A t Kid D f ti iA t Kid D f ti iAcute Kidney Dysfunction in Acute Kidney Dysfunction in the ICUthe ICU
Slide Sub-Title
Learning ObjectivesLearning Objectives
Upon completion of this module you should:Upon completion of this module you should: • Be able to define acute kidney dysfunction and sub-classify it into its
main forms.• Understand the clinical consequences of acute kidney dysfunctionUnderstand the clinical consequences of acute kidney dysfunction.• Be able to list common risk factors for acute kidney dysfunction. • Be able to identify which agents are likely to be useful and which agents
are likely to ineffective or harmful in the prevention and treatment of y pacute kidney dysfunction.
OutlineOutline
Epidemiology and DefinitionsEpidemiology and Definitions
Etiology/Diagnosis
OOutcome
Prevention
Treatment
Acute Kidney DysfunctionAcute Kidney Dysfunction
Acute kidney dysfunction (AKD) is characterized by abrupt and sustained decline in glomerular filtration rate which gleads to accumulation of urea and other toxins in the blood.• Glomerular filtration rate = rate of transfer of protein free plasma filtrate
(ultrafiltration) across the walls of the glomerular capillaries. ( ) g p• In its most severe form AKD is referred to as acute renal failure.
Until recently, no standard criteria existed for diagnosis and l ifi ti f AKD A t i t ti lclassification of AKD. A recent international,
interdisciplinary consensus panel has classified AKD according to a change from baseline serum creatinine or g gurine output (RIFLE criteria).• RIFLE = Risk, Injury, Failure, Loss, ESKD• ESKD = End-stage kidney diseaseESKD End stage kidney disease
RIFLE Criteria for Acute Kidney DysfunctionRIFLE Criteria for Acute Kidney Dysfunction
Risk Increased creatinine x 1.5 or GFR decrease >25%
GFR Criteria* Urine Output Criteria
UO <.5ml/kg/hx 6 hrs
HighSensitivity
Injury
%
UO <.5ml/kg/hx 12 hrs
Increased creatinine x 2or GFR decrease >50%
Sensitivity
FailureUO <.3ml/kg/h
x 24 hrs or Increase creatinine x 3
or GFR dec >75% HighFailureanuria x 12 hrsor creatinine ≥4mg/dl
(Acute rise of ≥0.5 mg/dl)
Specificity
Loss
ESRD End Stage Renal Disease
Persistent AKD** = complete loss of renal function > 4 weeks
ESRD g
www.ADQI.netBellomo R, et al. Crit Care. 2004;8:R204–R212.
RIFLERIFLEAKD is classified according to the worst grade for each domain
(creatinine or urine output). If baseline serum creatinine is abnormal, a smaller relative increase is required to reach “failure.”
Baseline 0.5 (44) 1.0 (88) 1.5 (133) 2.0 (177) 2.5 (221) 3.0 (265)
Risk 0.75 (66) 1.5 (133) 2.3 (200) 3.0 (265) 3.8 (332) ---
Injury 1.0 (88) 2.0 (177) 3.0 (265) --- --- ---
Failure 1 5 (133) 3 0 (265) 4 0 (350) 4 0 (350) 4 0 (350) 4 0 (350)Failure 1.5 (133) 3.0 (265) 4.0 (350) 4.0 (350) 4.0 (350) 4.0 (350)
Creatinine is expressed in mg/dL and (mcmol/L).Creatinine is expressed in mg/dL and (mcmol/L).
Bellomo R, et al. Crit Care. 2004;8:R204–R212.
Epidemiology of AKDEpidemiology of AKD
The prevalence of AKD among patients in the intensive p g pcare unit is not known. • As many as 70% of critically ill patients experience some degree of
AKD.
Approximately 5% of patients in the ICU receive renal replacement therapy (e.g., hemofiltration, hemodialysis).• Hospital mortality in this group is 40 - 80%.
