WorkupandManagementofAcuteKidneyInjury
MatthewRivara,MD,FASNAssistantProfessorofMedicine
DivisionofNephrologyUniversityofWashington
Objectives
1. Reviewcommonandsomeuncommoncausesofacutekidneyinjury(AKI)inhospitalizedpatients
2. DiscusspracticaldiagnosticevaluationforthehospitalizedpatientwithAKI
3. DiscusspreventionandmanagementofselectAKIetiologies
Case1
HPI:• 43y/owomanwithahistoryofchronicHCV,presentstoEDwithabdominalpain,vomitingx3days• Temp38,BP95/60,HR100• Examshowsabdominaltenderness,1+LEedema▫ Receives1literLR,vancomycinandcefepimex1▫ F/uBP105/70àadmittedtomedicine
PMH:• H/owristfracture1yearago,creatinine0.7mg/dL
Laboratory/imagingevaluation
Urinalysis: 1+ RBCs, 1+ protein Urine protein/creat: 0.5 g/g 134
4.2 102
21
20
1.2 94
CBC:WBC14k,Hgb10,Platelets110kHCVviralload:800,000IU/LC3,C4bothlowINR:1.4AST/ALT:110/90Totalbilirubin:2.0mg/dL
Case1,continued
0
0.5
1
1.5
2
2.5
3
0 2 4 6 8 10 12
SERU
MCRE
ATININE(M
G/DL
)
HOSPITALDAY
Trendinserumcreatinine
Vanco level 35
Vanco/cefepime
Whatiscausingthispatient’sAKI?
AcuteKidneyInjury
Pre-renal(lowEABV)
Acutetubularinjury/necrosis
Hepatorenalsyndrome
Acuteinterstitialnephritis
Vancomycinnephrotoxicity
GN/MPGNrelatedtoHepatitisC
“AcuteKidneyInjury"isaclinicalsyndrome
ElevatedCreatinine/DecreasedeGFR Lowurineoutput
KDIGO AKI Guidelines, 2012
UrinarybiomarkersforAKI–NOTYET!
Ostermann M, et al.. Crit Care. 2016.
Tubularfunctionasastresstest
77 patients with AKI who received FST à followed for development of stage 3 AKI, RRT, death FUROSEMIDE OUTPERFORMED URINARY BIOMARKERS FOR ALL OUTCOMES
Koyner et al, JASN, 2015
AKIiscommoninhospitalizedpatients!
Zeng et al, CJASN, 2014
CausesofAKI
Pre-renal Post-renalIntra-renal
• Volume depletion • Cardiorenal syndrome • Hepatorenal syndrome • Abdominal compartment
syndrome • Renal artery occlusion/ • Dissection • Renal vein thrombosis
• Glomerular disorders • Microvascular disorders • Tubulointerstitial Disorders • Acute tubular necrosis
• Ureteral obstruction • Bladder outlet • Obstruction
DecreasedEABV/Renal
veincongestion
Jefferson, Haseley. Comprehensive Clinical Nephrology. Chapter 66, Sixth edition.
CausesofAKI–AnAnatomicApproach
Case2• 20y/omanhospitalizedforvolumedepletionafterreturningfromMexico• Reports5daysof6-10loosestools/day,nausea,poorPOintake• BPis80/50,dizzywithstanding• Creatinine1yearago0.9.
126 4.5
90
16
75
3.5 90
Urine: UNa 8 mEq/L Ucreat: 35 mg/dL Uosm: 560 mOsm/kg Fe Na 0.6% Urine sediment: Bland
CausesofAKIinhospitalizedpatients
Nash et al., AJKD, 2002
55
39
2 4 30
10
20
30
40
50
60
ATN Decrease EABV Obstruction Parenchymal diseases not
ATN
Not classified
%
> 90% of all AKI!
