Antihypertensive Medications in Kidney Disease

Question 1

Case 1. Patient is a 58 year old male with slowly progressively chronic kidney disease due to adult polycystic kidney disease.

Blood pressure is 157/94 mmHg despite full dose lisinopril (80mg PO daily) and chlorthalidone (25mg PO daily). Serum creatinine is 3.4 mg/dL and estimated glomerular filtration rate (GFR) is less than 30 ml/min.

What adjustment needs to be made in his antihypertensive regimen?

Answer 1

You want to control any degree of HTN with CKD

Note that at GFRs that low, thiazides are not going to be effective (below 30 usually), so switching to a loop diuretic may help

Question 2

What is chlorthalidone?

Answer 2

thiazide diuretic

Question 3

What kind of things would urinalysis show in this patient?

Answer 3

minimal proteinuria- probably normal urinalysis

Question 4

What would be the effect of ARBs/ACEIs on potassium?

Answer 4

they would promote hyperkalemia (via lack of aldosterone)

Question 5

Would this patient have salt-sensitive HTN?

Answer 5

Yes, in CKD salt restrictions should always be part of consouling

Question 6

Why would dosage of loop diuretics need to be higher to promote diuresis in someone with kidney dysfunction (Like CKD) vs a person with normal kidney function

Answer 6

It is mostly the fact that in someone with CKD you cannot get enough of the drug to the site of action because of dysfunction

Question 7

Case 2. 48-year-old female with type 2 diabetes mellitus has annual albumin /creatinine ratio (ACR) screening performed and it demonstrates the presence of microalbuminuria (40 mg/gm). Repeat testing confirms microalbuminuria. Blood pressure is 130/80 mmHg. Serum creatinine is 1.0 mg/dL What treatment would you recommend?

Answer 7

Initiate an ACEI or ARB (as long as non-pregnant!!!)

Question 8

Why are ACEIs/ARBs so good when protein is getting into the urine?

Answer 8

They decrease intraglomerular filtration pressure by inhibitng efferent constriction and thus decrease protein loss

Question 9

Case 3. 48-year-old female with type 2 diabetes mellitus has annual albumin/creatinine ratio screening performed and it demonstrates the presence of macroalbuminuria (ACR - 800mg/gm creatinine). Repeat testing confirms macroalbuminuria. Blood pressure is 140/90 mmHg. Serum creatinine is 1.0 mg/dL. What treatment would you recommend?

Answer 9

Regardless of the degree of proteinuria, go with ACEIs or ARBs in hopes of halting the progression

Question 10

What do you need to monitor when giving an ACEI/ARB?

Answer 10

definitely BP but Pcr as well to make sure GFR isn’t dropping too low

Question 11

Case 4. 62-year-old male with type 2 diabetes mellitus with chronic non-nephrotic range proteinuria. Physical exam demonstrates the presence of edema. Serum creatinine is 2.6 mg/dL and serum potassium is 5.0 mEq per liter. Blood pressure is 150/90. His primary care physician increased his lisinopril from 20 mg to 40 mg daily. At two week follow up blood pressure has improved 136/80, serum creatinine is 2.9 mg/dL and potassium is 5.9 mEq per liter. Plasma bicarbonate is 17 mEq per liter. How do you account for these laboratory changes and what adjustments need to be made in his treatment plan?

Answer 11

GFR decreases so Pcr increases

Pk increases because aldosterone is inhibited

H+ also increases (needs K+ in the urine to secrete) so HCO3- decreases (think about how the intercalated cells in the CD work)

Add a loop diuretic

Question 12

Case 5. 46-year-old male with dilated cardiomyopathy, chronic congestive heart failure with chronic edema requiring diuretic therapy. He is now receiving high-dose furosemide orally but is still edematous. Other medications include carvedilol and lisinopril. Serum creatinine is 1.0 mg/dL. What steps should be done at this point to better manage his fluid overload?

Answer 12

If ejection fraction is less than 35%, consider adding an aldosterone inhibitor but this probably wont help a ton with the edema

assuming Na intake is good, limit water intake

consider a synergistic effect- add a thiazide

Question 13

How to assess his diet?

Answer 13

Do a 24 hr urine collection (can only do here because weight is constant)

100mEq is good
higher is bad

Question 14

What adjustments can and should be made in his diuretic therapy?

Answer 14

Is your dose enough? GFR is probably good here so dose should be good

make sure frequency is enough

Question 15

How long does furosemide work?

Answer 15

aka Lasix (lasts 6 hours)

Question 16

What is a major problem with long term loop diuretic use?

Answer 16

tolerance

Question 17

How does the body develop tolerance to loop diuretics?

Answer 17

the segments distal to the thick ALH will hypertrophy and promote increased Na+ reabsorption

Question 18

Case 6. 54-year-old African-American male with very difficult to control hypertension. Lifestyle changes have not been successful in reducing blood pressure. He is receiving maximum dose of angiotensin receptor blocker (losartan) and blood pressure remains 160/104 mm Hg. Serum creatinine is 1.0 mg/dL.

How would you assess dietary sodium intake? What medication adjustments should be made at this point?

Answer 18

ACE I and ARB alone are often less effective as monotherapy for blood pressure lowering in African Americans, due to higher prevalence of low renin hypertension (have lower renin dependent HTN)

add a thiazide

Question 19

Case 7. 58-year-old male with coronary artery disease with intermittent angina pectoris and chronic kidney disease, serum creatinine 2.4 mg/dL, blood pressure 140/90 mmHg and heart rate 72 bpm.

He is prescribed the BB atenolol 25 mg daily (low dosage). During follow-up he feels tired and heart rate is 40 bpm? How do explain this change in vital signs?

Answer 19

While most beta blockers are hepatically metabolized, atenolol is highly dependent on renal elimination (roughly 50% renal and 50% feces) and here it is not being excreted well

nadolol (highly) and bisoprolol (partial) are also kidney dependent

Question 20

Case 8. 34-year-old African-American female with biopsy-proven focal segmental glomerulosclerosis with nephrotic syndrome with marked lower extremity edema. Serum creatinine 0.9 mg/dL.

Treatment includes full dosage lisinopril and furosemide 80 mg once daily. What adjustments need to be made in diuretic management?

Answer 20

Once daily is not enough (only lasts 6 hours)

block Enac-triamterene/amiloride

Question 21

What would be the effect of the addition of spironolactone?

Answer 21

effective

Question 22

T or F. Loop diuretics need functioning kidneys to work

Answer 22

T. They must be delivered to the site of action, so the worse the GFR the more needed

Similarly, loop diuretics can be bound to proteins so heavy proteinuria will result in more of the drug being excreted without functioning properly AND the diuretics and thiazides must be secreted by the PT and use albumin as a transporter so the more loss of albumin= less efficacy

Question 23

Purely nephrotic patients have normal plasma volumes. Why?

Answer 23

because there is avid salt and water retention that is restricted to the ECF. So you lose some to the interstitium but you gain extra to normalize the plasma volume at the expense of edema

Question 24

Case 9. 62-year-old Caucasian male with ischemic cardiomyopathy and chronic kidney disease, serum creatinine 2.4 mg/dL.

He is receiving carvedilol and lisinopril therapy. Blood pressure is 130/80 mmHg and heart rate is 50 bpm.

His primary care physician adds low-dose spironolactone to his treatment regimen. What potential complications may occur?

Answer 24

Risk of hyperkalemia substantially higher with elevated SCr (>1.6 mg/dl) and also other drugs causing hyperkalemia (aka: ACEIs, ARB, NSAIDs)

start at a low dose and FOLLOW UP quickly to look at K+ levels