Risk Factors for AKDRisk Factors for AKD
HypovolemiaHypotensionHypotension Sepsis• Frequently as part of multiple organ failureq y p p g
Pre-existing renal, hepatic, or cardiac dysfunctionDiabetes mellitus Exposure to nephrotoxins • Aminoglycosides, amphotericin, immunosuppressive agents, nonsteroidal
anti-inflammatory drugs, angiotensin converting enzyme inhibitors,anti inflammatory drugs, angiotensin converting enzyme inhibitors, intravenous contrast media
Two or more risk factors are usually present.
Types of Acute Types of Acute Kidney DysfunctionKidney Dysfunction
Pre-renal (40 - 80%)Pre renal (40 80%)• renal artery disease• systemic hypotension• Dehydrationy
Intra-renal (10 - 50%)• acute tubular necrosis• interstitial nephritis
Significant overlap
• interstitial nephritis
Post-renal (< 10%)• obstruction
Types of Kidney DysfunctionTypes of Kidney DysfunctionBiochemical indices useful to distinguish a pre-renal from a renal ARF episode
pre-renal renal( O / )osm u (mOsm/kg) > 500 < 400
Na u (mmol/L or meq/L) < 20 > 40
BUN/s creatinine > 20 < 10
u/s creatinine > 40 < 20
u/s osmolality > 1.5 > 1
FeNa (%)* < 1 > 2
________________________________________________________________* ( (u Na / s Na) / (u creat / s creat) ) X 100u for urinary, s for serum, Fe = fractional excretion
Etiology of (intraEtiology of (intra--renal) AKDrenal) AKDand Typical* Urinalysis Findingsand Typical* Urinalysis Findingsand Typical Urinalysis Findingsand Typical Urinalysis Findings
Acute Tubular Necrosis (ATN) [~ 90% of AKD cases]• urine sediment benign mild proteinuria/hematuriaurine sediment benign, mild proteinuria/hematuria• muddy-brown casts
Allergic Interstitial Nephritisi i hil• urine eosinophils
• variable urine sediment, proteinuria and hematuria
Rhabdomyolysisy y• brown urine, dip stick (+) blood but RBC (-) by microscopy• myoglobin (+)
GlomerulonephritisGlomerulonephritis• marked proteinuria• RBC casts (highly specific)
* urinalysis is often non-diagnostic
Cellular Injury and Repair in acute tubular Cellular Injury and Repair in acute tubular necrosis (ATN)necrosis (ATN)necrosis (ATN)necrosis (ATN)
ProliferationAnd
NormalTubular
Injury
PropagationInflammation
Redifferentiation CellsRecovery
(rapid)
Injured Cells
Recovery(slow)
De-Differentiated
Cells ApoptoticCells
Necrotic *Cells
(slow)
* very few necrotic cells are observed from patients with ATN
Cells
ExfoliationInto the Urine
Presence of AKD is Strongly Associated Presence of AKD is Strongly Associated with Hospital Mortalitywith Hospital Mortalitywith Hospital Mortalitywith Hospital Mortality
After adj sting for differences in comorbiditAfter adjusting for differences in comorbidity, AKD was associated with a 5.5 times greater
chance of death compared to matched controlschance of death compared to matched controls without AKD.
Levy et al JAMA 1996;275:1489 94Levy et al. JAMA. 1996;275:1489-94.
Need for Renal Replacement Therapy (RRT) is Need for Renal Replacement Therapy (RRT) is Strongly Associated with Hospital MortalityStrongly Associated with Hospital MortalityStrongly Associated with Hospital MortalityStrongly Associated with Hospital Mortality
Metnitz et al. Intens Care Med. 2002
Metnitz et al. Intens Care Med. 2002
Prevention of AKDPrevention of AKDGoals of therapy are to prevent AKD or need for RRTGoals of therapy are to prevent AKD or need for RRT
Effective Ineffective/harmfulHydrationPrevent hypotension
DiureticsDopamine
Avoid nephrotoxins
UnknownOther renal vasoactive drugs• DA-1 agonists
N-acetylcysteineSodium Bicarbonate
g• PDE inhibitors• Ca++ blockers• Adenosine antagonists
Prophylactic Hemofiltration
g• Natriuretic peptides
Kellum JA, Leblanc M, Venkatraman, R. Clinical Evidence. 2004;11:1094-118.
