DrshahramsajjadiehMD nephrologist IDENTIFICATION Azotemia Uremia or Uremic syndrome ARF hours to days RPRFdays to weeks CRF months to years ID: 776648
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Slide1
Slide2Acute kidney injury
Dr.shahram.sajjadieh.MD nephrologist
Slide3IDENTIFICATION
Azotemia
Uremia or Uremic syndrome ARF (hours to days) RPRF(days to weeks) CRF (months to years)
Slide4ARF
Acute
kidney injury (AKI) or Acute renal failure (ARF)
Abrupt decrease of renal function sufficient to result in: Retention of nitrogenous waste products loss of regulation of extracellular volume and electrolytes Rapid deterioration of renal function (increase of serum cr of >0.3-0.5 mg/dl in <48-72hrs or a percentage increase of >50%)Decreased urine output(<0.5 ml/kg/hr for >6hr) (usually but not always) Oliguria: <400 ml urine output in 24 hours Anuria: <100 ml urine output in 24 hours
Slide5Definition of Acute Kidney Injury (AKI) based on “Acute Kidney Injury Network”
StageIncrease in Serum CreatinineUrine Output11.5-2 times baseline OR 0.3 mg/dl increase from baseline<0.5 ml/kg/h for >6 h22-3 times baseline<0.5 ml/kg/h for >12 h33 times baseline OR0.5 mg/dl increase if baseline>4mg/dlORAny RRT given <0.3 ml/kg/h for >24 hOR Anuria for >12 h
Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve outcomes in
Acute Kidney Injury.
Critical Care
2007; 11: R31.
Slide6RIFLE classification
ARF
Indicator Classes
R
isk
of renal injury Injury to the kidneyFailure of kidney function
Outcome Classes
Loss
of kidney function
E
nd-stage Kidney Disease
Slide7RIFLE classification
GFR/Cr criteriaUrine Output criteriaRiskIncrease in cr x1.5Or GFR decrease >25%UO < 0.5ml/kg/hr for 6hrsInjuryIncrease in cr x 2Or GFR decrease >50%UO < 0.5ml/kg/hr for 12hrsFailureIncrease in cr x 3Or GFR decrease >75%UO < 0.3ml/kg/hr for 24 hrs or Anuria for 12hrsLossPersistent ARF = complete loss of renal function > 4 weeksESRDEnd Stage Renal Disease > 3 months
Slide8ARF
8
Median hospital length of stay stratified by single acute organ system dysfunction, including ARF
Slide9Mortality
Dialysis requiring = 40-90%
Increased mortality even in patients not requiring dialysis
25% increase in creatinine associated with a mortality rate of 31% compared with 8% for matched patients without renal failure
Slide10Non-Oliguric vs. Oliguric vs. Anuric
Oliguric renal failure.
Functionally, urine output less than that required to maintain solute balance (can’t excrete all solute taken in).
Defined as urine output < 400ml/24hr.
Anuric renal failure.
Defined as urine output < 100ml/24hr.
Less common – suggests complete obstruction, major vascular catastrophy, or more commonly severe ATN.
Slide11Non-Oliguric vs. Oliguric vs. Anuric
Classifying by urine output may help establish a cause.
Oliguria – more common with obstruction, prerenal azotemia
Nonoliguric – intrarenal causes – nephrotoxic ATN, acute GN, AIN.
More importantly, assists in prognosis.
Significantly higher mortality with oliguric renal failure.
80% vs. 25% mortality in Oliguric vs. non-oliguric ARF
Nonoliguric renal failure may also suggest greater liklihood of recovery of function.
Slide12ARF
12
Etiology of ARF
Slide13ARF
Prerenal
Azotemia 55% Renal 40% ATN 90%(Ischemic , nephrotoxic)AINAGN or Vasculitis Acute Renovascular DiseaseMicrovascular (HUS_TTP, atheroemboli)Post renal 5% Admission in wards ~ 5% Admission in ICU ~ 30%
Slide14Useful Features That Suggest CRF or ARF
Chronic Hx of:
Nocturia, polyuria, edema or hematuria
Pruritus, neuropathy, impotence, other uremic symptoms
Underlying predisposing illness (DM, HTN)
Slide15Useful Features That Suggest CRF or ARF (cont.)
Objective Findings:
Bilateral Small Kidneys
Renal OsteoDystrophy
Band keratopathy
Carbamylated Hemoglobine
Slide16Useful Features That Suggest CRF or ARF (cont.)
