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Non-specialist Management of Acute Renal Failure
What Do I Need To Know?
Dr Paul StevensConsultant Nephrologist
East Kent Hospitals University Trust
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Acute Renal Failure
• 'The abrupt transition from functioning kidneys to kidney function which is unable to accomplish biochemical homeostasis'
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RIFLE Criteria
• Risk• Injury• Failure• Loss• End stage kidney
diseaseSarah Palin - Sniper KittenMaking the world a better place shot by shot
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Acute Kidney Injury Network Criteria
Stage Creatinine Criteria UOP Criteria
1↑SCr ≥ 26.4 μmol/L or
↑SCr ≥ 150-200%< 0.5 mL/kg/hr for > 6 hr
2 ↑SCr > 200-300% < 0.5 mL/kg/hr for >12 hr
3
↑ SCr >300% or
SCr ≥354 μmol/L + acute ↑ ≥44 μmol/L in ≤24hr or
RRT initiated
< 0.3 mL/kg/hr for 24 hr
or
anuria for 12 hr
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Pathogenesis
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Renal Perfusion
Parenchymal Structures
Urine output
Induce ↓GFR
Pre-renal
Parenchymatous (intrinsic)
Post-renal
Sudden causes affecting
ARF
Called
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Acute Renal Failure
Postrenal ARFIntrinsic ARFPrerenal ARF
Acute interstitial nephritis
Acute tubular necrosis
Acute GNAcute vascular
syndromesIntratubular obstruction
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What I’m Not Going to Talk About
• Vasopressors• Dopamine agonists• Natriuretic peptides• Adenosine agonists• N-acetylcysteine• Loop diuretics and osmotic diuretics• Prophylactic dialysis/HF
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What I Am Going to Talk About
• Everyday life in Margate• Why does it matter?• What’s important?• The real world• Avoiding ARF
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Everyday Life in Margate
• 37 year old man, depressed• 1 litre of Brandy, 24 paracetamol, 12
Nurofen plus at c. 18.00 hrs• Vomited, fell asleep against a radiator
and woke up the following morning• Left leg was uncomfortable on waking
and swollen
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Why Does it Matter?
• AKI is commoner than many realise• Mortality from AKI remains high• AKI doubles hospital length of stay• AKI predicts subsequent mortality• AKI is costly
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ICNARC: AKI Length of StayDays
Severe AKI accounted for 9.4% of all bed days
Survivors
Deaths
17,326/276,731 (6.3%) ICU admissions
Mean age 63.2 ± 15.6 yrs
Kolhe, Stevens, Crowe et al Critical Care 2008;12(Suppl 1):S2 (13 October 2008)
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US National Hospital Discharge Survey
• Projected 29,039,599 hospital admissions, 558,032 coded as ARF (1.92%)
Without ARF With ARF
Median age (yr) 58.0 73.0
Median LOS (d) 3.0 7.0
Death (%) 2.3 21.3
Liangos et al. CJASN 2006 Jan;1(1):43-51
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The Effect of AKI on Mortality
• 16,248 radiocontrast media procedures• 183 subjects with contrast-media associated AKI• 174 paired subjects (age, procedure, baseline Cr)• Mortality
– 7% in those without renal failure– 34% in those with renal failure
• After comorbidity adjustment renal failure conferred an odds ratio risk of dying of 5.5
Levy, Viscoli & Horwitz. JAMA 1996;275:1489-94
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One Year of ARF in East Kent
• 291 patients, 188 male, 103 female• Mean age at presentation 73.1 years• Overall incidence 491 pmp/year• 81 pmp/year received dialysis
Stevens et al, QJ Med 2001;94:553-560
• Survival to discharge from hospital 53%• Survival at 90 days 32%• Survival at 120 months 14%
• In those <65 post-discharge SMR was 14.1
Kolhe et al, Unpublished data
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Hamel, M. B. et. al. Ann Intern Med 1997;127:195-202
Cost per QALY of ICU Severe AKI