PreventionPrevention
Maintain hydration (Isotonic IVF)y ( )Reducing risk from nephrotoxins • Single vs. multiple daily doses of aminoglycosides• Lipid complex vs standard amphotericin• Lipid complex vs. standard amphotericin• Iso-osmomotic vs. standard or “low” osmolality radiocontrast media
Maintain “perfusion pressure” (? Optimal)
Kellum JA, Leblanc M, Venkatraman, R. Clinical Evidence. 2004;11:1094-118.
Should We Use Loop Diuretics to Should We Use Loop Diuretics to Prevent ATN?Prevent ATN?Prevent ATN?Prevent ATN?
Radiocontrast ATNFor prevention (no)
Strength of EvidenceLevel I
Ischemic ATNVascular surgery (no)Oth tti (?)
Level I *No data in humans
Other settings (?)
* diuretics were begun after surgery
Kellum JA. Crit Care. 1997;1:53-59
Dopamine is not EffectiveDopamine is not Effective0.1 1 10
Death All Studies
Excludes Radio-contrast
Heart Disease Only
ARF All StudiesAll Studies
Excludes Radio-contrast
Heart Disease Only
Excludes Outliers
HemodialysisAll Studies
Excludes Radio-contrast
Heart Disease Only
Excludes Outliers
Harm Benefit
Kellum & Decker, Crit Care
Med. 2001;29:1526-1531.
Dopamine is not EffectiveDopamine is not Effective
328 patients in 23 ICUsDopamine 2 μg/kg/min vs. placeboPeak serum creatinine: 245 ± 144 vs. 249 ± 147
l/Lμmol/L# with ARF: 56 vs. 56 # di RRT 35 40# needing RRT: 35 vs. 40ICU LOS: 13 vs. 14 days# f d th 69 66# of deaths: 69 vs. 66
Bellomo et al. Lancet. 2000;356:2139-43.
Dopamine Can Increase Urine Output by Dopamine Can Increase Urine Output by Various MechanismsVarious MechanismsVarious MechanismsVarious Mechanisms
Di t l dil t ti (DA 1 t )Direct renal vasodilatation (DA-1 receptors) Increased cardiac output (β-receptors)I d l f i ( t )Increased renal perfusion pressure (α-receptors)Inhibition of Na-K ATPase at the tubular epithelial cell level resulting in natriuresislevel resulting in natriuresis
Seri I et al. Am J Physiol. 1988;255:F666-73.
Risks of “LowRisks of “Low--dose” Dopaminedose” Dopamine
Bowel mucosal ischemiaBowel mucosal ischemia
Digital necrosis
Pro arrhythmicPro-arrhythmic
Hypo-pituitarism
Immune suppression
Other Vasoactive AgentsOther Vasoactive Agents
DA-1 Agonists Adenosine Antagonistsg• Dopexamine
• Fenoldapam
g• Theophylline• Pentoxifylline• Rolipram
Natriuretic Peptides• Atrial natriuretic peptide
Rolipram
Calcium Antagonists• Nifedipinep p
• Urodilatin• B-type natriuretic peptide
• Diltiazem
DADA--1 Agonists: Fenoldapam1 Agonists: Fenoldapam
Pure DA-1 effect (no α or β)Pure DA 1 effect (no α or β)
Potent anti-hypertensive
Fi bli h d li i l t i l ( 28 31 45 80 d 315)Five published clinical trials (n = 28, 31, 45, 80 and 315)• Largest: Stone et al. JAMA. 2003;290:2284-91.
