Nephrology Potpourri March 22, 2017

Transcription

1 Nephrology Potpourri March 22, Kantima Phisitkul, MD Clinical Assistant Professor Renal Diseases and Hypertension Division University of Iowa

2 Disclosure My spouse, Phinit is a paid consultant of Arthrex Inc, Smith & Nephew Inc We have stocks in First Ray & Mortise Medical LLC I have no actual or potential conflict of interest pertaining to the content of this educational activity

3 Objectives 1. Identify resistant HTN and uncontrolled HTN causes 2. Provide pharmacologic treatment of primary resistant HTN 3. Identify hidden nephrotoxic agents associated with decreased renal function in outpatient setting 4. Understand recent guidance of Metformin use in CKD

4 A 51-year-old man is evaluated for a 1-year history of uncontrolled HTN. He has no FH of HTN. He has never smoked cigarettes and has no other medical problems. Current medications are maximum doses of chlorthalidone, lisinopril, and amlodipine. Seated blood pressure is 160/94 mm Hg, and pulse rate is 76/min. The remainder of the examination is unremarkable. Cr 1.1 mg/dl, K 4.1 and egfr >60 This patient has? A) Resistant HTN B) Uncontrolled HTN C) A & B MKSAP 16 Renal Question 62

5 Resistant Hypertension BP above a goal despite adherence to at least 3 optimally dose antihypertensive agents of different classes, one of which is a diuretic. Uncontrolled Hypertension Resistant HTN Pseudo-resistant HTN

6 JNC 8 P James, JAMA. 2014;311(5):

7 SPRINT redefines BP target goals Among adult persons ( including > 75) at high risk for CVD event without diabetes Target SBP < 120 ( vs < 140) resulted in lower rates of fatal/nonfatal major CVD events and death but with higher rates of adverse events; hypotension, syncope, electrolyte abnormalities, and AKI. Wright JT Jr N Engl J Med 2015; 373: Williamson JD JAMA. 2016;315(24):

8 Based on a review and meta-analysis of 21 RCT comparing BP targets and treatment intensity including ACCORD, HOT, HYVET, SHEP, and SPRINT. In patients > 60, target BP of < 150/90 mm can reduce the risk of mortality by 10%, cardiac events by 23% and stroke by 26% In patients > 60 with history of stroke, TIA or increased CVD risk target SBP < 140 to reduce risk of recurrent stroke or cardiac events. Amir Qaseem Ann Intern Med Jan 17 [Epub ahead of print]

9 What Is the Right Target?? Aim: Lower BP as low as you can as long as it does not interfere with Quality of Life & kidney function 1.A Chobanian JAMA. Feb 2017;317(6): An Interview With Franz Messerli, MD 02/21/2017

10 Management of Resistant HTN Identify pseudoresistance Patient Physician BP technique Medication nonadherence -8-40% 50-60% -Self-report overestimated adherence by 80% White coat Syndrome ~30% -High office BP but normal 24- hr ABP Identify barrier Side effects Complex regimens Financial limitations Cognitive dysfunction Reluctant to adjust BP meds -Inappropriate drug combinations -Suboptimal doses BP cuff size -encircle 80% or more of arm circumference Patient position -relaxed and seated with legs uncrossed and back and arm supported Practice Guideline Am Fam Physician Oct 1;72(7): Faselis C Int J Hypertens Mar 2;2011: Vongpatanasin W JAMA Sep 17;312(11):1157

11 Drug-induced HTN Which of the following medications does not increase BP? A. Relafen (nabumetone) B. Toradol (ketorolac) C. Celebrex (celecoxib) D. DMPA; Depo-Provera Practice Guideline Am Fam Physician Apr ;75(8): Faselis C Int J Hypertens Mar 2;2011:236239

12 Diet Lifestyle Interventions Eat Healthy: DASH Na intake < 2400 mg or 1 tsp of salt ~ 6 g/d Moderate alcohol < 3 drinks or 30 g/d Activity Aerobic activity 30 min/day Walking on a treadmill 3 times/wk Smoking cessation -- BP rises transiently within 30 min after the last smoke Vongpatanasin W JAMA Sep 17;312(11):1157 Husain K World J Cardiol May 26; 6(5): UTDOL: Smoking and hypertension accessed 3/20/17 JNC8 HTN GuidelinesBookBooklet.pdf

13 Secondary HTN Vongpatanasin W JAMA 2014;311(21):

14 A 51-year-old man is evaluated for a 1-year history of uncontrolled HTN. He has no FH of HTN. He has never smoked cigarettes and has no other medical problems. Current medications are maximum doses of chlorthalidone, lisinopril, and amlodipine. Seated blood pressure is 160/94 mm Hg, and pulse rate is 76/min. The remainder of the examination is unremarkable. Cr 1.1 mg/dl, K 4.1 and egfr >60 Which of the following is the most appropriate next step in management? A. Discontinue chlorthalidone; begin furosemide B. Discontinue lisinopril; begin aliskiren C. Obtain kidney Doppler ultrasonography D. Obtain a plasma aldosterone-plasma renin activity ratio MKSAP 16 Renal Question 62

