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Page 1: Acute  Renal  Failure

Acute Renal Acute Renal FailureFailure

Internal Medicine Resident Half-Day

Ahsan Alam, MD

Page 2: Acute  Renal  Failure

Acute Kidney Acute Kidney InjuryInjury

Internal Medicine Resident Half-Day

Ahsan Alam, MD

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What is Acute Kidney Injury Abrupt decline in GFR

Increase in serum creatinine

PUF = (PGC - PT) - (GC - T)

Varying definitions (RIFLE, AKIN, etc)

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Rising Prevalence of AKI

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Why do we care about AKI?

10.6

22

30.7

37.8

0

5

10

15

20

25

30

35

40

<1 mg/dL 1.1-2 mg/dL 2.1-3 mg/dL >3 mg/dL

Mo

rtal

ity

%

Nash K et al. Am J Kidney Dis 2002;39(5):930-936Lassnigg, A. et al. J Am Soc Nephrol 2004;15:1597-1605

Mortality post cardiac surgeryMortality with hospital-acquired AKI

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Case #1

A 76 yr old female presents to ED with abdominal pain and dyspnea

Serum creatinine is 135 mol

Does she have AKI?

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Diagnostic Approach

Time of onset – prior serum creatinine Careful review of history and physical

examComorbiditiesMedicationsCurrent illness (vomiting, diarrhea, blood

loss, etc)BP, volume status, skin lesions,

flank/abdominal signs

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Case #1

DM2, HTN, CAD (CABG 2004), CVA 2000 (right CEA 2009), hypothyroidism

Medicationstelmistartan 80 mg, ramipril 10 mg,

furosemide 40/80 mg, metoprolol, clonidine, atorvastatin, clopidogrel, insulin, thyroxine

If this is AKI, what are the most likely diagnoses?

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Causes of Hospital-Acquired AKI and Mortality

0

20

40

60

80

100

120

140

160

N

Episodes 147 61 43 25 7 7

Mortality 20 9 6 19 2 5

Pre-renal Medications CIN Sepsis Obstruction Hepatorenal

Nash K et al. Am J Kidney Dis 2002;39(5):930-936

4,622 consecutive patients7.3% with AKI

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Case #1 The patient

undergoes investigations for her symptoms in hospital…

Day SCr

0 135

1 106

2 115

3 122

4 172

5 247

6 337

7 361

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Case #1Day Procedure Rx SCr

0 135

1 Abdo U/S (ED)

CT Abdo/Pelvis (ED)

‘light’ hydration 106

2 CT Abdo/Pelvis/Ext r/o DVT + PE study

NAC 600 mg bid 115

3 NAC 600 mg bid 122

4 172*

5 247

6 337

* CI-AKI

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Case #1Day Procedure Rx SCr

0 135

1 Abdo U/S (ED)

CT Abdo/Pelvis (ED)

‘light’ hydration 106

2 CT Abdo/Pelvis/Ext r/o DVT + PE study

NAC 600 mg bid 115

3 NAC 600 mg bid 122

4 172*

5 247

6 337

7 Nephrology consult 361*

* CI-AKI* Stage 2-3 AKI

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AKI Network (AKIN) ClassificationStage SCr UOP (ml/kg/hr)

1 >1.5-2X

or >27 mol/L increase

<0.5 for >6 h

2 >2-3X <0.5 for >12h

3 >3x

or >360 mol/L

or RRT

<0.3 for 24h or anuria for 12h

Lopes, J. A. et al. Crit Care 2008;12(4):R110

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Risk Factors for AKI

Lameire et al. NDT. 2008;6:392

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Consistent Risk Factors

Age Hypovolemia Hypotension Sepsis CKD Hepatic dysfunction Cardiac dysfunction DM Exposure to nephrotoxins

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Differential Diagnosis of AKI Pre-renal

Renal

Post-renal

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Pre-renal Hypovolemia

Diuretics, trauma, surgery, burns, hemorrhage, pancreatitis, GI loss, etc.

