Acute Renal Failure

Definition
Syndrom characterized by:
Partial or total loss of renal function:
acute i brutal (hours, days), usually, in persons with previous normal kidney but also in persons with previous kidney damage;

Etiology
many factors acting in association

Pathology
commonly, acute tubular necrosis (ATN);

Clinical presentation
oligo-anuria, abrupt decline (hours, days) in GFR, rapid increase in blood urea, and severe distrubances of water, electrolytes and A-B balance

Evolution
generally, full recovery of renal function but depends on patholgy
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NM, 75 years old

Personal antecedents
HBP (20 years), relatively controlled with ACEI

Intermitent claudication in the last 5 yrs Normal lab tests (CrS 1.1mg/dL; june) Smoker, 1 pack/day, 50 ani; he lives alone

History
Abdominal pain, vomiting and diarhea, subfever, after eating icecream (august) The general practitioner, consulted after 36 hours, prescribed antibiotics He was found by his neiboroughs laying in the bed and transported to the hospital

At admision
AP115/70 clino and 90/60 orto; HR 110 Dry tongue Diuresis 500mL CrS 2mg/dL, UreeS 250mg/dL Urine analysis: D 1010; Prot (+); L (+), H (-)

Acute Renal Dysfunction

AKIN (Acute Kidney Injury Network) criteria

A 48 hours interval is necessary to exclude CRF

An abrupt (48 hrs) reduction in renal function, defined by: An increase in sCr with 0.3mg/dL An increase with 50% in sCr (1.5 times higher) or Oliguria could appear Proved oliguria 0.5mL/kg for 6 hrs before sCr increase, but its specificity is low [240mL/6 ore]

and should be interpreted in the clinical seting

To measurements of sCr at 48 hrs interval are mandatory

Stadiile AKIN (Acute Kidney Injury Network)

sCr Urinary flow

Risk

or
2

Increase in sCr with 0.3 mg/dl (26.4mol/lL) 150%-200% (1.5-2 ori) Increase in sCr >200% - 300% (> 2-3 times) 0.5 mg/dl [44 mol/l])

<0.5mL/kg per hr, >6 hrs [240mL/6 hrs] <0.5mL/kg per hr, >12 hrs [500mL/12 hrs]

Injury

or

3 or

Failure Loss ESRD

Increase in sCr >300% (>3 times) <0.3mL/kg per hrs, 24 hrs sCr 4.0 mg/dL [300mL/24 ore] 0.5 mg/dl [44 mol/l] or anuria 12 hrs [354 mol/L] with and acute increase of at least 0.5 mg/dL [44 mol/L]

Are any biomarkers for AKI ?

Lipocalina AssociatedNeutrophil Gelatinase - NGAL

Cut off 100ng/mL la 2ore dup CPB

7 Bennett M et al: Clin J Am Soc Nephrol 3: 665-673, 2008

Incidence
General population:
New cases Needing HD 150-200 (500) pmp/yr 40-50 (200) pmp/yr 40 pmp/yr 1/20.000 births 45-72% of cases - General Hosp 2-4,5% - ICU >30% (55% iatrogenic factors)
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In special population:
Children (<18yr) Pregnant women Elderly (>75yr) Admited patients

Classification
ARF

PRE-RENAL
functional, circulatory (no kidney lession)

RENAL
intrinsic renal, organic (specific kidney lessions)

POST-RENAL
obstructive mechanical

50-80%

15-40%

3-5%

Acute tubular necrosis [Acute tubulo-interstial nephritis] (>50%)]

Acute interstitial nephritis (2-11%)

Acute glomerulonephritis (1-5%)

Vascular kidney disease (4%)

Ischaemia

Toxic
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Etiologic factors
Effective circulatory volume Central baroceptors activation

1. RBF self regulation

rfx myogen feed-back

At II

NA

AVP

2. V-constriction efferent aa 3. V-dilatation afferent aa

PGE2; PGI2 NO ET

PRE-RENAL ARF (INITIAL PHASE OF RENAL ARF)

