acute kidney injury chronic kidney disease · • 1909 bright’s disease – a consequence of...
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Acute kidney injury chronic kidney disease
www.imbm.sk
Gross structure and location
Kidney anatomy
Nephron
Nephron
Ultrastructure
µ-structure – the renal corpuscle
µ-structure – tubular segments
µ-structure – tubular segments
Glomerulus
Ultrastructure
2D 3D
Vasculature
Kidney functions
• Excretion(bloodfiltration,reabsorption,secretion)• Homeostasis=minerals,water,pH• Osmolality• Endocrinefunctions
Urine formation
Filtration
Reabsorption,secretion
Useful terms
• Creatinine• Urea/Bloodureanitrogen• Glomerularfiltrationrate• Renalclearance
Creatinine
• Breakdownproductofcreatinephosphate(energyreservoir)• Usuallyproducedatconstantrate(dependingonmusclemass)• Excretedunchangedbythekidneys:• glomerularfiltration-mostly• proximaltubularsecretion–minor
• Littletonotubularreabsorption• 45-90μmol/L(0.5-1.0mg/dL)forwomen;60-110μmol/L(0.7-1.2mg/dL)formen
Urea / Blood urea nitrogen
• Urea–producedintheliverasawasteproductofproteindigestion• BUN–themassofnitrogenwithinurea/volume• Normalrange1.8-7.1mmol/Lurea(6–20mg/dLBUN)• Increasedurea/BUN–decreasedkidneyfunction• Highproteindiet• Hypovolemia• Hemorrhage• Fever• Increasedcatabolism
BUN-to-creatinine ratio
• Todeterminethecauseofacutekidneyinjuryordehydration• Principle:• Bothureaandcreatininearefreelyfilteredthroughglomeruli
• Reabsorptionofurea(notcreatinine)canberegulated(upordown)
BUN:Cr Urea:Cr Location Mechanism
>20:1 >100:1 Prerenal(beforethekidney)
BUNreabsorptionisincreased.BUNisdisproportionatelyelevatedrelativetocreatinineinserum.Dehydrationorhypoperfusionissuspected.
10-20:1 40-100:1NormalorPostrenal(afterthekidney)
Normalrange.Canalsobepostrenaldisease.BUNreabsorptioniswithinnormallimits.
<10:1 <40:1 Intrarenal(withinkidney)
RenaldamagecausesreducedreabsorptionofBUN,thereforeloweringtheBUN:Crratio.
But...
• BUNandcreatininewillnotberaisedabovethenormalrangeuntil60%oftotalkidneyfunctionislost• Therefore,moreaccuratemethodsareuseful
Glomerular filtration rate
• Volumeofbloodfilteredperminute• ml/min/1.73m2• Flowrateoffilteredfluidthroughthekidneys
• EstimatedGFR(eGFR)–serumcreatinine• Sex,age,weight,height,race
Creatinine clearance
• ApproximationofGFR• Volumeofbloodplasmathatisclearedofcreatinineperunitoftime
Estimated clearance
• Basedonserumcreatinineconcentration
Acute kidney injury
• Lossofkidneyfunctionthatdevelopswithin7days• Previously:acuterenalfailure• Widespectrumofinjuries,notjustfailure• Commonincriticallyillpatients• 13-18%ofallpeopleadmittedtohospital
History
• 1802ischuriarenalis• 1909Bright’sdisease–aconsequenceoftoxicagents,pregnancy,burn,traumaoroperations• FirstWW–warnephritis• SecondWW–acutetubularnecrosis• 1951–acuterenalfailure• 2004–acutekidneyinjury
Classification
• RIFLE–risk,injury,failure,loss,end-stagekidneydisease• AKIN–AcuteKidneyInjuryNetworkgroup
Classification
• KDIGO–KidneyDisease:ImprovingGlobalOutcomes
Biomarkers of AKI
Additional diagnosis
• Urinedipstick• Blood• Protein• Leukocytes• Nitrites• Glucose
• Urinemicroscopy• Redcellcasts• Dysmorphicredcells• Tubularepithelialcells
• Ultrasound• Auto-immuneprofile• Biopsy
Urine microscopy
Urine microscopy
Etiology
• Prerenal(55%)• Intrinsic(40%)• Postrenal(5%)
Etiology
• Mostcommoncauses:• Ischemia• Sepsis• Hypovolemia• Drugs
Precipitating factors for AKI
Ischemic AKI
• Themostcommon• Highsusceptibilityofkidneytoischemicinjury• Structuralassociationsbetweenrenaltubulesandbloodvesselsinoutermedulla• vasoconstriction• epithelialinjury(lowATP)–necrosisorapoptosis• activationofinflammatoryprocesses
• Allsegmentsofnephroncanbeaffected,butproximaltubularcellsaremostcommonlyinjured
Consequences of AKI
• Accumulationof• wasteproducts–azotemia(accumulationofnitrogenouscompounds)
• electrolytes–disruptedhomeostasisofwater,mineralsandacid-basebalance
