Lessons from Caring for Renal Patients

Transcription

1 Declaration Lessons from Caring for Renal Patients Dan Martinusen BSc(Pharm), ACPR, PharmD, FCSHP UBC Continuing Education March 2016 O I have provided education through events sponsored by Amgen, Hospira, Johnson & Johnson, Leo Pharma & Pfizer O No Commercial entity had any influence on this presentation Objectives O Discuss how pharmacists can have a positive impact on renal patients O Discuss lessons learned from years of nephrology practice O Be able to apply lessons at the patient and the population level Lessons 1. Renal patients are like cardiovascular patients maybe much more 2. Take a holiday 3. Sitting ducks 4. It all adds up 5. Avoid the fall 6. Dose: which formula in whom? 7. Adherence: Usually good, sometimes bad How to identify a kidney patient O Ask the patient if they have a problem with their kidneys O Prescription written by a nephrologist O Dose is small and/or interval is long O Prescription includes orders for sodium bicarbonate, alfacalcidol, sodium polystyrene sulfonate, lanthanum, sevelamer, cinacalcet & so on. O They complain of frothy urine, frequent UTIs, low urine volume, lethargy, itchiness, nausea etc Meet Mr. Blogs O 80yo type II DM man with treated hypertension (ACEI) readmitted with an infected hip 15 days post op. O 3 day history of N&V & poor intake x 1 week O History: Heart attack 3 yrs ago, afib x 5 years with one stroke 2.5 years ago. O Takes ibuprofen intermittently for pain & inflammation O Cefazolin 2 g IV q8h & gentamicin 100 mg IV q12h & rifampin 600 mg daily for staph aureus bacteremia O Steady state Peak = 3.8 mg/l Trough = 0.6 mg/l O Completed five days of gentamicin therapy O (sensitivity: cefazolin, clindamycin, cloxacillin, cotrimoxazole,vancomycin) UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 1

2 Age Standardized Rate of Death from Any Cause (per 100 Person-yr) Lessons learned from caring for kidney patients March 5, 2016 Cardiovascular Risk - greater in renal patients! Renal patients are like cardiovascular patients maybe much more Lesson 1 O As egfr declines, cardiovascular event rate rises O The heart of a 40 year old dialysis patient is like that of an 80 year old with normal renal function. O Perhaps the benefits of cardiovascular medication should be reported according to kidney function? (HINT: those at greatest risk derive the greatest benefit) Relative importance of contributing factors Estimated Prevalence of Complications Related to Chronic Kidney Disease, According to the Estimated GFR in the General Population Lancet 1997; 350 Suppl 1:29-32 Stevens L et al. N Engl J Med 2006;354: All Cause Mortality and Chronic Kidney Disease > < 15 Estimated GFR (ml/min/1.73 m 2 ) Go AS, et al. N Engl J Med 2004;351(13): Estimates of the Rates of Death at Three Years According to the Estimated GFR at Baseline Anavekar N et al. N Engl J Med 2004;351: UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 2

3 Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril: The HOPE Randomized Trial 1 outcome = cardiovascular death, myocardial infarction, or stroke. Take a Holiday Lesson 2 Date of download: 10/23/2015 Ann Intern Med. 2001;134(8): Mr. Blogs O egfr = 85ml/min on admission (Scr = 90mmol/L) O On exam after rehydration: Patient is euvolemic O Medication list: O Rifampin 600 mg PO daily x 4 wk. O Metformin 500 mg BID PO O Glyburide 10 mg PO BID O Hydrochlorothiazide 12.5 mg PO daily O Verapamil 240 mg PO Daily O Ramipril 10 mg PO BID O Metoprolol 50 mg PO BID O Ibuprofen 200 mg PO BID O Warfarin titrated to INR 2-3 Renal Function and Major Post-Operative Complications Society of Thoracic Surgeons National Adult Cardiac Database (Risk Adjusted ORs and 95% CIs for Events) Variable (Renal Function) Operative mortality Normal ( 90) (n = ) Mild RD (89-60) (n = ) Moderate RD (59-30) (n = ) Severe RD (< 30) (n = 9686) Dialysis Dependent (n = 7152) ( ) 1.55 ( ) 2.87 ( ) 3.82 ( ) Stroke ( ) 1.47 ( ) 1.76 ( ) 2.00 ( ) Prolonged ventilation Deep sternal wound infection Any reoperation Prolonged length of stay (> 14 d) New dialysis requirement* ( ) 1.49 ( ) 2.43 ( ) 2.77 ( ) ( ) 1.25 ( ) 1.35 ( ) 2.44 ( ) ( ) 1.30 ( ) 1.79 ( ) 2.05 ( ) ( ) 1.54 ( ) 2.82 ( ) 3.25 ( ) ( ) 4.65 ( ) ( ) NA Cooper WA, et al. Circulation 2006;113(8): Volume depleted? Take a drug holiday! O Consider holding other anti-hypertensives O Diuretics O Metformin ( risk of lactic acidosis) O Sulfonylureas O NSAIDS O Smoking O Volume depletion / infection with continued ACEI/ARB/SGLT2 inhibitor use can lead to acute kidney injury O Reasons for acute dialysis: O Severe infection (22), volume depletion (9), post surgery (7), drugs (5), specific renal disease (5), other (23) O So, instruct patients to avoid ACEI & ARB if volume depleted UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 3

