acute kidney injury 2013

acute renal failure…from basics to the latest advances

Joel M. Topf, MDClinical Nephrologist

http://pbfluids.com

the housemoment

Dr. Haas invented the first dialysis machine designed for humans and in 1928 he treated 6 patients.

Dr. Haas invented the first dialysis machine designed for humans and in 1928 he treated 6 patients.

All of them died.

In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings.

In 1943 he dialyzed his first patient, a young man with acute nephritis.



Dr. Haas



Dr. Haas0 for 22



In 1945, a 67-year-old woman in uremic coma presented to Dr Kolff.

Dr. Haas0 for 22



In 1945, a 67-year-old woman in uremic coma presented to Dr Kolff.

Dr. Haas

Regained consciousness after 11 hours of hemodialysis.

0 for 22

0

20

40

60

80

Mo

rtality (%

)

75

45

Sepsis Other Causes

Mortality by Etiology

Commonly quoted mortality of 70% is for dialysis requiring ICU patients

For hospital acquired ARF: 20%

Am J Med 2005 118, 827-832

Patients with primary diagnosis of AKI have higher mortality when they are:

admitted on week-ends

admitted to smaller hospitals

James et al. Weekend Hospital Admission, Acute Kidney Injury, and Mortality. Journal of the American Society of Nephrology (2010) vol. 21 (5) pp. 845-851

ICU associated AKI is characterized by a d e l a y b e t w e e n a d m i s s i o n a n d d e v e l o p m e n t o f acute renal injury

R isk

I njury

F ailure

L oss of function

E nd-Stage Renal disease

rifle criteria for stratifying arf

R isk

Increase in Cr of 1.5-2.0 X baseline or urine output < 0.5 mL/kg/hr for more than 6 hours.

I njury

F ailure

L oss of function


R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs

I njury

increase in Cr 2-3 X baseline (loss of 50% of GFR) or urine output < 0.5 mL/kg/hr for more than 12 hours.

F ailure

L oss of function



I njury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs

F ailure increase in Cr rises > 3X baseline Cr (loss of 75% of GFR) or an increase in serum creatinine greater than 4 mg/dL, or urine output < 0.3 mL/kg/hr for more than 24 hours or

anuria for more than 12 hours.

L oss of function




F ailure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for more than 12 hours

L oss of function persistent renal failure (i.e. need for dialysis) for more than 4

weeks.





L oss of function: Need for dialysis for more than 4 weeks

E nd-Stage Renal disease persistent renal failure (i.e. need for dialysis) for more than 3

months.




L oss of function: Need for dialysis for more than 4 weeks

E nd-Stage Renal disease : Need for dialysis for more than 3 months

nice criteria. do they work?

20,126 consecutive admissions to a university hospital Excluded kids Kidney transplant and

dialysis patients Patients admitted for <

24 hours Using RIFLE:

Risk 9.1% Injury 5.2% Failure 3.7%

Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.

nice criteria. do they work?

20,126 consecutive admissions to a university hospital Excluded kids Kidney transplant and

dialysis patients Patients admitted for <

24 hours Using RIFLE:

Risk 9.1% Injury 5.2% Failure 3.7%

No Renal failure82%

Failure4%

Injury5%

Risk9%

Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.

Hos

pita

l Mor

talit

y

>3x

BL

Cr

Cr >

4

Hos

pita

l Mor

talit

y

nice criteria. do they work in the icu?

University of Pittsburgh has 7 ICUs

5,383 patients Excluded dialysis

Subsequent admissions

Frequency of acute Kidney failure: No AKD 1,766

Risk 670

Injury 1,436

Failure 1,511Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310

nice criteria. do they work in the icu?