PathophysiologyoflowEABV-relatedAKI
Impairedrenalperfusionà
êGlomerularcapillaryfiltrationpressureàActivationofRAAS
↓GFR, LESS Na filtered
ReninAII
Aldosterone
ADH
1. DecrUvolume~oliguria2. DecrUNa-<10,FeNa<1%(orFEUrea<35%ifondiuretics)
• êRBFàGFR• IncrNa,H20,urea
reasbsorptioninPCT• éAldosteroneàéNa
reabsorption• éADHàéH2O
reabsorption
DecreasedEABVAKI–morethan“pre-renal”
Intravascularvolumedepletion
Hemorrhage
GIorrenallosses
Reducedcardiacoutput
CHF/cardiogenicshock
Pericardialdiseases
Systemicvasodilation
Sepsis
Cirrhosis
Anaphylaxis
RenalVasoconstriction
Hepatorenalsyndrome
Acutehypercalcemia
Drugs–ACEI,NSAIDS,calcineurininhibitors
Pre-renal ATNUOP/hemodynamicsrespondquicklytofluidsifgivenenough
UOP/hemodynamicsdonotrespondtofluids
BUNoutofproportiontoCr BUN/Cr<20:1
UOP<15ml/hrbutnotanuric Canbeanuric
Courseimprovedwithintervention Courseunaffectedbyinterventionprovidedfurtherinsultavoided
Urinesodiumlow(<10meq/L),FeNalow(<1%)
UrinesodiumNOTlow(>20meq/L),FeNanotlow(>2%)
Somecaseshaveconsiderableoverlap
FENa
65%
20-25%
5-7%
2-5%
= Excreted Na Filtered Na = Urine Na x Serum Cr x 100 Serum Na x Urine Cr • FENa <1% prerenal azotemia
• Sensitivity: 90% Specificity: 93%
• FENa > 1% ATN • Sensitivity: 93%
Specificity: 90%
Espinel. JAMA. 1976:236(579-581) Miller et al. Ann Int Med. 1978;89(47-50)
Na
ON DIURETICS? ✔FEUrea
65%
20-25%
5-7%
2-5%
= Excreted Urea Filtered Urea = Urine Urea x Serum Cr x 100 Serum Urea x Urine Cr • Normal FE Urea 50-65 %
• Prerenal Azotemia < 35%
Urea
Urea
What’swrongwithfractionalexcretionmeasures?
Perazella et al. CJASN 2012
• Restorerenalperfusion/treatunderlyingcondition
MANAGEMENT OF PRERENAL AKI
OthercommonlowEABVAKIconditions
Type1cardiorenalsyndrome
Hepatorenalsyndrome(HRS)
CardiorenalsyndromesType1(acute)–AcuteHFresultsinacutekidneyinjuryType2–Chroniccardiacdysfunction(eg,chronicHF)causesprogressiveCKD.Type3–Abruptandprimaryworseningofkidneyfunctiondue,forexample,torenalischemiaorglomerulonephritiscausesacutecardiacdysfunction,whichmaybemanifestedbyHF.Type4–PrimaryCKDcontributestocardiacdysfunction,whichmaybemanifestedbycoronarydisease,HF,orarrhythmia.Type5(secondary)–Acuteorchronicsystemicdisorders(eg,sepsisordiabetesmellitus)thatcausebothcardiacandrenaldysfunction.
MechanismsofCRS
Soni Clinical Queries: Nephrology 2014
Clinicalconundrumwithacutecardiorenalsyndrome,type1
Heartfailureexacerbation
Fluidoverload
Venouscongestion
LowBP
Gentlediuresis?
Aggressivediuresis?
Mechanicalultrafiltration?
Worsevs.improvedkidney
function?
Diureticdosing• DOSE trial • 308 patients with acute decompensated heart failure • Randomized to furosemide IV bolus q12 hours vs. infusion and at either low
dose (equivalent to home oral dose) vs. high dose (2.5x home oral dose) • No difference in the groups
Felker NEJM 2011
Take home message: diuretic dosing is flexible
Ultrafiltration• CARRESS-HF trial • 188 patients with acute decompensated heart failure, AKI and
persistent congestion • Stepped pharmacologic therapy (IV diuretics) vs. ultrafiltration • No difference in weight loss between groups • Higher rate of adverse events and greater increase in Cr in UF group
Bart NEJM 2012
Take home message: diuresis is likely a safer strategy (vs. UF)
HEPATORENAL SYNDROME
Reversiblefunctionalrenalimpairmentthatoccursinpatientswithadvancedliverdisease.
