1. No category

WHEN DID RENAL FAILURE
BECOME AKI? KEEPING UP WITH
THE BEANS
David Robinson, MD, MS, MMM
Professor and Vice Chairman
Department of Emergency Medicine
University of Texas Medical School
at Houston
OBJECTIVES
¡ R ecognize common causes of Acute Kidney
Injuries (AKI)
¡ L earn diagnostic and treatment strategies
for effective renal disease management
¡ U nderstand Benefits and Liabilities of
present treatment options
EPIDEMIOLOGY – RENAL FAILURE
¡ O ne of three causes of death
with highest increase globally
since 1990*
¡ A fter age 40, 1/50 lifetime risk
for renal failure
¡ 5 th most common cause of
death in developing countries
deJager. JAMA 2009;302;1782-89
WHAT’S THE CLINICAL RISK IN THE
PRESENTING AKI/CKD PATIENT?
¡  ESRD patients aged 65-74 have life expectancy 50% lower
than matched groups (about 5 years)*
¡  Cardiovascular disease most common cause of death
§  Is 10-20 times higher than the general population
§  100 times higher in those aged < 45
¡  Vascular Complications not infrequent on presentation
§  Sudden cardiac death (25% of deaths) seen after long interhemodialysis intervals, and in 12 hours after HD
§  MI, stroke, and other cardiovascular diseases were 12,11, and 8
times higher than the general population
¡  Mortality from Septicemia and lung infections 50 and 15x
higher than general population, respectively
ERA-EDTA 2010 data
CHRONIC KIDNEY DISEASE
¡ C auses volume overload, metabolic acidosis
¡ U remia results in trimethylamine-N-oxide
accumulation, accelerating CV disease
¡ P hosphate accumulation results in mineral
bone disorders
¡ V itamin D and calcium disorders result in
negative mineral bone balance, and acute ECG
changes
¡ … .and then there’s that potassium issue
HYPERKALEMIA: BACKGROUND AND
DEFINITIONS
¡ Significant hyperkalemia seen in 5-10% of ED visits
¡ Threshold for treatment varies but most guidelines
treat K+ > 6.5 mmol/L
¡ Current classifications are:
§ Mild (5.5-5.9), Moderate (6.0-6.4), Severe (≥6.5)
¡ Diagnostic and management strategies are
essentially unchanged for decades
Mandal AK. Hypokalemia and hyperkalemia. Med Clin North Am 1997;81:611–39.
FACTS ABOUT POTASSIUM
¡ I ntracellular K+ is 100-150mmol/l
¡ A verage American diet has 100mmol of K+
¡ R enal adaptive mechanisms work until GFR
drops to <15/ml/min/1.73 m²
¡ E xcretion primarily from the cortical collecting
duct (CCD)
¡ A ldosterone key regulator of K+ excretion
¡ 1 0% of daily K+ cleared in GI tract
Putcha N and Allon M. Seminas in Dialysis
POTASSIUM CONTENT OF SELECTED FOODS
Food and Drink
Potassium Content (mmol)
1 Banana (85g)
8.6
Blueberries (100g)
1.9
White Mushrooms (75g)
8.1
Broccoli, cooked (75g)
5.8
Green beans, cooked (75g)
3.9
Onions, cooked (75g)
1.5
French Fries (150g)
17.7
Parboiled Rice (150g)
2.2
Spaghetti (150g)
2.3
Orange juice (100 ml)
7.9
Milk (200 ml)
7.7
Cola
0.1
Potato chips (20g)
5.1
Milk Chocolate bar (20g)
2.4
Pediatr Nephrol (2011) 26:377–384
ECG CHANGES WITH WORSENING
HYPERKALEMIA
¡ Tall t waves (K:6-7)
¡ S mall Broad P waves
or absent P (K: 7-8)
¡ W ide QRS
¡ P rolonged QT
¡ A v dissociation or
VT/VF (K>9)
Sensitivity for diagnosing
hyperkalemia from ECG is 62%
Ljutic D, Rumboldt Z.Ren Fail 1993;15:73–6.