- For prevention of contrast nephropathy- No differences between either group in any outcome
Adenosine Antagonists: TheophyllineAdenosine Antagonists: Theophylline
Adenosine decreases renal blood flow (tubular l l f db k)glomerular feedback)
Contrast Nephropathy
C ( )Four RCTs to date (n = 39, 58, 80, 100)• ¾ studies: hydration status is unclear• One study (n = 80) hydration was well defined and no difference
b t t t t d t lbetween treatment and control
CABG patients (n = 56)• No difference
Atrial Natriuretic PeptideAtrial Natriuretic Peptide
Contrast Nephropathy (n = 247, 3-doses)• No effect
ATN (n = 504)• No overall effectNo overall effect• Harm to non-oligurics; benefit in oliguria
Oliguric ARF (n = 220) N ff h i• No effect; hypotension
Urodilatin (ANP analog - no hypotension)• No benefit
BB--type Natriuretic Peptide (BNP)type Natriuretic Peptide (BNP)
An expensive diuretic?An expensive diuretic? The next “renal dose dopamine”?No data!!No data!!Should be avoided in AKD given results with other natriuretic peptides.
NN--acetylcysteine (NAC)acetylcysteine (NAC)
83 patients with chronic renal insufficiency (mean crt 2.4) p y ( )CT scans, low-osmolal contrast agent N-acetylcysteine (600 mg p.o. BID) with saline hydration y y ( g p ) yor placebo and saline hydration. Control patients: 21% (9/42) had an increase in crt > 0.5 at 48 h vs 2% of NAC pts (P= 0 01)at 48 h vs. 2% of NAC pts (P= 0.01). The mean crts: NAC: decreased from 2.5 +/- 1.3 to 2.1+/-1.3 (P < 0.001), placebo: increased( ) p
Tepel M et al. N Engl J Med. 2000;343:180-184.
Tepel et al. N Engl J Med.2000;343:180-184.
NAC reduces the risk of AKD (increased creatinine) by 50%.
Birck et al. Lancet. 2003;362:598-603.
Does NAC prevent AKD or just decrease Does NAC prevent AKD or just decrease Serum creatinine?Serum creatinine?Serum creatinine?Serum creatinine?
Hoffman et al. J Am Soc Nephrol. 2004;15:407-410.• Healthy volunteers given NAC showed a fall in Scrt without any change
in cystatin C• NAC increases creatinine kinase activity• Increases tubular secretion of creatinine?
N=154
Does isotonic sodium bicarbonate work better than isotonic sodium chloride solution for prevention of AKD after radiocontrast?
Merten et al. JAMA. 2004;291:(19).
Hemofiltration for RCN?Hemofiltration for RCN?
Marenzi et al. N Engl J Med. 2003;349(2)1333-40.g ; ( )• n = 114, hydration alone vs. hydration plus hemofiltration • > 25% rise in Scrt: 5% vs. 50% P < 0.001• Need for acute RRT post-procedure: 3% vs. 25% P < 0.001Need for acute RRT post procedure: 3% vs. 25% P 0.001• In-hospital mortality: 2% vs. 14% P = 0.02
Results not consistent with hemodialysis studies • Awaiting conformation
RadioRadio--contrastcontrast
So-called “low osmolality” radio-contrastSo called low osmolality radio contrast• Iohexol: 700 - 800 mOSM• Iodixanol: 200 - 300 mOSM (iso-osmolar)
Incidence of AKD was 3% (iodixanol) compared with 26% (iohexol) (p = 0.002).
Aspelin et al. N Engl J Med. 2003;348:491-9
Treatment of AKDTreatment of AKDGoals of therapy are to prevent death reduce complicationsGoals of therapy are to prevent death, reduce complications,
hasten/permit renal recovery
Effecti e Ineffecti e/harmf lEffectiveHemodialysisBiocompatible
Ineffective/harmfulDiuretics *DopamineBiocompatible
membranesMore dialysis
Dopamine
UnknownCRRT vs. IHDEarlier dialysis
* Diuretics are never a treatment for oliguria but are sometimes required for management of volume overload.
Kellum JA, Leblanc M, Venkatraman, R. Clinical Evidence. 2004; 11:1094-118.
