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TUTOR - PHARMACOLOGY
  • Test Id: 1911666766f08408f5
  • QId: 16521
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As per the JNC VIII committee recommendation, for individuals that are part of the African American population, including those with diabetes, the initial treatment should include a thiazide type diuretic or calcium channel blocker (CCB).  

Which of the following thiazide type diuretic is preferred as the initial antihypertensive therapy?

 

A. Hydrochlorthiazide 
B. Chlorthalidone 
C. Indapamide 
D. Metalazone 
E. Polythiazide 
The correct answer is B 
Chlothalidone

Explanation:

• Chlorthalidone at the same dose is approximately 1.5 to 2 times as potent as hydrochlorothiazide.

• Chlothalidone has a longer duration action than hydrochlorothiazide.

• There are No randomized clinical trials that directly compare outcomes in hypertensive patients treated with hydrochlorothiazide versus chlorthalidone. A multiple treatment (network) meta-analysis of nine trials including 50,946 patients was conducted in which hydrochlorothiazide and chlorthalidone were indirectly compared by evaluating their efficacy against common comparative drugs (ACE inhibitors were compared with hydrochlorothiazide in ANBP2 trial and with chlorthalidone in ALLHAT trial). The major findings of this meta-analysis showed that chlorthalidone significantly reduced the risk of cardiovascular events compared to hydrochlorothiazide (relative risk 0.79, 95% CI 0.72 to 0.88) and heart failure (relative risk 0.77, 95% CI 0.61 to 0.98). The authors calculated that 27 patients would need to be treated with chlorthalidone instead of hydrochlorothiazide over five years to prevent one cardiovascular event. Chlorthalidone remained superior to hydrochlorothiazide even after the meta-analysis was controlled for achieved office systolic blood pressure (relative risk for cardiovascular events 0.82, 95% CI 0.70 to 0.97). This finding may reflect the longer duration of action and lower nocturnal blood pressure associated with chlorthalidone.

• Multiple Risk Factor Intervention Trial (MRFIT) - Men Hypertensive 2392 were treated with chlorthalidone and 4049 were treated with hydrochlorothiazide. During six years of follow-up, cardiovascular events (defined as myocardial infarction, stroke, coronary artery bypass surgery, heart failure, left ventricular hypertrophy, peripheral artery disease, or angina) were significantly less common with chlorthalidone compared with hydrochlorothiazide (hazard ratio 0.79, 95% CI 0.68 to 0.92). Through the course of the study, systolic blood pressure and LDL cholesterol levels were also lower with chlorthalidone compared with hydrochlorothiazide. 

• Indapamide - is a thiazide like diuretic and has a half-life of 14-16 hours. This drug has been used in HYVET trial alone or in combination with perindropril in treatment of hypertension in patients more than 80 years old. Study showed 30% reduction in stroke, 39% reduction in the rate of death .21%in death from any cause, 23%reduction in CV death and 64%reduction in the rate of heart failure. The trial has shown careful BP lowering in very elderly is beneficial. Indapamide is not preferred over chlorthalidone.

• Metalazone - There are many studies with metalazone available. An important additional property is its effectiveness as a diuretic at lower GFR value. The duration of action is about 24 hours.
It is not preferred over chlorthalidone.

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Created On: 09/20/2017
Last Modified: 10/28/2024

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TUTOR - Hypertension
  • Test Id: 1911666766f08408f5
  • QId: 165212
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The ACCOMPLISH trial is the first major trial addressing the issue of combination therapy in 11,506 patients who were at high cardiovascular risk. The goal blood pressure was less than 130/80 mm Hg in the patients with diabetes or impaired renal function, and less than 140/90 mm Hg in the patients with prior cardiovascular disease.

Which of the following combinations of blood pressure medications was the best in reducing cardiovascular events and slowing the progression of nephropathy in patients with hypertension who were at high risk for such events?

A. ACEI + Diuretics
B. ACEI + CCB 
C. ACEI + Beta-blocker 
D. CCB + Beta-blocker 
The correct answer is B
ACEI + CCB

Explanation:

• The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension  - (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality.

• ACCOMPLISH ACCOMPLISH was a double-blind, randomized trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals.

• The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.

• The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events.

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TUTOR - Hypertension
  • Test Id: 1911666766f08408f5
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An 18 year-old male is brought to the renal clinic for evaluation of hypertension. There is no history of edema of the feet, puffiness of the face, hematuria, oliguria ,or recurrent urinary tract infections. He is an active football player, but lately he complains of weakness and muscle cramps. His blood pressure for the last 3-4 years has always been borderline high and during this visit was as noted below.

