managing complications of therapy in ckd dr. vincent cheung the diabetes and nephrology symposium...
TRANSCRIPT
Managing complications of therapy in CKD
Dr. Vincent Cheung
The Diabetes and Nephrology Symposium
November 19th, 2014
Disclosure
• Faculty: Dr. Vincent Cheung
• Relationships with commercial interests:– Advisory Board Honoraria:
• Takeda• Astra Zeneca
– Speakers Honoraria: • Servier Canada• Canadian Heart Research Centre
Disclosure of Commercial Support
• This program may receive financial support from Servier Canada in the form of an honorarium.
• Servier Canada products are not specifically discussed in this program.
3
Diabetes and renal care
Outline
• Too wet too dry
• K+ Too high too low
• Hyperuricemia/Gout
Too wet too dry
“Bruce”, a diabetorenocardiopath
Bruce
• 73 years old
• Type diabetes for 10 years
• MI, PCI 3 years ago• Meds: Ramipril 10 mg od
Amlodipine 10 mg od
Metformin 500 mg tid
Saxagliptin 2.5 mg od
ASA 81 mg od
Bruce
• Good diabetic control
• Recent cardiac testing – echo moderate systolic dysfunction, no ischemia
• Presents with SOB, orthopnea, leg swelling, weight gain of 15 lbs
Bruce
• Furosemide 40 mg po od• 2 days later no better• Furosemide increased to 80 mg od• Excellent urine output, feeling better after
4 days• 3 weeks later, after weekend trip,
Furosemide “didn’t work”, weight up 12 lbs in 2 days
• Furosemide increased to 120 mg bid
Bruce
• Excellent urine output, weight back down after 4 days
• Furosemide reduced to 120 mg od• 1 week later, diarrhea, weak, almost
fainted• Seen in ER. Felt to be “dry”, Cr 244• Furosemide, ramipril and metformin
stopped, IV fluid given, Cr down to 190 • Sent home within 24 hours
Bruce
• Feeling stronger, improved appetite
• Restarted on Furosemide 40 mg bid
• 3 days later back to ER with 14 lb weight gain, SOB
Why is Bruce so unstable?
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185
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0 10 20 30 40
Wei
ght
in lb
s
Days
40 mg
80 mg120 mg bid
120 mg
Stopped
40 mg bid
Diabeto-renal conceptsGlycemic instability
Too high
Too low
Pushes glucose down• Reduced intake• Insulin/sulfonylurea• Exercise• BB, quinolones• EtOH
Pushes glucose up• Increased intake• Insufficient insulin• Inactivity• Steroid, Thiazide
Ser
um G
luco
se
Why is volume so unstableand what can we do about it?
• Diet? Na+ restriction/dietary routine• Ischemia? Cardiac optimization• A Fib? Rate control• NSAIDs/COX-2 inhibitors Avoid• Other Na+ retaining meds – steroids, glitazones• Dehydration? Sick Day Med Advice• Cardiac Output variation with volume status• Diuretic resistance
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185
190
0 10 20 30 40
Wei
ght
in lb
s
Days
40 mg
80 mg120 mg bid
120 mg
Stopped
40 mg bid
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 to avert renal failure, hypotension, hyperK+
• Can resume usual meds when better
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0 10 20 30 40
Wei
ght
in lb
s
Days
40 mg
80 mg120 mg bid
120 mg
Stopped
40 mg bid
Frank-Starling curveC
ardi
ac O
utpu
t
LV Filling Volume
Frank-Starling curveC
ardi
ac O
utpu
t
LV Filling Volume
Frank-Starling curveC
ardi
ac O
utpu
t
LV Filling Volume
Heart failure
Normal
Cardiac function and Volume
• Changes in volume status can result in marked changes in cardiac output
• Reduction in cardiac output leads to heart failure and renal dysfunction
• In decompensated heart failure patient renal function may improve with diuresis
Advances in Heart Failure Therapy
• ACE/ARB• Aldactone blocker• Cardio-selective beta-blockers• Antiarrhythmics• Implantable defribrillator• Cardiac resynchronization therapy• Valve repair• Revascularization• LV restoration
Furosemide
• Loop diuretic• Introduced 1966• Excretion 2/3 renal 1/3 hepatic• Half life 100 minutes
Diuretic resistance
Dose response characteristic• All or none response• Dose threshold
Distal AdaptationBreaking Phenomenon
NSAIDs
Furosemide dose-response curveU
rine
prod
uctio
n in
6 h
rs
Dose
40 80 120 160 200 240 280
Furosemide dose-response curve
40 80 120 160 200 240 280
Worsening heart and/or renal function
Urin
e pr
oduc
tion
in 6
hrs
Dose
Furosemide dose-response curve
40 80 120 160 200 240 280
Urin
e pr
oduc
tion
in 6
hrs
Dose
40 80 120 160 200 240 280
Uri
ne p
rod
uctio
n in
6 h
rs
Dose
AB
C
Furosemide changed from 80 mg po to 40 mg po bidWhat is the intention?