University of Pittsburgh has 7 ICUs

5,383 patients Excluded dialysis

Subsequent admissions

Frequency of acute Kidney failure: No AKD 1,766

Risk 670

Injury 1,436

Failure 1,511

No Renal failure33%

Failure28%

Injury27%

Risk12%

Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310

No AKI Risk Injury Failure0

5

10

15

20

25

30

RRTLOSICU LOSMortality

AKIN criteria

refinement of RIFLE criteria smaller change in Cr 0.3 time constraint of 48 hours for the diagnosis of

AKI anyone requiring dialysis is stage 3 AKI

RIFLE v AKIN

RIFLERIFLE

R Cr increased by 50-100%

I Cr increased by 100-200%

F Cr increased by more than 200% or Cr > 4

L Need for dialysis for > 4 weeks

E Need for dialysis for > 3 months

RIFLE v AKIN

RIFLERIFLE

R Cr increased by 50-100%

I Cr increased by 100-200%

F Cr increased by more than 200% or Cr > 4

L

E

RIFLE v AKIN

RIFLERIFLE AKINAKIN

R Cr increased by 50-100% 1 Cr increased by 0.3 or

50-100%

I Cr increased by 100-200% 2 Cr increased by

100-200%

F Cr increased by more than 200% or Cr > 4 3 Cr increased by more

than 200%, Cr > 4, or renal replacement therapyL

Cr increased by more than 200%, Cr > 4, or renal replacement therapy

E

AKIN vs RIFLE120,123 critically ill patients in 57 ICUs in New Zealand and Australia


64%

16%

14%6%

RIFLE

63%18%

10%9%

AKIN

NoneRisk / 1Injury / 2Failure / 3


64%

16%

14%6%

RIFLE

63%18%

10%9%

AKIN

NoneRisk / 1Injury / 2Failure / 3

2.24

3.95

5.13

2.45

4.23

5.22

Risk / 1 Injury / 2Failure / 3

mortality odds ratio vs no AKI

oliguria: sensitive or specific?

oliguria is a biomarker of ARF

Used in the definition of RIFLE and AKIN

How good is it at predicting AKICreatinine

ICU patients and tracked hourly urine outputs

oliguria: <0.5 ml/kg/hr

primary outcome: how predictive was oliguria for subsequent AKI as defined by creatinine

239 patients, 723 days, 23 cases of hospital acquired AKI

duration of oliguria AKI the next day No AKI next day

None 5 443

≥1 hour 18 257

≥2 hours 15 194

≥3 hours 13 125

≥4 hours 12 95

≥5 hours 7 75

≥6 hours 5 50

≥12 hours 4 9

ICU associated AKI is characterized by a d e l a y b e t w e e n a d m i s s i o n a n d d e v e l o p m e n t o f acute renal injury

4"days"

1"day"

N=29,269

N=29,269

AKI 1,738 (5.7%)

T h i s d e l a y i n t h e development of AKI is an opportunity.

T h i s d e l a y i n t h e development of AKI is an opportunity.

Often AKI is the result of a second hit. Don’t hit your patient.

risk factors for AKI

CKD

Age >75

Peripheral vascular disease

Heart failure

Liver disease

Diabetes

Nephrotoxins NSAIDs

Aminoglycoseide

Hypotension Hypovolemia

Cardiac disease

Iatrogenic

Sepsis

etiologies of arf

Seventy percent have concurrent oliguria

< 400 mL/day

< 0.5 mL/kg/hr in children

< 1 mL/kg/hr in infants

Complicates 5-7% of hospitalizations

Community acquired49.7%

Hospital acquired50.3%

Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8.Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6.

Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.

Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8.Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6.

Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.

hospital acquired acute renal failure

Sepsis7%

Other2%

CHF4%

Unknown3%

Other7%

Obstruction2%

Hypotension11%

Volume Contraction21%

Post-Op15%

Contrast11%

Medication16%

hospital acquired acute renal failure

differentiation of prerenal from intrinsic renal disease

Excreted Na

Excreted NaFiltered Na


Fractional excretion of sodium:

Excreted Na = Urine Na x Urine Volume

Calculating the Numerator

Calculating the Denominator


Filtered Na = Serum Na x GFR


GFR = Urine Cr x Urine Volume Serum Cr



GFR = Urine Cr x Urine Volume Serum Cr


Filtered Na = Serum Na x UrCr x UrVol Serum Cr


FENa =


FENa =

FENa =


FENa =

Urine Na x Urine VolumeFENa =


FENa =

Urine Na x Urine VolumeSerum Na x UrCr x Urine Volume Serum Cr

FENa =


FENa =


FENa =

Urine NaSerum Na x UrCr Serum Cr

FENa =


FENa =


FENa =

Urine NaSerum Na x UrCr Serum Cr

FENa =

Urine Na x Serum CrSerum Na x UrCr

FENa =

FENa the easy way

FENa the easy way

FENa is a small number 0.1% to 3%

FENa the easy way

FENa is a small number 0.1% to 3% So the calculation will be 0.001-0.03 prior to

converting to percent by X 100

FENa the easy way


converting to percent by X 100 So make the fraction small by putting the small

numbers over the big numbers

Sr Na

FENa the easy way




Sr Na

Sr Na

FENa the easy way




Sr Na Sr Cr

Sr Na

FENa the easy way




Sr Na Sr Cr

Sr Na

Sr Cr

FENa the easy way




Sr Na

Ur Na Sr Cr

Sr Na

Sr Cr

FENa the easy way




Sr Na

Ur Na Sr Cr

Sr Na

Sr Cr x Ur Na

FENa the easy way




Sr Na

Ur Na Ur Cr

Sr Cr

Sr Na

Sr Cr x Ur Na

FENa the easy way




Sr Na

Ur Na Ur Cr

Sr Cr

Sr Na

Sr Cr x Ur Na

x Ur CrFENa =

FENa the easy way




Why is the feNa high in ATN

Normally tubules reabsorb 98-99% of the filtered sodium

serum Na x GFR x minutes in a day

urinary Na excretion





140 x 0.1 x 1440

180



20160

180



0.8%



0.8%

So does ATN cause the tubules to fail to reabsorb the 99%?



0.8%

So does ATN cause the tubules to fail to reabsorb the 99%?

NO

false positive FeNa

Contrast nephropathy Acute glomerulonephritis ATN with heart failure ATN with burns ATN with cirrhosis


Low FeNa not pre-renal


Low FeNa not pre-renal

these are cases of ATN where the tubules effectively hold on to sodium


Normally tubules reabsorb 98-99% of the filtered sodium but now the GFR is 30 not 100

The fena reflects the behavior of the tubules that are undamaged. Tubules affected by ischemia have a GFR of zero.

serum Na x GFR x minutes in a day

urinary Na excretion





140 x 0.03 x 1440

180




6048

180




2.9%



Acute renal success

GFR is normally 100 mL/min

Total plasma volume is only 3 liters

without massive fluid reabsorption, 30 minutes to filter all the plasma

Acute renal success

GFR is normally 100 mL/min

Total plasma volume is only 3 liters

without massive fluid reabsorption, 30 minutes to filter all the plasma

Tubuloglomerular feedback

Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54.

fractional excretion of urea

Based on the physiologic increase in urea reabsorption with pre-renal azotemia

Normal FE Urea is 50-65% in well hydrated individuals

In prerenal azotemia this falls below 35% Not affected by diuretics

Sr Na

Sr Cr x Ur Na

x Ur CrFENa =

Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54.

fractional excretion of urea

Based on the physiologic increase in urea reabsorption with pre-renal azotemia

Normal FE Urea is 50-65% in well hydrated individuals

In prerenal azotemia this falls below 35% Not affected by diuretics

Sr Urea

Sr Cr x Ur Urea

x Ur CrFEurea =

Carvounis, Sabeeha, Nisar, Et al. Kidney Int, 2002 Vol 62. p 2223-2229

FEurea in the differential diagnosis of atn

102 patients with ARF

Gold standard was consultants full analysis and retrospective analysis of response to treatment.