Physical examination shows: Pulse 100/min, all peripheral pulsations are well felt. BP 150/100 mm Hg, Temp. 37.4 degrees C. He is pale. His growth is stunted. His cognitive function is normal and no focal neurological deficits are noted. Other systems are unremarkable. Laboratory examination is as follows:

Hemoglobin   13.5 g/dL

Hematocrit   42%

Platelet Count   150,000 mm3

White Blood Cells  8,000 mm3


Urinalysis: 

Protein     100 mg/24 h

Glucose       None

Red Blood Cells      None

White Blood Cells     None

Leukocyte Esterase   Negative

Nitrites     Negative


Chemistry: 

BUN   13.5 mg/dL

Creatinine  0.9 mg/dL

Sodium   140 mEq/L

Potassium  5.8 mEq/L

Bicarbonate  18.5 mEq/L

Chloride   112 mEq/l

Calcium   9.2 mEq/L

Phosphorus  3.2 mg/dL

Aldosterone  5 ng/mL

PRA    <1.0ng/dl/hr


Glucose   100 mg/dL

HbA1C    5.30%

S. Osmolality   282 mOsmol

Uric Acid   5.3 mg/dL

ESR    9.8 mm/h


ABG: 

pH   7.25

PCO2  32 mm Hg

HCO3 16 mEq/L

PO2   90 mm Hg

USG  Normal size kidneys, no hydronephrosis 

Considering the history and the laboratory findings, which of the following is most likely the cause of hypertension in this patient?


A. Liddle's Syndrome 
B. Gordon's Syndrome 
C. Congenital adrenal hyperplasia 
D. Glucocorticoid-remediable aldosteronism 
E. Mineralocorticoid receptor activating mutation 
The correct answer is B
Gordon’s syndrome

Explanation:

Gordon’s syndrome - Young male with hypertension, hyperkalemia, hyperchloremic metabolic acidosis, normal renal function, low rennin, and low aldosterone is highly characteristic of Gordon’s syndrome. This syndrome is also known as pseudohypoaldosteronism type II. Recently it has been reported that Gordon’s syndrome is linked to chromosomes 1, 12, and 17. Hyperkalemia and hypertension in Gordon’s syndrome are caused by abnormalities in WNK kinases, proteins that are localized to the distal nephron and affect the thiazide-sensitive Na-Cl Cotransporter. Mutations affecting either WNK4 or WNK1 result in increased chloride reabsorption in the distal nephron, thereby reducing lumen electronegativity and lowering the force for potassium secretion. These mutations also result in decreased expression of the potassium channels through which potassium enters the collecting duct. Thus, mutant WNK4 increases sodium chloride reabsorption in the distal tubule and decreases potassium secretion in the collecting tubule resulting in sodium retention and decreased potassium excretion resulting in hypertension, hyperkalemia, and metabolic acidosis. The volume expansion leads to suppression of rennin and aldosterone. 

(Choice A) Liddle’s syndrome presents as hypertension in childhood. It is usually resistant to standard antihypertensive drugs. This is due to gain of function mutation at chromosome 16 affecting the beta or gamma subunit of ENaC channel in collecting duct of the nephron. This results in sodium retention and volume expansion causing hypertension and hypokalemia. The volume expansion leads to suppression of rennin and aldosterone. These patients will have hypertension, hypokalemia, metabolic alkalosis, low rennin and low aldosterone. 

(Choice C) Congenital adrenal hyperplasia presents in childhood with hypertension and virilization in girls and precocious puberty in boys. The other features include primary amenorrhea, delayed sexual maturation, ambiguous genitalia, with clitoral enlargement in girls. The 11 beta hyroxylase (CYP11B1) and (17 alpha hydroxylase (CYP17) deficiencies lead to excess deoxycoticosterone which leads to hypertension through a mineralocorticoid action. Biochemically it is characterized by metabolic alkalosis, low rennin and low aldosterone.

(Choice D) Glucocorticoid-remediable aldosteronism (GRA) is also known as familial hyperaldosteronism type I. In this disorder there is a chimeric gene formed from portions of the 11-beta-hydroxylase gene (CYP11B2) and the aldosterone synthase gene (CYP11B2). Patients with GRA have ectopic aldosterone synthesis occurring in the zona - fasciculata under the direct influence of ACTH rather than the renin. GRA presents with hypertension, hypokalemia, metabolic alkalosis, low rennin and high aldosterone. GRA resembles a primary hyperladosterone state with excessive urinary potassium loss. Look for a clue of family history of CVA or brain haemorrhage in the stem of the question.