What will happen?
Furosemide 120 mg in AM, 40 mg in PMWhat is the intention?
What will happen?
Adaptation
• Longstanding furosemide use can result in hypertrophy of distal tubular cells
• Compensatory Na+ reabsorption occurs to counter diuretic effect of loop
• Thiazide diuretics effective either as permanent fixture of rescue therapy
From Knauf & Mutschler Klin. Wochenschr. 1991 69:239-250
70%
20%
5%
4.5%
0.5%Volume 1.5 L/day
Urine Na 100 mEq/LNa Excretion 155 mEq/day
100%GFR 140 L/day
Plasma Na 140 mEq/LFiltered Load 26,100 mEq/day
CA InhibitorsProximal tubule
Loop DiureticsLoop of Henle
ThiazidesDistal tubule
Antikaliuretics
Collecting duct
Thick Ascending Limb
0
50
100
150
200
250
300U
rin
e so
diu
m ,
mE
q/6
hr
F F F F
Adaptations: Rebound sodium retention“Breaking phenomenon”
F – Furosemide 40 mEq/d
Wilcox, et al, Kidney International 31:135, 1987
Why is volume so unstable?
Volume
Cardiac Output
Renal Function
Diuretic resistance
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0 10 20 30 40
Wei
ght
in lb
s
Days
40 mg
80 mg120 mg bid
120 mg
Stopped
40 mg bid
Diabeto-renal concepts
• Sliding scale– Strategy of prescribed proportional dosage
adjustments to provide acute correctional action
• Target Weight– Use of a set weight as a surrogate for optimal
body volume status
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
Diuretic Sliding ScaleWEIGHT FUROSEMIDE ZAROXOLYN POTASSIUM
less than 167 No Furosemide, take in more salt167 to 168 No Furosemide169 to 170 80 mg in AM 1 tab171 to 173 80 mg in AM and PM 2 tabs174 to 176 120 mg in AM and PM 2.5 mg 2 tabs177 to 179 160 mg in AM and PM 5 mg 2 tabs bid
greater than 180 200 mg in AM and PM, call MD 10 mg 2 tabs bid
40 80 120 160 200 240 280
Urin
e pr
oduc
tion
in 6
hrs
Dose
AB
C
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150
155
160
165
170
175
180
185
190
0 10 20 30 40
Wei
ght
in lb
s
Days
40 mg
80 mg120 mg bid
120 mg
Stopped
40 mg bid
Diuretic Sliding Scale
• Patient should weigh self daily, record weight and follow scale instructions
• Once established need regular follow-up• Volume check to adjust target weight
– Lean weight changes, constipation, amputation, hardware
• Reassessment of diuretic response/threshold
“When you take your water pill(s), do you pee soon after?”
