The CKD patient in the office or ER. Dr. Vincent Cheung Nephrologist Peterborough Regional Renal Program November 9 th, 2016

Transcription

1 The CKD patient in the office or ER Dr. Vincent Cheung Nephrologist Peterborough Regional Renal Program November 9 th, 2016

2 Presenter Disclosure Dr. Vincent Cheung Relationships with commercial interests (in past 2 years): Grants/Research Support: none Speakers Honoraria: Servier, Janssen Consulting Fees: none Other: none

3 Disclosure of Commercial Support This presentation has received no financial on inkind support Potential for conflict (s) of interest: Dr. Cheung has not received any payment or funding in-kind for this program

4 Mitigating Potential Bias Where possible recommendations are supported by evidence Off label options are clearly indicated as such Many agents discussed are non proprietary

5 Objectives A Fib and NOACs in CKD Diuretics in CKD Treatment of Gout and Hyperuricemia in CKD Hyperkalemia Vaccines in CKD

6 Atrial Fibrillation and Non Vit K Oral Anticoagulants in CKD

7 Anticoagulation with Warfarin reduces ischemic stroke risk in Nonvalvular Atrial Fibrillation in the general population Effect on all stroke

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10 NOACs vs. Warfarin No need for blood testing/dose titration No interaction with food Less drug interactions Rapid onset of action, short half-life Equivalent (?better) risk reduction for ischemic stroke Better safety profile Little evidence/experience in advanced CKD/ERSD Lack of reversibility/antidote

11 Relative risk 0.81 Lancet Mar 15;383(9921):

12 Relative risk 0.86 Lancet Mar 15;383(9921):

13 Chronic Kidney Disease Increased risk of stroke (RR 3.7 in CKD, RR 5.8 in ESRD) Increased prevalence of atrial fibrillation CKD/ESRD patients largely excluded from trials Increased risk of bleeding if treated with anticoagulation Effect of anticoagulation on stroke risk in advanced CKD not clear no direct randomized trial data

14 Risk of bleeding with anticoagulation increases with decreasing GFR Median follow-up 2.1 years Jun M et al, BMJ 2015: 350, h246

15 Sardar et al, Can J Cardiol, 2014

16 Patients with moderate renal insufficiency moderate/relevant bleeding Sardar et al, Can J Cardiol, 2014 Sardar et al, Can J Cardiol, 2014

17 Stroke risk Bleeding risk

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19 Dosing considerations for NOACs in CKD FDA: indication for CrCl >15, and HD pt as of Jan 2014 FDA: indication for CrCl dose 75 mg bid FDA: indication for CrCl dose 15 mg od

20 Conclusions - NOACs Patients with CKD have a greater risk of stroke and bleeding For CKD 3 and above (CrCl >30), there is benefit to anticoagulation, and NOACs are as efficacious and as safe as warfarin For patients with stage 4 and 5 CKD, benefit for stroke is unclear, and risks of bleeding high. If anticoagulation is pursued, warfarin is indicated. NOACs off label. Patients with CKD treated with anticoagulation require close monitoring of INR, renal function, signs of bleeding

21 Diuretic dosing considerations in CKD

22 Furosemide Loop diuretic Introduced 1966 Excretion 2/3 renal 1/3 hepatic Half life 100 minutes

23 Diuretic resistance Dose response characteristic Dose threshold All or none response Distal Adaptation

24 Response Response Dose response curves Graded response Threshold response Dose Dose

25 Urine production in 6 hrs Furosemide dose-response curve Dose

26 Urine production in 6 hrs Furosemide dose-response curve Worsening heart and/or renal function Dose

27 Urine production in 6 hrs Furosemide dose-response curve Dose

28 Urine production in 6 hrs A B C Dose Furosemide changed from 80 mg po od to 40 mg po bid

29 CA Inhibitors Proximal tubule Thiazides Distal tubule 5% Antikaliuretics 70% Thick Ascending Limb 4.5% Collecting duct 100% GFR 140 L/day Plasma Na 140 meq/l Filtered Load 26,100 meq/day 20% Loop Diuretics Loop of Henle 0.5% Volume 1.5 L/day Urine Na 100 meq/l Na Excretion 155 meq/day From Knauf & Mutschler Klin. Wochenschr :

30 Diuretic sliding scale Escalating or declining loop diuretic dose dictated by daily weight Can incorporate thiazide diuretic as maintenance or rescue to counter adaptation Can incorporate potassium supplement to compensate for increased potassium losses Patient feedback and self management