(Choice E) Mineralocorticoid receptor activating mutation is a very rare autosomal dominant disorder. The mutation lies in the mineralocorticoid receptor, which causes it to be activated by steroid lacing 21 –hyroxyl groups, such as progesterone and spironolactone. Both normally antagonize the receptor but have opposite effect on this mutant receptor. It usually present as early onset hypertension in females. It may get accelerated during pregnancy due to elevated levels of progesterone. Biochemically it is characterized by hypokalemia, metabolic alkalosis low renin and low aldosterone.

Educational objective:

IF YOU KNOW THESE 5 POINTS FOR THESE 5-6 SYNDROMES YOU CAN ANSWER ALL NEPHROLOGY BOARD QUESTIONS ASKED ON THESE SYNDROMES:

Blood pressure - Normotension or hypertension
Potassium        - Hyperkalemia or hypokalemia
Acid-Base         - Acidosis or alkalosis
Renin                - Low or High
Aldosterone      - Low or High

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Last Modified: 01/25/2021

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TUTOR - Acute Kidney Injury / ICU Nephrology
  • Test Id: 1911666766f08408f5
  • QId: 165256
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A 30 year-old man comes to your office for a painful rash on the neck. He has fever and malaise. He has history of HIV. He is currently taking Tenofovir, emtricitabine, and indinavir.  The rash is suggestive of Herpes Zoster rash :

Physical examination does not reveal any oral cavity lesions. His current CD4 count is 250/mm3. His chemistry is normal. He is started on an intravenous medication for his rash. Two days later his chemistry is as follows:

Na    135 mEq/L

K     4.5 mEq/L                  

CL    100 mEq/L

HCO3   24 mEq/L                  

BUN  21 mg/dL                       

Cr   2.0 mEq/L

Glucose  95 mg/dL

Calcium   9.4 mg/dl

Urinalysis shows needle-shaped crystals in the sediment.

Which of the following is most likely the cause of his renal problem?


A.  Indinavir
B.  Tumor lysis syndrome
C.  Antifreeze ingestion
D.  Acyclovir
E.  IV TMP/SMX
The correct answer is D

Acyclovir

Explanation:

This patient has a characteristic lesion of herpes zoster on his neck. The vesicles are 2-3 mm in size with erythematous base. They are in different stages of development. Herpes zoster is commonly seen in elderly and immunocompromised. This patient is 30 year old and immunocompromised (HIV positive with AIDS). The treatment of choice for herpes zoster in immunocompromised patient is IV acyclovir. High dose Acyclovir is one of the causes of crystal-induced nephropathy. The crystals are needle-shaped.

Indinavir (Choice A), a protease inhibitor, is a common cause of nephrolithiasis in HIV patients. Patients would often present with flank pain. Urinalysis would show hematuria and needle shaped crystals. This patient, however, had normal serum chemistry on presentation. Following two days of IV medication (acyclovir) his serum chemistry showed elevated creatinine suggesting acyclovir as the most likely cause.

Tumor lysis syndrome (Choice B) occurs in the setting of chemotherapy for lymphoma.  It leads to the formation of uric acid crystals which are also needle shaped. This patient has no such presentation.

Patients with Anti-freeze ingestion (Choice C) present with metabolic acidosis with an elevated anion gap. The initial test of urinalysis shows envelope-shaped oxalate crystals.

Trimethoprim-sulfamethoxazole (TMP/SMX) (Choice E) has sulfonamide in it. Sulfonamide also leads to crystal-induced nephropathy. The crystals are often dumb-bell shaped.

