtered in the glomeruli and undergoes net secretion in the renal tubules. The majority of this tubular secretion occurs in the proximal tubule. Additional information regarding this patient's renal function and the renal processing of Compound X is included below: Inulin clearance: 120 mL/min Plasma concentration of Inulin: 1 mg/mL PAH clearance: 600 mL/min Plasma concentration of PAH: 0.2 mg/mL Total Tubular Secretion of Compound X: 60 mg/min Net Renal Excretion of Compound X: 300 mg/min Which of the following is the best estimate of the plasma concentration of Compound X in this patient?

A 35-year-old woman is started on a new experimental intravenous drug X. In order to make sure that she is able to take this drug safely, the physician in charge of her care calculates the appropriate doses to give to this patient. Data on the properties of drug X from a subject with a similar body composition to the patient is provided below: Weight: 100 kg Dose provided: 1500 mg Serum concentration 15 mg/dL Bioavailability: 1 If the patient has a weight of 60 kg and the target serum concentration is 10 mg/dL, which of the following best represents the loading dose of drug X that should be given to this patient?

An experimental drug, ES 62, is being studied. It prohibits the growth of vancomycin-resistant Staphylococcus aureus. It is highly lipid-soluble. The experimental design is dependent on a certain plasma concentration of the drug. The target plasma concentration is 100 mmol/dL. Which of the following factors is most important for calculating the appropriate loading dose?

A researcher is investigating the effects of a new antihypertensive medication on renal physiology. She gives a subject a dose of the new medication, and she then collects plasma and urine samples. She finds the following: Hematocrit: 40%; Serum creatinine: 0.0125 mg/mL; Urine creatinine: 1.25 mg/mL. Urinary output is 1 mL/min. Renal blood flow is 1 L/min. Based on the above information and approximating that the creatinine clearance is equal to the GFR, what answer best approximates filtration fraction in this case?

A 74-year-old female with a history of lung adenocarcinoma status post lobectomy, chronic obstructive pulmonary disease, congestive heart failure, and diabetic nephropathy presents to clinic complaining of hearing loss. Over the last week, she has noticed that she has had difficulty hearing the telephone or the television. When sitting in a quiet room, she also has noticed a high-pitched ringing in her ears. She denies any vertigo or disequilibrium. Further review reveals ongoing dyspnea on exertion and worsening cough productive of whitish sputum for the last month. The patient was recently discharged from the hospital for a congestive heart failure exacerbation. She lives alone and keeps track of all her medications, but admits that sometimes she gets confused. She has a 20 pack-year tobacco history. Her home medications include aspirin, lisinopril, furosemide, short-acting insulin, and a long-acting ß-agonist inhaler. Two weeks ago she completed a course of salvage chemotherapy with docetaxel and cisplatin. Her tympanic membranes are clear and intact with no signs of trauma or impaction. Auditory testing reveals bilateral hearing impairment to a whispered voice. The Weber test is non-lateralizing. Rinne test is unrevealing. Hemoglobin: 11.8 g/dL Leukocyte count: 9,400/mm^3 Platelet count: 450,000/mm^3 Serum (Present visit): Na+: 134 mEq/L K+: 3.8 mEq/L Cl-: 95 mEq/L HCO3-: 30 mEq/L BUN: 45 mg/dL Creatinine: 2.1 mg/dL Serum (1 month ago): Na+: 135 mEq/L K+: 4.6 mEq/L Cl-: 102 mEq/L HCO3-: 24 mEq/L BUN: 22 mg/dL Creatinine: 1.2 mg/dL On follow up visit two weeks later, the patient's hearing has significantly improved. Which of the following is the most likely cause of her initial hearing loss?

