11.Anderson Kidney - Continuing Medical Education - …€¦ · · 2011-11-18– Severe$(or$recurrent)$AKI=risk$factor$for$CKD$ 1.5 2.0 7.0 4.5 3.2 ... • Atleast2$dozen$case$reports$

11/3/11

1

Acute Kidney Injury I: E1ology and Diagnosis

Sharon Anderson, M.D. Div. of Nephrology and Hypertension Oregon Health & Science University

Portland VA Medical Center October 2011

UCSF 2011 AKI-1

Take Home Messages

•  ALWAYS

–  Stop ACEI/ARBs, NSAIDs, PPI –  IniAate basic workup; consider renal ultrasound or postvoid residual

– Maximize BP (paAent’s normal range) and consider intravenous fluids (but not too much)

–  ScruAnize all drug doses •  SOMETIMES

–  Stop diureAcs, staAn •  NEVER

–  Order 24-‐hour urine for anything, or prot/Cr raAo

Acute Kidney Injury

•  DefiniAons, epidemiology, and prognosis •  Diagnosis and EvaluaAon •  Current controversies •  Management principles

11/3/11

2

•  There are more than 35 definiAons of AKI in the literature!

•  Encyclopaedia Britannica, 1983: – Sudden parAal or complete loss of kidney funcAon

You know it when you see it . . .

Useful for clinical research; doesn’t help management!

Epidemiology and EAology

•  1% at Ame of admission

•  5% of all hospital admissions; 30% of ICU admissions

•  Complicates 25% of inpaAent stays

11/3/11

3

Incidence of Organ Failure in the ICU Murugan R, et al. Nat Rev Nephrol 7:209, 2011

Rates of AKI, by Age [Medicare]

www.usrds.org

Incidence of AKI in Medicare Patients Xue JL, et al. JASN 17:1135, 2006

OVERALL BY AGE

BY RACE BY GENDER

92   93 94 95 96 97 98 99 00 01 Year

92   93 94 95 96 97 98 99 00 01 Year

92   93 94 95 96 97 98 99 00 01 Year

92   93 94 95 96 97 98 99 00 01 Year

11/3/11

4

Outcomes of AKI in Hospitalized Patients Liangos O, et al. CJASN 1:43, 2006

•  Review of discharge data from 29,039,599 U.S. hospitalizaAons, 2001

•  558,032 cases of AKI (19.2 per 1000)

•  Risk factors: older age, male gender, black race; presence of CKD, CHF, COPD, sepsis, cardiac surgery

Median LOS (days)

Acute Kidney Injury

•  DefiniAons, epidemiology, and prognosis •  Diagnosis and evaluaAon •  Current controversies •  Management principles

Serum Cr does not increase until half of kidney function is lost!

11/3/11

5

The Pitfalls of Automated eGFR

Caveats to eGFR

•  An esAmate based on populaAon data -‐-‐ not the paAent’s actual GFR

•  Not reliable when used in paAents: – With GFR > 60 ml/ min/1.73 m2

– With rapidly changing creaAnine levels (e.g., acute kidney injury in the ICU)

– With extremes in muscle mass, e.g. cachexia, paraplegia, ESLD

– Under age 18 No urine = no GFR, no matter what Cr or eGFR is reported

IniAal EvaluaAon

•  Careful H+P (drugs) •  Urinary studies

– UA with micro – FENa (or FEurea) – Urine eosinophils

Hortus sanitatis (Mainz: Jacob Meydenbach, 23 June 1491)

11/3/11

6

Diagnostic Utility of Urine Microscopy Perazella MA, et al. CJASN 3:1615, 2008

•  Cross-‐secAonal study of 267 consecuAve paAents seen by consult service over one year

•  Developed a scoring system (1-‐3), based on presence or absence of renal tubular epithelial cells and granular casts

•  In paAents with high pretest probability of ATN, score > 2 → high PPV, low NPV for diagnosis of ATN

Diagnostic Utility of Urine Microscopy Perazella MA, et al. CJASN 3:1615, 2008

•  “Can we get a urine spin?”