Educational Objective:

Drugs causing Crystal-induced nephropathy:

ACYCLOVIR --- Needle shaped crystals

INDINAVIR --- Needle shaped crystals

SULPHONAMIDE --- Dumbell shaped crystals

CALCIUM OXALLATE (Antifreeze) --- Envelope shaped crystal

CALCIUM PO4---- Coffin shaped crystals

URIC ACID --- Hexagonal crystals

CYSTIENE --- Hexagonal crystals


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Last Modified: 08/29/2018

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TUTOR - Fluids and Electrolytes
  • Test Id: 1911666766f08408f5
  • QId: 167254
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A 20 year-old-male was at a party where after dancing he ate a lot of cake because it was “delicious”. After 2-3 hours he developed sudden onset of weakness in all 4 limbs. He has had two similar episodes in the past. He was rushed to the nearest ER. On examination: P: 88/min, BP: 140/96 mm Hg, Pallor+, No thyroid enlargement. He is alert and oriented. There is no cranial nerve involvement and no neck muscle weakness. Motor power is grade 2-3 in all extremities, reflexes sluggish to absent. Sensory exam is normal. Laboratory results reveal the following:

pH   7.4

pCO2    40 mm Hg

paO2  98 mm Hg

HCO3  24 mEq/L

O2 saturation  98%

Na  140 mEq/L

K   2.2 mEq/L

Cl   103 mEq/

BUN  10 mg/dl

S.Cr  0.8 mg%

S. Ca  10.2 mg/dl

PO4  2.5 mg/dl

Mg   2.2 mg/dl

Urine Electrolytes

Urine Na  100 mEq/L

Urine K  15 mEq/L

Which of the following is the MOST likely diagnosis?

A.  Familial periodic paralysis.
B. Renal tubular acidosis
C. Primary hyperaldosternism.
D.  Thyrotoxic periodic paralysis
The correct answer is A 

Familial periodic paralysis

Explanation:

In familial hypokalemic periodic paralysis, the hypokalemia is classically precipitated by carbohydrate load without any acid base disturbance. This typically occurs in the first or second decade of life. The low urinary K favors diagnosis of extra renal loss.

Renal tubular acidosis (Choice B) will have hypokalemia with metabolic acidosis and high urinary potassium, quadriparesis is uncommon in hypokalemia of RTA.
Primary hyperaldosteronism (Choice C) rarely presents with quadriparesis. Hypokalemia is associated with hypertension and metabolic alkalosis. High aldosterone and low renin levels are present.
Thyrotoxic periodic paralysis (Choice D) occurs after 20 years of age. Symptoms of thyrotoxicosis like palpitations, tachycardia, thyroid neck mass, low TSH with high T3 or high T4 is commonly seen. It is very common in Asians.

 Educational Objective:
Differentiate between familial periodic paralysis and thyrotoxic periodic paralysis.

FAMILIAL PERIODIC PARALYSIS –
Hypokalemia in the absence of acidosis
Weakness is precipitated by carbohydrate load and Exercise
Low urinary potassium

THYROTOXIC PERIODIC PARALYSIS –
YOUNG, usually female, very common in ASIANS
Symptoms of thyrotoxicosis and Often NECK MASS.
LOW TSH and high T3 or T4.

IF YOU KNOW ABOVE POINTS NO MATTER HOW THE ABIM QUESTION IS FRAMED, YOU WILL BE ABLE TO ANSWER IT.

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Created On: 09/12/2017
Last Modified: 12/30/2017

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1911666766f08408f5
  • QId: 165258
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 In a CKD and ESRD patient, Vitamin D seems to protect against cardiovascular disease events by controlling secondary hyperparathyroidism. The OPERA trial evaluated the effect of paricalcitol Vitamin D analog in CKD stages 3-5 with left ventricular hypertrophy. The study observed the effect on left ventricular mass and function.

Which of the following statements is true about the effect of paricalcitol in CKD and ESRD patients?

A. Paricalcitol treatment reduced LV mass
B. Paricalcitol treatment preserved LV ejection fraction
C. Paricalcitol treatment improved pulse wave velocity and arterial stiffness
D. Paricalcitol treatment improved blood pressure control
E. Paricalcitol treatment significantly reduced PTH and alkaline phosphatase 
The correct answer is E

Paricalcitol treatment significantly reduced PTH and alkaline phosphatase

Explanation:

Vitamin D Rx DOES NOT reduce LV mass OR LV ejection fraction OR arterial stiffness
Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial.

OPERA trial was a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy.
Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 ?g) one time daily (n=30) or matching placebo (n=30) for 52 weeks.

The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function.
Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo).
Changes in LV volume, ejection fraction, and tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups.

Paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo.

52 weeks of treatment with oral paricalcitol (1 ?g one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD and ESRD.

OPERA and PRIMO are two recent randomized clinical trials in patients with CKD, which evaluated paricalcitol for slowing the progression of left ventricular mass. Both these trials were found to have negative results.