Cumulative Survival vs. Ultrafiltration RateCumulative Survival vs. Ultrafiltration Rate
1001009090 p < 0.001p < 0.001
808070706060
p < 0.001p < 0.001 p n.s.p n.s.60605050
40403030303020201010
41 % 57 % 58 %
00Group 1(n=146)Group 1(n=146)((UfUf = 20 ml/h/Kg)= 20 ml/h/Kg)
Group 2 (n=139)Group 2 (n=139)((Uf Uf = 35 ml/h/Kg)= 35 ml/h/Kg)
Group 3 (n=140)Group 3 (n=140)((UfUf = 45 ml/h/Kg)= 45 ml/h/Kg)
Ronco et al. Lancet. 2000; 355:26-30.
Cumulative Proportion SurvivalCumulative Proportion Survival
1.01.0
.9.9
.8.8
.7.7Group 3Group 3 (p = 0.0013)(p = 0.0013)
.6.6
.5.5
Group 3Group 3
Group 2Group 2 (p = 0.0007)(p = 0.0007)
(p 0.0013)(p 0.0013)
.4.4
.3.3
Group 1Group 1
.2.2
.1.1
.0.0Survival Time (Days)Survival Time (Days) 5050404030302020101000
.0.0
Ronco et al. Lancet. 2000; 355:26-30.
Survival vs. Dialysis Dose In IntermittentSurvival vs. Dialysis Dose In IntermittentH di l iH di l i
100100
HemodialysisHemodialysis
909080807070606050504040 72 %303020201010
54 %
003/wk HD3/wk HD
wKT/V = 3.6wKT/V = 3.67/wk HD7/wk HD
wKT/V = 7.4wKT/V = 7.4
Adapted from Shiffl et al. N Engl J Med. 2002;346:305-10.
Membrane BiocompatibilityMembrane Biocompatibility
199452Schiffl YearN1st Author
1996166Neveu199651Assouad *199557Kurtal
1999160Jorres1998153Himmelfarb 199866Albright *1996166Neveu
1.37
1.46857Combined
2000159Gastaldello1999160Jorres
1* - Abstracts 0.5 2.0
698Excluding Gastaldello
Odds Ratios for Survival
Subramanian et al. Kidney Int. 2002;62:1819-23.
Odds Ratios for Survival
Continuous vs. Intermittent RRTContinuous vs. Intermittent RRT
Unadjusted
0.2 0.6 1 1.4Relative Risk of Death
Insufficient evidence severity thresholdquality threshold
all studies
su c e t e de cefrom published studies to determine which therapy is best Adjusted
quality rawquality wgt
se erit
which therapy is best.
However, CRRT appears to be severity
both q & sTreatment of x-overs*
as CRRT
appears to be superior under most sets of assumptions.
as CRRTexcluded
Favors CRRT
FavorsIRRT
Kellum et al. Intens Care Med. 2002;28:29-37.
CRRT v IHDCRRT v IHD
• Most recent study (NEJM May 2008)Most recent study (NEJM May 2008)– Multicenter, RCT of CRRT v IHD v SLED
Also compared “low dose” v “moderate dose”– Also compared low dose v moderate dose CRRT (20 cc/kg v 35 cc/kg)
– No difference in renal recovery or mortality– No difference in renal recovery or mortality– BUT:
• Actual dialysis dose delivered was variable• Actual dialysis dose delivered was variable• 35cc/kg may not be enough. > 40cc/kg?
Treatment: DiureticsTreatment: Diuretics
Diuretics: Effects on outcome (small RCTs)( )• 66 patients randomized to receive furosemide (1.5 - 6.0 mg/kg)• No significant differences in recovery or need for HD.
Kl i k ht t l N h 1976 17 51 58Kleinknecht et al. Nephron. 1976;17:51-58.
• 58 patients randomized to single dose (1g) vs. continued dosing of furosemide (3g/day).O 2/30 2 /28• Oliguria was reversed in 2/30 vs. 24/28.
