Management of acute kidney injury

Jodi S Loekman
 AKI (Acute Kidney Injury)

• Definition and diagnostic Criteria

– An abrupt (within 48hr) reduction in kidney function
currently defined as an absolute increase in serum
creatinine of either >0.3 mg/dL or a percentage increase of
>50% or a reduction in UOP (documented as oliguria of
<0.5 ml/kg/hr for >6hr)
 Definition and classification/staging system for acute kidney injury (AKI)

• AKI stage Creatinine criteria Urine output criteria

• AKI stage I Increase of serum creatinine by

≥ 0.3 mg/dl (≥ 26.4 μmol/L)
or
increase to ≥ 150% – 200% from baseline < 0.5 ml/kg/hour for > 6 hours
•
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• AKI stage II Increase of serum creatinine to

> 200% – 300% from baseline < 0.5 ml/kg/hour for > 12 hours
•
-------------------------------------------------------------------------------------------------------------------

• AKI stage III increase of serum creatinine to

> 300% from baseline < 0.3 ml/kg/hour for > 24 hours
or or
serum creatinine ≥ 4.0 mg/dl anuria for 12 hours
≥ 354 μmol/L) after a rise of at least 44 μmol/L
or
treatment with renal replacement therapy
 Epidemiology

• Prevalence
– 1% 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%
 Mortality
• 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
 Non-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.
 Non-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.
 Evaluation of Renal Failure

• Is the renal failure acute or chronic?

– laboratory values do not discriminate between acute
vs. chronic
– oliguria supports a diagnosis of acute renal failure

• Clues to chronic disease

– Pre-existing illness – DM, HTN, age, vascular disease.
– Uremic symptoms – fatigue, nausea, anorexia, pruritis,
altered taste sensation, hiccups.
– Small, echogenic kidneys by ultrasound.
 Clinical Approach to Acute Kidney Injury
Acute Renal Failure

Clinical Assessment (Volume Status,

Urinalysis and Ultrasound)

Pre-Renal Intra-Renal Post-Renal

Absolute Decrease Decreased Altered Intra-Renal Tubulointerstitial Glomerular Disorders Anatomic Obstruction Tubular Obstruction
In ECF Volume Renal Hemodynsmics Disorders Glomerulonephritis Bladder Outlet Crystals
GI losses Blood Flow Drug-induced Tubular Injury Thrombotic Prostate Calcium oxalate
Hemorrhage Heart failure NSAIDS/COX-2 Ischemic microangiopathies Pelvic Tumor (Ethylene glycol
Renal artery Inhibitors Nephrotoxic Atheroembolic Ureteral poisoning)
stenosis Calcineurin inhibitors Interstitial Nephritis disease Tumor Drugs
ACE inhibitors Allergic-type Stones Indinovir
AII Receptor Blockers NSAID-type Stricture Methotrexate
Sepsis Proteins
Hypercalcemia Myeloma cast
Cirrhosis/Hepatorenal nephropathy
syndrome
Abdominal compartment
syndrome
5 Key Steps in Evaluating Acute Kidney Injury

1) Obtain a thorough history and physical;

review the chart in detail
2) Do everything you can to accurately
assess volume status
3) Always order a renal ultrasound
4) Look at the urine
5) Review urinary indices
 Acute Kidney Injury
– Identify an insult
• Volume depletion (diarrhea, blood loss, emesis, over-
diuresis), Hypotension, CHF.
• Drug exposure – toxin or reduction of renal perfusion.
• Contrast exposure.
• Infections – inflammatory mediators v. direct infection
• Endogenous toxins/insults – myoglobin,hemoglobin,
uric acid.
 Acute kidney Injury
• Symptoms:
– Fever, rash, joint pains, myalgias
• Concern for SLE, vasculitis, acute interstitial nephritis.
– Dyspnea – heart failure.
– Hemoptysis – Goodpasture’s, Wegener’s.
– Preceding bloody diarrhea – HUS.
– Preceding pharyngitis – post-Strep GN, post-
infectious GN.
 Acute kidney Injury
• Urine output.
– Abrupt anuria.
• Acute obstruction, severe acute GN, sudden vascular
catastrophe.
– Slowly diminishing.
• Ureteral stricture.
• Prostatic enlargement.
– Presence of hematuria
• Painless – suggests GN.
• Painful – suggest ureteral obstruction.
 Acute Kidney Injury
• Physical Exam.
– Skin – new rashes.
• Livedo reticularis – atheroemboli, SLE, cryoglobulins.
• Petechiae – HSP.
• Malar rash – SLE.
– Eye
• Papilledema – malignant HTN.
• Roth’s spots – endocarditis.
– CV
• Rub – suggestive of uremic pericarditis, lupus.
• Gallop – suggesting CHF.
 Acute Kidney Injury
• Physical Exam.
– Assessing volume status.
• Is the patient intravascularly volume depleted?
– Neck veins – JVP
– Peripheral edema or lack of.
– Orthostatic vitals.
– Not always straightforward.
– Pt. may be edematous (low albumin) or have
significant right sided heart disease.
• BUN/Creatinine ratio.
– > 20:1 – suggest prerenal or obstruction.
– Can be elevated by anything leading to increased urea
production/absorption.
• GI bleed
• TPN
• Steroids
• Drugs – Tigecycline.