Less reliable:
Anemia
Hypocalcemia
Hyperphosphatemia
Slide17Differentiation between ARF and CRF
AcuteChronicHistoryShort (days-weeks)Long (month-years)Hb concentrationNormalLowRenal sizeNormalReducedRODAbsentPresentPeripheral neuropathyAbsentPresentSerum CrAcute reversible increaseChronic irreversible
Slide18Epidemiology
Prevalence
1-5% all patients admitted to hospital
10-30% patients admitted to ICU
Etiology
Hemodynamic 30%
Parenchymal
65%
Acute tubular necrosis 55%
Acute
glomerulonephritis
5%
Vasculopathy
3%
Acute interstitial nephritis 2%
Obstruction 5%
Slide19Clinical Approach to Acute Renal Failure
Slide20AKI: Diagnostic studies-urine
Urinalysis for sediment, casts
Response to volume repletion with return to baseline SCr 24-72 hr c/w prerenal event
Urine Na; FENa
FENa (%) =
UNa x SCr
x 100
SNa x UCr
FENa < 1%: Prerenal
FENa 1-2%: Mixed
FENa > 2%: ATN
Hansel’s stain
Slide21BUN/Creatinine ratio.
> 20:1 – suggest prerenal or obstruction.
Can be elevated by anything leading to increased urea production/absorption.
GI bleed
TPN
Steroids
Drugs – Tetracycline.
Creatinine in anephric state typically only rises 1mg/dl/day.
If greater – should be concerned for rhabdomyolysis
Slide22ATN vs. Prerenal Azotemia
Indices Prerenal ATN
UNa < 20 > 40
FeNa < 1% > 1%
U/PCreat > 40 < 20
Slide23Confounding Variables in the Diagnosis of Pre-renal Azotemia versus ATN
A low urine Na can also be seen in:
Contrast induced ATN
Early ATN or obstruction
Acute Glomerulonephritis and Nephrotic Syndrome
Diuretics can elevate the urine Na
Jaundice may induce “muddy brown” cast formation
Slide24Urinalysis in Acute Kidney Injury
Prerenal
PostrenalAKI
GlomerulopathyVasculitisThrombotic MA
PyelonephritisInterstitial nephritis
AINAthero-embolic AKI
ATNMyoglobinHemoglobin
Uric acidToxinsDrugs
Plasma cell dyscrasia
HematuriaRBC castsproteinuria
WBCWBC casts
Eosinophils
RTE cellsPigmentedcasts
Crystalluria
Non-albuminproteinuria
Abnormal sediment
Normal/bland
Slide25Urinary Sediment Findings in Intra-Renal Acute Renal Failure
Intra-renal Acute Renal Failure
Dysmorphic Hematuria
Red cell casts
Oval fat bodies
Fatty Casts
Muddy brown castsRenal tubular epithelial cells and casts
White cellsWhite cell castsEosinophiluria
GlomerulonephritisAtheroembolic diseaseThrombotic microangiopathy
Minimal change diseaseFocal segmental glomerulosclerosis
Albuminuria
Tubular proteinuria
Tubular epithelial
injury
-Ischemic
Nephrotoxic
Interstitial nephritis
Urinary tract
infection
Crystalluria
Drug toxicity
Urate crystals
-Urate nephropathyCalcium oxalate crystals -ethylene glycol
Slide26ARF
Clinical feature of ARF
Symptoms and/or signs of RF:Weakness and easy fatiguability (from anemia), Anorexia Vomiting Mental status changes or SeizuresEdema,…Systemic symptoms and findings:Fever, arthralgias, pulmonary lesions
Slide27ATAPOUR
Slide28Acute Kidney Injury
Prerenal Azotemia: - fall in GFR secondary to renal hypoperfusion that potentially has rapid reversible component with restoration of effective intravascular volume or perfusion pressure.
Slide29Syndromes of Renal Hypoperfusion
Pre renal A.