4 Canadian Diabetes Association Insert PRA holiday card here Insert CDA letter here Sodium Glucose co-transporter 2 inhibitors (SGLT2) O Canagliflozin O Empafliglozin O Dapagliflozin O Act to block sodium and glucose reabsorption in the proximal tubule O No direct injury to the kidney but diuretic effect in a volume depleted state may contribute to an acute kidney injury Sitting ducks Lesson 3 Mr. Blogs O 80yo type II DM man with treated hypertension (ACEI) readmitted with an infected hip 15 days post op. O 3 day history of N&V & poor intake x 1 week O Significant PMHx: NSTEMI 3 yrs ago, afib x 5 years with one stroke 2.5 years ago. O Takes ibuprofen intermittently for pain & inflammation O Ordered: Cefazolin 2 g IV q8h & gentamicin 100 mg IV q12h for staph aureus bacteremia O Levels (4 th dose SS) Pk = 3.8 mg/l Tr = 0.6 mg/l O Level 5 days after stopping gentamicin = 1.1 mg/l O (Staph A sens: cefazolin, clindamycin, cloxacillin, cotrimoxazole, vancomycin) Mr. Blogs renal Date Scr (umol/l) egfr (ml/min) Urea (mmol/l) Oct Oct Oct Nov Nov Nov 8* UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 4

5 Mr. Blogs Nov 1 O On exam: blood pressure 178/75 Pulse=74 O Jugular Venous Pressure = 1 cm ASA O Medication list: O Rifampin 600 mg PO daily x 4 wk. O Metformin 500 mg BID PO O Gliclazide 40 mg PO daily O Hydrochlorothiazide 12.5 mg PO daily O Amlodipine 10 mg PO daily (was verapamil) O Ramipril 10 mg PO BID O Metoprolol 50 mg PO BID O Ibuprofen 200 mg PO BID O Warfarin titrated to INR 2-3 O egfr = 18 ml/min (Serum creatinine = 310 mmol/l) O Dx = ATN after only 5 days of gentamicin therapy Beware of sitting ducks O Volume depleted patient O Taking NSAIDS O Diabetic O Elderly (stiff vasculature) O Taking diuretics O Taking gliflozins O Existing diminished kidney function It all adds up Lesson 4 Mr. Blogs renal Date Scr (umol/l) egfr (ml/min) Urea (mmol/l) Nov 8* Nov Dec Dec Dec months later months later* *Another heart attack, BPH, requires insulin (but BP & A1c controlled) Risk of AKI in diabetics 1 outcome = <30 ml/min (stage 4 CKD) Diabetic patients UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 5

6 Each injury to the kidney is cumulative O We should always try to protect and preserve kidney function O We should recognize episodes of prior AKI O We should recognize risk factors prior to ordering drugs, ideally O We should try to use less nephrotoxic alternatives O We should recognize the elevated CV event risk in worsening egfr Avoid falls Lesson 5 EnsrudKE et al., Nickolas TL et al., 2006 From Dr. S Jamal 2010, Vancouver Radius & Fibula (xray) Healthy postmenopausal woman Predialysis CKD woman no fracture Predialysis CKD woman prevalent fracture Approximately 40% of type 2 diabetes patients have renal complications CKD prevalence was greater among people with diabetes than among those without diabetes (40.2% versus 15.4%) Data missing NO CKD CKD stage CKD stage CKD stage 3 CKD stage 4/ CKD Stage egfr (ml/min) No CKD 90* ** * No signs of kidney damage ** Albuminuria kidney damage 4-5 <29 Based on data from 1462 patients aged 20 years with T2DM who participated in the Fourth National Health and Nutrition Examination Survey (NHANES IV) from 1999 to J Am Soc Nephrol Aug; 21(8): Koro CE, et al. Clin Ther. 2009;31: ; 2. Saydah S, et al. JAMA. 2007;297(16):1767. UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 6

