ASN BOARD REVIEW 2014
AKI Pathogenesis, Diagnosis, Biomarkers and Risk Assessment
Anupam Agarwal, MD
Division of Nephrology
University of Alabama at Birmingham
Outline
• Pathogenesis of Acute Kidney Injury and Repair• Prerenal and Ischemic AKI• Sepsis• Toxin
• Pathogenesis of AKI in the Elderly• Definition, Incidence• Diagnosis, Biomarkers• Clinical Risk Assessment of AKI
TubulesApoptosisNecrosisMitochondrial dysfunctionBack-leakDetachmentObstruction
Systemic factorsProinflammatory cytokinesAntiinflammatory cytokines
VasculatureVasoconstrictionFocal IschemiaVasodilationThrombosisCoagulationInflammationPluggingNo ReflowIntermittent flow
MicroenvironmentInnate immunityAdaptive immunityParacrine factorsAutocrine factors
Pathogenesis of AKIAKI
Biophysical Basis of Decreased GFR
Prowle, J. R. et al. Nat. Rev. Nephrol.;6(2):107-15
Effect of Ischemia on Regional Blood and Medullary PO2
0
20
40
60
80
100
Re
lati
ve
Blo
od
Flo
w
Cortex Outer medulla
Innermedulla
Pre-ischemia
Postischemia
P.O.A. Hellberg, et.al. Kidney Int. 40:625,1991
95
50
20
15
10
Renal Artery
50
10
8
O2 Diffusion
PO2, mm Hg
Cortex
Inner Cortex
Medulla
Renal Vein
Pathogenesis of AKI
PGC
PreRenal AKI
RC Blantz 53:512-523, 1998
Intrarenal Mechanisms for Autoregulation of the Glomerular Filtration Rate
Abuelo JG. N Engl J Med 2007;357:797-805.
NSAIDS ACEI/ARB
M. Epstein Am J. Med: 49: 175-185, 1970
HRS: antemortem HRS: postmortem
Hepatorenal Syndrome Severe Vasoconstriction
Cirrhosis
Portal Hypertension and Splanchnic Arterial Vasodilation
Impaired effective arterial blood volume
Low Arterial Pressure
Activation of Vasoconstrictor System
Renal Vasoconstriction
HEPATORENAL SYNDROME
Abnormal DistributionOf Blood Volume
Cirrhotic Cardiomyopathy
Low SVR Cardiac Preload
Intrahepatic Resistance Splanchnic Vasodilators
IntraabdominalCompartment Syndrome
Ridings, et al 1995Pickhardt et al. 1999
Patel et al 2007
Hemodynamic effect of IAH
Ca
rdia
c In
de
x (L
/min
/m2)
Abdominal Pressure (mmHg above baseline)
Wed
ge
Pre
ssu
re (
mm
Hg
)
Physiologic Sequelae
• Elevated intra-abdominal pressure causes:• Compression of renal
veins and IVC• Reduced cardiac output
to kidneys• Renal failure,
oliguria/anuria
The Result:• Reduced blood flow to
kidney• Renal congestion and
edema• Decreased glomerular
filtration rate (GFR) • Acute tubular necrosis
(ATN)
Adapted from Bonventre and Weinberg
JASN 14:2199-2210, 2003 Courtesy of Bruce Molitoris
Ischemia
Continued Ischemia
DECREASED GFR
Acute Tubular Injury
ApoptosisNecrosis
Tubular ObstructionBackleak
MicrovascularInjury
VasoconstrictionLeukocyte Adhesion
↑ Permeability
MicrovascularCongestion
Innate Immunity
Inflammation
DAMPSImmune Cells
Cytokines
EndotheliumMicrovascular endothelial injury and dysfunction during IRI
Ischemia
Endothelial Cell activation, Dysfunction,
Injury and/or Detachment
Impaired VasodilationCoagulation
Leukocyte Adhesion
Capillary Obstruction and Continued Ischemia
Extension of ARF
Inflammation
TA Sutton, CJ Fisher, BA Molitoris Kidney Int (2002) 62, 1539–15490
Microvascular Blood Flow at 24h Post Ischemia Effect of sTM
sTM treatedSaline treated
Blood Flow velocity (µm/sec)
253.36+/-95.01 786.75 +/- 280.75 *
Early Pathogenic Mechanisms of AKIEndothelial, Epithelial, Immune Cells and Interstitium
Sharfuddin, A. A. & Molitoris, B. A. (2011) Nat. Rev. Nephrol.