ACN
ATN
Intermediate syndrome
Slide30Syndromes of Renal Hypoperfusion
Postulated Major Pathologic MechanismSyndromeGFR(ml/min)PreventabilityCortical hypoperfusionPrerenal Azotemia40-100ImmediateMedullary hypoperfusionIntermediate syndrome20 - 60Within 1–3 daysMedullary ischemiaATN0 - 25Within 1–3 weeksCortical ischemiaACN0 - 5Unpredictable
Slide31ARF
Pre-renal AKI
Volume depletion Renal losses (diuretics, polyuria) GI losses (vomiting, diarrhea) Cutaneous losses (burns,…) Hemorrhage Decreased cardiac output HF Pulmonary embolus Acute MI Severe valvular heart disease Abdominal compartment syndrome (tense ascites)
Slide32Conditions that Lead to Pre-renal Acute Renal Failure
Generalizedor Localized Reduction in Renal Blood Flow
Ischemic Acute Renal Failure
Intravascular Volume Depletion
Decreased Effective Circulating VolumeCHF Cirrhosis Nephrosis
MedicationsCsA, TacrolimusACE inhibitors NSAIDSRadiocontrast Amphotericin BAminoglycosides
HepatorenalSyndrome
Sepsis
Large-vessel Renal Vascular Disease Renal Artery Thrombosis Renal Artery Embolism Renal Artery Stenosis or Crossclamping
Small-vessel Renal Vascular Disease Vasculitis Atheroemboli Thrombotic Microangiopathies Transplant Rejection
Slide33Slide34ARF
Acute
Tubular Necrosis(ATN)
Most common cause of intrinsic cause of ARFOften multifactorialIschemic ATN:Hypotension, sepsis, prolonged pre-renal stateNephrotoxic ATN:Contrast, Antibiotics, Pigments, heme protein,…
Slide35Course of Ischemic ATN
Prerenal AzotemiaATNInitiationExtensionMaintenanceRecovery
ARF
Slide36Phases of Ischemic Epithelial Tubular Injury
Time
GFR
Pre-renal
Initiation
Extension
Maintenance
Recovery
Slide37ATN - Pathophysiology
Initiation (hours to days) GFR due to: Renal blood flowObstruction of tubules by castsBack leak of filterate
ARF
Slide38ATN - Pathophysiology
2. Extension:Continued ischemic injury & inflammation Cellular apoptosis/necrosis /sloughing Disruption of normal epithelial integrityAbnormal tubular functionLuminal obstructionCapillary sloughing and worsening ischemia
ARF
Slide39ATN - Pathophysiology
3. Maintenance (1-2 weeks)Release of vasoactive mediators from injured endothelial cellsCongestion of medullary blood vesselsReperfusion injury induced by reactive oxygen species & inflammatory mediators release by leukocytes & parenchymal cellsTubuloglomerular feedback
ARF
Slide40ATN - Pathophysiology
4. RecoveryTubular epithelial cell repair and regeneration gradual return of GFR toward premorbid levels
ARF
Slide41Slide42Urine Indices Used in the
D.Dx of Prerenal & Intrinsic Azotemia
Diagnostic Index
Prerenal
Azotemia
Intrinsic
Azotemia
Urine SG
>1.018
<1.012
Urine Osmolality
> 500
< 250
BUN / Cr
>20
<10 - 15
Urinary Na conc
.(mEq/l)
<10
>20
Fractional Excretion of Na(%)
UNa×Pcr×100 / PNa×Ucr
<1
>1
Urine sediment
Hyaline casts
Muddy brown granular casts
Slide43ATN and Mortality
Rising RIFLE class associated with increasing mortalityPatients who are treated with RRT still have a mortality of 50-60%
ARF
Slide44Risk Factors for Ischemic Tubular Injury
Volume depletion
Aminoglycosides
Radiocontrast
NSAIDs, Cox-2 inhibitors
Sepsis
Rhabdomyolysis
Preexisting renal disease
HTN
Diabetes mellitus
Age > 50
Cirrhosis
Slide45ARF
Slide46ARF
Post-renal AKI
Ureteric obstruction
Stone, Clot,… Ligation during pelvic surgery Bladder neck obstruction BPHNeurogenic bladder Drugs (TCA, ganglion blockers) Stone disease, hemorrhage/clot Urethral obstructionStrictures, Clot,…
Slide47Slide48Sepsis and AKI
Sepsis accounts for nearly 50% of all causes of AKICombination of FactorsImmunologicalToxicInflammatoryEffect renal microvasculature and Tubular cells
ARF
Slide49Tubulointerstitial Nephropathy
Definition
:
A group of clinical disorders that affect principally the renal tubules and
interstitium
with relative sparing of
glomeruli
and renal vasculature
Classification:
AIN
CIN
Slide50Acute Interstitial Nephritis
AIN is a clinicopathologic syndrome of:
ARF
Associated with interstitial edema and cellular infiltrate
Etiology
Idiopathic
Secondary
Slide51Acute Interstitial Nephritis
10-20% of pts with ARF who have had a renal biopsy have AIN
Slide52Acute Interstitial Nephritis
Etiology( Secondary):DrugsAntibiotics, NSAIDs, Allopurinol, Diuretics,…Systemic infectionsLegionnaires disease, Leptospirosis, Strep, CMV,…Primary Renal InfectionsAcute bacterial pyelonephritisReflux nephropathyImmune disordersSLE, Sjogrens syndrome,…