• No differences in mortality, renal recovery, or need for RRT.• Permanent deafness in one patient.
Brown et al. Clin Nephrol. 1981;15:90-6.
Treatment: DiureticsTreatment: Diuretics
Diuretics: Effects on outcome (large observational studies)• 4-center, retrospective analysis of patients referred for nephrology
consults (1989 - 1995; n = 552)• With adjustments for co-variates and propensity score, diuretic use
was associated with:Si ifi l i d i k f d h f l f i– Significantly increased risk of death or non-recovery of renal function (odds ratio 1.77; 95% CI 1.14 - 2.76)
Mehta et al. JAMA. 2002;288:2547-53.
• 52-center, prospective inception cohort of ICU patients (n = 1743)• No differences in mortality, or renal recovery, even after adjustment
for the same co-variates and propensity scoreOdd ti 1 22 ( 0 15)– Odds ratio 1.22 (p = 0.15)
• However, no benefit associated with diuretics either!Uchino et al. Crit Care Med. 2004;32:1669 –77.
Acute Kidney Dysfunction in the ICUAcute Kidney Dysfunction in the ICU
ConclusionsAKD is a common ICU syndrome.• As many as 70% of ICU patients develop AKD.• Approximately 5% of ICU patients receive RRTApproximately 5% of ICU patients receive RRT.
AKD in the critically ill carries a very high mortality, and current treatment is disappointing.pp g
Inflammation likely plays a significant role in the development of AKD.
Conclusions/RecommendationsConclusions/Recommendations
For Prevention of AKD in the ICU:• Avoid nephrotoxins, hypotension, and dehydration.
- Grades B - D for various options• Don’t use diuretics, dopamine, or other vasoactive drugs.
- Grade A +• N - acetylcysteine + fluids for high-risk patients undergoing radio-
contrast studies.G d A- Grade A -
• Consider bicarbonate-based fluids for prevention of radio-contrast induced AKD.
- Grade CGrade C
Conclusions/RecommendationsConclusions/Recommendations
For Treatment of AKD in the ICU• Avoid further injury from nephrotoxins, hypotension, and dehydration.
- Grades B - D for various options• Don’t use dopamine or other vasoactive drugs.
- Grade A +• Avoid diuretics.
- Grade D• Use biocompatable membranes.
- Avoid cuprophane (Grade A -)- Avoid cuprophane (Grade A -)- Avoid all cellulosic membranes (Grade C)
• Use 35 ml/kg/min for CRRT and possibly daily dialysis for IRRT.- Grade C
• Use CRRT?• Use CRRT?- Grade D
AKD: Special CircumstancesAKD: Special Circumstances
Hepatorenal Syndromep y• profound renal vasoconstriction• low RBF and low GFR• marked Na and water retentionmarked Na and water retention• “pre-renal” urine chemistries• bland pathology and urine sediment• Type I (rapid renal failure) and Type II (diuretic-resistant ascites)Type I (rapid renal failure) and Type II (diuretic resistant ascites)
Hepatorenal SyndromeHepatorenal Syndrome
Managementg• low Na diet and diuretics• paracentesis• shuntshunt• liver transplant• aquaretic agents (? effectiveness)
• AVP - V2 receptor antagonistsp g• selective kappa-opioid agonists
• vasopressors
Pathophysiology of HRSPathophysiology of HRS
HRS = arterial hypotension, very low SVRI, very high i NE d ADH d t i ti irenin, NE and ADH, and vasoconstriction in non-
splanchnic arterial vascular territories, including the kidneys, the brain, and the muscle and skin. y
Splanchnic circulation: marked arterial vasodilation = impairment in circulatory function and the homeostatic activation of the endogenous vasoconstrictor systems.
Drug treatment (limited efficacy data)O i i t li i d i• Ornipressin, terlipressin, and vasopressin
• Midodrine (an oral alpha-agonist)
Arroyo V, Jimenez W. J Hepatol. 2000;32:157-70.