No kidney lession

Afferent aa vasoconstriction Mesangium contraction

Renal blood flow GFR

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Normal and Impaired Autoregulation of the GFR during Reduction of Mean Arterial Pressure

Abuelo J. N Engl J Med 2007;357:797-805

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Intrarenal Mechanisms for Autoregulation of the GFR under Decreased Perfusion Pressure and Reduction of the GFR by Drugs

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Abuelo J. N Engl J Med 2007;357:797-805

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Pathophysiological Mechanisms of Ischemic Acute Tubular Necrosis

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Abuelo J. N Engl J Med 2007;357:797-805

Alterations in renal circulation autoregulation

1. Pre-glomerulary vasoconstriction
Sepsis Hepato-renal syndrome Hypercalcemia Drugs: NSAD, cyclosporin A, tacrolimus, amphotericyn B, Contrast media, epinephrine, nor- epinephrine

2. Post-glomerulary vasodilatation
ACEI Sartans

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Ischaemic kidney injury

Endotelial disfunction Medulary ischaemia

Medulary Nephrocytes lesions (PCT, HL) congestion Tubules obstruction GFR Back diffusion

ANURIC PHASE RENAL ARF Acute tubular necrosis

persistent GFR
Recovery (GFR, Epitelium)
POLYURIC PHASE 16 RENAL ARF

Mechanisms of oligo-anuria
Glomerulus
1. Vasoconstriction

1) Alterations in glomerular hemodinamycs 2) Decreased glomerular permeabilty 3) Tubular obstruction 4) Back diffusion of urine

2. Permeability Surface 3. Tubular obstruction nephrocytes casts interstitial edema 4. Back diffusion of urine epitelial lesions tubulorrhexis

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Diagnosis

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Positive diagnosis
1. High suspicion, in case of a suggestive background 2. Symptoms and signs of acute uremia, the most characteristic being oligo-anuria (500-300mL/24 h) 3. Acute, recent (hours, days) increase in urea (50-80mg/dL) and creatinine (1,2-1,4mg/dL) 4. Urinanalysis 5. Changes in serum electrolytes and AB parameters 6. Normal or high kidney dimensions

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Diagnostic flow-chart in ARF

High urea/Oligo-anuria ARF CRF differentiation Obstructive ARF exclusion Pre-renal ARF Renal ARF diffrentiation Diagnosis of the underlying condition

NTA

NIA

GN

Boli vasculare
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ARF vs CRF Differentiation

ARF History of CKD HBP Sygns and symptoms of RF Previous normal renal function Clinical examination Skin signs Malnutrition Pericarditis Cardiomegaly/OF Polyneuropathy Lab tests Anemia Kidney dimensions Renal ostheodystrophy (Rx) CRF Utility

++ ++ ++ + + + ++ +

+ + + ++++
+ + ++ ++ +

N -

++ ++

++ ++ ++++
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Diagnostic flow-chart in ARF

High urea/Oligo-anuria ARF CRF differentiation Obstructive ARF exclusion Pre-renal ARF Renal ARF diffrentiation Diagnosis of the underlying condition

NTA

NIA

GN

Boli vasculare
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Obstructive ARF exclusion

Clinical Data A. Suggestive history
Urolithyasis, gout, cancer, recent surgery Trauma, previous therapy (anticoagulants, cytotoxic/radiotherapy etc) Complete anuria suddenly installed or extreme day to day variation of diuresis (anuria polyuria), eventually after a renal colic, and accompanied by hematuria Symptoms suggesting lower urinary tract obstruction: dysuria, polakyuria, nicturia

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Obstructive ARF exclusion

Clinical data B. Examen obiectiv
Palpable, painful kidney(s) (uni-, bilaterally); Urinary bladder:
Distended in under-bladder obstruction Empty in upper urinary tract obstruction

Signs of the underlying condition (trauma, cancer etc) Rectal and/or vaginal examination are mandatory

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Obstructive ARF exclusion

Renal Rx (KUB, CT):
Radioopaque calculi (their absence could not exclude obstruction) Normal/increased dimensions of kidney

Renal ecography:
Dimensions of the kidneys Infromation about renal parenchaima The consequences of the urinary obstruction: distension of urinary tract, depending on acutness of obstruction The site of obstruction (sometimes)
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Obstructive ARF exclusion

Others Radio-urography seldom indicated:
Absent nephrograme total tubular obstruction; Progressive nephrograme lower tract obstruction; Could establish the site of obstruction (late examination).