Divided the cases into: ATN

Prerenal without diuretic

Prerenal treated with diuretics

0

25

50

75

100

Sensitivity (%

)

92

50

91 90

Pre-Renal, No diuretics Pre-Renal, Diuretics

FENaFEUrea

FENa

FEUrea

outcomes

Nephrology Dialysis Transplantation 23 2235-41, 2008Clin J Am Soc Nephrol 3: 881-886, 2008

Acute kidney injury as a cause of CKD

3,679 diabetic veterans baseline creatinine 1.1, average age 61 primary outcome: development of CKD 4 secondary outcome: all-cause mortality

1,822 hospitalized 530 developed AKI at least once

88% AKIN 1

12% AKIN 2, 3

39,805 Kaiser Permanente Hospitalized 1996-2003 all had pre-hospitalization GFR <45 among those who developed ARF (50%

increase in Cr and dialysis) 26% died in the hospital among survivors:

GFR 30-44 42% required permanent dialysis within a month of discharge

GFR 15-29 63% required permanent dialysis within a month of discharge

26%

5%

20%

49%

ARF in hospital

Death in Hosp Died after d/c Alive, No dialysis ESRD

5%4%

90%

2%

No ARF in hospital

34.7%

27.6%28.4%

45.2%

14.4%

77.0%

Death during Hospital

ESRD after D/C

GFR 30-44 GFR 15-29 GFR <15

even the lucky ones, not so lucky

Survivors of ARF, not dialysis dependent

No ARF

dial

ysis

-free

sur

viva

l

used to be...No dialysis. No foul.

Acute renal failure is a risk factor for progression of CKDAcute renal failure is a risk factor for progression of CKD

therapy

Internist management

Patient empowerment

Renal replacement therapy


CKD

Age >75


Heart failure

Liver disease

Diabetes

Nephrotoxins NSAIDs

Aminoglycoseide


Cardiac disease

Iatrogenic

Sepsis

Internist management

Monitor I’s and O’s, daily weights

Frequent labs BMP, phosphorous,

albumin, U/A

Consult nephrology

Avoid hypotension

Dose adjust for renal failure

Follow-up after d/c for high risk of CKD

Avoid Iodinated contrast Aminoglycosides ACEi/ARB

Thoughtful fluid management


CKD

Age >75


Heart failure

Liver disease

Diabetes

Nephrotoxins NSAIDs

Aminoglycoseide


Cardiac disease

Iatrogenic

Sepsis

Patient empowerment

talk to patients about what to do if they become acutely ill

increase fluid intake

decrease diuretics

monitor blood pressure

renal replacement therapy

Dialysate

1405.8

10817

76

7.8

1452

11035

0

0

Conventional Dialysis: combination of diffusive and convective Clearance

1405.8

10817

67

3.8

BloodUltra-filtrate

1365.8

10817

67

3.8

Isolated Ultrafiltration: CHF SolutionsMinimal clearance

1365.8

10817

67

3.8

1365.8

10817

67

3.8


1365.8

10817

67

3.8

1365.8

10817

67

3.8

80 mmol KIsolated Ultrafiltration: CHF SolutionsMinimal clearance

1365.8

10817

67

3.8

1365.8

10817

67

3.8

80 mmol K5.8 mmol/L


1365.8

10817

67

3.8

1365.8

10817

67

3.8

80 mmol K5.8 mmol/L

= 13.8 litersIsolated Ultrafiltration: CHF SolutionsMinimal clearance

Ultrafilter 3+ liters/hour

Replace all ultrafiltratewith sterile fluid at idealplasma concentrations

1365.8

10817

67

3.8

140 2

10830

0

0

CVVHConvective clearance

Ultrafilter 3+ liters/hour

Replace all ultrafiltratewith sterile fluid at idealplasma concentrations

1365.8

10817

67

3.8

140 4

10830

0

0


Post-filter replacement fluid


Pre-filter replacement fluid


CVVHDFConvective and Diffusive

high dose dialysissu

rviva

l

Severity of illness (CCARF Score)


rviva

l


Low dose


rviva

l


High dose

Low dose

Ronco’s landmark dialysis dose study

425 patients with dialysis dependent acute renal failure were randomized to one of three doses of CVVH

20 mL/kg/hr of effluent

35 mL/kg/hr

45 mL/kg/hr

20 mL/kg/hr

35 mL/kg/hr

45 mL/kg/hr

Ronco C, Bellomo R, Hormea P, Et al. Lancet 2000; 355: 26-30.