Key ReferencesKey References
1. Lameire N. The pathophysiology of acute renal failure. Crit Care Clin. 2005 21(2) 197 2102005;21(2):197-210.
2. Metnitz PG, Krenn CG, Steltzer H, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med. 2002;30:2051–2058.2002;30:2051 2058.
3. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–R212.
4. Kellum JA, Leblanc M, Venkataraman R. Acute renal failure. Clin Evid. 2004;(11):1094-118.
5 U hi S D i GS B ll R t l Di ti d t lit i t l5. Uchino S, Doig GS, Bellomo R, et al. Diuretics and mortality in acute renal failure. Crit Care Med. 2004;32:1669-1677.
Case 1Case 1
A.B. is a 53-year-old male with a past medical history of “poorly controlled” hypertension (taking an ACE inhibitor and a Ca++ channel blocker). He
i h 80 k d t ith t d hi t f f d h dweighs 80 kg and presents with a two-day history of fever and cough, and his chest radiograph shows an RLL infiltrate. His BP on admission is 88/54, and he is given IV fluids (saline) and antibiotics (ampicillin sulbactam).
His admission labs show a serum creatinine of 1.5 mg/dL (133 mcmol/L) and his BUN is 42. Six months ago, his serum creatinine was 1.2. Over the next six hours his urine output is 20 - 30 ml/hr. He is given 2L of 0.9% saline and 500 ml of 5% hetastarch. His BP improves to 110/60 and his pulseand 500 ml of 5% hetastarch. His BP improves to 110/60 and his pulse decreases from 128 to 109. He is admitted to the ward and you are called by his nurse for continued low urine output.
Case 1 page 1
Case 1 Case 1 (cont.)
The patient’s UO has been < 0.5ml/kg/hr for more than 6 hours. This may indicate AKD (“risk” category for urine output by RIFLE criteria), but it might just as easily represent inadequate circulating blood volume or (much less likely) an obstructive uropathy.
You place a Foley catheter and there is only 20 ml of urine. While this does not rule out obstructive uropathy, it makes it very unlikely. Additional testing (e.g., renal ultrasound) might be indicated if there is still a diagnostic question but pre-renal or intra-renal disease is far more likely.
You send the urine for electrolytes and this reveals a uNa of 10 mmol/L, uCr yof 50 mg/dL, and you calculate a fractional excretion (FE) of Na of 0.5%. These results are consistent with pre-renal disease but urine studies are not themselves diagnostic.
Examination of the urine reveals no WBCs or casts. These findings make interstitial or glomerulular nephritis very unlikely. The absence of muddy brown casts do not exclude the diagnosis of ATN.
Case 1 page 2
Case 1 Case 1 (cont.)
You also send a repeat BUN and serum creatinine which are 40 and 1.8 mg/dL. The ratio of BUN/creatinine > 20 is consistent with (but not diagnostic g ( gof) pre-renal disease.
You decide to give additional fluid (1L 0.9% saline) over the next hour, but the urine output remains low and the BP decreases to 90/55.p
You now need to establish the etiology of the persistent hypotension. Possibilities include: hypovolemic (even though the patient has received 3.5 L of fluid), septic (distributive), cardiogenic, and obstructive. Options for ) p ( ) g pdetermining the etiology range from noninvasive (e.g., echocardiography) to invasive (e.g., pulmonary arterial catheterization). No technique is completely failsafe but if cardiac output is increased, the diagnosis must be di t ib tidistributive.
Case 1 page 3
Case 1 Case 1 (cont.)
You determine that the cardiac output is increased and you also measure an arterial lactate (2.7) and mixed venous oxygen saturation (72%). You also d t i th t th t l i 14 H Th fi didetermine that the central venous pressure is 14 mm Hg. These findings make hypovolemia unlikely.