J. V. Bonventre and L. Yang J. Clin Invest. 2011;121(11):4210–4221.
Injury and Repair in Ischemic Acute Kidney Injury Human Acute Kidney InjuryBackleak
TS Olsen, HS Olsen, HE Hansen Vichows Arch 1985, 406:75
Regenerating Cell NonReplacement Site
DEAD CELLS, GRANULAR CASTS, REGENERATING EPITHELIUM
Courtesy of MA Venkatachalam
Outline
• Pathogenesis of Acute Kidney Injury and Repair• Prerenal and Ischemic AKI
• Sepsis
• Toxin
• Definition, Incidence
• Diagnosis, Biomarkers
• Clinical Risk Assessment of AKI
Sepsis Related AKI
Mechanisms
• Pro-inflammatory State
• Systemic Vasodilation
• Impaired Microcirculation
• Cytokine mediated cell injury
(Schrier, RW, NEJM, 2004)
Hyperdynamic Circulation in Experimental Septic AKI: Systemic Parameters
C Langenberg…R Bellomo, Kidney Int (2006) 69, 1996–2002
MAP HR
CO TPCConductance
Ecoli Ecoli
C Langenberg…R Bellomo, Kidney Int (2006) 69, 1996–2002
Hyperdynamic Circulation in Experimental Septic AKI: Renal Parameters
E Coli
Hyperemic AKI: Loss of glomerular filtration pressure
• Septic AKI may represent a unique form of AKI: hyperemic AKI.
• GFR is determined by glomerular filtration pressure.
• If afferent arteriole dilates and the efferent arteriole dilates even more, RBF will markedly increase, yet pressure within the glomerulus will fall. GFR will also decrease.
Sepsis is a Disorder of the Microcirculation
Trzeciak S et al. Acad Emerg Med 2008; 15:399-413
PO2
Outline
• Pathogenesis of Acute Kidney Injury and Repair• Prerenal and Ischemic AKI• Sepsis• Toxin
• Pathogenesis of AKI in the Elderly• Definition, Incidence• Diagnosis, Biomarkers• Clinical Risk Assessment of AKI
Site Specificity of Common Nephrotoxins
V.S. Vaidya, J.V. BonventreComprehensive Toxicology2010, Pages 197–211
TMACalcineurin Inh
ClopidogrelCocaine
MitomycinQuinine
Proximal Tubule InjuryAcyclovirAminoglycosidesCadmiumCidofovirCisplatinFoscarnetLeadMercuric chloride
HemodynamicsACEI/ARBAmpho BCalcineurin inhDiureticsNSAIDSContrast
Distal Tubule InjuryAmpho BCalcineurin inhLithiumSulfadiazine
Tubular ObstructionAcyclovirIndinavirMethotrexateSulfonamides
Interstitial NephritisAllopurinolAristolochic acidCephalosporinsCiprofloxacinDiureticsNSAIDSPenicillinsPhenytoinPPIs
Aminoglycosides
• GFR is not apparent until 7‐10 days after initiating therapy.