A 67-year-old man presents to his physician with increased thirst and polyuria for the past 4 months. Patient also notes a decrease in his vision for the past 6 months and tingling in his feet. The medical history is significant for a chronic pyelonephritis and stage 2 chronic kidney disease. The current medications include losartan and atorvastatin. He reports a daily alcohol intake of 3 glasses of whiskey. The blood pressure is 140/90 mm Hg and the heart rate is 63/min. The BMI is 35.4 kg/m2. On physical examination, there is 2+ pitting edema of the lower legs and face. The pulmonary, cardiac, and abdominal examinations are within normal limits. There is no costovertebral angle tenderness noted. Ophthalmoscopy shows numerous microaneurysms and retinal hemorrhages concentrated in the fundus. The neurological examination reveals a symmetric decrease in vibration and 2 point discrimination in the patient’s feet and legs extending up to the lower third of the calves. The ankle-deep tendon reflexes are decreased bilaterally. The laboratory test results are as follows: Serum glucose (fasting) 140 mg/dL HbA1c 8.5% BUN 27 mg/dL Serum creatinine 1.3 mg/dL eGFR 55 mL/min The patient is prescribed the first-line drug recommended for his condition. Which of the following side effect is associated with this drug?

Q10

A 47-year-old man comes to the physician for a routine health maintenance examination. He states that he has felt fatigued and dizzy on several occasions over the past week. He has back pain for which he takes ibuprofen. Digital rectal examination shows no abnormalities. Laboratory studies show a hemoglobin concentration of 15 g/dL, a serum urea nitrogen concentration of 22 mg/dL, a serum creatinine concentration of 1.4 mg/dL, and a serum calcium concentration of 8.4 mg/dL. His prostate-specific antigen (PSA) level is 0.3 ng/mL (N < 4.5). An intravenous infusion of para-aminohippurate (PAH) is administered and its clearance is calculated. The patient's effective renal plasma flow is estimated to be 660 mL/min (N = 500–1350). The filtration fraction is calculated to be 9% (N = 17–23). Which of the following is the most likely cause of this patient's laboratory abnormalities?

Dosing in renal impairment US Medical PG Practice Questions and MCQs

Question 1: A 25-year-old college student is diagnosed with acute myelogenous leukemia after presenting with a 3-week history of fever, malaise, and fatigue. He has a history of type 1 diabetes mellitus, multiple middle ear infections as a child, and infectious mononucleosis in high school. He currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and denies any illicit drug use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 87/min, and respiratory rate 17/min. On physical examination, his pulses are bounding; his complexion is pale, but breath sounds remain clear. A rapidly progressive form of leukemia is identified, and the patient is scheduled to start intravenous chemotherapy. Which of the following treatments should be given to this patient to prevent or decrease the likelihood of developing acute renal failure during treatment?

A. Sulfinpyrazone
B. Indomethacin
C. Probenecid
D. Colchicine
E. Allopurinol (Correct Answer)

Explanation: ***Allopurinol*** - **Allopurinol** inhibits **xanthine oxidase**, preventing the conversion of xanthine and hypoxanthine to uric acid. - This is crucial in **tumor lysis syndrome** (TLS), a common complication of chemotherapy for rapidly proliferating cancers like AML, where massive cell death releases intracellular contents, including **purines**, which are metabolized to uric acid and can cause **acute renal failure**. *Sulfinpyrazone* - **Sulfinpyrazone** is a uricosuric agent, meaning it increases the excretion of uric acid in the urine. - It is generally contraindicated in TLS because the increased uric acid load in the renal tubules can **aggravate crystal formation** and worsen renal damage, rather than prevent it. *Indomethacin* - **Indomethacin** is a non-steroidal anti-inflammatory drug (NSAID) primarily used for pain and inflammation management. - While it can be used to treat the inflammation associated with **gouty arthritis**, it does not prevent the formation of uric acid during TLS and can even cause direct **renal toxicity**, which would be detrimental in a patient at risk of acute renal failure. *Probenecid* - **Probenecid** is another uricosuric agent, similar to sulfinpyrazone, that works by inhibiting the reabsorption of uric acid in the renal tubules. - Like other uricosurics, it is generally **contraindicated in TLS** due to the risk of exacerbating uric acid nephropathy and acute renal failure by increasing uric acid concentrations in the kidneys. *Colchicine* - **Colchicine** is an anti-inflammatory drug mainly used for the treatment of **acute gout attacks** and familial Mediterranean fever. - It does not lower serum uric acid levels and therefore offers no protection against the **hyperuricemia** and potential renal damage associated with tumor lysis syndrome.