Slide53Acute Interstitial Nephritis-Etiology
Allergic/Drug induced
Autoimmune
Sarcoid ,SLE ,Sjogren’s
Toxins
Chinese herb nephropathy
Heavy metals
Light chain cast nephropathy
Infiltrative
Leukemia ,Lymphoma
Infections (Legionella, CMV, HIV, Toxoplasma)
Slide54Acute Interstitial NephritisClinical Presentation
Non-oliguric ARF
Fever in allergic and infectious types (except NSAID type)
Rash in allergic type (except NSAID induced)
Eosinophilia
UA: WBC casts
Eosinophiluria (allergic)
Lumphocyturia (NSAID related)
Slide55Acute Kidney Injury: AIN causes
DRUGSACEIAllopurinolCephalosporinsCimetidineFluoroquinolonesLoop diueticsNSAIDSPCNPhenytoinRifampinSulfonamidesTegretolThiazides
INFECTION
Bacterial
Agents causing pyelonephritis
Legionella
Brucella
Yersinia
Viral
Hantavirus
HIV
CMV,EBV,HSV
Slide56Pathophysiology – drug induced AIN
Drug-induced AIN
is secondary to immune reaction
AIN occurs only in a small percentage of individuals taking the drug
AIN is not dose-dependent
Association with extrarenal manifestations of hypersensitivity
Recurrencence after re-exposure
Slide57NSAID versus Beta-lactam AIN
Beta-lactam NSAID
Duration of exposure 2 weeks 5 months
Fever/rash/eosinophilia 80% 20%
Eosinophiluria 80% 15%
> 3 gm proteinuria < 1% 83%
Rate of recovery Fast Slow
Chronic renal failure Rare Common
Benefit of steroids Probably Probably not
Slide58Laboratory Findings in AIN
Acute rise in plasma
cr
Eosinophilia
Sterile
pyuria
Positive Hansel stain (>1% total WBCs are
eosinophil
)
Active urine sediment with: WBC, RBC, and WBC casts
Normal or mildly increased protein excretion (usually no more than 1g/day)
Renal tubular acidosis
Slide59Clinical features of AIN
ARF
Hypersensitivity reaction (fever, skin rash, peripheral eosinophilia, and artheralgia)
Hypertension and edema are uncommon
Hematuria, sterile pyuria, leukocyte casts
Eosinophiluria
Mild to moderate proteinuria (< 1gr/day)
Electrolyte abnormalities (hyperkalemia, RTA, renal sodium wasting
Slide60Eosinophiluria
Other
conditions
associated with
Eosinophiluria
Prostatitis
RPGN
Bladder Cancer
Renal
Atheroembolic
disease
Slide61Diagnostic Studies
CBC
Urinalysis
Hansel stain
Renal ultrasound
Gallium scan
Gold standard is renal biopsy.
Indications are:
Uncertainty of diagnosis
Advanced RF
Lack of spontaneous recovery after cessation of offending drug
If
immunosupressive
therapy is considered
Slide62Treatment of AIN
Discontinue offending agent!!
Most cases improve spontaneously
Prednisone (1mg/kg/day) for minimum of 1-2 weeks
Much less commonly used
Mycophenylate
mofetil
Cyclosporine
Cyclophosphamide
Slide63Heme pigment-induced acute tubular necrosis
Myoglobinuria: rhabdomyolysis.
Hemoglobinuria: intravascular hemolysis.
Slide64Heme pigment-induced acute tubular necrosis
The urine may have a low FENa despite tubular injury.
Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria or hemoglobinuria.
Heme-pigmented granular casts.
Plasma is normal color in myoglobinuria and red brown in hemoglobinuria.
Slide65Crush Syndrome: Pathophysiology
Resultant effects of derangements due to rhabdomyolysis and reperfusionPotassium Hyperkalemia ArrhythmiasCalcium Hypocalcemia ArrhythmiasPhosphate Hyperphosphatemia Renal damage Myoglobin Myoglobinemia Renal damageFluid shifts Hypovolemia Renal failureReperfusion Free radicals Renal damagePurines Hyperuricemia Renal damageHypoxemia Lactic acid AcidosisThromboplastin Complement system DICCreatinine Elevated serum levelsSodium Hyponatremia
ARF
Slide66Crush Syndrome:outcome
Delay in treatment associated with greater morbidity and mortality50% renal failure at 6 hours100% renal failure at 12 hoursRhabdomyolysis induced renal failure has 40% mortality
ARF
Slide67Entrapped Patient Treatment
Fluid resuscitation before victim extricated1 L NS bolus, followed by 1-1.5 L per hour Limb stabilizationMinimize potential systemic effects of reperfusion Use of tourniquets prior to releaseAlkalinization by giving 1 ampule of sodium bicarbonate (50 mEq) immediately prior to extrication, followed by adding 1 ampule of sodium bicarbonate to each liter of NS infused at 1-1.5 L per hour keep second IV line open without sodium bicarbonate
ARF
Slide68Hemolysis
Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure.
Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency.