Ronco 425 CVVH 20/h vs. 35-45 ml/kg/h*

Bouman 106 CVVH 20ml/kg/h* vs. 48 ml/kg/h

Schiffl 160 Alternate day vs. daily hemodialysis

Saudan 206 CVVH 25 ml/kg/h vs. CVVHDF 42 ml/kg/h

Total (fixed effects)

Total (random effects)

1 10Odds ratio

Study n treatment groups

*For purposes of analysis the two high-dose arms in Ronco were combined, as were the two low-dose arms in Bouman. If these groups are removed the odds ratio is unchanged (1.94; P <0.001).

Kellum J. Nature Clin Practice Nephrol 2007 3: 128-9.

ATN trial

US trial Prospective randomized, multi-center trial

27 institutions primarily veterans hospitals

Dose finding study, modality agnostic Conventional

dialysis SLED

CVVH CVVHD

CVVHDF

interventions

endpoint

Primary Endpoint: All-cause mortality at day 60.

Secondary endpoints: In-hospital death Recovery of renal function (CrCl>20)

defined as complete if Cr was <0.5 over the baseline

Duration of renal replacement therapy Dialysis free at 60 days Duration of ICU stay Return to previous home at day 60

results

results

563 enrolled in standard care561 randomized to intensive therapy

60% sepsis

80% vented

Apache II score 26 predicted mortality 55%

BUN at initiation of RRT 65

half in the MICU half in the SICU

This report currently should be viewed as the definitive study defining dialysis dosing in critically ill patients with AKI

H. David Hume

…the patient dies from multi-organ failure while in exquisite electrolyte

& fluid balance.

Fluid balance?

Patients stratified by net fluid gain from admission to initiation of CRT

Fluid in – fluid outICU admit weight X 100

longer ICU stay

higher mortality

more multi-organ dysfunction

more likely to be intubated

more inotropes

more sepsis

higher PRISM score

More fluid. More sick.

Worse fluid overload severity remained independently associated with mortality (OR, 1.03; 95% CI, 1.01-1.05). The relationship was satisfactorily linear and the OR suggests a

3% increase in mortality for each 1% increase in degree of fluid overload at CRRT initiation.

80 kg adult Is and Os: 2,400 mL in (100 mL/hr) and

1,600 mL of urine (67 mL/hr) Positive balance of 800 mL. If after 3 days the

patient becomes oliguric with 200 mL of urine output for two days (2,200 mL positive per day) before initiating CRT.

That patient would be up 6,800 mL or 8% of bodyweight

24% increase in mortality compared to someone with matched ins and outs

observational data from SOAP study of ICU care in Europe

198 ICUs 24 countries 147 patients 1120 had AKI ARF defined as a Cr >3.5 or urine output <

500 mL

Moreover, this would suggest that prevention or management of fluid overload is evolving as a primary trigger/indicator for e x t r a - c o r p o re a l fl u i d remova l , and th is may be independent of dose delivery or solute clearance.

Critical Care 2008, 12:169

summary

Prognosis is grim We have two validated, consensus definitions

R isk I njury F ailure L oss of function E srd

Outpatient and inpatient acquired ARF differ in etiology

Hospital acquired disease is your fault

AKIN Stage 1 Stage 2 Stage 3

summary

FE of Urea is a validated way to separate pre-renal from AKI even in the presence of diuretics

Use of high dose dialysis regardless of methodology offers no survival benefit

Do not fluid overload your patient Dopamine doesn’t work

Acute kidney injury is not a specialist’s emergency; it is seen commonly in acute medicine and, as such, it is essential that all physicians have the confidence and ski l ls to identify and manage it.

acute kidney injury 2013

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