Question 2: A 54-year-old African American man presents to the clinic for his first annual well-check. He was unemployed for years but recently received health insurance from a new job. He reports feeling healthy and has no complaints. His blood pressure is 157/90 mmHg, pulse is 86/min, and respirations are 12/min. Routine urinalysis demonstrated a mild increase in albumin and creatinine. What medication is indicated at this time?

A. Hydrochlorothiazide
B. Metoprolol
C. Furosemide
D. Lisinopril (Correct Answer)
E. Amlodipine

Explanation: ***Lisinopril*** - This patient presents with **hypertension (157/90 mmHg)** and **mild albuminuria with elevated creatinine**, indicating early chronic kidney disease (CKD). An **ACE inhibitor (e.g., lisinopril)** is the first-line treatment for hypertension in **any patient with CKD or proteinuria**, regardless of race or ethnicity. - ACE inhibitors are **renoprotective** by reducing intraglomerular pressure and slowing progression of kidney disease. The presence of albuminuria represents a **compelling indication** that overrides other considerations for initial antihypertensive selection. - Note: While ACE inhibitors are typically **less effective** as monotherapy in African Americans without compelling indications, the presence of CKD/proteinuria makes them the preferred agent. *Hydrochlorothiazide* - While a **thiazide diuretic** like hydrochlorothiazide would be an appropriate first-line agent for this African American patient with uncomplicated hypertension, it is **less effective** than an ACE inhibitor in patients with **proteinuria or kidney disease**. - It does not offer the same degree of **renoprotection** as an ACE inhibitor in this clinical scenario with documented albuminuria. *Metoprolol* - **Beta-blockers** like metoprolol are effective antihypertensives but are generally **not considered first-line** for uncomplicated hypertension unless there are compelling indications like heart failure, angina, or history of myocardial infarction. - They also do not provide the specific **renoprotective benefits** seen with ACE inhibitors in patients with albuminuria. *Furosemide* - **Loop diuretics** such as furosemide are potent diuretics primarily used for managing **symptoms of fluid overload** (e.g., heart failure, severe edema) and are not typically the first choice for chronic hypertension without such indications. - For patients with **mild kidney impairment and hypertension without volume overload**, an ACE inhibitor is preferred for its renoprotective effects. *Amlodipine* - **Calcium channel blockers** like amlodipine are effective antihypertensives and would typically be an excellent first-line choice for an African American patient with hypertension. - However, for this patient with **documented albuminuria**, an ACE inhibitor is preferred due to its **specific renoprotective effects** and proven benefit in slowing CKD progression, which amlodipine does not provide.

Question 3: A 65-year-old female patient with a past medical history of diabetes mellitus and an allergy to penicillin develops an infected abscess positive for MRSA on the third day of her hospital stay. She is started on an IV infusion of vancomycin at a dose of 1000 mg every 12 hours. Vancomycin is eliminated by first-order kinetics and has a half life of 6 hours. The volume of distribution of vancomycin is 0.5 L/kg. Assuming no loading dose is given, how long will it take for the drug to reach 94% of its plasma steady state concentration?