LowGFR
Absenceofshock,currentinfection,fluidlosses,nephrotoxic
drugs
Noimprovementinrenalfunctionafter
diureticwithdrawalandexpansionofvolume
Proteinuria<500mg/d
Noobstruction
Nointrinsicrenaldisease(noATN,no
GN)
Typically IV albumin 1g/kg of body weight x 2 days
PrecipitatingfactorsinHRS
3 interrelated pathways: 1. Splanchnic
vasodilation decreasing EABV
2. Renal sympathetic stimulation
3. Cardiac dysfunction leading to renal hypo-perfusion
Wadei et al, CJASN, 2006
HRSTreatmentIncriticallyillpatients:• NorepinephrineIVtoraiseMAPby10mmHguntilnoresponseorresolutionofAKI(atleast2days)
Innon-criticallyillpatients:• Midodrine7.5-15mgTID• Octreotide100mcg-200mcgTID• Trialx2days
Innon-responders:• ConsiderTIPS(controversial)• Iflivertransplantcandidate,dialysisasbridgetotransplant
Case3• 20y/omanhospitalizedforvolumedepletionafterreturningfromMexico• Reports5daysof6-10loosestools/day,nausea,poorPOintake• BPis80/50,dizzywithstanding• Creatinine1yearago0.9.
126 4.5
90
16
75
3.5 90
Urine: UNa 30 mEq/L Ucreat: 42 mg/dL Uosm: 300 mOsm/kg Fe Na 2%
Case3:urinesediment
WhydoesATNcauseelevatedcreatinine?
Lameire and Vanholder, JASN, 2001
ValueofUrineSediment
Perazella et al. CJASN 2012
ISCHEMIC ATN
• Failure to restore renal blood flow (RBF) during low EABV stage à tubular cell injury.
NEPHROTOXINS AND ATN
Endogenous Exogenous/Drugs Myoglobin(Rhabdomyolysis)Uricacid(TumorLysisSyndrome)Hemoglobin(Hemolysis)
AmphotericinAminoglycosidesCisplatinIfosfamideAcetaminophenSalicyclatesRadiocontrastagents(?)IntravenousimmunoglobulinZolendronateVancomycin
Isvancomycinnephrotoxic?• Isitthis?
• Orisitthis?
Vanco levels Serum creatinine
causality
causality Serum creatinine Vanco levels
Notamenabletorandomizedcontrolledtrial!
Nolin, CJASN 2016
Vancomycinnephrotoxicity
7 randomized and controlled trials N = 4033 6 – vancomycin vs linezolid 1 – vancomycin vs certaroline 6/7 – vancomycin associated with higher risk of AKI
RR 2.45 (95% confidence interval, 1.69 to 3.55)
Ray et al, CJASN 2016
Vancomycinnephrotoxicityasafunctionoftroughlevel
Troughconcentration(mg/L) Toxicity
5–1010.1–1515.1–2020.1–35>35
5%3%11%23%82%
Horey et al. Ann Pharmacother. 2012;46:1477-83
Whatabout“contrastnephropathy?”
• 6,000,000 hospitalized pts; no AKI on admit, LOS < 10 d
• Evaluated for hospital-acquired AKI Contrast No Contrast 5.5% 5.6% (unadjusted)
5.6% 5.1% (adjusted)
Conclusions: “…our analyses suggest that the incremental risk of AKI that can be attributed to radiocontrast is modest at worst, and almost certainly overestimated by patients, physicians, surgeons, radiologists, and other decision-makers.”