Slide69Slide70Common Nephrotoxic Agents
Antimicrobial agentsAminoglycosidesAmphotericin BAcyclovirFoscarnetPentamidineChemotherapeutic agentscisplatinmitomycin Cstreptozocin
Vasoactive drugs
NSAIDS
ACE inhibitors
CSA and tacrolimus
Radiocontrast agents
Slide71Aminoglycoside Nephrotoxicity
Generally presents 1 week after exposure
Non-oliguric
Low trough levels do not guard against nephrotoxicity
Incidence of ATN
10% after 1 week
40% after 2 weeks
Risk factors for ATN
Advanced age - Superimposed sepsis
Liver disease - Hypotension
Slide72Radiocontrast-Induced Acute Renal Failure
Induces renal vasoconstriction and direct cytotoxicity via oxygen free radical formation
Risk factors:
Renal insufficiency - Diabetes
Advanced age - > 125 ml contrast
Hypotension
Usually non-oliguric ARF; irreversible ARF rare
Slide73Contrast Induced Nephropathy(CIN)
Assess CIN risk
eGFR <30 – Hospital admission, Nephrology consult, Dialysis planning, renal protection
eGFR 30-59 – Discontinue NSAIDs, IV volume expansion, Intra-arterial: isoosmolar, Intra-venous: iso-osmolar or low osmolar contrast; limit contrast volume
eGFR >60, Discontinue metformin
Optimal Volume Status
Low-osmolality contrast media
F/U Creatinine 24 – 72hr after contrast exposure
Adequate IV volume expansion with isotonic crystalloid for 3 – 12hr before the procedure and continue for 6 – 24hr afterward. Oral fluid data is insufficient
No adjunctive medical or mechanical treatment has been proved to be efficacious
Prophylactic hemodialysis and hemofiltration not validated
Slide74Prevention of Radiocontrast Nephropathy
Intervention
Strength of EvidenceClarity of Risk-BenefitGrade of RecommendationVolume expansion with normal salineGoodClearA: Intervention is always indicatedand acceptableVolume expansion with sodium bicarbonateFairClearB: Intervention may be effective and is acceptableIso-osmolar contrastFairClearB: Intervention may be effective and is acceptableTheophyllineFairUnclearC: May be considered; minimal orno relative impactN-acetylcysteineGoodUnclearC: May be considered; minimal orno relative impactHemofiltrationFairUnclearI: Insufficient evidence to recommend for or againstFenoldopamGoodUnclearD: Not usefulHemodialysisGoodUnclearD: Not useful
Slide75Acute Renal Failure due toIntratubular Obstruction
Crystalluria
Ethylene glycol: Calcium oxalate
Tumor lysis: Urate and Calcium phosphate
Medications
Acyclovir
Methotrexate
Sulfonamides
Anti-retroviral agents
Myeloma cast nephropathy
Slide76Acute Urate Nephropathy
Acute
oliguric
renal failure associated with
urate
levels > 18 mg/dl
Associated with overproduction and excretion of
urate
in patients undergoing chemotherapy or with a heavy tumor burden
Urine
urate
/
creatinine
>
1
Prevention:
allopurinol
600-900 mg/d + NS (
uo
> 2.5 l/d)
Urinary
alkalinization
may worsen calcium phosphate precipitation and NS is as effective as urinary
alkalinization
alone
Early dialysis indicated for
oliguric
ARF to decrease
urate
burden
Slide77Renal Disease Associated with Multiple Myeloma
Myeloma cast nephropathy
direct precipitation of casts in tubules
Factors favoring cast precipitation:
-affinity of light chains for Tamm-Horsfall protein
-high luminal Cl
-
-volume depletion
Plasmapheresis may be beneficial
Hypercalcemic nephropathy
Glomerular lesions (MPGN, Amyloid, Light chain deposition disease)
Slide78Slide79AKI: Glomerulonephritis (RPGN)
Immune-Complex MediatedSLECryoglobulinemic vasculitisHenoch-Schönlein purpuraPost-strep GNDirect Ab attackAnti-GBM diseaseGoodpasture’s syndrome
Pauci-immune vasculitis
Microscopic polyangiitis
Wegener’s granulomatosis
Churg-Strauss syndrome
Thrombotic Microangiopathy
TTP
HUS
Scleroderma renal crisis
Preeclampsia
Malignant hypertension
Slide80Acute Glomerulonephritis (RPGN)
Accounts for a minority of AKI: ~5%
May have severe morbidity, mortailty
Extra-renal manifestations may be present
Pulmonary
Dermal
GI
Hematologic
HTN may be present, especially in absence of prior Hx
UA: differentiates from ATN, AIN
Dysmorphic RBC, RBC casts, proteinuria > 0.5gm/24h
Serologies, complement activation
Need for specific therapy to reduce Ab critical towards attenuating/reversing AKI
Slide81Acute Glomerulopathies
RPGN most commonly seen with:
Lupus nephritis (DPGN, class IV)
Pauci-immune GN (ANCA associated)
Anti-GBM disease
less commonly: IgA, post-infectious
Nephrotic presentations of ARF
Collapsing FSGS (HIV nephropathy)
Minimal change disease with ATN
Thrombotic microangiopathies (HUS, TTP, malignant hypertension, scleroderma kidney, pre-eclampsia)
Slide82Atheroembolic Renal Disease
ARF in patient with erosive atherosclerosis
Often follows aortic manipulation (angiography, surgery, trauma) or anticoagulation
Pattern is often an acute worsening of renal function due to showering of emboli, followed by more insidious progression over several weeks to months due to ongoing embolization of atheromatous plaques
Livedo reticularis
Nephritic sediment, eosinophilia, eosinophiluria, low C3
Poor prognosis
Slide83Livedo reticularis
Patient with lupus and anti-phospholipid antibodies with livedo reticularis (manifested by a reddish-cyanotic, reticular pattern of the skin) which has resulted in ulcer formation (arrows). Courtesy of Samuel Moschella, MD.