Decreased effective circulating volumeNephrotic sydrome, cirrhosis, CHF, tamponade,

massive PE, etc. Renovascular obstruction

RAS/atherosclerosis/thrombosis/embolism, dissecting aneurysm, vasculitis, compression

Impaired glomerular autoregulationNSAIDs, ACEi/ARB, calcineurin inhibitors

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Intrinsic Renal

Glomerular and small vessel diseasesRapidly progressive GN, endocarditis, post-strep

GN, vasculitides, scleroderma/malignant HTN, HUS, PET, DIC

Interstitial nephritisInfection-related, inlammation, drug-induced,

infiltrative (lymphoma, leukemia, sarcoidosis)

Tubular LesionsPost-ishemia, nephrotoxic (drugs, contrast,

anesthetics, heavy metals), pigment nephropathy, light chain, hypercalcemia

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Post-renal

Bladder flow obstructionUrethral, bladder neck (BPH), neurogenic

bladder

Ureteral obstruction (bilateral or single kidney)Stones, clots, tumours, papillary necrosis,

retroperitoneal fibrosis, surgical ligation

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Urine Output and AKI

Anuric< 50 cc / 24 hrs

Oliguric< 500 cc / 24 hrs

Non-olguricNormal urine output, but inadequate

clearanceGFR 2 ml/min will produce ~3L of urine/day

if there is no tubular reabsorption

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Diagnostic Approach

Urine dipstick Urine microscopy Cellular elements

○ RBC, WBC, Renal tubular epithelial cells

○ Other (squamous, vaginal)

Casts○ Hyaline, granular, waxy,

RBC, WBC, tubular cell Organisms

○ Bacteria, yeast Crystals Lipiduria

Specific gravity

pH

Leukocytes

Nitrites

Protein

Glucose

Ketones

Urobilinogen

Bilirubin

Blood

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Urine Findings

WBC casts - pyelonephritis WBC

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Urine Findings

Crystalluria – uric acid Crystalluria – calcium oxalate

(ethylene glycol toxicity)

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Urine Findings

RBC casts - GN Dysmorphic RBC - GN

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Urine Findings

Muddy brown casts – acute tubular necrosis

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Urine FindingsSpecific gravity

pH

Leukocytes

Nitrites

Protein

Glucose

Ketones

Urobilinogen

Bilirubin

Blood

1.030

5.0

+

++++

80 yo female found on the floor of her apartment after 2 days, SCr 400 mol/L, K 6.8 mmol/L, CK 54,000

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Urine Indices

Perfusion-related ATN

Una (mEq/L)

FeNa (%)

Urine Osm (mOsm/L)

BUN/PCr ratio

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Urine Indices

Perfusion-related ATN

Una (mEq/L) <20 >40

FeNa (%) <1 >1

Urine Osm (mOsm/L)

>500 300-350

BUN/PCr ratio >20 10

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FeNa

Limitations of FeNa Diuretic use Post-ischemic ATN who have less severe disease AKI on chronic pre-renal disease (cirrhosis, CHF) Contrast or pigment nephropathy Acute GN or vasculitis

Alternatives FE of urea, lithium, uric acid

FeNa = UNa/PNa x 100

UCr/PCr

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ImagingAssess kidney size/morphology

Hydronephrosis

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Kidney Biopsy Intrinsic renal AKI Indications

Isolated glomerular hematuria with proteinuria

Nephrotic syndrome Acute nephritic syndrome Unexplained acute or rapidly

progressive AKI

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Kidney Biopsy

Crescentic GN

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RPGN

Anti-GBM disease

Pauci-immune GN

Immune complex GN

Mimickers

Anti-GBM Ab ANCA Low C3 Normal C3

Anti-GBM diseaseGoodpasture’s

Wegener’sMicroscopic polyarteritis

MPGNPost-infectiousLupus nephritis

CryoglobulinemiaEndocarditis

Shunt nephritis

IgA NephropathyHSP

Fibrillary GNVisceral abscess

Malignant HTNHUS/TTP

Interstitial nephritisScleroderma

Pre-eclampsiaAtheroemboli

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Principles of AKI Management Identify AKI Avoid further nephrotoxic injury Optimize renal hemodynamics Treat complications