• Creatinine in anephric state typically only rises

1mg/dl/day.
– If greater – should be concerned for rhabdomyolysis
 Confounding 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
 Urinary Sediment

• Can be helpful in identifying underlying disease

states (proteinuric disease, underlying chronic GN) as
well as examining acute insult.
 Urinary Sediment Findings in Intra-
Renal Acute Kidney Injury

Intra-renal Acute
Kidney Injury

Tubular proteinuria Crystalluria

Albuminuria

Dysmorphic Hematuria Oval fat bodies Muddy brown casts White cells Drug toxicity
Red cell casts Fatty Casts Renal tubular epithelial White cell casts Urate crystals
cells and casts Eosinophiluria -Urate nephropathy
Calcium oxalate crystals
-ethylene glycol

Glomerulonephritis Minimal change Tubular epithelial Interstitial nephritis

Atheroembolic disease disease injury Urinary tract
Thrombotic Focal segmental -Ischemic infection
microangiopathy glomerulosclerosis -Nephrotoxic
 Acute Kidney Injury
• Introduction to casts…
Hyaline Casts:
Better seen with low
light.
Non-specific.
Composed of Tamm-
Horsfall mucoprotein.
 Acute Kidney Injury
Granular Casts:
Represent degenerating
cellular casts or aggregated
protein.
Nonspecific.

Waxy Casts:
Smooth appearance.
Blunt ends.
May have a “crack”.
Felt to be last stage of
degenerating cast –
representative of chronic
disease.
UpToDate Images.
 Acute Kidney Injury
Fatty Casts:
Seen in patients with
significant proteinuria.
Refractile in appearance.
May be associated with free
lipid in the urine.
Can see also “oval fat
bodies” – RTE’s that have
ingested lipid.
Polarize – demonstrate
“Maltese cross”.

UpToDate Images.
 Acute Kidney Injury
Muddy Brown
Casts:
Highly suggestive of
ATN.
Pigmented granular
casts as seen in
hyperbilirubinemia can
be confused for these.

UpToDate Images.
 Acute Kidney Injury
White Blood Cell
Casts:
Raises concern for
interstitial nephritis.
Can be seen in other
inflammatory disorders.
Also seen in
pyelonephritis.

UpToDate Images.
 Acute Kidney Injury
• Hematuria
Nonglomerular hematuria:
Urologic causes.
Bladder/Foley trauma.
Nephrolithiasis.
Urologic malignancy.
May be “crenated” based upon age
of urine, osmolality – NOT
dysmorphic.
Acute Kidney Injury
Dysmorphic Red Cells:
Suggestive of glomerular
bleeding as seen with
glomerulonephritis.
Blebs, buds, membrane
loss.
Rarely reported in other
conditions – DM, ATN.

Red Blood Cell Casts:

Essentially diagnostic of
vasculitis or
glomerulonephritis.
 Acute Kidney Injury
Crystals – Pretty and important.
Uric acid crystals:
Seen in any setting of
elevated uric acid and an
acidic urine.
Seen with tumor lysis
syndrome.

Calcium oxalate crystals:

Monohydrate – dumbell
shaped, may be needle-like.
Dihydrate – envelope shaped.
Form independent of urine pH.
Seen acutely in ethylene glycol
ingestion.
UpToDate Images.
 Diagnostic Evaluation of Kidney
Injury
100-
15%
80-
25%

Cumulative 60-
% Correct
Diagnosis 40-
60%
20-

0-
Hx, PE, Labs Therapeutic Renal
Trials Biopsy
Diagnosis-Observation and
Therapeutic Trials
 Fluid replacement

 Relief of obstruction

 Discontinuation of medications
Renal Biopsy-When?

 Exclude pre- and post-renal failure, and

clinical findings are not typical for ATN
 Extra-renal manifestations that suggest a
systemic disorder
 Heavy proteinuria
 RBC casts
 Conditions that Lead to Pre-renal Acute kidney Injury
Intravascular Volume Depletion

Large-vessel Renal Vascular Disease

Decreased Effective Circulating Volume Renal Artery Thrombosis
CHF Cirrhosis Nephrosis Renal Artery Embolism
Renal Artery Stenosis or Crossclamping
Generalized
or Localized Reduction in
Renal Blood Flow
Medications Sepsis
CYA, Tacrolimus
ACE inhibitors NSAIDS
Radiocontrast Amphotericin B
Aminoglycosides Small-vessel Renal Vascular Disease
Vasculitis Atheroemboli
Hepatorenal Thrombotic Microangiopathies
Transplant Rejection
Syndrome

Ischemic
Acute Kidney Injury
Phases of Ischemic Epithelial Tubular
Injury
Pre-renal