CAT/RMN usefull for defining the site and the nature of the obstruction. Isotopyc nephrogaphy sometimes indicated

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Diagnostic flow-chart in ARF

High urea/Oligo-anuria ARF CRF differentiation Obstructive ARF exclusion Pre-renal ARF Renal ARF diffrentiation Diagnosis of the underlying condition

NTA

NIA

GN

Boli vasculare
27

Pre-renal ARF Renal ARF diffrentiation

Conditions which can produce pre-renal ARF Signs of reduction in effective circulatory volume Indexes Pre-renal Oliguric renal ARF ARF Density U >1016 <1016 Osm U (mOsm/L) >500 <350 Na U (mEq/L) <20 >40 Ur P/Cr P >60 <60 Osm U/Osm P >1,5 <1,1 Ur U/Ur P >8 <3 Cr U/Cr P >40 <20 EF% Na <1 >2 EF%Na Na Fractional excretion (NaU x CrP)/(NaP x CrU) U urine; P plasma; Cr creatinine; Ur urea; Na Sodium, Osm osmolality
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Evaluation of volemia
a) Intra-vascular effective volume depletion
1. Reduced jugulary veins pressure 2. Colabated peripheral veins 3. Arterial hypotension (AP lower >10mmHg and HR higher >10/min standing (or sitting, if standing not possible) 4. Cold extremities (nouse, fingers) 5. Small and rapid pulse 6. Oliguria

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Evaluation of volemia
b) Extracelullary volume depletion
1. 2. 3. 4. 5. 6. Thirst, asthenia Recent, high amplitude variation in weight Reduced skin temperature Reduced turgor Dryness of mucous membranes Hypotonia of eyes (low intra-ocular pressure)

7. Low juglar pressure 8. Colabated peripheral veins 9. Arterial hypotension (AP lower >10mmHg and HR higher >10/min standing (or sitting, if standing not possible) 10. Cold extremities (nouse, fingers) 11. Small and rapid pulses 12. Oliguria 30

Evaluation of volemia
c) Hypervolemia
Presiune venoas crescut Increased jugular jugular veins pressure crescut Galop S3 Creterea presiunii arteriale Increased AP Edeme, hepatomegalie congestiv, raluri de staz Edema, congestive hepatomegaly, bi-basal crakles

Hemodynamic parameters
Central venous pressure Pulmonary capillary (edge) pressure

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Oliguric ARF(<30mL/h) Identify & treat causes Yes Correct hypovolemia

0.9 saline Coloidal solution Blood

Hypovolemia ? No

Evaluate volemia
PVC >8cm H2O Signs of hypervolemia

Diuresis increases

No increase

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Furosemid 80mg iv (bolus)

Diuresis increase

No answer
Furosemid 2-4mg/min iv Dopamin 3mcg/kgb min 4 h Diuresis increase Stop furosemid Reduced diuresis Restart furosemid No answer RRT

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Diagnostic flow-chart in ARF

High urea/Oligo-anuria ARF CRF differentiation Obstructive ARF exclusion Pre-renal ARF Renal ARF diffrentiation Diagnosis of the underlying condition

NTA

NIA

GN

Boli vasculare
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Diagnosis of the underlying condition

Urine sediment
Pre-renal Renal ATN AIN normal or hyalin casts

Osm U/P
1 1 1 1 1

CrU/P

Na FENa (mEq/L) > 40 < 20 < 1%

< 40 < 40 > 20 > 20 1% 1%

granular and epithelial casts pyuria, hematuria, proteinuria, leukocytes, granular, epithelial casts GN hematuria, heavy proteinuria erytrocytes, granular casts Vascular normal or hematuria, Diseases light proteinuria

< 40 < 40

< 20 > 20

<1% < 1%

Post-renal

normal or hematuria, granular casts, pyuria

< 40

> 20

1%

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