Fluid balance, electrolytes, uremia

Nutritional support Renal Support (RRT) Monitoring after AKI

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Medications Pre-renal

Calcineurin inhibitors, radiocontrast, ACEi/ ARB, NSAIDS, amphotericin B

Intra-renalaminoglycosides, amphotericin B, cisplatin,

cephalosporins, sulfa, rifampin, NSAIDS, interferon

Post-renalacyclovir, MTX, indinavir, sulfadiazine

Review renal dosing of medications

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Fluid Management Correct fluid deficit

Will not guarantee AKI preventionStudies of PA catheters did not reduce AKI

High urine flow in specific conditionsMyoglobinuria, tumour lysis, contrast media, etc.

Little evidence on fluid choiceCrystalloidsHypooncotic colloids (4% albumin) Hyperoncotic solutions (HES, dextrans) carry

risk of renal dysfunction

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Renal Perfusion and Vasoactive Agents No support for

Loop diureticsDopamine

Selected use ofMannitol (Rhabdomyolysis, post-cardiac

surgery)

Unclear support forNatriuretic peptides (ANP, BNP)Fenoldopam (DA agonist)Theophylline (adenosine antagonist)

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Renal Perfusion

Vasopressors Inotropes to improve low cardiac

function Target MAP needs to be individualized

Commonly 65 mmHgHigher in elderly where autoregulation

impaired

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Nutrition in AKI AKI is a catabolic state

Inadequate nutritional support can delay renal recovery

Cochrane review 2010:“There is not enough evidence to support the

effectiveness of nutritional support for AKI…”

Adequate calorie delivery in anuric patient will necessitate RRT

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Treat Complications

Monitor and correct electrolytes, acidosis

Renal replacement therapyIf indicated, do not withhold until patient is

anuric

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Indications for Dialysis

A E I O UAcidosisElectrolyte disturbanceIngestionsOverload (volume)Uremia

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AKD CKDAKI

New Paradigm for AKI

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Natural history of AKI

Cerda et al. cJASN. 2008;

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Follow up after AKI

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Questions?

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Case #1Day Procedure Rx SCr

0 135

1 Abdo U/S (ED)

CT Abdo/Pelvis (ED)

‘light’ hydration 106

2 CT Abdo/Pelvis/Ext r/o DVT + PE study

NAC 600 mg bid 115

3 NAC 600 mg bid 122

4 172*

5 247

6 337

7 Nephrology consult 361*

* CI-AKI* Stage 2-3 AKI

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Fluids – Isotonic vs. Hypotonic Isotonic saline (0.9%) more protective

than half normal (0.45%)1,620 pts undergoing cardiac catheterization

Goal is to achieve ‘good’ urine flow

Mueller C et al. Arch Intern Med. 162: 329-336, 2002

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Fluids

Optimal rate and duration is not clear

IV rate >1-1.5 ml/kg/hr to achieve urine flow >150 ml/hr

At least 1hr (3-12hr) prior and 3-6hr (6-12hr) after contrast

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Zoungas S et al. Ann Intern Med 2009;151:631-638

Bicarbonate vs Saline

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Zoungas S et al. Ann Intern Med 2009;151:631-638

Bicarbonate vs Saline

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Zoungas S et al. Ann Intern Med 2009;151:631-638

Bicarbonate vs Saline – Adverse Events

Dialysis(15/1552)

Mortality

CHF

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Bicarbonate

Effectiveness is uncertain

Evidence that it should be preferred over isotonic saline is weak and inconsistent

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N-Acetylcysteine – Rationale Scavenger of free radicals

Vasodilatory properties; enhanced NO availability

Attenuates ischemic injury in animals

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N-Acetylcysteine

Kelly AM et al. Ann Intern Med 2008;148:284-294

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Standard vs. High Dose NAC

Marenzi G et al. N Engl J Med 2006;354:2773-2782

In-hopsital mortality:11% placebo 4% low-dose3% high dose

N=354, <12h post STEMI

Standard: 600 mg IV pre, 600 mg PO bid post

High: 1200 mg IV pre, 1200 mg PO bid post

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N-Acetylcysteine

Actual benefit is debatable, but safe* and inexpensive

Appropriate to give IV or high-dose oral

Give in combination with IV isotonic fluids

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Contrast Medium Limit ‘volume’ of iodine