Slide84Hollenhorst plaque (cholesterol cyrstal, arrow) in retinal artery
Reproduced with permission from: Digital Reference of Opthalmology, Edward S. Harkness Eye Institute, Columbia University, NY.
Slide85Hepatorenal SyndromeMajor Criteria
Chronic or acute liver disease with advanced hepatic failure and portal hypertension
Low GFR, as indicated by a serum creatinine >1.5 mg/dL or a creatinine clearance < 40 mL/min
Absence of shock, ongoing bacterial infection, fluid loss, and current or recurrent treatment with nephrotoxic drugs. Absence of gastrointestinal fluid losses (repeated vomiting or intense diarrhea) or renal fluid losses (as indicated by weight loss > 500 gm/d for several days in patients with ascites without peripheral edema or > 100 gm/d in patients with peripheral edema)
No sustained improvement in renal function (decrease in serum creatinine to 1.5 mg/dL or less or increase in creatinine clearance to 40 ml/min or more) after withdrawal of diuretics and expansion of plasma volume with 1.5 L of isotonic saline
Proteinuria < 500 mg/d and ultrasonographic evidence of obstructive uropathy or parenchymal renal disease.
Slide86Hepatorenal syndromeMinor Criteria
Urine volume < 500 mL/day
Urine sodium < 10 mEq/L
Urine osmolality > plasma osmolality
Serum sodium concentration < 130 mEq/L
Slide87Other AKI….
Abdominal Compartment Syndrome
Presence of IAP >20 that is associated with a single or multiple organ system failure. Causes severe oliguric or anuric renal failure. Tx: surgical decompression.
Acute Phosphate Nephropathy
AKI from Nephrocalcinosis after use of oral sodium phosphate (phospho soda) for colonoscopy.
Orlistat associated AKI
AKI from Oxalate nephropathy due to enhancing oxalate absorption with increased urinary excretion.
IVIG associated AKI
AKI from osmotic nephrosis from sucrose-containing formulation.
Herbal, Home remedies
Arsenal X, Chromium picolinate, Chineses Herb Xi Xin with aristolochic acid; tea from Mouring Cypress, Snake gallbladder, Star fruit (oxalate), Ma Huang (ephedra), Noni Juice
Slide88Slide89ARF
Diagnosis
BUN and serum crCBC, peripheral smear, serologyUrinalysisUrine electrolytesU/S kidneysSerology: ANA,ANCA, Anti DNA, HBV, HCV, Anti GBM, cryoglobulin, CK, urinary Myoglobulin
Slide90Ranges of Biochemical Abnormalities in ARF
Daily rise in Noncatabolic & NonoliguricCatabolic & OliguricBUN (mg/dl)10 – 2020 -100Cr (mg/dl)0.5 – 1> 2K (mEq/l)< 0.51 – 2 (more) Hco3 (mEq/l)< 1> 2
Slide91Diagnosis
Urinalysis
Unremarkable in pre and post renal causesDifferentiates ATN vs. AIN. vs. AGNMuddy brown casts in ATNWBC casts in AINRBC casts in AGNHansel stain for Eosinophils
Slide92ARF
Diagnosis
Urinary Indices; UNa x PCr FENa = —————— x 100 PNa x UCr FENa < 1% (Pre-renal state)May be low in selected intrinsic causeContrast nephropathyAcute GNMyoglobin induced ATNFENa > 1% (intrinsic cause of ARF)
Slide93Urine Indices Used in the
D.Dx of Prerenal & Intrinsic Azotemia
Diagnostic Index
Prerenal
Azotemia
Intrinsic
Azotemia
Urine SG
>1.018
<1.012
Urine Osmolality
> 500
< 250
BUN / Cr
>20
<10 - 15
Urinary Na conc
.(mEq/l)
<10
>20
Fractional Excretion of Na(%)
UNa×Pcr×100 / PNa×Ucr
<1
>1
Urine sediment
Hyaline casts
Muddy brown granular casts
Slide94ARF
Diagnosis
Laboratory Evaluation:Scr, More reliable marker of GFRFalsely elevated with Cimetidine,….small change reflects large change in GFRBUN, generally follows Scr increaseElevation may be independent of GFRSteroids, GIB, Catabolic state, hypovolemiaBUN/Crratio> 20:1 suggests prerenal cause
Slide95Diagnosis
Indications for Renal Biopsy in AKI:Acute nephritic syndromeHematuria, cellular casts, proteinuria in setting of new-onset or exacerbation of HTN, rising SCrMay also have serologic (+) i.e. ANA, ANCA, aGBM that tissue dx also provides treatment options and prognosisUnexplained AKIUncertain or multiple competing ddx, of which treatment differs greatly with definitive dx; AIN vs ATN Young pts with AKI often are considered based on long-term renal survival outcomes maximized with definitive dx
ARF
Slide96ARF
-
+
Slide97ARF
Slide9898
Differential diagnosis of acute renal failure
Slide9999
Slide100WBC (Pyuria)
Slide101101
Slide102RBC Cast
Slide103ARF
Slide104104
Slide105Slide106106
Slide107Hydronephrosis
Slide108Normal Renal Ultrasound
Slide109Hydronephrosis
Slide110Hydronephrosis
Slide111Prevention of ARF
Strategies that are likely to be effectiveIsotonic hydration (IV route)Once-daily dosing of aminoglycosidesUse of lipid formulations of amphotericin BUse of iso-osmolar nonionic contrast mediaStrategies of unknown efficacyNACTheophyllineLow-dose recombinant ANP (in cardiac surgical patients)Strategies that are not effectiveLoop diureticsDopamine and dopamine receptor agonistsANPsProphylactic hemofiltration
Slide112Can We Prevent AKI?