Preventionofcontrast-nephropathy
Myapproach:• IfeGFR>45mL/min,nochangeinmanagementwithanyiodinatedcontrastscan• IfeGFR30-45mL/min,USUALLYnochangeinmanagementàevaluateforriskfactorsforAKI• IfeGFR<30▫ Ifcantoleratefluid,give1cc/kg/hrisotonicfluid(NSversusLR)for6hourspre-procedure,andfor6hourspost-procedure▫ DonotgiveNAC,donotwithholdACEI/ARB,statins
• Restorerenalperfusion/treatunderlyingcondition• Avoidfurtherinsultsifpossible;ifdrug-related,withdrawntheoffendingdrug• Manageaccompanyingvolume/electrolyte/acid-baseabnormalities• Adjustrenally–excretedmedstocurrentlevelofkidneyfunction• Watchforuremicmanifestations,orotherindicationsforinitiationofdialysis
MANAGEMENT OF ATN
Obstructivenephropathy,anuncommoncauseofAKI
• Evaluation:▫ Bladderscan,bladdercatheterization▫ Renalu/s
Intrarenalobstruction Ureteralobstruction Bladderoutletobstruction
• Stones • Transitional cell
carcinoma • Clots • Papillary necrosis
• Stones • Transitional cell
carcinoma • External compression
• Tumors • RP fibrosis • Lymph nodes
• BPH • Neurogenic bladder
• Ifrelatedtonephrolithiasis,sometimesureteralstent▫ Sometimesrequiressurgicalintervention• IfBPHàbladdercatheterization• Ifduetobladdermalignancy,orexternalcompression,generallyrequirespercutaneousnephrostomytubeplacement(IRtypically)• Watchforpost-
MANAGEMENT OF OBSTRUCTIVE NEPRHOPATHY
ShouldyougetarenalultrasoundinallAKI?
No,butyoushouldatleastconsider….• Largekidneys-amyloid(otherinfiltrativedisease),AIN,HIV,diabetes• Smallkidneys-likelychronicprocess,unlikelytobenefitfromtreatment• Polycystickidneydisease• Singlekidney• RPstranding/fibrosis• Biopsyconsiderations
Case4• 55y/omanhospitalizedforsepsis,foundtohaveMRSAbacteremia2/2severesofttissueinfection• TreatedwithIVvancomycin• Initiallabs:
134 4.5
100
20
20
1.5 90
Urine: UNa 20 mEq/L Fe Na 1% Urine sediment: dysmorphic RBCs
Creatinine subsequently climbed daily: 1.5 à 1.7 à 2.1 à 2.3 à 2.6 à 2.9
C3: low C4: WNL
DYSMORPHIC RBCS
• NearlyalwaysassociatedwithCONCURRENTstaphinfection• Distinctfrompost-streptococcalGN▫ Post-strepGNoccursAFTERinfection• Canbeaccompaniedbyvasculitisskinrash• Serumcomplementslow▫ LowC3morecommonthanlowC4• Noserologictestavailable;definitivediagnosisrequireskidneybiopsy
INFECTION-RELATED GLOMERULONEPHRITIS
GLOMERULONEPHRITIS/RPGN
SystemicDisease Mechanism Disease
Antibody-mediatedPauci-immuneImmunecomplex
Anti-GBMdiseaseSmallvesselvasculitis(GPA,MPA,Churg-Strauss)LupusnephritisCryoglobulinemia
Laboratory evaluation: Complement levels, ANCA group, anti GBM, ANA with reflexive panel Definitive diagnosis: Kidney biopsy
PrimaryGlomerularDisease Mechanism Disease
Immunecomplex
IgAnephropathyMPGN(HCV)Infection-relatedGN
Clinicalcluesthatshouldpromptnephrologyconsultation
RenalConsult
Nephroticsyndrome
Concernforpulmonary-
renalsyndromes
ConcernforAIN
PersistentoligoanuriawithAKI
Take-homepoints• Urinemicroscopyisasimpleandusefultool▫ Granularcastsàif>6/hpf,likelytobeATN▫ DysmorphicRBCSàthinkaboutglomerularpathology
• >90%ofAKIinhospitalizedpatientsislowEABV(includingpre-renal,cardiorenal,hepatorenal)orATN
• AKIinthecontemporaryhospitalizedpatientcanbemultifactorialwithoverlappingcauses
Questions?
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