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Last Modified: 08/06/2018

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TUTOR - PHARMACOLOGY
  • Test Id: 1911666766f08408f5
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As per the JNC VIII committee recommendation, for individuals that are part of the African American population, including those with diabetes, the initial treatment should include a thiazide type diuretic or calcium channel blocker (CCB).  

Which of the following thiazide type diuretic is preferred as the initial antihypertensive therapy?

 

A. Hydrochlorthiazide 
B. Chlorthalidone 
C. Indapamide 
D. Metalazone 
E. Polythiazide 
The correct answer is B 
Chlothalidone

Explanation:

• Chlorthalidone at the same dose is approximately 1.5 to 2 times as potent as hydrochlorothiazide.

• Chlothalidone has a longer duration action than hydrochlorothiazide.

• There are No randomized clinical trials that directly compare outcomes in hypertensive patients treated with hydrochlorothiazide versus chlorthalidone. A multiple treatment (network) meta-analysis of nine trials including 50,946 patients was conducted in which hydrochlorothiazide and chlorthalidone were indirectly compared by evaluating their efficacy against common comparative drugs (ACE inhibitors were compared with hydrochlorothiazide in ANBP2 trial and with chlorthalidone in ALLHAT trial). The major findings of this meta-analysis showed that chlorthalidone significantly reduced the risk of cardiovascular events compared to hydrochlorothiazide (relative risk 0.79, 95% CI 0.72 to 0.88) and heart failure (relative risk 0.77, 95% CI 0.61 to 0.98). The authors calculated that 27 patients would need to be treated with chlorthalidone instead of hydrochlorothiazide over five years to prevent one cardiovascular event. Chlorthalidone remained superior to hydrochlorothiazide even after the meta-analysis was controlled for achieved office systolic blood pressure (relative risk for cardiovascular events 0.82, 95% CI 0.70 to 0.97). This finding may reflect the longer duration of action and lower nocturnal blood pressure associated with chlorthalidone.

• Multiple Risk Factor Intervention Trial (MRFIT) - Men Hypertensive 2392 were treated with chlorthalidone and 4049 were treated with hydrochlorothiazide. During six years of follow-up, cardiovascular events (defined as myocardial infarction, stroke, coronary artery bypass surgery, heart failure, left ventricular hypertrophy, peripheral artery disease, or angina) were significantly less common with chlorthalidone compared with hydrochlorothiazide (hazard ratio 0.79, 95% CI 0.68 to 0.92). Through the course of the study, systolic blood pressure and LDL cholesterol levels were also lower with chlorthalidone compared with hydrochlorothiazide. 

• Indapamide - is a thiazide like diuretic and has a half-life of 14-16 hours. This drug has been used in HYVET trial alone or in combination with perindropril in treatment of hypertension in patients more than 80 years old. Study showed 30% reduction in stroke, 39% reduction in the rate of death .21%in death from any cause, 23%reduction in CV death and 64%reduction in the rate of heart failure. The trial has shown careful BP lowering in very elderly is beneficial. Indapamide is not preferred over chlorthalidone.

• Metalazone - There are many studies with metalazone available. An important additional property is its effectiveness as a diuretic at lower GFR value. The duration of action is about 24 hours.
It is not preferred over chlorthalidone.

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Last Modified: 10/28/2024

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TUTOR - Hypertension
  • Test Id: 1911666766f08408f5
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The ACCOMPLISH trial is the first major trial addressing the issue of combination therapy in 11,506 patients who were at high cardiovascular risk. The goal blood pressure was less than 130/80 mm Hg in the patients with diabetes or impaired renal function, and less than 140/90 mm Hg in the patients with prior cardiovascular disease.

Which of the following combinations of blood pressure medications was the best in reducing cardiovascular events and slowing the progression of nephropathy in patients with hypertension who were at high risk for such events?

A. ACEI + Diuretics
B. ACEI + CCB 
C. ACEI + Beta-blocker 
D. CCB + Beta-blocker 
The correct answer is B
ACEI + CCB

Explanation:

• The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension  - (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality.

• ACCOMPLISH ACCOMPLISH was a double-blind, randomized trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals.

• The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.

• The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events.

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TUTOR - Hypertension
  • Test Id: 1911666766f08408f5
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An 18 year-old male is brought to the renal clinic for evaluation of hypertension. There is no history of edema of the feet, puffiness of the face, hematuria, oliguria ,or recurrent urinary tract infections. He is an active football player, but lately he complains of weakness and muscle cramps. His blood pressure for the last 3-4 years has always been borderline high and during this visit was as noted below.