31 Urine production in 6 hrs Diuretic Sliding Scale WEIGHT FUROSEMIDE ZAROXOLYN POTASSIUM less than 167 No Furosemide, take in more salt 167 to 168 No Furosemide 169 to mg in AM 1 tab 171 to mg in AM and PM 2 tabs 174 to mg in AM and PM 2.5 mg 2 tabs 177 to mg in AM and PM 5 mg 2 tabs bid greater than mg in AM and PM, call MD 10 mg 2 tabs bid A B C Dose

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33 Management of Gout/Hyperuricemia in CKD

34 Hyperuricemia and Gout in CKD Common issue in CKD Decreased uric acid excretion due to reduced GFR Hyperuricemia associated with metabolic syndrome Frequent use of drugs which increase uric acid: Diuretics, Low dose ASA, Beta blockers, cyclosporine/tacrolimus Similar to management in general population, but with considerations regarding drug selection and dosing Acute gout Uric acid lowering for prevention

35 Anti-inflammatory treatment of acute gout - Initiate treatment as early as possible - Consider renal function and comorbidities in drug selection - Do not start or alter urate lowering therapy during acute episode

36 Anti-inflammatory treatment of acute gout NSAID Avoid in patients on anticoagulation Watch renal function, consider temporary reduction/withdrawal of ACE/ARB to avoid AKI Adverse effects: Volume retention, renal dysfunction, peptic ulceration, hypertension, increased CV risk Colchicine Lower dose in patients with CrCl<30, avoid in patients with CrCl<10 Less effective if late presentation Adverse effects: Diarrhea, sensimotor neuromyopathy, myelosuppression Corticosteroids Oral or parenteral Relapse likely if stopped too soon Adverse effects: Volume retention, hyperglycemia, thrush, peptic ulceration, Weight gain, sleep disturbance, AVN Hip, osteoporosis, cataracts

37 Urate Lowering Therapy Start 1-2 week after acute attack treated with anti-inflammatory therapy Anti-inflammatory prophylaxis for 6 9 months recommended to avert flare Aim for uric acid level 360 Continue indefinitely

38 Urate Lowering Therapy Allopurinol Max dose 300 mg daily for CrCl 20-50, 200 mg for CrCl < 20 Can cause rash, pruritis, elevated LFTs, hypersensitivity reaction Febuxostat For use if intolerant to Allopurinol No data for CrCl < 30 Probenecid Uricosuric, use only with CrCl > 50

39 Reducing Hyperuricemia Reduce diuretics, especially thiazides Consider once daily or alternate day loop diuretic dose Low purine diet Weight loss/exercise Consider switching ACE/ARB to Losartan Consider stopping ASA

40 Am J Kidney Dis 47:51-59.

41 Hyperkalemia

42 Emergent treatment of Hyperkalemia peaked T wave flat or absent P wave widened QRS increased PR interval sine wave ventricular standstill

43 Emergent treatment of Hyperkalemia Membrane stabilization Calcium Gluconate 1 gm IV push over 2 min. Effect lasts min. Contraindication if on Digoxin Shifting strategies Beta agonist: Ventolin puffer or mask. Effects last min. Caution if cardiac ischemia or tachycardia. Alkalinization: IV Na Bicarbonate Insulin Excretion/Removal Gut: Kayexalate/Ca resonium. Effect onset 4-6 hours Kidney: Loop/Thiazide diuretics. Effect onset 4-6 hours Dialysis Time to machine???

44 Emergent treatment of Hyperkalemia 1. Give calcium IV and/or Ventolin 2. Start IV D5 with 3 amp/l NaBicarb and 20 u/l insulin R and run at 75 to 150 cc/h 3. Start Kayexalate 30 gm q2h x 3 and/or Lasix mg IV 4. Check glucose and K+ q1h x 4 5. Watch ECG/monitor

45 Vaccines for CKD

46 Vaccines for CKD Inactivated Influenza Vaccine 23 Valent Pneumococcal Vaccine Hepatitis B Vaccine Live vaccines should be avoided in transplant patients, and others on immunosuppressive medications

47 Sick Day Medication Advice

48 Sick Day Medication Advice Pre-emptive temporary withdrawal of certain medications during period of dehydrating illness Diarrhea, vomiting, poor intake Excessive heat exposure, bowel prep, high output ostomy Instruct patients to stop ACE, ARBs, diuretics, NSAIDs and NSAID creams, SGLT2 inhibitors to avert renal failure and hypotension Stop metformin, gliclazide, rosuvastatin,??noacs Can resume usual meds when better

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