• Occurs in setting of hypotension, prerenal
azotemia other nephrotoxins
• UNa>20 meq/L, FENA>2
• Usually reversible
• Risk factors: prolonged treatment, volume
depletion, preexisting renal disease, hypokalemia,
old age, other nephrotoxins
• Monitor drug levels and creatinine every 2‐3 days
Aminoglycoside binds to the anionic phospholipid of the PTC, it is transferred to the transmembrane protein megalinand endocytosed
Megalin-expressed in the renal proximal tubules, podocytes and ciliary and inner ear epithelium
After endocytosis, endosomes -accumulate in organelles such as the mitochondria and the nucleus- disrupting in mitochondrial function
1.Nagai J; Takano M. Drug Metab Pharmacokinet. 2004 Jun;19(3):159-702.Ford DM et al. Am J Physiol. 1994 Jan;266(1 Pt 1):C52-73.Sandoval RM; Molitoris BA, Am J Physiol Renal Physiol. 2004 Apr;286(4):F617-24.
J.M. Lopez-Nova et al, Kidney Int 79:33, 2011
Aminoglycoside Nephrotoxicity Aminoglycoside Nephrotoxicity
Myeloid bodies
Sodium Diatrizoate-ionic monomer(1500-1800 mosm/kg)
Iohexol-nonionic monomer(780 mosm/kg)
Iodixanol-nonionic dimer(290 mosm/kg)
Structure of Contrast Media
Adapted from C.M. Sandler N.Engl.J.Med 348:551, 2003
Contrast Media-Nephrotoxicity
Contrast Media
Blood Flow OxygenDelivery
OxygenConsumption
Renal Medullary Hypoxia
SystemicHypoxemiaBlood viscosity
PGE2 EndothelinANP VasopressinAdo PGI2
Osmotic Load
Direct Cellular Toxicity
modified from Rudnick et. al. Seminars in Nephrology 17:15-26, 1997
Pathogenesis of CIAKI
Calvin, A. D. et al. (2010) Contrast-induced acute kidney injury and diabetic nephropathyNat. Rev. Nephrol. doi:10.1038/nrneph.2010.116 J. Cerdá et al. Clin J Am Soc Nephrol 3: 881-886, 2008
Progession of AKI to CKD/ESRD
.Loss of Peritubular Capillaries Lead to Chronic Hypoxia
• Decreased oxygen diffusion from peritubular capillaries to tubular and interstitial cells• Stagnation of peritubular capillary blood flow • Decreased peritubular capillary blood flow as a result of imbalance of vasoactive substances• Inappropriate energy usage as a result of uncoupling of mitochondrial respiration induced by oxidative stress• Increased metabolic demands of tubular cells • Decreased oxygen delivery as a result of anemia
Nangaku M JASN 2006;17:17-25
MSCs Repair Kidney
Florian E. Tögel & Christof Westenfelder Nature Reviews Nephrology 6, 179-183 (March 2010)
What is the origin of myofibroblasts in the kidney?
10%
5%
60%
30%
VS LeBleau…R. Kalluri et al. Nature Medicine 19, 1047–1053 (2013)
Molecular Mechanisms of FibrosisCell Cycle and Epigenetic Modification
T.A.Wynn Nature Medicine 16, 523–525 (2010); L. Yang Nature Med 16:535-543, 2010W. Bechtel Nature Med 16:544-550, 2010
Rasal 1
RAS inactivation
Cell Proliferation
HypermethylationRasal 1
RAS activation
Cell Proliferation
Outline
• Pathogenesis of Acute Kidney Injury and Repair• Prerenal and Ischemic AKI• Sepsis• Toxin
• Pathogenesis of AKI in the Elderly• Definition, Incidence• Diagnosis, Biomarkers• Clinical Risk Assessment of AKI
Population incidence of dialysis-requiring AKI in the United States by age groups from 2000 to 2009
Hsu R K et al. JASN 2013;24:37-42
AKI Susceptibility in Elderly
Anderson S et al. JASN 2011;22:28-38
Prevention of AKI in elderly depends on awareness of reduced GFR
• Age dependent decline in GFR; worse with clinical risk factors
• CKD is risk factor for AKI
• Prevention depends on awareness of reduced GFR in elderly despite normal creatinine
M. C. Odden et al. Nephrol Dial Transplant (2010) 25(2): 463‐469 Redrawn from USRDS 2009, P. Eggers
Senile NephrosclerosisAmong 1,203 living kidney donors
AD Rule et al. Nephron Physiol. 2011 August; 119(Suppl 1): p6–p11.