Physical examination shows: Pulse 100/min, all peripheral pulsations are well felt. BP 150/100 mm Hg, Temp. 37.4 degrees C. He is pale. His growth is stunted. His cognitive function is normal and no focal neurological deficits are noted. Other systems are unremarkable. Laboratory examination is as follows:

Hemoglobin   13.5 g/dL

Hematocrit   42%

Platelet Count   150,000 mm3

White Blood Cells  8,000 mm3


Urinalysis: 

Protein     100 mg/24 h

Glucose       None

Red Blood Cells      None

White Blood Cells     None

Leukocyte Esterase   Negative

Nitrites     Negative


Chemistry: 

BUN   13.5 mg/dL

Creatinine  0.9 mg/dL

Sodium   140 mEq/L

Potassium  5.8 mEq/L

Bicarbonate  18.5 mEq/L

Chloride   112 mEq/l

Calcium   9.2 mEq/L

Phosphorus  3.2 mg/dL

Aldosterone  5 ng/mL

PRA    <1.0ng/dl/hr


Glucose   100 mg/dL

HbA1C    5.30%

S. Osmolality   282 mOsmol

Uric Acid   5.3 mg/dL

ESR    9.8 mm/h


ABG: 

pH   7.25

PCO2  32 mm Hg

HCO3 16 mEq/L

PO2   90 mm Hg

USG  Normal size kidneys, no hydronephrosis 

Considering the history and the laboratory findings, which of the following is most likely the cause of hypertension in this patient?


A. Liddle's Syndrome 
B. Gordon's Syndrome 
C. Congenital adrenal hyperplasia 
D. Glucocorticoid-remediable aldosteronism 
E. Mineralocorticoid receptor activating mutation 
The correct answer is B
Gordon’s syndrome

Explanation:

Gordon’s syndrome - Young male with hypertension, hyperkalemia, hyperchloremic metabolic acidosis, normal renal function, low rennin, and low aldosterone is highly characteristic of Gordon’s syndrome. This syndrome is also known as pseudohypoaldosteronism type II. Recently it has been reported that Gordon’s syndrome is linked to chromosomes 1, 12, and 17. Hyperkalemia and hypertension in Gordon’s syndrome are caused by abnormalities in WNK kinases, proteins that are localized to the distal nephron and affect the thiazide-sensitive Na-Cl Cotransporter. Mutations affecting either WNK4 or WNK1 result in increased chloride reabsorption in the distal nephron, thereby reducing lumen electronegativity and lowering the force for potassium secretion. These mutations also result in decreased expression of the potassium channels through which potassium enters the collecting duct. Thus, mutant WNK4 increases sodium chloride reabsorption in the distal tubule and decreases potassium secretion in the collecting tubule resulting in sodium retention and decreased potassium excretion resulting in hypertension, hyperkalemia, and metabolic acidosis. The volume expansion leads to suppression of rennin and aldosterone. 

(Choice A) Liddle’s syndrome presents as hypertension in childhood. It is usually resistant to standard antihypertensive drugs. This is due to gain of function mutation at chromosome 16 affecting the beta or gamma subunit of ENaC channel in collecting duct of the nephron. This results in sodium retention and volume expansion causing hypertension and hypokalemia. The volume expansion leads to suppression of rennin and aldosterone. These patients will have hypertension, hypokalemia, metabolic alkalosis, low rennin and low aldosterone. 

(Choice C) Congenital adrenal hyperplasia presents in childhood with hypertension and virilization in girls and precocious puberty in boys. The other features include primary amenorrhea, delayed sexual maturation, ambiguous genitalia, with clitoral enlargement in girls. The 11 beta hyroxylase (CYP11B1) and (17 alpha hydroxylase (CYP17) deficiencies lead to excess deoxycoticosterone which leads to hypertension through a mineralocorticoid action. Biochemically it is characterized by metabolic alkalosis, low rennin and low aldosterone.

(Choice D) Glucocorticoid-remediable aldosteronism (GRA) is also known as familial hyperaldosteronism type I. In this disorder there is a chimeric gene formed from portions of the 11-beta-hydroxylase gene (CYP11B2) and the aldosterone synthase gene (CYP11B2). Patients with GRA have ectopic aldosterone synthesis occurring in the zona - fasciculata under the direct influence of ACTH rather than the renin. GRA presents with hypertension, hypokalemia, metabolic alkalosis, low rennin and high aldosterone. GRA resembles a primary hyperladosterone state with excessive urinary potassium loss. Look for a clue of family history of CVA or brain haemorrhage in the stem of the question.