A. 30 hours
B. 12 hours
C. 6 hours
D. 18 hours
E. 24 hours (Correct Answer)

Explanation: ***24 hours*** - For a drug eliminated by **first-order kinetics**, it takes approximately **4 half-lives** to reach **93.75%** of steady state concentration, which is conventionally rounded to **94%**. - Since the half-life of vancomycin is **6 hours**, reaching 94% of steady state requires: 4 × 6 hours = **24 hours**. - This follows the pharmacokinetic principle that each half-life brings the drug closer to steady state: 1 t½ = 50%, 2 t½ = 75%, 3 t½ = 87.5%, 4 t½ = 93.75%. *30 hours* - This duration represents **five half-lives** (5 × 6 hours), at which point approximately **96.875%** (often rounded to 97%) of steady state would be reached. - This exceeds the 94% target specified in the question. *18 hours* - This duration represents **three half-lives** (3 × 6 hours), at which point approximately **87.5%** of steady state concentration would be reached. - This falls short of the 94% target. *12 hours* - This duration represents **two half-lives** (2 × 6 hours), at which point approximately **75%** of steady state concentration would be reached. - This is insufficient time to reach 94% of plasma steady state concentration. *6 hours* - This duration represents **one half-life**, at which point approximately **50%** of steady state concentration would be reached. - This is far too short to achieve near-steady state levels.

Question 4: A patient is receiving daily administrations of Compound X. Compound X is freely filtered in the glomeruli and undergoes net secretion in the renal tubules. The majority of this tubular secretion occurs in the proximal tubule. Additional information regarding this patient's renal function and the renal processing of Compound X is included below: Inulin clearance: 120 mL/min Plasma concentration of Inulin: 1 mg/mL PAH clearance: 600 mL/min Plasma concentration of PAH: 0.2 mg/mL Total Tubular Secretion of Compound X: 60 mg/min Net Renal Excretion of Compound X: 300 mg/min Which of the following is the best estimate of the plasma concentration of Compound X in this patient?

A. 2 mg/mL (Correct Answer)
B. 3 mg/mL
C. There is insufficient information available to estimate the plasma concentration of Compound X
D. 1 mg/mL
E. 0.5 mg/mL

Explanation: ***2 mg/mL*** * The **net renal excretion of Compound X (300 mg/min)** is the sum of the filtered load and the net tubular secretion. * Given that Compound X is **freely filtered** and undergoes **net secretion (60 mg/min)**, we can calculate the filtered load and subsequently its plasma concentration. * **Net excretion = Filtered load + Net tubular secretion** * **300 mg/min = Filtered load + 60 mg/min** * **Filtered load = 300 mg/min - 60 mg/min = 240 mg/min** * Since **Filtered load = Glomerular Filtration Rate (GFR) * Plasma concentration (P_X)**, and GFR is estimated by **inulin clearance (120 mL/min)**: * **240 mg/min = 120 mL/min * P_X** * **P_X = 240 mg/min / 120 mL/min = 2 mg/mL**. *3 mg/mL* * This value would imply a significantly higher filtered load or a different contribution from tubular secretion. * Calculations using this plasma concentration would not align with the provided excretion and secretion rates. *There is insufficient information available to estimate the plasma concentration of Compound X* * The problem provides all necessary values: **Inulin clearance (GFR)**, **net tubular secretion of Compound X**, and **net renal excretion of Compound X**. * These parameters are sufficient to determine the filtered load and thus the plasma concentration of Compound X. *1 mg/mL* * A plasma concentration of 1 mg/mL would result in a lower filtered load than calculated and would not account for the observed net renal excretion. * **Filtered load = 120 mL/min * 1 mg/mL = 120 mg/min**. Total excretion would then be 120 mg/min + 60 mg/min = 180 mg/min, which contradicts the given 300 mg/min. *0.5 mg/mL* * This plasma concentration would lead to an even lower filtered load, making it impossible to achieve the *net renal excretion of Compound X* given the tubular secretion. * **Filtered load = 120 mL/min * 0.5 mg/mL = 60 mg/min**. Total excretion would be 60 mg/min + 60 mg/min = 120 mg/min, which is much lower than the given 300 mg/min.

Question 5: A 35-year-old woman is started on a new experimental intravenous drug X. In order to make sure that she is able to take this drug safely, the physician in charge of her care calculates the appropriate doses to give to this patient. Data on the properties of drug X from a subject with a similar body composition to the patient is provided below: Weight: 100 kg Dose provided: 1500 mg Serum concentration 15 mg/dL Bioavailability: 1 If the patient has a weight of 60 kg and the target serum concentration is 10 mg/dL, which of the following best represents the loading dose of drug X that should be given to this patient?