7 Who is at Risk for Hypoglycemia? O Risk factors for hypoglycemia O variable eating O variable activity O poor recognition of hypoglycemia (elderly, dementia) O chronic kidney disease O High-risk consequences of hypoglycemia O living alone O existing falls risk Why do CKD stages 3-5 have a higher risk for hypoglycemia? o Decreased clearance of insulin and some of the hypoglycemic agents 1/3 of insulin degradation is renal Active metabolites of glyburide o Impaired kidney gluconeogenesis Renal glucose production = 20% of total o Poor glycogen reserves caused by uremia-induced anorexia *Nephrol. Dial. Transplant. (2011) 26 (9): Nephrol Dial Transplant (2011) 26: Insulin requirements are related to creatinine clearance Type 1 diabetic patients insulin-treated Type 2 diabetic patients P < P < Creatinine Clearance (ml/min) Diabet. Med. 20, (2003) Avoid falls O Fractures, risk & therapy are different in renal failure O What is the optimal HgbA1C & BP in a kidney patient? O HgA1c may be falsely lower in renal failure as RBCs survive 60 vs. 120 days & reticulocyte effect O Must consider the risks of aggressive BP targets O DM & hypertensive management but within safe limits O May require a separate pause when reviewing the patient (opiates / other CNS: active/toxic metabolites) Dose: which formula and in whom? Lesson 6?? mg q?hour UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 7

8 Can egfr be used to dose drugs in the elderly? O 85 yo caucasian ABW=55 kg IBW = 50 kg, Ht=156 cm BSA = 1.53 m 2 SCr = 64 Scr rounded up = 91 umol/l SCr = 200 egfr (ml/min/1.73m 2 ) Can egfr be used to dose drugs in the obese? O 45 yo African-Canadian IBW = 82 kg, Ht=188 cm SCr = 273 ABW= 90 kg BSA = 2.21 m 2 ABW= 140 kg BSA = 2.66 m 2 ABW = 200 kg BSA = 3.2 m 2 CG TBW (ml/min) 39 59! 85! egfr ind (ml/min) CG normalized (ml/min/72 kg)* CG TBW (ml/min) CG IBW (ml/min) egfr ind (ml/min)* CG adjusted (ibw + 40% of diff)* Salazar Corcoran (ml/min)* CG IBW (ml/min) CG normalized (ml/min/72 kg) egfr ckdepi (ml/min/1.73m 2 ) Dose O Please, please ask after each patient s kidney function (egfr, %, stage) O Is the drug >30% cleared by the kidney? O If elderly, start low and go slow (use ideal body weight for lowest dose estimate) O If obese, kidney function may be better than egfr describes (so dose/frequency greater) O Otherwise, dose as patient describes (% or ml/min or egfr Adherence usually good; sometimes bad Lesson 7 Improve adherence O Medication reconciliation renal patients are at the highest risk of adverse events due to med errors O Renal contract pharmacies O Encourage one pharmacy O Blister packing, phone apps etc. etc. O Timing around dialysis time and day of dialysis Adhering to some meds may be harmful O Meds may need to change - patients transition through renal failure O Gabapentin - dose O Amantadine - dose O ACEI /ARB if volume depleted O Sulfonylureas (glyburide) O Insulin without measurement or adjustment O Opiates some have toxic metabolites UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 8

9 Morphine and Hydromorphone in ESRD Summary 25:1 M3G:morphine 4:1 H3G:hydromorphone M3G and H3G have no pain relieving effects, but are potent neuroexcitants and are at least TEN FOLD more potent neuroexcitants than the respective parent opioids (delerium, myoclonus, hyperalgesia, seizures) O Cardiovascular risk increases as egfr falls O Fracture risk increases as egfr falls O Preserve and protect kidney function O A dedicated falls risk assessment is worthwhile O BP & BG assessment may be involved O Be careful when estimating renal function in the elderly or obese for dosing O As kidney function declines, pay attention to dose AND choice of drug Palliative Care Tips March 2004 #18 Myoclonus-Seizures-Hyperalgesia Dr. Robin Fainsinger Royal Alexandra Hospital Thank you Dan.Martinusen@viha.ca UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 9