Vasodilatory – Worse after prolonged
upright posture– Better after prolonged
supine– Worse with hot
weather– Venous insufficiency– Absence of other risks
or signs of volume excess
Intravascular Expansion– Sustained, not
intermittent– Wt gain, SOB,
orthopnea– History of cardiac
disease, high Na+ intake,
– Renal insufficiency– JVD, creps, wheeze,
effusions
Assessing Edema
K+ too high too low
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0 10 20 30 40
Wei
ght
in lb
s
Days
40 mg
80 mg120 mg bid
120 mg
Stopped
40 mg bid
2
3
4
5
Ser
um
Po
tass
ium
6
3.2
6.0
2.8
K+ Too high Too low
Potassium
• Disorders of potassium common in CKD and DM
• Like glucose and volume, various factors can drive potassium up or down
• Vigilance for these factors, frequent checking and early corrective action can improve K+ management
Diabeto-renal conceptsPotassium Balance
Too high
Too low
Pushes K+ down• Reduced intake• Loop/thiazide diuretics/steroids• Kayexalate • Diarrhea/vomiting• Alkalosis
Pushes K+ up• Increased intake• ACE, ARB, Spironolactone, NSAID• Sulfa • Renal failure• Acidosis• Tissue breakdown, internal bleeding
Ser
um P
otas
sium
K+ Management Tips
• Combining K+ sparing with K+ wasting agents can aid in K+ balance
• Check K+ 2-3 weeks after change in medication that can affect K+ handling ACE/ARB, diuretic, NSAID, Sulfa
• Check K+ with worsening overload or dehydrating illness
• Instruct patients on dietary K+
K+ Management Tips
• Replacement requires 80 – 100 mEq to correct serum potassium by 1 mmol/L in average sized person
• Kayexalate: – 30 gm po will reduce serum K+ by about 0.3
mmol/L– Excessive dose can cause hypoMg++,
hypoCa++, constipation– Use may be limited by sodium load
Hyperuricemia
Urate 680
No history of gout or stones
Hyperuricemia
• Common in – Metabolic syndrome– Heart failure – Renal insufficiency– Alcohol use– Diuretic use
• Causes gout, uric acid kidney stones, urate nephropathy
• Associations with hypertension, LVH, renal decline in CKD, CV events, but treatment of assymptomatic hyperuricemia not indicated
Uric Acid/Gout
• Anti-inflammatory treatment of acute gout– NSAID
– Volume retention, renal dysfunction, peptic ulceration, hypertension, increased CV risk
– Colchicine– Diarrhea, sensimotor neuromyopathy, myelosuppression
– Corticosteroids– Volume retention, hyperglycemia, thrush, peptic ulceration
– Weight gain, sleep disturbance
– AVN Hip, osteoporosis, cataracts
Uric Acid/Gout
• Anti-inflammatory treatment of acute gout– NSAID
– Consider holding ACE/ARB during course– Monitor volume and renal function closely– Consider PPI
– Colchicine– Give trial supply and plan B
– Corticosteroids– Watch volume and glycemia– Quick taper to low dose– Consider PPI
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
Urate Lowering Therapy
• Allopurinol – Dose 50 - 300 mg daily in CKD– Can cause rash, pruritis, elevated LFTs,
hypersensitivity reaction
• Febuxostat– For use if intolerant to Allopurinol
• Probenecid– Uricosuric, use only with eGFR > 50
Urate Lowering Therapy
• Start 1-2 weeks after acute attack settled with anti-inflammatory therapy
• Aim for uric acid level 360• Continued anti-inflammatory prophylaxis for
6 – 9 months recommended to avert flare• Continue ULT indefinitely
Am J Kidney Dis 47:51-59.
Summary
Multiple factors in diabetorenocardiopath patients conspire to cause instability in volume and potassium status.
Strategies to monitor, anticipate and rapidly correct perturbations can help maintain stability
Patient self management contributes to optimization in these complex patients
Thank You