CASE 1
OLD GUY WITH HYPERTENSION
¡ 72 yo M for follow up
HTN, weak and dizzy
¡ PMX: PUD, DM, CKD
¡ Meds: lansoprazole,
ASA, HTCZ, ramipril
¡ Ramipril, recently
increased 2 weeks pta
¡ BP 124/70, p:80
¡ Serum K: 6.7mmol/L
¡ ECG: sinus peaked T
waves, prolonged QT,
narrow QRS
¡ GFR was 30 ml/min/
1.73M²
What was his likely cause of
hyperkalemia?
CASE 1
‘ACE’ THE ‘K’ASE
¡ 72 yo M for follow up
HTN, weak and dizzy
¡ PMX: PUD, DM, CKD
¡ Meds: lansoprazole,
ASA, HTCZ, ramipril
¡ Ramipril, recently
increased 2 weeks pta
¡ BP 124/70, p:80
¡ Serum K: 6.7mmol/L
¡ ECG: sinus peaked T
waves, prolonged QT,
narrow QRS
¡ GFR was 30 ml/min/
1.73M²
What was his likely cause of
hyperkalemia?
MEDICINE EFFECTS ON RENAL SYSTEM
CAUTION WITH HYPERTENSION MEDS IN
PTS WITH LOW GFR
¡ R eview meds, especially with DM and CHF
Pharmacotherapy for heart failure in patients with renal insufficiency Annals of Int
Med. June 2003
CASE2
HYPERKALEMIA IN AN ESRD PATIENT
¡ Initial BP 180/120, P80,
RR:26, O2 sat: 94% on RA
¡ K: 6.8 mmol/l
¡ ECG: sinus arrhythmia with
QT: 478
**Always check an ECG on all ESRD
patients presenting to the ED
Ø  Dialysis is not available
for a few hours!
ECG CHANGES OF HYPERKALEMIA
¡ Easily Dis)nguished ECG signs: § peaked T w ave. § prolonga)on o f t he P R i nterval § ST c hanges ( which m ay m imic m yocardial i nfarc)on) § very w ide Q RS, w hich m ay p rogress t o a s ine w ave paFern a nd a systole. ¡ Pa)ents may have severe hyperkalemia with minimal ECG changes, and prominent ECG changes with mild hyperkalemia. THE TREATMENT MODALITIES
THE ‘BIG K DROP’
¡ B IG K D rop § B -­‐ b eta a gonists, b icarbonate § I -­‐ I nsulin § G -­‐ G lucose § K -­‐ K ayexalate, C alcium § D -­‐ D iure)cs, D ialysis STEP 1: PROTECT THE HEART
CALCIUM
¡ 0.5-1 ml/kg over 5-10 min
¡ May use CaCl (higher Ca 2+
load), through CVL
§  10 ml 10% calcium chloride = 6.8
mmol Ca 2+ / 10ml
§  10 ml 10% calcium gluconate =
2.26 mmolCa 2+ / 10ml
¡  Use Ca-Gluconate if small
peripheral lines/ stable
¡  Use Ca-Chloride if unstable
The renal association. guidelines final, July 2012 (www.renal.org/guidelines)
INSULIN / DEXTROSE
¡ Most reliable agent for promoting intracellular shifts
(5 studies)
¡ Onset: 10-20 min. Duration: 2-6 hours
§ 2.5-5ml/kg/h 20% dextrose (0.5-1g/kg/hr) plus Insulin
0.2 Units / g, or
§ 2 amps 25g Dextrose and 0.1 units/kg Insulin
§ Transient hyperglycemia at 15 min
¡ Expected decrease in K+: 0.5-1.5 meq/L (varies by
dose)
¡ ***Monitor blood sugar
http://www.renal.org/guidelines/modules/treatment-of-acutehyperkalaemia-in-adults#sthash.FpaCuenc.dpbs
HYPOGLYCEMIA CONCERNING ADVERSE
EFFECT OF INSULIN /DEXTROSE THERAPY
STUDY
N
Dose of Soluble
Insulin
Time of
max
action
Duration Hypoglycemia
of Effect (%)
(min)
10 units
Dose of Mean
Peak
+
Glucose initial K reduction
(mmol/L) in K+
(mmol/L)
40g
6.7
1.0
Lens13
1989
Allon7 1990
10
60
>360
20
12
10 units
25g
5.48
0.65
45
>60
75
Ljutic11 1993 9
10 units
25g
6.33
0.76
60
>60
11
Allon8 1996