(Choice E) Mineralocorticoid receptor activating mutation is a very rare autosomal dominant disorder. The mutation lies in the mineralocorticoid receptor, which causes it to be activated by steroid lacing 21 –hyroxyl groups, such as progesterone and spironolactone. Both normally antagonize the receptor but have opposite effect on this mutant receptor. It usually present as early onset hypertension in females. It may get accelerated during pregnancy due to elevated levels of progesterone. Biochemically it is characterized by hypokalemia, metabolic alkalosis low renin and low aldosterone.

Educational objective:

IF YOU KNOW THESE 5 POINTS FOR THESE 5-6 SYNDROMES YOU CAN ANSWER ALL NEPHROLOGY BOARD QUESTIONS ASKED ON THESE SYNDROMES:

Blood pressure - Normotension or hypertension
Potassium        - Hyperkalemia or hypokalemia
Acid-Base         - Acidosis or alkalosis
Renin                - Low or High
Aldosterone      - Low or High

Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 01/25/2021

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TUTOR - Acute Kidney Injury / ICU Nephrology
  • Test Id: 1911666766f08408f5
  • QId: 165256
  • 10 of 12
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A 30 year-old man comes to your office for a painful rash on the neck. He has fever and malaise. He has history of HIV. He is currently taking Tenofovir, emtricitabine, and indinavir.  The rash is suggestive of Herpes Zoster rash :

Physical examination does not reveal any oral cavity lesions. His current CD4 count is 250/mm3. His chemistry is normal. He is started on an intravenous medication for his rash. Two days later his chemistry is as follows:

Na    135 mEq/L

K     4.5 mEq/L                  

CL    100 mEq/L

HCO3   24 mEq/L                  

BUN  21 mg/dL                       

Cr   2.0 mEq/L

Glucose  95 mg/dL

Calcium   9.4 mg/dl

Urinalysis shows needle-shaped crystals in the sediment.

Which of the following is most likely the cause of his renal problem?


A.  Indinavir
B.  Tumor lysis syndrome
C.  Antifreeze ingestion
D.  Acyclovir
E.  IV TMP/SMX
The correct answer is D

Acyclovir

Explanation:

This patient has a characteristic lesion of herpes zoster on his neck. The vesicles are 2-3 mm in size with erythematous base. They are in different stages of development. Herpes zoster is commonly seen in elderly and immunocompromised. This patient is 30 year old and immunocompromised (HIV positive with AIDS). The treatment of choice for herpes zoster in immunocompromised patient is IV acyclovir. High dose Acyclovir is one of the causes of crystal-induced nephropathy. The crystals are needle-shaped.

Indinavir (Choice A), a protease inhibitor, is a common cause of nephrolithiasis in HIV patients. Patients would often present with flank pain. Urinalysis would show hematuria and needle shaped crystals. This patient, however, had normal serum chemistry on presentation. Following two days of IV medication (acyclovir) his serum chemistry showed elevated creatinine suggesting acyclovir as the most likely cause.

Tumor lysis syndrome (Choice B) occurs in the setting of chemotherapy for lymphoma.  It leads to the formation of uric acid crystals which are also needle shaped. This patient has no such presentation.

Patients with Anti-freeze ingestion (Choice C) present with metabolic acidosis with an elevated anion gap. The initial test of urinalysis shows envelope-shaped oxalate crystals.

Trimethoprim-sulfamethoxazole (TMP/SMX) (Choice E) has sulfonamide in it. Sulfonamide also leads to crystal-induced nephropathy. The crystals are often dumb-bell shaped.