A. 300 mg
B. 450 mg
C. 150 mg
D. 1000 mg
E. 600 mg (Correct Answer)

Explanation: ***600 mg*** - First, calculate the **volume of distribution (Vd)** using the provided data: **Vd = Total Dose / Serum Concentration**. Converting units: 15 mg/dL = 150 mg/L. Therefore, Vd = 1500 mg / 150 mg/L = **10 L** (for the 100 kg subject). - Since the Vd value is for a 100 kg person, Vd per kg = 10 L / 100 kg = **0.1 L/kg**. For the 60 kg patient, the Vd = 0.1 L/kg × 60 kg = **6 L**. - The **loading dose = Target Serum Concentration × Vd / Bioavailability**. Converting target concentration: 10 mg/dL = 100 mg/L. Therefore: (100 mg/L × 6 L) / 1 = **600 mg**. *300 mg* - This value is obtained if an incorrect **Vd** or target concentration was used, potentially through miscalculation or incorrect unit conversion. - For instance, if the **Vd** was inaccurately calculated at 3 L (instead of 6 L), this could lead to the incorrect answer. *450 mg* - This result might occur if the **Vd calculation** was flawed or if the target concentration was incorrectly interpreted. - A potential error could involve using a Vd of 4.5 L which would result in 450 mg, or if the drug amount was simply prorated by weight without properly considering the Vd per kg. *150 mg* - This value suggests a significant error in the calculation of the **volume of distribution** or the target concentration. - It might be obtained if the **Vd** was mistakenly taken as 1.5 L or if the dose was divided by the original serum concentration without accounting for the new patient's weight and desired concentration. *1000 mg* - This value is significantly higher than the correct answer, indicating an overestimation of the **Vd** or target concentration. - It could result from using the original dose (1500 mg) and attempting to scale it incorrectly by weight alone (1500 mg × 60/100 = 900 mg, close to 1000), or if unit conversions were mishandled during the Vd determination.

Question 6: An experimental drug, ES 62, is being studied. It prohibits the growth of vancomycin-resistant Staphylococcus aureus. It is highly lipid-soluble. The experimental design is dependent on a certain plasma concentration of the drug. The target plasma concentration is 100 mmol/dL. Which of the following factors is most important for calculating the appropriate loading dose?

A. Volume of distribution (Correct Answer)
B. Half-life of the drug
C. Therapeutic index
D. Clearance of the drug
E. Rate of administration

Explanation: **Volume of distribution** - The **loading dose** is primarily determined by the desired **plasma concentration** and the **volume of distribution (Vd)**, as it reflects how extensively a drug is distributed in the body. - The formula for loading dose is: Loading Dose = (Target Plasma Concentration × Vd). *Half-life of the drug* - The **half-life** is crucial for determining the **dosing interval** and the time it takes to reach **steady-state concentrations**, not the initial loading dose. - It reflects the rate at which the drug is eliminated from the body. *Therapeutic index* - The **therapeutic index** is a measure of a drug's relative safety, indicating the ratio between the **toxic dose** and the **effective dose**. - While important for drug safety, it does not directly determine the magnitude of the loading dose itself. *Clearance of the drug* - **Clearance** is the rate at which the drug is removed from the body and is a primary determinant of the **maintenance dose** required to sustain a desired plasma concentration. - It does not directly calculate the initial loading dose needed to achieve an immediate target concentration. *Rate of administration* - The **rate of administration** (e.g., infusion rate) primarily influences how quickly the drug reaches its target concentration, but not the total quantity of drug needed for the initial loading dose. - It affects the kinetics of how the loading dose achieves the target concentration, rather than defining the dose amount.

Question 7: A researcher is investigating the effects of a new antihypertensive medication on renal physiology. She gives a subject a dose of the new medication, and she then collects plasma and urine samples. She finds the following: Hematocrit: 40%; Serum creatinine: 0.0125 mg/mL; Urine creatinine: 1.25 mg/mL. Urinary output is 1 mL/min. Renal blood flow is 1 L/min. Based on the above information and approximating that the creatinine clearance is equal to the GFR, what answer best approximates filtration fraction in this case?