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Acute Kidney Injury and Costs• Consecutive sample of 19,982 adults
• In 1237/9210 (13.4%) SCr ↑ by ≥44 µmol/L• 6.5x risk of death, 3.5d increased LOS
Chertow et al. JASN 2005;16:3365-3370
Unadjusted Age and gender adjusted Multivariably adjusted
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What’s Important?Baseline risks Clinical conditions Drugs
Advanced age Sepsis Contrast media
Diabetes Hypotension/Shock Antibiotics
CKD Volume depletion Chemotherapy
Heart failure Rhabdomyolysis NSAIDs
Liver failure Cardiac/vasc surg ACEI/ARB
Male gender Non-renal solid organ Tx
Race/genetic Mechanical ventilation
Low albumin Abdominal compartment syndromeArterial disease
ADQI 4th Consensus Conference
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Avoiding Acute Kidney Injury
1. Recognise and assess the patient at risk2. Avoid nephrotoxic agents3. Maintain effective circulatory volume4. Recognise and treat hypoxia 5. Treat infection, avoid nosocomial infection6. Pharmacological manipulation to maintain RBF,
perfusion pressure and GFR
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The Patient at Risk From AKICardiovascular Health Study: observational community cohort study5731 patients ≥65 yr at baseline, median follow up 10.2 yr
Haz
ard
ratio
3.9% developing AKI during follow up
Prevalent CVD doubled the risk of AKI
Mittalhenkle et al. Clin J AM Soc Nephrol 2008;3:450-456
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UK Demographics
• 60.2 million people• Mean age 38.8 years• 4% Asian• 2% African -caribbean• Diabetes 4%• Hypertension 12.5%• Coronary HD 3.7%• Stroke 1.8%• Heart failure 0.8%
ONS & QMAS data 2005/2006/2007
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GFR (ml/min/1.73m2) <30 30–44 45–59
Prevalence 0.38% 1.79% 6.33%
Mean age (yr ± SD) 76.8 ± 14.1 78.4 ± 10.4 69.7 ± 13.5
All CVD (%) 50.7 42.7 27.1
Diabetes (%) 23.0 16.1 12
Hypertension (%) 87.8 86.6 71.4
ACE/ARB (%)* 32.5 37.5 43.0
UK At Risk Population Characteristics
*ACE/ARB prescription in those with hypertension
Stevens et al. Kidney Int 2007 Jul;72(1):92-9
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Racking Up The Risk
71
60 59
48
0
10
20
30
40
50
60
70
80
P P /AC E /BF Z D D/AC E /BF Z
GF
R (
ml/m
in)
Juhlin et al, Eur J Heart Fail 2005;7:1049-1056
14 healthy elderly aged 67-78
Single dose of oral Diclofenac (50mg) or placebo
With or without pre-treatment with Enalapril & BFZ
* *******
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Assessment of ARF
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Key Assessments: All Patients
All 3 Key Assessments
2 of 3 Key Assessments
1 of 3 Key Assessments
No Key Assessments
Stevens et al, QJ Med 2001;94:553-560
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Key Assessments: Age ≥70
All 3 Key Assessments
2 of 3 Key Assessments
1 of 3 Key Assessments
No Key Assessments
Stevens et al, QJ Med 2001;94:553-560
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Key Assessments: Age <70
All 3 Key Assessments
2 of 3 Key Assessments
1 of 3 Key Assessments
No Key Assessments
Stevens et al, QJ Med 2001;94:553-560
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Community Acquired ARF
• 163/291 ARF present at time of admission• 45% were associated with intravascular
volume depletion and/or hypotension • 28% were associated with obstruction• 23% were associated with sepsis• 23% were drug-related
Stevens et al, QJ Med 2001;94:553-560
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• 125/291 ARF developed after admission• 55% were associated with intravascular
volume depletion and/or hypotension• 34% were drug-related• 29% were associated with sepsis• 10% were associated with obstruction
Stevens et al, QJ Med 2001;94:553-560
Hospital Acquired ARF
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Potentially Avoidable ARF: 101 of 291
ACEI/AII related 56 Aminoglycoside/ Vancomycin toxicity
4
NSAID related 33 Lithium toxicity 2