GlomerulosclerosisTubular atrophyInterstitial fibrosis >5%Arteriosclerosis
20 yo kidney donor
70 yo kidney donor
Renal Reserve in Elderly
GF
R m
l/min
0
50
100
150
200
250
Young Old Oldest Old
Baseline
Meat Meal
Renal Reserve
CG Musso et al. Int Urol Nephrol (2011) 43:253–256
Pathogenesis of AKI Key Points
• Ischemic, septic or toxin induced AKI often occur concomitantly
• Ischemic AKI results is a summation of events that involve capillary endothelium, tubular epithelial cells, and inflammatory cells and humoral mediators (cytokines and chemokines).
• Nephrotoxins-site specificity
• Sepsis models of AKI • Pro-inflammatory cytokines due to host response.
• Disorder of microcirculation
• AKI in aging• Due to comorbid factors (heart failure, diabetes) and
• Due to noncomorbid factors that relate to age related changes in kidney function.
• Due in part to decrease in renal reserve
• Chronic medullary hypoxia and activation of myofibroblasts are thought to contribute to mechanisms by which AKI leads to CKD.
Pathogenesis of AKI: Key Points: Update
• Role of mesenchymal stem cells –• i) Immediate effects ameliorate injury (paracrine)
• ii) late effects in recovery (“homing”)
• Single episode of kidney injury triggers long-term changes to structure & function.
• Epithelial regeneration leads to repair and fibroblast/pericyte proliferation leads to fibrosis.
Outline
• Pathogenesis of Acute Kidney Injury and Repair• Prerenal and Ischemic AKI• Sepsis• Toxin
• Pathogenesis of AKI in the Elderly• Definition, Incidence• Diagnosis, Biomarkers• Clinical Risk Assessment of AKI
Population incidence of dialysis-requiring AKI in the United States by sex from
2000 to 2009
Hsu R K et al. JASN 2013;24:37-42
Overall
Gender
Age
Over 30 definitions of AKI/ ARF exist in the literature
1. Creat ∆ 0.1 mg/dL2. Creat increase >0.5 mg/dL3. Creat>= 0.5 mg/dL4. Creat >= 1.7 mg/dL5. Creat >= 1.5 mg/dL6. Creat >= 2 mg/dL7. Creat>= 2.1 mg/dL and x 28. Creat >= 177µmol/L ∆>62µmol/L9. Creat > 200µmol/L (2.36 mg/dL)10. Creat> 3.2 mg/dL or x 211. Creat>5 mg/dL or K > 5.512. RIFLE13. Creat increase >= 25%14. Creat increase >= 50%15. Creat increase >= 100%16. ∆Cr72h >0µmol/L17. ∆Cr72h >25µmol/L18. ∆Cr72h >44µmol/L
19.∆Cr72h >50µmol/L20.∆Cr72h >100µmol/L21.Cockcroft-Gault Cr Cl < 30 mL/min22.Cockcroft-Gault Cr Cl 30–60 mL/min23.∆Cockcroft-Gault72hr <0%24.∆Cockcroft-Gault72hr <-15%25.∆Cockcroft-Gault72hr <-25%26.∆Cockcroft-Gault72hr <-50%27.MDRD: 50% change in GFR28.UO <100 q 8hr29.U α1-microglob30.U β2- microglobulin31.U N-acetyl- β-D-glucosaminidase32.U gluthation transferase-π33.U gluthation transferase- α34.NGAL35.RRT36.…
ADQI Rifle Criteria – Consensus Definition
BellomoetalCritCare2004www.ADQI.net
Mortality Risk in Hospitalized Patients
0.0
5.0
10.0
15.0
20.0
Mu
ltiv
ari
ab
le O
R
↑SCr↑SCr> 0.3 > 0.5 > 1.0 > 2.0
mg/dLChertow et al, JASN 16: 3365-3370, 2005Chertow et al, JASN 16: 3365-3370, 2005
R (I)
I (II)
F (III)
Increased SCr x1.5OR > 0.3 mg/dL
UO < .3ml/kg/hx 24 hr or Anuria x 12 hrs
UO < .5ml/kg/hx 12 hr
UO < .5ml/kg/hx 6 hr
Increased SCr x2
Increase SCr x3or SCr 4mg/dl
(Acute rise of 0.5 mg/dl)
HighSensitivity
HighSpecificity
RRT Started
Modifications proposed by AKINAmsterdam, 2005
R (I)
I (II)
F (III)
Criterion must be reached within 48hr
AKIN Criteria (Rifle V2.0)
Riskvs Non-AKI
Injuryvs Non-AKI
Failurevs Non-AKI
1 102.4 4.2 6.4Relative Risk
Increase in All-Cause Mortality with worse RIFLE Class
n=71,527
Ricci et al KI 2008
KDIGO Definition of AKI
• Increase in SCr by ≥0.3 mg/dl within 48 hours; or
• Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
• Urine volume <0.5 ml/kg/hour for 6 hours.