A. 10%
B. 17% (Correct Answer)
C. 33%
D. 50%
E. 25%

Explanation: ***17%*** - First, calculate **GFR** using the creatinine clearance formula: GFR = (Urine creatinine × Urinary output) / Serum creatinine = (1.25 mg/mL × 1 mL/min) / 0.0125 mg/mL = **100 mL/min**. - Next, calculate **Renal Plasma Flow (RPF)** from Renal Blood Flow (RBF) and Hematocrit: RPF = RBF × (1 - Hematocrit) = 1000 mL/min × (1 - 0.40) = **600 mL/min**. - Finally, calculate **Filtration Fraction (FF)** = GFR / RPF = 100 mL/min / 600 mL/min = 0.1667 = **16.7%, which approximates to 17%**. - This is the correct answer based on the physiological calculations and represents a normal filtration fraction. *10%* - This would correspond to a filtration fraction of 0.10, which would require either a GFR of 60 mL/min (lower than calculated) or an RPF of 1000 mL/min (higher than calculated). - This value is too low given the provided parameters and doesn't match the calculation from the given data. *25%* - This value would suggest FF = 0.25, requiring a GFR of 150 mL/min with the calculated RPF of 600 mL/min. - This is higher than the calculated GFR of 100 mL/min and doesn't match the given creatinine values. *33%* - This would imply FF = 0.33, requiring a GFR of approximately 200 mL/min with RPF of 600 mL/min. - This is significantly higher than the calculated GFR and would represent an abnormally elevated filtration fraction. *50%* - A filtration fraction of 50% is unphysiologically high and would indicate severe pathology. - This would require a GFR of 300 mL/min with the calculated RPF, which is impossible given the provided creatinine clearance data.

Question 8: A 74-year-old female with a history of lung adenocarcinoma status post lobectomy, chronic obstructive pulmonary disease, congestive heart failure, and diabetic nephropathy presents to clinic complaining of hearing loss. Over the last week, she has noticed that she has had difficulty hearing the telephone or the television. When sitting in a quiet room, she also has noticed a high-pitched ringing in her ears. She denies any vertigo or disequilibrium. Further review reveals ongoing dyspnea on exertion and worsening cough productive of whitish sputum for the last month. The patient was recently discharged from the hospital for a congestive heart failure exacerbation. She lives alone and keeps track of all her medications, but admits that sometimes she gets confused. She has a 20 pack-year tobacco history. Her home medications include aspirin, lisinopril, furosemide, short-acting insulin, and a long-acting ß-agonist inhaler. Two weeks ago she completed a course of salvage chemotherapy with docetaxel and cisplatin. Her tympanic membranes are clear and intact with no signs of trauma or impaction. Auditory testing reveals bilateral hearing impairment to a whispered voice. The Weber test is non-lateralizing. Rinne test is unrevealing. Hemoglobin: 11.8 g/dL Leukocyte count: 9,400/mm^3 Platelet count: 450,000/mm^3 Serum (Present visit): Na+: 134 mEq/L K+: 3.8 mEq/L Cl-: 95 mEq/L HCO3-: 30 mEq/L BUN: 45 mg/dL Creatinine: 2.1 mg/dL Serum (1 month ago): Na+: 135 mEq/L K+: 4.6 mEq/L Cl-: 102 mEq/L HCO3-: 24 mEq/L BUN: 22 mg/dL Creatinine: 1.2 mg/dL On follow up visit two weeks later, the patient's hearing has significantly improved. Which of the following is the most likely cause of her initial hearing loss?