5
5 mU/kg/min
60g
4.28
0.85
60
>60
0
Duranay12
1996
Kim14 1996
20
10 units
30g
>6.0
0.98
180
>360
0
8
5 mU/kg/min
40g
6.3
0.7
60
>60
0
Ngugi10 1997 70
10 units
25g
6.9
0.9
60-120
>360
20
Mahajan9
2001
12 units
25g
6.59
0.83
180
>360
3.3
30
www.renal.org. July 2012 guidelines for Treatment of acute hyperkalemia in adults
BETA-ADRENERGIC AGONISTS
¡ IV salbutamol can decrease mean K+ by 1.6-1.7
mmol/L after 2 hrs
¡ 7 studies of inhaled, nebs, or IV (n=219)
¡ 0.3 to 0.6 mmol/L decrease in K at 30 min
Ø D ecreased K+ 0.85 mmol/L (neb) or 0.99 mmol/L (IV) at
60 min
§  Albuterol achieves faster onset than salbutamol
§  Paradoxical Increase in K with MDI
§  Palpitations and increased HR common
§  Not used as a single agent
CMAJ • OCTOBER 19, 2010 • 182(15)
DIURETICS BENEFICIAL IN AKI AND CKD
¡ May be effective, even in chronic dialysis patients
with some renal function
¡ Furosemide 40-80mg IV,Onset 5-30 min, Duration:
2-6 hours , Reduces serum K
¡ Dialysis Outcomes Heart Failure Aldactone
(spironolactone) Study (DOHAS) noted CV and
admission benefits in CKD
¡  Aldosterone Antagonist Chronic Hemodialysis
Interventional Survival Trial (ALCHEMIST, ongoing)
Mushiyakh Y, et al. J Community Hospital Internal Med Perspectives. 2011;1:1-6
SODIUM BICARBONATE 8.4%
¡ 1-2 mmol/kg over 30-60 min or calculated from
base deficit
¡ Monitor for sodium load
¡ Two studies reported
Ø 1 negative
Ø O ne with 0.47 mmol/L at 30 min
§  May be helpful in severe acidosis
CMAJ 2010. DOI:10.1503/cmaj.100461
THE OTHER 10%, ION EXCHANGE RESINS
¡ S LOW. Onset unpredictable, lasts 4-6 hours
¡ O ne study on normal K pts: No significant
mean decrease in K!
¡ M ore effective orally If PR, must be retained
minimum of 2 hours
¡ O ften given with sorbitol
¡ M onitor for osmolar load
¡ U seful in ED?
CMAJ 2010. DOI:10.1503/cmaj.100461
EMERGENT HEMODIALYSIS?
¡  ‘sine qua non’ for unstable AKI
¡  Removes 50-80 mmol K+ in 4 hr.
1mmol/L in first 60 min
¡  No change in mortality for high
membrane –flux versus low
membrane flux HD
¡  No change in mortality for
Increased dose versus standard
dose HD
Q: Is there an advantage to Early HD? A: No
DEAL (Initiating Dialysis Early and Late) Trial*
•  No advantage to early 12.0 ml/min eGFR vs 9 ml/min eGFR
From renalfellow.blogspot/2010
*Cooper NEJM 2010;363:609-19
SHOULD MUPIROCIN BE APPLIED?
( NASAL OR CATHETOR EXIT SITE APPLICATION)?
¡ Mupirocon is more effective than placebo at reducing
S aureus exit site infections from CAPD patients
¡ Does not reduce rate of catheter tunnel infections or
peritonitis in CAPD
¡ May reduce S aureus infections in HD when applied
to catheter exit site
Ortiz, et al. Lancet 2014;383:1831-41
ERY THROPOIETIN AND DARBEPOETIN
BENEFICIAL IN CKD?
¡ M ay improve hemoglobin levels in ESRD
patients
¡ N ormalizing hemoglobin levels in patient with
ESRD and CVD may increase mortality
§ R CT from Cochrane data base note ‘normalizing’
HGB to ~13 g/L resulted in higher risk of HTN
and stroke.