Muddy brown granular casts

FENa vs. FEurea on Diuretics Carvounis CP, et al. Kidney Int 62:2223, 2002

•  Compared FENa and FEurea in 102 paAents with AKI, and effect of diureAcs

•  Conclusion: Low FEurea (< 35%) was more sensiAve and specific than FENa, especially in the presence of diureAcs

11/3/11

7

FENa vs. FEurea on Diuretics Pepin MN, et al. AJKD 50:566, 2007

•  In paAents not on diureAcs, FENa is beser than FEurea at diagnosing prerenal AKI

•  In paAents on diureAcs, because of low specificity, FEurea is not very helpful

Sensi1vity Specificity

No diure1cs FENa 78% 75%

FEurea 48% 75%

Diure1cs FENa 58% 81%

FEurea 79% 33%

IniAal EvaluaAon

•  Oten useful: Renal ultrasound or postvoid residual

Ultrasound in Acute Kidney Injury Licurse A, et al. Arch Intern Med 170:1900, 2010

•  Cross-‐secAonal study of 997 paAents admised to one hospital, Jan. 2005-‐May 2009, who had AKI and had renal ultrasound

•  MulAvariate logisAcal regression model to create risk strata for hydronephrosis ± intervenAon

11/3/11

8


•  7 factors associated with hydronephrosis: – History of hydronephrosis – Recurrent UTIs – Diagnosis c/w obstrucAon – Nonblack race – Absence of: nephrotoxin exposure, CHF, prerenal AKI


IniAal EvaluaAon


•  Oten useful: CPK; bladder pressure

11/3/11

9

IniAal EvaluaAon


•  Oten useful: CPK; bladder pressure •  Not useful:

– 24-‐hour urine (for anything) – Urine protein/Cr raAo (inaccurate in absence of steady state, consistent creaAnine excreAon)

Non-Oliguric vs. Oliguric vs. Anuric

•  Urine output is helpful – Oliguria: more common with obstrucAon, prerenal azotemia

– Nonoliguric: intrarenal causes – nephrotoxic ATN, acute GN, AIN

•  Degree of oliguria helps with prognosis – Higher mortality with oliguric AKI – Lower likelihood of renal funcAon recovery with oliguria

– Severe (or recurrent) AKI = risk factor for CKD

1.5 2.0

7.0

4.5

3.2 3.6 3.9

June Oct

Recurrent AKI→ CKD

SCr (mg/dl)

11/3/11

10

AKI Increases Risk of CKD Lo LJ, et al. Kidney Int 76:893, 2009

•  Analysis of 556,090 Kaiser pts over 8 yrs, with baseline eGFR > 45 ml/min/1.73m2

•  Dialysis-‐requiring AKI was independently associated with a 28x risk of developing Stage 4-‐5 CKD and 2x risk of death

Adj hazard ratio 28.1 [21.1-37.6]

+ AKI

- AKI

Causes of AKI

Hilton, R. BMJ 2006;333:786-790

Acute kidney injury

Pre-‐Renal Causes

•  Normotensive ischemic nephropathy •  Cardiorenal syndromes

•  Intra-‐abdominal hypertension

•  “SepAc ATN”

11/3/11

11

Prerenal Causes

•  It is not always necessary to find documented overt hypotension or volume depleAon

Prerenal Causes

•  It is not always necessary to find documented overt hypotension or volume depleAon

•  In the presence of drugs which impair the kidney’s ability to autoregulate, even modest insults can result in AKI

Normotensive Ischemic AKI Abuelo JG. NEJM 357:797, 2007

11/3/11

12

Normotensive Ischemic AKI Abuelo JG. NEJM 357:797-805, 2007

Normal Perfusion Pressure Decreased Perfusion Pressure

↑ vasodilatory prostaglandins

↑ Ang II

Normal GFR Normal GFR Maintained


Decreased perfusion pressure in presence of NSAIDs


↑ Ang II

↓ vasodilatory prostaglandins

↑ Ang II


Low GFR

H H H H H H H H Hh

H h

11/3/11

13

Afferent Arterioles in the Aging Human Glomerulus Hill GS, et al. Kidney Int 63:1027, 2003