Baseline Day 1 Day 2 Day 3 Day 7 RIFLE AKIN
0.4 0.5 0.6 0.7 0.4 YES NO
1.0 1.1 1.3 1.2 1.0 NO YES
Examples
5 Problems (at least) with Serum CreatinineRIFLE/AKIN/KDIGO-Creatinine based
1. Not sensitive: There is lot of cellular injury that does not affect (GFR)/creatinine
2. Not Specific: Creatinine can increase without kidney injury (pre-renal state)
3. Delayed: The rise is serum creatinine is delayed by 2-3 days
4. Fluid therapy may dilute serum creatining delaying diagnosis
5. Inter-laboratory variation in measuring creatinine, and bilirubin and other compounds interfere with the colorimetric modified Jaffe assay hence affect serum creatinine levels.
Serum Creatinine and GFR In AKI
Muscle mass
Protein metabolism
Serum creatinine
Renal excretion
Tubular excretion Filtration (GFR)
Drugs Nonlinear
Nutrition Infection
Edema
Volume of distribution
Star RA, Kidney Int, 1998
Definition and Incidence:Summary• RIFLE or AKIN Definitions
• Increase in stage associated with increase in mortality
• Both have important limitations
• KDIGO Definition• Consensus definition- Combines RIFLE and AKIN into a single
definition
• Limitations-number of limitations
Need to integrate biomarkers of injury
Outline
•Pathogenesis of Acute Kidney Injury
•Definition, Incidence
•Diagnosis, Biomarkers
•Clinical Risk Assessment of AKI
Primary and Secondary PreventionRisk Profiling and Biomarkers
High riskHigh risk Prerenal AKIPrerenal AKI AKIAKI
Therapeutic Window
Glomerular Filtration Rate
Sensitive Biomarkers Creatinine
Jo, S.K. M.H. Rosner and M.D. Okusa, Clin. J. Am. Soc. Nephrol. 2: 356 – 365, 2007.
Primary Prevention
Secondary Prevention
What Can An Ideal AKI Biomarker Teach Us?