Iso-osmolar or low-osmolar contrast preferredIA: iso-osmolarIV: low or iso-osmolar

grams iodine/GFR < 1

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MUHC CT Contrast

Iohexol (Omnipaque)• Low-osmolar; Omni 300 ~ 650 mOsm/kg

Iodixanol (Visipaque)• Iso-osmolar; Visi270 or 320 ~ 290 mOsm/kg

Both non-ionic Concentration from 140-400 mg

iodine/ml

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Hemodialysis/Hemofiltration 5 trials with conflicting results

RR for AKI 1.35 (95%CI 0.93-1.94)

Insufficient evidence to recommend prophylactic hemodialysis or hemofiltration

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Case #2

58M with EtOH cirrhosis, admitted for SBP

4 months ago creatinine 68 , now 220

What may be the cause of his kidney dysfunction, and how would you manage?

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HRS Chronic or acute liver disease with advanced hepatic

failure and portal hypertension SCr > 133 mg/dl or 24-hr CrCl < 40 ml/min No improvement in SCr after diuretic withdrawal and

plasma volume expansion (saline 1.5 L) +/- with albumin (1 g/kg to max of 100 g/day)

No nephrotoxin, shock, infection, GI loss No parenchymal renal disease (no proteinuria

microhematuria and/or abnormal US) Minor diagnostic criteria

Urine volume < 500 mL/d UNa < 10 mEq/L UOsm > POsm Urine RBC < 50/hpf Serum Na < 130 mEq/L

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Treatment to Reverse HRSWhich of the following have been shown to be effective?

1. Albumin

2. Combination Midodrine and Octreotide

3. Noradrenaline

4. Terlipressin

5. Dopamine

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Albumin

Intravenous albumin in addition to antibiotics improves survival in SBPSort et al. NEJM 1999;341:403

Albumin indicated when doing paracentesis

Improved outcomes when combined with pressors

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Midodrine and Octreotide Octreotide 100 ug sq TID increasing to 200 ug

sq TID inhibitor of endogenous vasodilators and glucagon

Midodrine 7.5 mg po TID increasing to 12.5 mg po TIDperipheral vasoconstriction

Midodrine and Octreotide sometimes helpfulResponse rate about 30-50%

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Noradrenalin Effects of Noradrenalin and albumin in patients with

Type I HRS: A Pilot Study. Hepatology 2002; 36:374

Noradrenaline started at 0.1 ug/kg/min and increased every 4 hrs based on BP by 0.05 ug/kg/min to max of 0.7 ug/kg/min

Combined treatment lowered creatinine from 2.6 to 1.6 over 10 days

Overall 2-month survival in this group of 12 patients was 58%

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Terlipressin Numerous studies have shown a benefit in

treating patients with HRS benefit is generally a 50% improvement in GFR.

Better when combined with albumin

Ischemic complications and worsening of cerebral hyperemia

Effect is not long lasting

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Terlipressin and Change in Serum Creatinine

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Case 3

68 year old female admitted with worsening dyspnea, leg edema

Known CAD, CHF (LVEF 10%), DM2, CKD (Cr 140), …

Meds: ACEi, BB, nitrate, loop diuretic, aldactone, statin, ASA, insulin, etc.

Aggressively diuresed for 3 days, Cr 250

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Cardio-Renal Conundrum

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Cardiorenal syndrome

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CRS Type 1

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CRS Type 2

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CRS Type 3

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CRS Type 4

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CRS Type 5

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Cardio-Renal Syndrome AT blockade interferes with autoregulation and

may need to be held if GFR deteriorates

Avoidance of agents which interfere with renal sodium handling NSAIDs, Coxibs, Thiazolidinediones Nephrotoxic agents (e.g. contrast)

Serum potassium may also limit continued use of RAS blockade or K-sparing diuretics