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Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 1
Lessons from Caring for Renal Patients
Dan Martinusen BSc(Pharm), ACPR, PharmD, FCSHP
UBC Continuing Education
March 2016
Declaration
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
Lessons1. 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. BlogsO 80yo type II DM man with treated hypertension (ACEI) re-
admitted 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)
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 2
Renal patients are like cardiovascular patients –
maybe much more
Lesson 1
Cardiovascular Risk -greater in renal patients!
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)
Lancet 1997; 350 Suppl 1:29-32
Relative importance of contributing
factors
Stevens L et al. N Engl J Med 2006;354:2473-2483
Estimated Prevalence of Complications Related to
Chronic Kidney Disease, According to the
Estimated GFR in the General Population
> 60 45-59 30-44 15-29 < 15
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Age
Sta
nd
ard
ize
d R
ate
of
De
ath
fro
m A
ny
Ca
use
(p
er
10
0 P
ers
on
-yr)
Estimated GFR (mL/min/1.73 m2)
All Cause Mortality and Chronic Kidney Disease
Go AS, et al. N Engl J Med 2004;351(13):1296-1305Anavekar N et al. N Engl J Med 2004;351:1285-1295
Estimates of the Rates of Death at Three Years
According to the Estimated GFR at Baseline
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 3
Date of download: 10/23/2015
Renal Insufficiency as a Predictor of Cardiovascular
Outcomes and the Impact of Ramipril: The HOPE
Randomized Trial
Ann Intern Med. 2001;134(8):629-636
1’ outcome = cardiovascular death, myocardial infarction, or stroke.
Take a HolidayLesson 2
Mr. BlogsO 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 ComplicationsSociety of Thoracic Surgeons National Adult Cardiac Database
(Risk Adjusted ORs and 95% CIs for Events)
Cooper WA, et al. Circulation 2006;113(8):1063-70.
Variable
(Renal
Function)
Normal
(≥ 90)
(n = 104 880)
Mild RD
(89-60)
(n = 247 535)
Moderate RD
(59-30)
(n = 114 661)
Severe RD
(< 30)
(n = 9686)
Dialysis
Dependent
(n = 7152)
Operative
mortality1.00 1.02 (0.96-1.09) 1.55 (1.45-1.65) 2.87 (2.61-3.16) 3.82 (3.45-4.25)
Stroke 1.00 1.17 (1.08-1.26) 1.47 (1.36-1.60) 1.76 (1.55-2.01) 2.00 (1.72-2.32)
Prolonged
ventilation1.00 1.04 (1.01-1.08) 1.49 (1.44-1.54) 2.43 (2.28-2.59) 2.77 (2.59-2.98)
Deep sternal
wound
infection
1.00 0.99 (0.88-1.11) 1.25 (1.10-1.43) 1.35 (1.06-1.73) 2.44 (1.96-3.05)
Any
reoperation1.00 1.03 (0.99-1.07) 1.30 (1.25-1.36) 1.79 (1.66-1.93) 2.05 (1.88-2.22)
Prolonged
length of stay
(> 14 d)
1.00 1.05 (1.01-1.10) 1.54 (1.47-1.61) 2.82 (2.64-3.02) 3.25 (3.01-3.51)
New dialysis
requirement*1.00 1.70 (1.42-2.04) 4.65 (3.87-5.60) 20.37 (16.6824.87) NA
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
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 4
Insert PRA holiday card here Insert CDA letter here
Canadian Diabetes Association
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. BlogsO 80yo type II DM man with treated hypertension (ACEI) re-
admitted 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 bacteremiaO Levels (4th 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 – renalDate Scr (umol/L) eGFR (mL/min) Urea (mmol/L)
Oct 22 80 85 6
Oct 27 90 80 7
Oct 31 310 18 11.5
Nov 2 450 12 16
Nov 5 580 9 19.5
Nov 8* 650 8 21.5
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 5
Mr. Blogs Nov 1O 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 – renalDate Scr (umol/L) eGFR (mL/min) Urea (mmol/L)
Nov 8* 650 8 21.5
Nov 23 300 19 17
Dec 7 230 25 26
Dec 14 140 45 13.5
Dec 29 90 74 7.5
36 months later 119 55
48 months later* 230 23
*Another heart attack, BPH, requires insulin (but BP & A1c controlled)
Risk of AKI in diabetics
Diabetic patients
1’ outcome = <30 mL/min (stage 4 CKD)
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 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
Ensrud KE et al., Nickolas TL et al., 2006
From Dr. S Jamal 2010, Vancouver
J Am Soc Nephrol. 2010 Aug; 21(8): 1371–1380
Radius & Fibula (xray)
Healthy post-
menopausal woman
Predialysis CKD woman
no fracture
Predialysis CKD woman
prevalent fracture
Approximately 40% of type 2 diabetes patients have renal complications†
* No signs of kidney damage
** Albuminuria – kidney damage
†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 2004.
9.5
50.8
8.6
11.1
17.7
2.3
Data missing
NO CKD
CKD stage 1
CKD stage 2
CKD stage 3
CKD stage 4/5
CKD prevalence was greater among people with diabetes than
among those without diabetes (40.2% versus 15.4%)
CKD Stage eGFR (mL/min)
No CKD ≥90*
1 ≥90**
2 60–89
3 30–59
4-5 <29
1. Koro CE, et al. Clin Ther. 2009;31:2608–17; 2. Saydah S, et al. JAMA. 2007;297(16):1767.
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 7
Who is at Risk for Hypoglycemia?
O Risk factors for hypoglycemiaO variable eating
O variable activity
O poor recognition of hypoglycemia (elderly, dementia)
O chronic kidney disease
O High-risk consequences of hypoglycemiaO 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): 2852-2859
Nephrol Dial Transplant (2011) 26: 1888–1894
Insulin requirements are related to creatinine clearance
Diabet. Med. 20, 642–645 (2003)
Type 1 diabetic patients insulin-treated Type 2 diabetic patients
Creatinine Clearance (ml/min)
P < 0.001 P < 0.001
Avoid fallsO 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
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 8
Can eGFR be used to dose drugsin the elderly?
O 85 yo caucasian ABW=55 kg IBW = 50 kg, Ht=156 cm BSA = 1.53 m2
SCr = 64 Scr rounded up = 91
umol/L
SCr = 200
eGFR (mL/min/1.73m2) 81 54 22
eGFRind (mL/min) 72 48 20
CGnormalized(mL/min/72 kg)* 65 45 21
CGTBW(mL/min) 49 35 16
CGIBW(mL/min) 46 32 15
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 m2
ABW= 140 kg
BSA = 2.66 m2
ABW = 200 kg
BSA = 3.2 m2
CGTBW(mL/min) 39 59 ! 85 !
eGFRind (mL/min)* 34 42 50
CGadjusted (ibw + 40% of diff)* 36 45 55
Salazar Corcoran (mL/min)* 33 41 50
CGIBW(mL/min) 35 35 35
CGnormalized(mL/min/72 kg) 31 31 31
eGFRckdepi (mL/min/1.73m2) 27 27 27
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
Lessons learned from caring for kidney patients March 5, 2016
UBC Pharmacy Update 2016 Copyright Dan Martinusen PharmD 9
Morphine and Hydromorphone in ESRD
4:1
H3G:hydromorphone
25:1
M3G:morphineM3G 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)
www.palliative.org Palliative Care Tips March 2004 #18 Myoclonus-Seizures-Hyperalgesia Dr. Robin Fainsinger Royal Alexandra Hospital
Summary
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
Thank you