A. Cisplatin
B. Furosemide (Correct Answer)
C. Lisinopril
D. Docetaxel
E. Aspirin

Explanation: ***Furosemide*** - The patient's **renal function has worsened** significantly, indicated by the rise in **BUN and creatinine**, making her more susceptible to **ototoxicity** from furosemide due to reduced drug clearance. - Her recent discharge for **congestive heart failure exacerbation** suggests she was likely on higher doses or had increased exposure to furosemide during hospitalization. - The **significant improvement in hearing within two weeks** is the key diagnostic feature, as **furosemide-induced ototoxicity is reversible** when the drug is discontinued or the dose is reduced, unlike other ototoxic agents. - Loop diuretics like furosemide cause ototoxicity by disrupting the ionic balance in the endolymph of the inner ear, but this effect is typically **transient and reversible**. *Cisplatin* - **Cisplatin** is a known **ototoxic chemotherapy agent**, and its timing (two weeks post-treatment) fits with the onset of symptoms. - However, cisplatin-induced ototoxicity is typically **irreversible and permanent**, involving destruction of the **outer hair cells** of the cochlea. - The **rapid improvement in the patient's hearing** within two weeks makes cisplatin an unlikely cause, as its ototoxicity results in persistent, dose-dependent bilateral sensorineural hearing loss. *Lisinopril* - **Lisinopril**, an **ACE inhibitor**, is not associated with **ototoxicity** or hearing loss. - Its primary mechanisms of action are related to **blood pressure regulation** and **cardiovascular remodeling**, with no direct known impact on auditory function. *Docetaxel* - **Docetaxel** is a **taxane chemotherapy drug** that can cause neurological side effects, including **peripheral neuropathy**, but it is not commonly associated with **ototoxicity** or hearing loss. - The rapid resolution of hearing loss makes ototoxicity from docetaxel improbable. *Aspirin* - **Aspirin** can cause **reversible ototoxicity** (tinnitus and hearing loss), particularly at high doses (typically >3 g/day) in a condition called **salicylism**. - However, the patient's hearing loss is more directly attributable to **furosemide** given the context of recent CHF exacerbation requiring aggressive diuretic therapy and worsening renal function that would increase furosemide levels.

Question 9: A 67-year-old man presents to his physician with increased thirst and polyuria for the past 4 months. Patient also notes a decrease in his vision for the past 6 months and tingling in his feet. The medical history is significant for a chronic pyelonephritis and stage 2 chronic kidney disease. The current medications include losartan and atorvastatin. He reports a daily alcohol intake of 3 glasses of whiskey. The blood pressure is 140/90 mm Hg and the heart rate is 63/min. The BMI is 35.4 kg/m2. On physical examination, there is 2+ pitting edema of the lower legs and face. The pulmonary, cardiac, and abdominal examinations are within normal limits. There is no costovertebral angle tenderness noted. Ophthalmoscopy shows numerous microaneurysms and retinal hemorrhages concentrated in the fundus. The neurological examination reveals a symmetric decrease in vibration and 2 point discrimination in the patient’s feet and legs extending up to the lower third of the calves. The ankle-deep tendon reflexes are decreased bilaterally. The laboratory test results are as follows: Serum glucose (fasting) 140 mg/dL HbA1c 8.5% BUN 27 mg/dL Serum creatinine 1.3 mg/dL eGFR 55 mL/min The patient is prescribed the first-line drug recommended for his condition. Which of the following side effect is associated with this drug?