The best approach to post-ischemic ATN is to prevent its development. 1. Identify persons at high risk for AKI, such as:CKDAtherosclerosisDMAdvanced malignancyPoor nutrition
Slide113Can We Prevent AKI?
2. Identify settings in which patients are subjected to procedures that may induce post-ischemic ATN:Major surgery particularly:Cardiac surgeryAbdominal aortic aneurysm surgerySurgery to correct obstructive jaundiceSepsisMarked hypovolemiaSevere pancreatitis
Slide114Can We Prevent AKI?
In patients at increased risk or early in the ischemic phase non-pharmacologic interventions are suggested, including:Optimizing volume status with IV fluidsMaintenance of adequate hemodynamic status to ensure renal perfusionAvoidance of further injury by removing or decreasing the effect of any nephrotoxins
Slide115Compounds for Prevention of AKI
DiureticsLoop diureticsMannitolDopamineFenoldopameANPAdenosine AntagonistsIntensive insulin therapy
Slide116Compounds for Prevention of AKI
Amino acids (Glycine and Alanine)Antiapoptotic/necrosis agentsMinocyclineGuanosinePifithrin-alphaPoly ADP-ribose polymerase (PARP) inhibitor [5-aminoisoquinolinone (5-AIQ)]
Slide117Compounds for Prevention of AKI
Free radical scavengers DeferoxaminePyruvateGrowth factors ErythropoiethineHGF IGF-1
Slide118Compounds for Prevention of AKI
Vasodilators Tezasartan, a dual ET-1 receptor antagonistHeme oxygenases (Hos)Anti-inflammatory drugs Anti-ICAM-1 antibodies and synthetic RGD peptides (arginine-glycine-aspartic acid)StatinsEnhancing tubular cell regeneration by infusion of stem cells
Slide119Compounds for Prevention of AKI
AntioxidantsOther compounds:Neutrophil gelatinase-associated lipocalinIL-6 and C5a antagonistsIL-10 Ghrelin (a compound with a GH releasing effect)
Slide120Diuretics
Diuretics should NOT be administered as prophylaxis for post-ischemic ATN
Slide121Is there a role for Dopamine in Prevention of AKI?
Clinical Outcomes:No effect on mortalityNo effect on the need for or incidence of RRTRenal Physiologic Outcomes:Diuretic effect and increased cr clearance on the first day which was not significant on the following days.Adverse effect:on the immune, respiratory, and endocrine system.
Slide122Potential risks associated with even low dose dopamine
TachycardiaArrhythmias (particularly among cardiac surgery patients)Myocardial ischemiaIntestinal ischemia (due to precapillary vasoconstriction)
Slide123Is there a role for Fenoldepam in prevention of AKI?
Dop-1 receptor agonist, lack of Dop-2, and a-1 receptor effect, make it a potentially safer drug than Dopamine!Reduces in hospital mortality and the need for RRT in AKIReverses renal hypoperfusion more effectively than renal dose DopamineSo far so good specially in cardiothoracic ICU patients
Slide124Is there a role for ANP in prevention of AKI?
ANP is a 28 AA polypeptide synthesized in cardiac atrial muscle.ANP augments GFR by:Afferent arteriolar vasodilatationInhibit the RASInhibits Na transport & lowers oxygen requirements in several nephrone segments ANP analog: Anaritide
Slide125Is there a role for ANP in prevention of AKI?
ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases hypotension and arrhythmias.
