Acute Renal Acute Renal FailureFailure
Internal Medicine Resident Half-Day
Ahsan Alam, MD
Acute Kidney Acute Kidney InjuryInjury
Internal Medicine Resident Half-Day
Ahsan Alam, MD
What is Acute Kidney Injury Abrupt decline in GFR
Increase in serum creatinine
PUF = (PGC - PT) - (GC - T)
Varying definitions (RIFLE, AKIN, etc)
Rising Prevalence of AKI
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
Case #1
A 76 yr old female presents to ED with abdominal pain and dyspnea
Serum creatinine is 135 mol
Does she have AKI?
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
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?
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
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
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
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
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
Risk Factors for AKI
Lameire et al. NDT. 2008;6:392
Consistent Risk Factors
Age Hypovolemia Hypotension Sepsis CKD Hepatic dysfunction Cardiac dysfunction DM Exposure to nephrotoxins
Differential Diagnosis of AKI Pre-renal
Renal
Post-renal
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
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
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
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
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
Urine Findings
WBC casts - pyelonephritis WBC
Urine Findings
Crystalluria – uric acid Crystalluria – calcium oxalate
(ethylene glycol toxicity)
Urine Findings
RBC casts - GN Dysmorphic RBC - GN
Urine Findings
Muddy brown casts – acute tubular necrosis
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
Urine Indices
Perfusion-related ATN
Una (mEq/L)
FeNa (%)
Urine Osm (mOsm/L)
BUN/PCr ratio
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
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
ImagingAssess kidney size/morphology
Hydronephrosis
Kidney Biopsy Intrinsic renal AKI Indications
Isolated glomerular hematuria with proteinuria
Nephrotic syndrome Acute nephritic syndrome Unexplained acute or rapidly
progressive AKI
Kidney Biopsy
Crescentic GN
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
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
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
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
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)
Renal Perfusion
Vasopressors Inotropes to improve low cardiac
function Target MAP needs to be individualized
Commonly 65 mmHgHigher in elderly where autoregulation
impaired
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
Treat Complications
Monitor and correct electrolytes, acidosis
Renal replacement therapyIf indicated, do not withhold until patient is
anuric
Indications for Dialysis
A E I O UAcidosisElectrolyte disturbanceIngestionsOverload (volume)Uremia
AKD CKDAKI
New Paradigm for AKI
Natural history of AKI
Cerda et al. cJASN. 2008;
Follow up after AKI
Questions?
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
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
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
Zoungas S et al. Ann Intern Med 2009;151:631-638
Bicarbonate vs Saline
Zoungas S et al. Ann Intern Med 2009;151:631-638
Bicarbonate vs Saline
Zoungas S et al. Ann Intern Med 2009;151:631-638
Bicarbonate vs Saline – Adverse Events
Dialysis(15/1552)
Mortality
CHF
Bicarbonate
Effectiveness is uncertain
Evidence that it should be preferred over isotonic saline is weak and inconsistent
N-Acetylcysteine – Rationale Scavenger of free radicals
Vasodilatory properties; enhanced NO availability
Attenuates ischemic injury in animals
N-Acetylcysteine
Kelly AM et al. Ann Intern Med 2008;148:284-294
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
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
Contrast Medium Limit ‘volume’ of iodine
Iso-osmolar or low-osmolar contrast preferredIA: iso-osmolarIV: low or iso-osmolar
grams iodine/GFR < 1
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
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
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?
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
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
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
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%
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%
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
Terlipressin and Change in Serum Creatinine
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
Cardio-Renal Conundrum
Cardiorenal syndrome
CRS Type 1
CRS Type 2
CRS Type 3
CRS Type 4
CRS Type 5
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
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