§ L ower HGB levels 9-11 g/L not associated with
higher risk
Ortiz, et al. Lancet 2014;383:1831-41
OTHER NOTABLE TRIALS FOR THE CKD
PATIENT
¡  Statins? YES…but
§  Meta-analysis (n=51099) reports all cause mortality if treated
before initiating dialysis
§  No benefits if starting statins after
¡  Non-calcium phosphate Binders: YES
§  Phosphate binders (Sevelamer) may slow arterial calcification, but
is no more effective than calcium salts in reducing CAD in the
ESRD population (eg.)
§  Cinacalcet (CA+ receptor agonist – Not signif. beneficial (n=7000)
¡  Antioxidants: NO
§  (ubidecarenone, acetylcysteine, recomb. Superoxide dismutase, Vit
E) NOT beneficial in CKD
KEY POINTS FOR THE ESRD’ER’
¡ A cidosis will impair therapeutic strategies
¡ F ollow the ECG for prolonged QT intervals.
Peaked t waves may not appear in chronic
dialysis patients
¡ I ndications for dialysis may include:
§ A bsolute K+ >6-6.5 mmol/L
§ A rrhythmia, severe hypertension
§ H ypoxia, pulmonary edema, shock, unstable
¡ T he definitive treatment is dialysis!
CASE 3: AKI – NO PREEXISTING RENAL
DISEASE – AND HE’S A BOARDER
¡  54 yo male with type 1 DM
with 5 days malaise and
diarrhea
¡  Presents dehydrated,
hypotensive, hypothermic
¡  Na+: 122, K:9.2 mmol/L
¡  GFR: 50 ml/min/m²
A
B
¡  Corrected from A-àC over
5 hours
What’s the diagnostic
approach?
C
WHAT’S WRONG WITH THE RAAS?
RENIN ANG IOT ENS IN ALDOS T ERONE SYS T EM ( RAAS )
FOR HYPER-K WITH NORMAL GFR
CALCULATE TTKG*
1.  Calculate TTKG
Ø  Normal 7-9
Ø  If TTKG<5 suspect
*Transtubular potassium gradient (TTKG)
hypoaldersteronism
2.  Identify high or low
aldosterone state
Ø  PAC:PRA (ARR)
3.  Get renin level
Ø  active renin conc
(ARC)
Clinica Chimica Acta 411 (2010) 657–663
For this formula to be accurate, urine
osmolality must exceed plasma
osmolality and urine sodium should be
greater than 25 mmol/L
*PAC: [Plasma Aldosterone Conc.]
*PRA: Plasma Renin activity
NORMAL GFR, LOW NA+, HIGH K+, LOW
TTKG – HYPOALDOSTERONISM
Clinica Chimica Acta 411 (2010) 657–663
DIFFERENTIATING ADRENAL
INSUFFICIENCY
¡ L ook at GFR
¡ C alculate Transtubular
potassium gradient
(TTKG)
¡ M easure serum renin or
PAC/PRA
¡ G et the patient upstairs
so the smart folks can
work this out
http://humanphysiology.tuars.com/program/
section7/7ch09/7ch09p45.htm
SUMMARY FOR HYPERKALEMIA
¡ A ll hyperkalemia is not only due to AKI/
chronic renal disease
¡ O ld folks + Meds + low GFR = Hyperk
¡ W ith AKI, check the heart first
¡ C heck FS often – use more glucose
¡ T hink about dialysis with the
decompensated patient
SUMMARY GUIDELINES FOR
HYPERKALEMIA TREATMENT
¡ Any Arrhythmia: Ca gluconate or chloride at
equivalent dosage (6.8 mmol) to all patients (1A)
¡ Insulin-glucose and beta agonist for K+ ≥ 6.5 (1B).
¡ Beta agonist not to be used as monotherapy (1a)
¡ Insulin-glucose and/or salbutamol for 6.0-6.4 (2c)
¡ Insufficient evidence for NA+ Bicarbonate in
hyperkalemia (2c)
¡ Cation-exchange resins do not have a role in ED for
severe HyperK (2B). Might be useful in mild/
moderate hyperk
The renal association. guidelines final, July 2012 (www.renal.org/guidelines)
FINALLY. CONSIDER GOOD PATIENT
INSTRUCTIONS
¡ Eliminate suspected food allergens,
¡ Avoid bananas, lentils, nuts, peaches, potatoes,
salmon, tomatoes, and watermelon.