15 Pharmacologic intervention 3 Different classes Synergistic actions ACEI/ARB CCB Diuretic -Thiazide-like diuretic is preferred (chlorthalidone/indapamide > HCTZ) - Loop diuretic: GFR < 30, bid dosing

16 What is the most effective 4 th drug for resistant HTN? A. α-blocker B. β-blocker C. Clonidine D. Spironolactone PATHWAY-2: -Spironolactone (25-50 mg daily) lowered home SBP by 8.7 mmhg doxazosin ( 4-8 mg) by 4 and bisoprolol (5-10 mg/d) by 4.5 -GFR > 45 ml. Hyperkalemia/gynecomastia ~ Eplerenone mg daily Williams B Lancet 2015 Nov ; 386:

17 Take Home # 1 Spironolactone works well in resistant essential HTN Dose mg/day Monitor serum K

18 ACEI/ARB -The cornerstone of CKD treatment -Decreases glomerular intracapillary pressure and decreases urine protein excretion -Benefits on progression of renal disease are independent of antihypertensive effect. JNC8 HTN GuidelinesBookBooklet.pdf Pena-Polanco JE Semin Nephrol Jul;36(4):331-42

19 ACEI/ARB use Slows the decrease in GFR and progression to ESRD in patients with UAE > 300 mg/g Cr Dual RAAS blockade: not recommended Pena-Polanco JE Semin Nephrol Jul;36(4):331-42

20 Take Home # 2 ACEI/ARB does not have an extra benefit on non-proteinuric CKD patients

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22 PPI One of the most widely prescribed classes of drugs on the market One of the most common causes of drug-induced Acute Interstitial Nephritis (AIN) worldwide Introduction of first PPI, Omeprazole, was in 1989 The first case report of PPI-induced AIN was published in 1992: A 74 y/o woman on PPI x 6 months presented with fatigue, nausea, weakness hematuria, proteinuria and eosinophiliuria. Moledina DG J Nephrol (2016) 29: P

23 PPI-induced AIN Symptoms appear from 1 wk-9 mo after initial exposure of PPI The classic triad of fever, peripheral eosinophilia, and rash is present in only a fraction (10%) of patients with AIN. Think of PPI-induced AIN in An unexplained gradual rise in Cr over weeks to mo. Development of AKI without obvious cause Early recognition and drug withdrawal and possibly early steroid therapy may lead to a better prognosis. Moledina DG J Nephrol (2016) 29: P

24 PPI and CKD > 50% of patients suffered PPI-induced AIN did not recover to baseline Significant number of patients left with residual CKD despite discontinuation of the drug and steroid therapy Unrecognized cases of AIN likely occur and result in CKD. Kidney Int Feb 20 [Epub ahead of print]

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26 Fenofibrate & Kidney

27 Fibric Acid Derivatives The evidence supporting the safety and efficacy of fibric acid derivatives is extremely weak in CKD. Most trials excluded CKD with GFR > 1.5 A clear association between new Rx for fibric acid derivatives in elderly &increased Cr, risk of hospitalization and nephrology consultation Could be considered in CKD with TG > 1000 to prevent hypertg-induced-pancreatitis Dose should be adjusted Combination with statin is not recommended. KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease volume 3 issue 3 November 2013 Zhao YY Ann Intern Med Apr 17;156(8): ;156:

28 Renal function should be judiciously monitored in patients receiving? A. PPI B. Fibric acid derivatives C. Piroxicam D. Metformin All answers are correct A-C: they are nephrotoxic and can worsen kidney function D: Worsening GFR < 30 can cause metformin associated lactic acidosis (MALA)

29 We have concluded from the review of studies published in the medical literature that metformin can be used safely in patients with mild impairment in kidney function and in some patients with moderate impairment in kidney function

30 T/F regarding new recommendations from FDA A. Metformin is contraindicated in patients with an egfr below 30 B. Starting metformin in patients with an egfr between is not recommended. C. Obtain an egfr annually in all patients taking metformin regardless of age D. Assess the benefits and risks of continuing treatment when GFR < 45. E. Discontinue metformin if the patient s egfr later falls below 30 F. Discontinue metformin at the time of or before an iodinated contrast use when egfr between 30 and 60 G. Metformin can be safely restarted after contrast use. No need to check egfr at 48 hr True in all statements except C and G

31 Matthew J. Crowley Ann Intern Med. 2017;166:

32 Take Home Points 1. Spironolactone works well with resistant essential HTN 2. ACEI/ARB do not benefit non-proteinuric CKD patients, from renal perspective 3. Fenofibrate, PPI and hidden NSAIDS can worsen kidney function 4. Metformin could be used safely in CKD with egfr > 30 ml/min

33 Thank You