Normal Hypertrophic

Dilated AA with large hyaline deposit


Decreased perfusion pressure in presence of NSAIDs Decreased perfusion pressure in presence of ACEI


↑ Ang II


↓ Ang II ↓ vasodilatory prostaglandins

↑ Ang II


Low GFR Low GFR

11/3/11

14

Cardiorenal Syndrome(s)

Ronco C. JACC 52:1527, 2008

Cardiorenal Syndromes Ronco C, et al. JACC 52:1527, 2008

•  CRS Type 1: acute cardiac decompensaAon → AKI

•  CRS Type 2: chronic heart failure → CKD •  CRS Type 3: “acute renocardiac syndrome”

– AKI → acute heart problems

•  CRS Type 4: “chronic renocardiac syndrome” – CKD → chronic heart problems

•  CRS Type 5: systemic condiAon → both cardiac and renal dysfuncAon

Abdominal Compartment Syndrome (Intra-‐abdominal Hypertension) •  DefiniAons

–  IAH: Sustained IAP > 12 mmHg

– ACS: Sustained IAP > 20 mmHg with new organ dysfuncAon

•  Kidneys are at risk with even relaAvely low levels of IAH

•  Originally described in post-‐surgical paAents; now recognized in many other sezngs

Mohmand H, et al. JASN 22:615, 2011

11/3/11

15

Abdominal Compartment Syndrome (Intra-‐abdominal Hypertension) •  Predisposing condiAons/risk factors

– Trauma, major burns, abdominal surgery

– ↓ abdominal wall compliance: mechanical venAlaAon, obesity, ↑ head of bed

– ↑ abdominal contents: ileus, ascites – ↑ capillary permeability: acidosis, sepsis, large volume resuscitaAon, polytransfusion, pancreaAAs, coagulopathy

Mohmand H, et al. JASN 22:615, 2011

What do IAP Measurements Mean?

Pressure (mmHg) Interpretation 0 Normal 1-10 Common in most ICU patients > 12 Intra-abdominal hypertension 15-20 Dangerous IAH - consider non-

invasive interventions >20-25 Impending ACS - strongly

consider decompression

Retroperitoneal Hematoma due to Enoxaparin Ernits M, et al. Am Surg 71:430, 2005

•  At least 2 dozen case reports •  Many are spontaneous (no anatomic cause) •  May lead to ACS, AKI, and death

•  Risk factors may include higher doses, presence of AKI or CKD, older age, concomitant meds affecAng hemostasis

•  Appropriate dosing, early recogniAon, reversal of anAcoagulaAon, treatment of ACS are essenAal

11/3/11

16

“Septic ATN” Schrier RW, et al. NEJM 351:159, 2004

Intrarenal Causes

•  Acute intersAAal nephriAs •  Rhabdomyolysis

•  Cholesterol emboli

•  Phosphate nephropathy

The Scourge of AIN

•  AIN is ALWAYS in the differen1al! •  Acute intersAAal nephriAs has been reported with dozens (hundreds?) of drugs

•  2011: PPIs are a leading cause of AIN

Praga M. Kidney Int 77:956, 2010

11/3/11

17

Myths about Drug-Induced AIN Michel D, et al. JASN 9:506, 1998

•  Myth: Occurs only ater 7-‐10 days of exposure

•  Truth: – Can occur ater months to years of exposure (especially NSAIDs)

– Can occur within 48 hours upon re-‐exposure to a previously tolerated drug

Myths about Drug-Induced AIN Michel D, et al. JASN 9:506,1998

•  Myth: Eosinophiluria is a hallmark •  Truth:

– 70% specific, but only 40% sensiAve – Can also be seen in:

•  Bladder cancer •  UTI •  RPGN •  Atheroemboli •  ProstaAAs

AIN: Beta-Lactams vs. NSAIDS Gonzalez E, et al. Kidney Int 73:940, 2008

Beta-‐Lactam An1bio1cs NSAIDs

Dura1on of exposure 2 weeks 5 months

Fever/rash/eosinophilia 80% 20%

Eosinophiluria 80% 15%

> 3 gms proteinuria < 1% 83%

Rate of recovery Fast Slow

Development of CKD Rare Common

Benefit of steroids Probably Probably not

11/3/11

18

Intrarenal Causes




Statin Rhabdomyolysis by Age Oshima Y. Int Med 50:845, 2011

Rhabdomyolysis

•  StaAns: any staAn; dose-‐related; ↑ risk with many other drugs (e.g., fibrates, calcineurin inhibitors)

•  Plasma staAn drug levels can ↑ in sepsis

•  Think about rhabdo in post-‐operaAve AKI – Typical: prolonged surgery in obese paAent – Less frequently, can occur even in minimally invasive surgery

11/3/11

19

Intrarenal Causes




Cholesterol Emboli

•  Rare complicaAon of aorAc manipulaAon, but can be spontaneous

•  Acute or subacute decline in funcAon 1-‐2 weeks ater the procedure

•  AnAcoagulaAon may precipitate it •  Purple toes, livido reAcularis may be present

•  Labs: Eosinophilia and low C3, C4 •  Renal prognosis is very poor; not reversible, no specific treatment

Intrarenal Causes




11/3/11

20

Hyperphosphatemic AKI after Bowel Prep Markowitz GS, et al. JASN 16:3389, 2005

•  31 cases of nephrocalcinosis on biopsy •  21 (68%) had recent bowel prep with oral sodium phosphate or equivalent → “acute phosphate nephropathy”

•  Mean baseline Cr 1.0 mg/dl; presented one month ater colonoscopy with mean Cr 3.9 mg/dl

•  4 (13%) required permanent dialysis

Special Considerations: AKI in the Elderly

•  In older paAents: – AKI is more frequent

– AKI is a risk factor for CV events, including mortality

– CV risk factors ↑ risk of AKI – AKI is a risk factor for subsequent CKD

Increased Susceptibility of Older Subjects to AKI Adapted from Anderson S, et al. JASN 22:28, 2011

HYPOALBUMINEMIA

11/3/11

21

Risk Factors for Peri-‐OperaAve AKI

Preopera1ve Factors Intraopera1ve Factors Postopera1ve Factors

Pre-‐exisAng AKI or CKD Diabetes Cardiac dysfuncAon Older age Sepsis Volume depleAon HepaAc dysfuncAon Crush injury Nephrotoxins Vascular disease Drugs (ACEI/ARBs, NSAIDs)

Hypovolemia (bleeding, insensible losses) Renal ischemia InflammaAon ↑ intra-‐abdominal pressure Anesthesia: vasodilaAon, ↓ cardiac output Nephrotoxins Embolism ImmobilizaAon (rhabdo)

Hypovolemia (bleeding, insensible losses) Renal ischemia InflammaAon ↑ intra-‐abdominal pressure Anesthesia: vasodilaAon, ↓ cardiac output Nephrotoxins Urinary tract obstrucAon Acute lung injury Mechanical venAlaAon

Adapted from Chronopoulos A. Nat Rev Nephrol 6:141, 2010

•  Areas for future research – Heterogeneity of AKI in older paAents – Mechanisms – Role of biomarkers – Management issues, with special asenAon to HRQOL

Anderson S, et al. JASN 22:28, 2011

New York Times Jan. 29, 2007

Thanks – Questions?

Documents

11.Anderson Kidney - Continuing Medical Education - …€¦ · · 2011-11-18– Severe$(or$recurrent)$AKI=risk$factor$for$CKD$ 1.5 2.0 7.0 4.5 3.2 ... • Atleast2$dozen$case$reports$