A. Lactic acidosis (Correct Answer)
B. Infections
C. Hypoglycemia
D. Iron deficiency anemia
E. Hyperkalemia

Explanation: ***Lactic acidosis*** - The patient presents with classic **Type 2 Diabetes Mellitus** (polyuria, polydipsia, HbA1c 8.5%, fasting glucose 140 mg/dL, diabetic retinopathy, peripheral neuropathy). - **Metformin** is the first-line medication for Type 2 Diabetes according to all major guidelines (ADA, AACE). - While **lactic acidosis** is a rare side effect of metformin, it is the most **serious** adverse effect and the answer to this question. - This patient has multiple risk factors for lactic acidosis: **moderate renal impairment** (eGFR 55 mL/min), **chronic alcohol use** (3 glasses whiskey daily), and advanced age. - Note: Current guidelines allow metformin use at eGFR ≥30 mL/min with dose adjustment, so metformin is not contraindicated in this patient but requires careful monitoring. - The most common side effects of metformin are GI-related (diarrhea, nausea), but lactic acidosis is the most clinically significant. *Infections* - Increased risk of **genitourinary infections** is associated with **SGLT2 inhibitors** (canagliflozin, empagliflozin, dapagliflozin), not metformin. - While the patient has a history of chronic pyelonephritis, this is unrelated to metformin therapy. *Hypoglycemia* - **Metformin** decreases hepatic glucose production and improves insulin sensitivity without stimulating insulin secretion. - Metformin monotherapy **rarely causes hypoglycemia**, which is more common with sulfonylureas (glyburide, glipizide) or insulin. *Iron deficiency anemia* - Iron deficiency anemia is **not** a recognized side effect of metformin. - Note: Metformin is associated with **Vitamin B12 deficiency** (due to malabsorption) leading to megaloblastic anemia, but not iron deficiency anemia. *Hyperkalemia* - Hyperkalemia is **not** a side effect of metformin. - This patient's losartan (ARB) and chronic kidney disease could cause hyperkalemia, but this is unrelated to metformin therapy.

Question 10: A 47-year-old man comes to the physician for a routine health maintenance examination. He states that he has felt fatigued and dizzy on several occasions over the past week. He has back pain for which he takes ibuprofen. Digital rectal examination shows no abnormalities. Laboratory studies show a hemoglobin concentration of 15 g/dL, a serum urea nitrogen concentration of 22 mg/dL, a serum creatinine concentration of 1.4 mg/dL, and a serum calcium concentration of 8.4 mg/dL. His prostate-specific antigen (PSA) level is 0.3 ng/mL (N < 4.5). An intravenous infusion of para-aminohippurate (PAH) is administered and its clearance is calculated. The patient's effective renal plasma flow is estimated to be 660 mL/min (N = 500–1350). The filtration fraction is calculated to be 9% (N = 17–23). Which of the following is the most likely cause of this patient's laboratory abnormalities?

A. Kidney stones
B. Multiple myeloma
C. Bacteremia
D. Hypovolemia
E. NSAID use (Correct Answer)

Explanation: ***NSAID use*** - The patient's **low filtration fraction (9%)** and **slightly elevated creatinine (1.4 mg/dL)** despite a normal effective renal plasma flow (ERPF) are highly suggestive of **impaired autoregulation of GFR**. - **NSAIDs** inhibit **prostaglandin synthesis**, which normally helps maintain GFR through **efferent arteriolar vasoconstriction**. - Loss of prostaglandin-mediated efferent constriction leads to **efferent arteriolar vasodilation**, reducing glomerular capillary hydrostatic pressure and causing a **disproportionate fall in GFR** compared to renal plasma flow, thus decreasing the filtration fraction. - This mechanism is particularly important in states of decreased renal perfusion where prostaglandins play a critical compensatory role. *Kidney stones* - While kidney stones can cause back pain, they typically lead to **obstructive nephropathy**, which would present with a decrease in both GFR and ERPF, and often with **hematuria**, none of which are specifically indicated here. - They do not directly cause the specific pattern of a low filtration fraction with preserved ERPF described. *Multiple myeloma* - Multiple myeloma commonly causes **renal impairment**, often due to **light chain cast nephropathy**, leading to elevated creatinine. - However, it typically presents with **hypercalcemia**, **anemia**, and evidence of paraproteinemia, which are not seen in this patient (normal hemoglobin, normal calcium). *Bacteremia* - **Bacteremia** can lead to **sepsis** and **acute kidney injury (AKI)**, often characterized by **hypotension** and a significant drop in GFR and ERPF. - This patient's symptoms are mild (fatigue, dizziness) and his ERPF is within the normal range, making severe sepsis less likely. *Hypovolemia* - **Hypovolemia** causes **prerenal acute kidney injury**, characterized by reduced ERPF, GFR, and an **increased BUN/creatinine ratio** due to increased tubular reabsorption of sodium and water. - This patient has a normal ERPF and a normal BUN/creatinine ratio, making hypovolemia less likely to be the primary cause of his specific renal abnormalities.

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