• Predict and diagnose AKI early (before increase inserum creatinine)
• Identify the primary location of injury (proximal tubule,distal tubule, interstitium)
• Pinpoint the type (pre-renal, AKI, CKD), duration andseverity of kidney injury
• Identify the etiology of AKI (ischemic, septic, toxic,combination)
• Predict clinical outcomes (dialysis, death, length of stay)
• Monitor response to intervention and treatment
• Expedite the drug development process (safety)
Prasad Devarajan: Biomarkers in Acute Kidney Injury :Search for a Serum Creatinine Surrogate
Biomarkers after AKIEarly Detection
Idealized
SCr
IL-18
NGAL
L-FABP
Kim-1
Value of Damage BiomarkersDifferential Diagnosis of AKI
Urinary NGAL Serum Creatinine
TK. Nicholas et al. Ann Intern Med. 2008;148:810-819
635 patients admitted to the hospital with AKI, prerenal azotemia, CKD, or normal kidney function. • RIFLE criteria for AKI used. • At a cutoff value of 130 g/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were
0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00),
Combined use of damage biomarkers and functionalbiomarkers Predicts clinical events
Clinical events (initiation of dialysis or in-hospital mortality)
T.K. Nicholas, et al. J Am Coll Cardiol. 2012 January 17; 59(3): 246–255
NGAL KIM-1
Diagnosis of AKI: Combination of Functional and Damage Markers
Dublin, Ireland, August 30th-September 1st, 2011
ZH Endre et al Contrib Nephrol. 2013;182:30-44
RenaStickPoint of Care Testing for AKI
V.S. Vaidya…J. V. Bonventre, et al.Kidney International (2009) 76, 108–114
Timing in Secondary PreventionEarlyARF Study
• Double-blind placebo-controlled trial -early treatment with erythropoietin (E) could prevent the development of AKI in ICU setting.
• Urinary levels of two biomarkers, γ-GT and AP (46.3) triggered randomization to either placebo or two doses of E
• Primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days.
• Of 529 patients, 162 were randomized within an 3.5 h of a positive sample.
• Early intervention with high-dose erythropoietin did not alter the outcome.
ZH Endre, et al,Kidney Int. (2010) 77, 1020–10301 hr 12 hr 7 d24 hr
RandomizationAv 3.5 h
Placebo or E
randomization
Thresholds for Detection of AKICaveats?
No AKI
AKI
No AKI
AKI
No AKI
AKI
No AKI
AKI
Healthy Adult Adult with CKD?? Pediatric Elderly Adult??
L-FABP, KIM-1, and IL-18Surgery, contrast-induced AKI, sepsis and critical illness.
What are the cut points for:
Urine microscopy in early diagnosis of AKI
• 267 hospitalized patients with a diagnosis of AKI.
• Findings on urine microscopy led change in the initial diagnosis of
• PRA to ATN in 27 patients (23%)
• ATN to PRA in 15 patients (14%)•
MA Perazella et al. Clin J Am Soc Nephrol 3: 1615-1619, 2008
Biomarkers: Summary
Biomarkers – General
• Transition from discovery to validation to clinical use: IL-18; Cystatin
C; KIM -1; NAG
• Combination of “functional” and “damage” biomarkers
• Optimal “context specific” cut-points for the diagnosis of AKI need to be developed for L-FABP, KIM-1, and IL-18 and other
Biomarkers - Older patients• The use of serum creatinine is the current gold standard but its
use necessitates a clear understanding of its limitations especially the older population
• Validation of lead biomarkers need testing in the older population• L-FABP, KIM-1, and IL-18 and others
• Cut-points need to be identified in the older population
Outline
•Pathogenesis of Acute Kidney Injury
•Definition, Incidence
•Diagnosis, Biomarkers
•Clinical Risk Assessment of AKI
Exposure
GFR
Damage
Acu
te K
idn
ey
Inju
ryNormal
Co-morbidities
Demographics
Medications
Su
scep
tib
ilit
y
ESRD/Death
CKD
Recovery
Ou
tco
mes
Inte
rven
tio
n
Before Exposure
After Exposure
During Development of AKI
After Recovery from AKI
Risk Assessment
Adapted from KDIGO; appendix C, Kidney Int. 2012
Pre-Exposure Risk Factors
Shared Susceptibility Factors
Dehydration
Hypoalbuminemia
Advanced Age
Female Gender
Black race?
Previous AKI
Chronic Co-morbidities
CKD
Diabetes Mellitus
Heart Disease
Pulmonary
Multiple myeloma
Acoholism
Preexposure medications
Medications
NSAIDs
ACEI/ARBs
Statins?