¡ Avoid refined foods, such as white breads,
pastas, and sugar.
¡ Reduce red meats. Eat cold water fish, or beans
for protein.
¡ Limit the intake of processed meats, fast foods
¡ Use healthy cooking oils, such as olive oil or
coconut oil.
¡ Reduce or eliminate trans-fatty acids,
¡ Avoid noni (Morinda citrifolia) juice
http://umm.edu/health/medical/altmed/condition/hyperkalemia
REFERENCES
A d a m s M G , Pe l te r M M . E l e c t r o l y te i m b a l a n c e s . A m J C r i t C a r e . 2 0 0 4 ; 1 3 ( 1 ) : 8 5 - 6 .
M a n d a l A K . H y p o k a l e m i a a n d hy p e r k a l e m i a . M e d C l i n N o r t h A m 1 9 97 ; 81 : 61 1 – 3 9 .
B r e n n e r : B r e n n e r a n d Re c to r ' s T h e K i d n ey, 8 t h e d . P h i l a d e l p h i a , PA : S a u n d e r s E l s ev i e r
I n c . 2 0 07.
C h e n g TO . H e r b a l i n te r a c t i o n s w i t h c a r d i a c d r u g s . A r c h I n te r n M e d . 2 0 0 0 ; 16 0 : 87 0 - 871 .
E l - H e n n aw y A S , N e s a M , M a h m o o d A K . T hy r o tox i c hy p o k a l e m i c p e r i o d i c p a r a l y s i s
t r i g g e r e d by h i g h c a r b o hy d r a te d i e t . A m J T h e r. 2 0 07 ; 1 4 ( 5 ) : 4 9 9 - 5 01 .
E l l i o t t M J , Ro n k s l ey P E , C l a s e C M , A h m e d S B , H e m m e l g a r n B R . M a n a g e m e n t o f
p a t i e n t s w i t h a c u te hy p e r k a l e m i a . C M A J . 2 010 : 1 8 2 ( 1 5 ) : 16 31 - 5 .
G a r c í a N H , B a i g o r r i a S T, J u n c o s L I . H y p e r k a l e m i a , r e n a l f a i l u r e , a n d c o nve r t i n g - e n z y m e
i n h i b i t i o n : a n ove r r a te d c o n n e c t i o n . H y p e r te n s i o n . 2 0 01 ; 3 8 ( 3 P t 2 ) : 6 3 9 - 4 4 .
M u s h i ya k h Y, e t a l . J C o m m u n i t y H o s p i t a l I n te r n a l M e d Pe r s p e c t i ve s . 2 01 1 ; 1 : 1 - 6
REFERENCES
¡ Evans KJ, Greenberg A. Hyperkalemia: a review. J Intensive Care Med. 2005 Sep-­‐Oct;20(5):272-­‐290. ¡ Kamel KS, Wei C. Controversial issues in the treatment of hyperkalaemia. Nephrol Dial Transplant. 2003;18:2215-­‐2218. ¡ Sood MM, Sood AR, Richardson R. Emergency management and commonly encountered outpa)ent scenarios in pa)ents with hyperkalemia. Mayo Clin Proc. 2007 Dec; 82(12):1553-­‐1561. ¡ Hollander JC, Calvert CJ. Hyperkalemia. Am Fam Physician 2006; 73:283-­‐90 T YPES OF ADRENAL INSUFFICIENCY
¡  „ Primary (gland failure): Adrenal failure/enzyme
deficiencies; surgical,polyglandular syndrome (diabetes,
hypothyroidism, adrenal insufficiency)
¡  „ Secondary (inhibited function): sepsis, etomidate;
ketoconazole; hemorrhage; adrenal TB or, infection;
tumors; increased cortisol metabolism by rifmapin,
phenytoin; suppression with exogenous steroid
¡  „ Tertiary/Quaternary: (Central ACTH deficiency):
hypopituitarism, Corticotropin /ACTH loss, (Hypothalamic
dysfunction): loss of CRH secretion