• fluids• Reducedimmunity• Dysfunctionofnon-renalorgans(organcross-talk)
Consequences of AKI
Distal organ injury
Kidney-lung interactions
Cardiorenal syndrome
Hepatorenal syndrome
• Rapiddecreaseinkidneyfunctioninindividualswithcirrhosisorfulminantliverfailure• 1.Alteredliverfunction• 2.Abnormalitiesincirculation–constrictionofvesselsinkidneysanddilationinsplanchniccirculation(intestines)• 3.Kidneyfailure
Therapy
• Fluids–expansionofintravascularvolume• Isotoniccrystalloidsratherthancolloids
• Vasopressors• Norepinephrine,vasopressin
• Hemodynamicmanagement
• Glycemiccontrolandnutritionalsupport• RenalReplacementTherapy• Considerbroaderclinicalcontext,trendsoflaboratorytests
Outcomes after AKI episode
• 1.Fullrecoveryandreturnofrenalfunctiontobaseline• 2.IncompleterecoveryofrenalfunctionresultinginCKD• 3.Exacerbationofpre-existingCKDacceleratingprogressiontoESKD• 4.Non-recoveryofrenalfunctionleadingtoESKD
Animal models of AKI
• Bilateralnephrectomy
• Bilateralischemiareperfusioninjury
• Bilateralureteralligation
• cisplatin,adriamycin,rapamycin,glycerol,folicacid…
Chronic kidney disease
• Progressivelossofkidneyfunctionoveraperiodofmonthsoryears• Previously:chronicrenalfailure• Definition:• Decreasedkidneyfunction-lessthan60ml/min/1,73m2OR
• MarkersofkidneydamageOR• Both• Atleast3monthsduration• Regardlessofcause
Markers od kidney damage
• Albuminuria(albumin:creatinineratio≥30mg/g)• Urinarysedimentabnormality• Electrolyteabnormality• Histologicalabnormality• Structuralabnormalitydetectedbyimaging• Historyofkidneytransplantation
Risk factors
Mortality attributed to CKD
Prevalence of CKD
Clinical manifestation
• Accumulationofnitrogenouswastes(uremia)• neurologicaldisorders(uremicencephalopathy)• uremicfrost
• Mineralbonedisease–disturbedvitaminD,calciumandphosphatemetabolism• Renalhypertension• Anemia• ReducedRBCsurvivalandirondeficiency• Alterationsinwater,acid-baseandelectrolytebalance
Etiology
• Diabetes(30-50%offallcases)• Hypertension
• Glomerulonephritis• Polycystickidneydisease• Chronicpyelonephritis
Diabetic nephropathy
• Majorcomplicationofdiabetes
• Highglucose• Hyperfiltration• Thickeningofbasementmembrane–sclerosis• Mesangioproliferativechanges• Microalbuminuria(30-300mgprotein/day)• Proteinuria
Hypertension
• Causeandconsequenceofkidneydisease
• Changesinglomerularstructures• Damagetobloodvessels• Decreasingfiltrationrate• Increasingbloodvolume
Glomerular vessels
GFR Renalperfusion
AfferentarterioleVasoconstriction
↓
↓
AfferentarterioleVasodilation
↑
↑
EfferentarterioleVasoconstriction
↑
↓
EfferentarterioleVasodilatation
↓ ↑
Diagnosis
• Asymptomaticornon-specificsymptoms:• Lethargy• Itch• Lossofappetite
• Oftenbychancefindings• Screeningtests• Severesymptoms
Complications
• Renalfibrosisasaresponsetoinjury• Replacementoffunctionaltissuebyfibrotictissue
Therapy
• Conservative• dietaryrestriction• BPmanagement
• Renalreplacementtherapy• Hemodialysis(diffusion)• Peritonealdialysis• Hemofiltration(convection–increasedhydrostaticpressure)
• Hemodiafiltration• Kidneytransplantation
Management
• AnnualfrequencyofeGFRtestinginCKDpatients
• BloodpressuretargetinCKDpatients
Animal models of CKD
• 5/6nephrectomy• Unilateralureteralobstruction• Ischemiareperfusioninjury• Alportmice
AKI vs. CKD
• Noindependententities
• AKIisariskfactorforCKD• CKDisariskfactorforAKI• Bothareriskfactorsforcardiovasculardisease
Acute-on-chronic kidney disease
• AKIoccursonthebackgroundofpre-existingCKD• CKDasriskfactorforAKI• Mostcommoncauses:• Systemicinfection• Drugs–diuretics,ACE-inhibitors• Dehydration• Urinarytractobstruction
Questions
• DiagnosisofAKIbasedon• sCrlevelsORurinevolume
• MostcommoncausesofAKIinclude• Ischemia,sepsis,hypovolemia,drugs
• DiagnosisofCKDbasedon• Decreasedkidneyfunction-lessthan60ml/min/1,73m2OR• MarkersofkidneydamageOR• Both• Atleast3monthsduration
• PrognosisofCKDbasedon• eGFRandproteinuria
• TwomajorcausesofCKDare• Diabetesandhypertension
• www.imbm.sk