At this point, even though the mean arterial pressure is 62 mm Hg, you are concerned that the patient’s BP is too low and that he may not have adequate perfusion pressure for his organs (including the kidneys). This is a significant concern, especially in a chronic hypertensive. Atherosclerotic disease is likely and a decreased blood pressure may result in insufficient flow. The slightand a decreased blood pressure may result in insufficient flow. The slight elevation in the arterial lactate also suggests this diagnosis.
This scenario is further supported by this combination of urine chemistries (pre-renal) and systemic hemodynamics (hyperdynamic) You decide to(pre renal) and systemic hemodynamics (hyperdynamic). You decide to increase the mean arterial pressure to 70 mm Hg using norepinephrine.
Case 1 page 4
Case 1Case 1 (cont.)
The patient is given activated protein C and his adrenal axis is evaluated using a short ACTH stimulation test (his response is normal).
Over the course of the next 12 hours, you maintain his mean arterial pressure > 70 mm Hg with 0.02 – 0.04 mcg/kg/min of norepinephrine. His urine output gradually increases, and his central venous pressure falls to 8
H Y d i i t dditi l fl id (l t t d Ri thi ti t idmm Hg. You administer additional fluids (lactated Ringers this time to avoid giving additional saline, which may cause acidosis) and continue supportive care.
Th t d th ti t’ C t i t 2 2 (BUN f ll t 32) R tThe next day, the patient’s Crt increases to 2.2 (BUN falls to 32). Repeat urine electrolytes show an Na of 35 and the FeNa is 1.8. Muddy brown casts appear in the urine. The next day the serum creatinine decreases to 2.0 and his blood pressure improves. You discontinue the norepinephrine and by the p p p p ynext day he is requiring antihypertensive therapy. He makes a complete recovery.
Case 1 page 5
Case 2Case 2C.D. is a 64-year-old female with a history of hypertension, 3-vessle coronary artery disease, and poor left ventricular function (ejection fraction: 20%). She weighs 80 kg and undergoes coronary arterial revascularization. Th i tf l b t h i fl id d tiThe surgery is uneventful but she requires fluids and vasoactive medications (epinephrine and dobutamine) to come off of cardiopulmonary bypass.
Her initial postoperative care is unremarkable except that she a borderlineHer initial postoperative care is unremarkable except that she a borderline urine output 30 - 40 ml/hr and her blood pressure is very labile.
Her admission labs (drawn 24 hours before surgery) showed a serum creatinine of 1 5 mg/dL (133 mcmol/L) Over the first 24 hours after surgerycreatinine of 1.5 mg/dL (133 mcmol/L). Over the first 24 hours after surgery, she makes 200 mL of urine. Her serum creatinine increases to 2.0 mg/dL (177 mcmol/L). She is maintained on vasoactive medications but is weaned from mechanical ventilation and extubated. Her cardiac function remains poor but cardiac index is 2.2 on epinephrine and dobutamine. She has not received any nephrotoxic agents. Urine chemistries and microscopy are consistent with a diagnosis of ATN.
Case 2 page 1
Case 2Case 2 (cont.)
The following day her serum creatinine increases to 3.0 mg/dL (266 mcmol/L) and her BUN increases to 65 mg/dL. She has made 300 mL of urine in the last 24 hours, and her total fluid intake has exceeded all output b 11L i th H i ht i 90 k d h h dby 11L since the surgery. Her weight is now 90 kg and she has edema on physical exam.
Furosemide is administered but she does not respond. The next day the creatinine is 4 0 mg/dl and she is started on continuous veno venouscreatinine is 4.0 mg/dl and she is started on continuous veno-venous hemofiltration at an ultrafiltration rate of 35 ml/kg/hr based on her admission weight. Initially 100 mL of fluid are removed per hour and this is increased to 150 mL/h, but her blood pressure becomes unstable, and the removal rate is preturned to 100.
Over the course of the next five days 8L of fluid are removed, and her heart function improves such that all vasoactive medications are discontinued. She is converted to intermittent dialysis and is discharged form the ICU.
A week later renal function gradually recovers, and one month later her serum creatinine has returned to baseline.
Case 2 page 2