Volume depletion/ overdiuresis
48 Other 12
Stevens et al, QJ Med 2001;94:553-560
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Definitely Avoidable ARF: 54 of 291
ACEI/AII blockers
18 Aminoglycoside/ Vancomycin toxicity
4
NSAIDs 17 Lithium toxicity 2
Volume depletion/ Overdiuresis
19 Lack of recognition of urinary retention Other
7
3
Stevens et al, QJ Med 2001;94:553-560
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Primary Instigating Factors for ARF
Vijayan & Miller, Seminars in Nephrology 1998;18:523-32
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Drug-related ARF
• Diuretics 99• ACEI 75• NSAIDs 61• Antibiotics 6• Contrast 5
ACEI & diuretics 46NSAIDs & diuretics 24ACEIs & NSAIDs 15ACEIs, NSAIDs & diuretics 8
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ARF and Volume Loading
• Korean War– Incidence of ARF 1:200
• Vietnam War– Incidence of ARF 1:600
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Acute Kidney Injury: Conceptual Model
Adapted from Himmelfarb et al Clin J Am Soc Nephrol 2008:3;962-967
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Fluid Balance Lesson for Surgeons
• “The body is not analogous to a tank into which water can be forced until it finally bursts out through the kidneys”
Lattimer, Lancet 1945
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Acute Renal Failure and Sepsis
ARF occurs in– 19% culture positive in
moderate sepsis– 23% culture positive in
severe sepsis– 51% culture positive in
septic shock
70% mortality in sepsis and ARF combined
Rangel-Frausto et al. JAMA 1995;273:117-123
Schrier & Wang NEJM 2004;351:159-69
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ARF in East Kent: Initial Assessments
All ARF
n=291
Sepsis & ARF
n=74
Respiratory rate 29% 38%
Oxygen status 30% 49%
Blood culture 42% 66%
MSU 57% 73%
CRP 18% 31%
Stevens et al, QJ Med 2001;94:553-560
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Assessment and monitoring: physiological observations
Initial assessment should include at least:
•heart rate•respiratory rate•systolic blood pressure•level of consciousness•oxygen saturation•temperature.
Acutely ill patients in hospital: NICE clinical guideline 50
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Change in BP Before Nosocomial AKI
• Non-critically ill patients developing nosocomial AKI in hospital
• Exclusions included ICU patients, absolute hypotension, renal Tx, AKI within 3 days of admission
• Changes in BP prior to maximum stage of AKI assessed
SBP DBP
ΔSBP ΔDBP
**
mm
Hg
Liu YL et al. Nephrol Dial Transplant; NDT advance access 3 September 2008
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Avoiding Acute Renal Failure
1. Recognise and assess the patient at risk2. Avoid nephrotoxic agents3. Maintain effective circulatory volume4. Recognise and treat hypoxia 5. Treat infection, avoid nosocomial infection6. Pharmacological manipulation to maintain RBF,
perfusion pressure and GFR
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Margate “London-By-The-Sea”
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• Presented to A&E 10.30 a.m. seen by Orthopaedic SHO, admitted, NBM in case of theatre, Voltarol analgesia
• Muddy brown urine (once)• Reviewed at 18.40 hrs
– Tachycardic, lying BP of 130/80– Unable to move his left leg, left KJ & AJ
were absent– Medical SHO called
Everyday Life in Margate
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• Treated with Parvolex, bloods sent• Results
– Na 138, K 5.2, Urea 19.1, Creatinine 280, Alb 40, AST 1738. Clotting was normal, FBC showed WCC 20.9 (19.3N), Hb 17.8, Plt 247. Paracetamol and aspirin levels were below toxic levels
• Medical registrar reviewed him at 23.15 and noted severe oedema in the left thigh, sensory and motor loss in the left leg and muscle fasciculation
Everyday Life in Margate
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Per Ardua Ad Urinam
Acknowledgements:Dr N A TamimiDr M K Al HasaniDr D I ProsserDr P CarmichaelDr N KohleDr B Klebe