Initiation

GFR
Extension

Maintenance
Recovery

Time
 Risk Factors for Ischemic Tubular
Injury
• Volume depletion
• Aminoglycosides
• Radiocontrast
• NSAIDs, Cox-2 inhibitors
• Sepsis
• Rhabdomyolysis
• Preexisting renal disease
• HTN
• Diabetes mellitus
• Age > 50
• Cirrhosis
 Acute 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)
 Acute Interstitial Nephritis
Clinical 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)
Hematuria (NSAID related)
 Common Causes of Drug Induced AIN

• NSAIDS
• Antibiotics
– Penicillins
• methacillin
• Ampicillin, amoxacillin, carbenacillin, oxacillin
• Cephalosporins
– Quinolones (ciprofloxacin)
– Anti-tuberculous medications (rifampin, INH, ethambutol)
– Sulfonamides (TMP-SMX, furosemide, thiazides)
• Miscellaneous
– Allopurinol, cimetidine, dilantin
 Acute Interstitial Nephritis
Treatment
• Withdrawal of offending agent

• Treatment of underlying process if infectious/autoimmune

etiology

• Trial of corticosteroids, especially in allergic presentations

1 mg/kg/day or 2 mg/kg every other day
– No randomized trials proving efficacy
– Reversal of renal failure usually seen in < 6 weeks
 Rhabdomyolysis
• Often develops in the setting of crush injury, especially if
superimposed circulatory shock
• Hallmarks of diagnosis
– CK > 10,000
– (+) dipstick for blood but no RBCs
• Treatment
– Volume expansion (judiciously if severe oliguria or
azotemia)
– Fasciotomy when indicated for compartment syndrome
(“second wave phenomenon”)
• Avoid calcium repletion unless neuromuscular manifestations
present
• Rebound hypercalcemia in recovery phase
 Common Nephrotoxic Agents

• Antimicrobial agents • Vasoactive drugs

– Aminoglycosides – NSAIDS
– Amphotericin B – ACE inhibitors
– Acyclovir – CSA and tacrolimus
– Foscarnet • Radiocontrast agents
– Pentamidine
• Chemotherapeutic agents
– cisplatin
– mitomycin C
– streptozocin
 Factors that Reduce Glomerular
Capillary Pressure
Efferent
Afferent
Arteriole
Arteriole

Vasoconstriction Vasodilation
NSAIDs ACE inhibitors
Cox-2 Inhibitors Angiotensin Receptor
Cyclosporine A Blockers
Tacrolimus
Iodinated contrast
Hypercalcemia
Hepatorenal syndrome
 Aminoglycoside 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
 Contrast Induced Nephropathy

• 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
Prevention of Radiocontrast Nephropathy

Intervention Strength of Clarity of Grade of Recommendation

Evidence Risk-Benefit

Volume expansion Good Clear A: Intervention is always indicated

with normal saline and acceptable

Volume expansion Fair Clear B: Intervention may be effective and is acceptable

with sodium
bicarbonate

Iso-osmolar contrast Fair Clear B: Intervention may be effective and is acceptable

Theophylline Fair Unclear C: May be considered; minimal or

no relative impact

N-acetylcysteine Good Unclear C: May be considered; minimal or

no relative impact

Hemofiltration Fair Unclear I: Insufficient evidence to recommend for or against

Fenoldopam Good Unclear D: Not useful

Hemodialysis Good Unclear D: Not useful

 Acute Kidney Injury due to
Intratubular Obstruction
• Crystalluria
– Ethylene glycol: Calcium oxalate
– Tumor lysis: Urate and Calcium phosphate
– Medications
• Acyclovir
• Methotrexate
• Sulfonamides
• Anti-retroviral agents
• Myeloma cast nephropathy
 Acute 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
 Renal 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)
 Acute 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)
 Atheroembolic Renal Disease

• AKI 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
Livedo Reticularis
 Hepatorenal Syndrome
Major 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.
 Hepatorenal syndrome
Minor Criteria
• Urine volume < 500 mL/day
• Urine sodium < 10 mEq/L
• Urine osmolality > plasma osmolality
• Urine red blood cells < 50 per high-power
field
• Serum sodium concentration < 130 mEq/L
 Obstructive Uropathy

• Urine output in partial obstruction

Normal Obstruction
GFR 150 L/day 10 L/day
Tubular resorption 148 L/day 8 L/day
Urine output 2L 2L
• Urine Na low over first 24-48 hours, then > 40
• Ultrasound 90% sensitive
• Prognosis depends on duration (< 1 week favorable, poor
if > 12 weeks)
 Other 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
 Conclusion
• Various aethiology of AKI and major advances in
understanding AKI,but not clear definition that
guides research on prophylaxis and prognosis
• AKI was still carries high Mortality and morbidity risk
• Improving volume status and hemodinamics rapidly
aids in minimizing Ischemic AKI risk .
• Advent of the novel biomarkers of ischemic tubular
injury will front in redefining AKI.
• Treatment option are conservative or renal
replacement therapy.
• Thankyou