Renal Week 2008: CKD and CVD: Antihypertensive therapy

Case report of a patient with HTN
Ray Townsend is the MC (sweet). He presnts a patient with HTN and modest CKD. Cr 1.4 up from 0.9 in 2001.

Ray passes off to Domenic Sica.

Antihypertensive Drug Therapy in patients with HTN and CKD.

Volume expansion

• Patient was on 25 mg of HCTZ. No need to change to loop if the patient is euvolemic. Chlorathalidone vs hctz
• Ernst HTN 2006. chlorathalidone reduced 24hr mean bp more (7 vs 12) non-ckd patients. night time bp drop was even more pronounced 6 vs 13 mmHg.
• Recommends switch within class from hctz to chlorthalidone
• the increase in calcium may help with PTH. interesting.
• elison JCI 83: 113; 1989 images of hypertrophy of DCT with loop diuretics
• He's pushing torsemide
• Using FeNa to determine if patient is responding to loops (look for fena>3%)
• Why is there variability in bioavailability of furosemide: floculation of pills stops some absorption. Use of liquid furosemide doesn't help because of only a limited area of absorbtion: early duodenum only.
• He likes the torsemide

Drug accumulation

At gfr 30-50 need to think about dose adjustment.
Renally cleared: atenolol, nadolol, betaxolol

Hepatically cleared
propanolol, metoprolol, carvedilol

Dose response to beta-blockers is flat in CKD.

Don't titrate atenolol. It is renally cleared and patients are already retaining the drug before you increase the dose. Though the BP effect is not dose dependent, the adverse effects are.

Aldosteronism

• 20% of patients with CKD.
• Likely this patient will have aldo level of 14-20 and renin less than 1
• Aldosterone antagonists (AA) reduce proteinuria
• Need diuretic on board to get much BP effect
• Half-life of spironolactone is 24 hours, in liver disease 120 hours, and in CKD multiple days. These figures include active metabolites. He feels eplerenone is safer because you won't get accumulation.
• Consider qod dosing of spironolactone. Consider 12.5 mg qd
• beware of heparin causing hyperkalemia with AA
• Similar warning for ACEi, ARB, TMP/SMX

Clonidine

• in CKD clonidine is renally cleared. This decreases rebound htn by extending the half life
• initially clonidine has a steep dose responce at low doses but then flattens
• causes dose dependent volume retension. this is worse with TTS
• at higher doses the peripheral alpha stimulation will overcome the central reduction in alpha activity so patients get increase in BP. This is seen in clonidine OD or with autonomic dysfunction.
  

CCB

• Amlodipine has half-life of 40 hours
• nifedipine's half-life goes from 2 to 4 hours in renal failure
• Edema with CCB is worse in patients with CKD because they already have increased volume

ACEi

• 10 in the US
• fosinopril and trandolopril have significant hepatic clearance
• ARB are not renally excreted
• dialyzable: captopril, enalepril, lisinopril. Use in overdose.

Statin

• AUC of simva increases 4 fold with diltiazem
• Cool case report of a patient on 80 of simva who was admitted for A-fib with RVR and gets started on a diltiazem gtt. He developed rhabdo a few days later.
  

That's it. Question time.