Pre
-Exp
osu
re R
isk
Fac
tors
Risk Prediction for RCIN
Hypotension
IABP
CHF
Age>75
Diabetes
Contrast volume
Cr>1.5 mg/dl
eGFR<60 ml/min/1.73 m2
Mehran et al. JACC 2004;44:1393‐1399
Risk Factors
RiskScore
Risk ofRCIN
Risk ofDialysis
≤ 5 7.5% 0.04%
6‐10 14% 0.12%
11‐16 26.1% 1.09%
≥ 16 57.3% ≤12.6%
5
5
5
4
3
1 for each 100ml
4
2 for 40‐604 for 20‐405 for <20
Score
5,561 pts in development set2,786 pts in the validation set
Risk Assessment of ARF Post CABG (1992‐2002)
Minimum score, 0 Maximum score, 17
Risk factors Score
Female gender 1
Congestive heart failure 1
Left ventricular ejection fraction <35%
1
Preoperative use of IABP 2
COPD 1
Insulin-requiring diabetes 1
Previous cardiac surgery 1
Emergency surgery 2
Valve surgery only (reference to CABG)
1
CABG + valve (reference to CABG)
2
Other cardiac surgeries 2
Preoperative creatinine 1.2 to <2.1 mg/dl (reference to 1.2)
2
Preoperative creatinine 2.1 (reference to 1.2)
5
C. Thakar J. Am Soc. Nephrol 16:162-168, 2005
Risk Factors for AKI: Importance of CKDKaiser Permanente Northern California
≥ 60 Reference30-44
15-29
Diabetes Mellitus
45-59
Documented Proteinuria
Diagnosed Hypertension
BaselineGFR
<15
C.Y. Hsu…GM. Chertow…and AS Go Kidney Int. 74, 101–107, 2008
Unadjusted Odds ratio
1,746 hospitalized AKI-D and 600,820 hospitalized with no AKI
Hyperglycemia increases AKI Risk
Van den Berghe, JASN, March 08
Proteinuria increases AKI Risk
T. Huang, et al. JASN Jan 1, 2011 22: 156-163
Obesity and Risk of Acute Kidney Injury Following Cardiac Surgery
F. T. Billings IV et al. JASN 23:1221-1228, 2012
• Examined body mass relationship between BMI and AKI in 445 patients undergoing cardiac surgery.
• Higher BMI –independently associated with increased odds of AKI
• 26.5% increase per 5 kg/m2 (4.3-53.4%; P-0.02).
• Baseline and intraop F2-isoprostane, and intraop PAI-1 independently predicted AKI
• Obesity independently predicts AKI after cardiac surgery in part through oxidative stress.
Predictive and intraoperative Risk Assessment
Demirjian S, et al. AJKD; 59(3): 382-9, 2012.
Non Dialysis AKI Associates with Increased Long Term Mortality
• .
J-P Lafrance and D. R. Miller J Am Soc Nephrol 21:435-42, 2010
Clinical Risk Assessment: Summary
• Understanding individual risk factors may help in preventing AKI
• Interaction of susceptibility of AKI and type/extent of exposure that determines risk of occurrence of AKI
• Susceptibility factors may be modified• Exposures can be avoided or tailored to reduce risk
• Most patients are seen after exposure-still opportunity for risk assessment – closer monitoring, general support measures
• AKI-recovery may lead to CKD/ESRD• Post AKI monitoring and transition of care is important
Cirrhotic Cardiomyopathy
• 50 ys ago Kowalski and Abel described hyperdynamiccirculation in cirrhotic patients
• Gould 1969 demonstrated cardiac contractile response was depressed in alcoholic cirrhosis, confirmed in several other studies (alcoholic cirrhosis)….alcohol cardiomyopathy?
• Depressed cardiac function due to cirrhosis• -adrenergic receptor density of lymphocytes of patients
• Animal studies confirmed
• Nonalcoholic cirrhosis with blunted cardiac inotropic and chronotropic response to exercise, drugs, hemorrhage, surgery and stress.
• Conduction abnormalities