Slide126Adenosine Antagonists (Theophylline)
Adenosine, in contrast to its general systemic effect as a vasodilator, is a renal arterial vasoconstrictor.Increases afferent arteriolar tone in response to increased distal tubular solute delivery. Acts synergistically with Ang II to constrict afferent arterioles.Possible mediator of the intrarenal hemodynamic changes that lead to ATN following radiocontrast administration.
Slide127Adenosine Antagonists (Theophylline)
Patients who received theophylline had a smaller increase in serum cr . It remains unclear if theophylline might be useful preventing contrast nephropathy in some patients.
Slide128Mannitol
Currently no evidence of protective effectCauses an osmotic diuresis with may benefit fluid balanceIncreasing flow through tubules, preventing obstructionOsmotic action, decreasing endothelial swellingDecreased blood viscosity with increased renal perfusion (???)Free radical scavenging
ARF
Slide129Prevention of ARF
Strategies that are likely to be effectiveIsotonic hydration (IV route)Once-daily dosing of aminoglycosidesUse of lipid formulations of amphotericin BUse of iso-osmolar nonionic contrast mediaStrategies of unknown efficacyNACTheophyllineLow-dose recombinant ANP (in cardiac surgical patients)Strategies that are not effectiveLoop diureticsDopamine and dopamine receptor agonistsANPsProphylactic hemofiltration
Slide130Novel biomarkers
Neutrophil Gelatinase-Assoc. Lipocalin (NGAL)Levels in blood and urine rise within a few hours after injuryCystatin CAbsorbed by kidney, but not secretedRises one day before CrInterleukin 6&18Produced by caspase-I which is implicted in pathogenesis of ARFKIM-1
Have been shown to predict AKI severity in post-op hearts
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Slide132Myths
FrusemideTheoretically may reduce tubular injuryDue to shutting down Na/K/Cl ATPase Reduces oxygen demandMay help with fluid balanceReduced energy consumption in the critical outer medulla (by 45% in-vitro)Wash out tubular debrisButNo clinical evidenceAccumulates in OliguriaNephrotoxic and OtotoxicMay actually increase mortality and or need for RRT
ARF
Slide133Myths
DopamineLow dose Dopamine (2-3µg/kg/min), known as “renal dose”No effect on mortality or need for Renal replacement therapy
ARF
Slide134Myths
Vasopressors and AKIAlthough Noradrenaline causes vasoconstriction with renal vasculatureNo evidence of worsening AKIBut should be used after adequate volume resuscitation
ARF
Slide135Myths
MannitolCurrently no evidence of protective effectCauses an osmotic diuresis with may benefit fluid balanceIncreasing flow through tubules, preventing obstructionOsmotic action, decreasing endothelial swellingDecreased blood viscosity with increased renal perfusion (???)Free radical scavenging
ARF
Slide136Myths
ANP
Improve renal function and decrease renal insufficiencyTheophylineAdenosine antagonist – prevents reduction in GFR.Growth FactorsAfter ischemic insult, infusion of IGF-I, Epidermal GF, Hepatocyte GF improved GFR, diminished morphologic injury, diminished mortalityNone of these things are well tested….
ARF
Slide137ARF - Prevention
Maintenance of blood flowCardiac output, isovolemia, etcAvoidance of toxinsAminoglycosides, amphoteracin, NSAIDs,…Dose adjustment of drugsEasy on paper….difficult in practice
ARF
Slide138Treatment
Prevent it in the First Place!!Treat / Remove the CauseRestore adequate circulating VolumeRestore adequate blood pressureRestore adequate flowControl fluid intakeWait, Patience is a virtue!Renal replacement therapy
ARF
Slide139ARF - Management
Nutrition managementInitially very catabolicGoals:Adequate caloriesLow proteinLow K and PhosphateDecreased fluid intake
ARF
Slide140Indication of dialysis in Acute Renal Failure
Slide141Indications of dialysis in ARF
Severe fluid overload
Refractory hypertension
Uncontrollable hyperkalemia
Nausea, vomiting, poor appetite, gastritis with hemorrhage
Progressive uremic encephalopathy (l
ethargy, malaise, somnolence, stupor, coma, delirium, asterixis, tremor, seizures)
Pericarditis (risk of hemorrhage or tamponade)
bleeding diathesis (epistaxis - GI bleeding and etc..)
attributable to uremia
Severe metabolic acidosis
BUN > 70 – 100 mg/dl
Slide142Dialysis
When initiated?When uremia can no longer be managed conservatively.Immediately when:Fluid overload unresponsive to diureticsPericarditis Neurologic manifestationsGI manifestations Unresponsive hyperkalemiaUnresponsive acidosis
ARF
Slide143Interventions: Summary
ARF
Prevention
Cause PreventionLoop DiureticsOsmotic DiureticsCa Channel BlockersN-AcetylcysteineTheophyllines
TreatmentLoop DiureticsNatriuretic PeptidesDopamineDialysis ModeDialysis Dosing
✔ ✔↔↔↔✔↔
↔↔↔↔✔ High dose
Slide144