Educational Objective:

Drugs causing Crystal-induced nephropathy:

ACYCLOVIR --- Needle shaped crystals

INDINAVIR --- Needle shaped crystals

SULPHONAMIDE --- Dumbell shaped crystals

CALCIUM OXALLATE (Antifreeze) --- Envelope shaped crystal

CALCIUM PO4---- Coffin shaped crystals

URIC ACID --- Hexagonal crystals

CYSTIENE --- Hexagonal crystals


Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 08/29/2018

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TUTOR - Fluids and Electrolytes
  • Test Id: 1911666766f08408f5
  • QId: 167254
  • 11 of 12
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A 20 year-old-male was at a party where after dancing he ate a lot of cake because it was “delicious”. After 2-3 hours he developed sudden onset of weakness in all 4 limbs. He has had two similar episodes in the past. He was rushed to the nearest ER. On examination: P: 88/min, BP: 140/96 mm Hg, Pallor+, No thyroid enlargement. He is alert and oriented. There is no cranial nerve involvement and no neck muscle weakness. Motor power is grade 2-3 in all extremities, reflexes sluggish to absent. Sensory exam is normal. Laboratory results reveal the following:

pH   7.4

pCO2    40 mm Hg

paO2  98 mm Hg

HCO3  24 mEq/L

O2 saturation  98%

Na  140 mEq/L

K   2.2 mEq/L

Cl   103 mEq/

BUN  10 mg/dl

S.Cr  0.8 mg%

S. Ca  10.2 mg/dl

PO4  2.5 mg/dl

Mg   2.2 mg/dl

Urine Electrolytes

Urine Na  100 mEq/L

Urine K  15 mEq/L

Which of the following is the MOST likely diagnosis?

A.  Familial periodic paralysis.
B. Renal tubular acidosis
C. Primary hyperaldosternism.
D.  Thyrotoxic periodic paralysis
The correct answer is A 

Familial periodic paralysis

Explanation:

In familial hypokalemic periodic paralysis, the hypokalemia is classically precipitated by carbohydrate load without any acid base disturbance. This typically occurs in the first or second decade of life. The low urinary K favors diagnosis of extra renal loss.

Renal tubular acidosis (Choice B) will have hypokalemia with metabolic acidosis and high urinary potassium, quadriparesis is uncommon in hypokalemia of RTA.
Primary hyperaldosteronism (Choice C) rarely presents with quadriparesis. Hypokalemia is associated with hypertension and metabolic alkalosis. High aldosterone and low renin levels are present.
Thyrotoxic periodic paralysis (Choice D) occurs after 20 years of age. Symptoms of thyrotoxicosis like palpitations, tachycardia, thyroid neck mass, low TSH with high T3 or high T4 is commonly seen. It is very common in Asians.

 Educational Objective:
Differentiate between familial periodic paralysis and thyrotoxic periodic paralysis.

FAMILIAL PERIODIC PARALYSIS –
Hypokalemia in the absence of acidosis
Weakness is precipitated by carbohydrate load and Exercise
Low urinary potassium

THYROTOXIC PERIODIC PARALYSIS –
YOUNG, usually female, very common in ASIANS
Symptoms of thyrotoxicosis and Often NECK MASS.
LOW TSH and high T3 or T4.

IF YOU KNOW ABOVE POINTS NO MATTER HOW THE ABIM QUESTION IS FRAMED, YOU WILL BE ABLE TO ANSWER IT.

Copyright © ABIM Exam World
Created On: 09/12/2017
Last Modified: 12/30/2017

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1911666766f08408f5
  • QId: 165258
  • 12 of 12
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 In a CKD and ESRD patient, Vitamin D seems to protect against cardiovascular disease events by controlling secondary hyperparathyroidism. The OPERA trial evaluated the effect of paricalcitol Vitamin D analog in CKD stages 3-5 with left ventricular hypertrophy. The study observed the effect on left ventricular mass and function.

Which of the following statements is true about the effect of paricalcitol in CKD and ESRD patients?

A. Paricalcitol treatment reduced LV mass
B. Paricalcitol treatment preserved LV ejection fraction
C. Paricalcitol treatment improved pulse wave velocity and arterial stiffness
D. Paricalcitol treatment improved blood pressure control
E. Paricalcitol treatment significantly reduced PTH and alkaline phosphatase 
The correct answer is E

Paricalcitol treatment significantly reduced PTH and alkaline phosphatase

Explanation:

Vitamin D Rx DOES NOT reduce LV mass OR LV ejection fraction OR arterial stiffness
Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial.

OPERA trial was a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy.
Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 ?g) one time daily (n=30) or matching placebo (n=30) for 52 weeks.

The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function.
Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo).
Changes in LV volume, ejection fraction, and tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups.

Paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo.

52 weeks of treatment with oral paricalcitol (1 ?g one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD and ESRD.

OPERA and PRIMO are two recent randomized clinical trials in patients with CKD, which evaluated paricalcitol for slowing the progression of left ventricular mass. Both these trials were found to have negative results.

Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 08/06/2018

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