ACUTE KIDNEY INJURY-ADVANCES IN DIAGNOSIS & MANAGEMENT

Dr.W.A.P.S.R Weerarathna.

Registrar in Medicine-WD 10/02

OBJECTIVES…

Anatomy /Physiology of the kidneys

Introduction- Acute Kidney Injury (AKI)

AKI-new classification/staging systems

Aetiology /mechanisms of AKI

Predisposing factors of AKI in adults

Novel markers of early detection of AKI

Evaluation & management-Recent thoughts

Summary

References

IMPORTANT ANATOMY/PHYSIOLOGY

20-25 % of cardiac output!

10% of resting oxygen consumption

Only 0.5% 0f human body mass!

Normal size- 11.5 cm diameter

Left kidney is 1.5 cm bigger than the right kidney

By 40 years- 10.5 cm by 70 years-9.5 cm

Size/e-GFR reduces with age!

INTRODUCTION

AKI complicates 5-7% of acute care hospital admissions

Up to 30% of ICU admissions!

In hospital mortality exceeds 50% in ICU setup.

In developing countries-diarrheal illnesses,infectious diseases like leptospirosis/malaria ect….

Small rises in S.Cr are associated with adverse patient outcomes including mortality.

Mortality- 10% in uncomplicated AKI to 80% in those with MOF!

AKI-DEFINITION

Acute kidney injury (AKI) has now replaced

the term Acute renal failure to reflect the

spectrum of illness severity & to facilitate

standardized research.

An universal definition and staging system

has been proposed to allow earlier detection

and management of AKI.

AKI

Is a clinical syndrome characterized by a

rapid deterioration of renal function over

hours to days due to variety of causes

resulting-

Failure to excrete nitrogenous waste

products

Disturbance in fluid balance

Abnormal electrolyte homeostasis

Disturbance in acid-base balance

DETECTING AKI-NICE

Detect AKI using (p)RIFLE, AKIN, KDIGO criteria:

Serum creatinine rise ≥ 26 micromol/litre (0.3mg/dl)from baseline within 48 hours OR

Serum creatinine rise by 50% or more in 7 days OR

Urine output < 0.5ml/kg body weight/hour for 6 consecutive hours in adults

AKI-CLASSIFICATION CRITERIA /STAGING

RIFLE-2004 VS AKIN-2007 CRITERIA

R isk

I njury

F ailure

L oss of function

E nd-Stage Renal disease

RIFLE-2004

AKIN-2007

CLASSIFICATION-PATHOPHYSIOLOGICAL

1. Pre renal azotemia/volume responsive

AKI-(50-60%)

2. Intrinsic renal parenchymal disease-

(20-30%)

3. Post renal obstruction- (5-15%)

AUTOREGULATION OF GFR UNDER DECREASED

PERFUSION PRESSURE BY DRUGS

INTRINSIC RENAL FALIURE

POST-RENAL FALIURE

AKI-OLIGURIC VS NON OLIGURIC

Non- Oliguric:

In hospital set-up, secondary Nephrotoxic

agents.

Non-oliguric has better prognosis than oliguric

AKI.

AKI- ICU VS NON ICU

Non-ICU AKI-

the kidney is usually the only failed organ

mortality rates of up to 10%.

ICU AKI-

is often associated with sepsis and with non-

renal multi-organ system failure(MOF)

mortality rates of over 50%

PREDISPOSING FACTORS FOR AKI IN ADULTS• Chronic kidney disease (or history of) (STAGE 3-5/eGFR<60)

• Diabetes

• Heart failure (CCF/AHF)

• Hypotension-SBP<100mmHg/drop of >40mmHg from the base

line)

• Sepsis

• Hypovolaemia

• Age 65 years or over

• Use of drugs with nephrotoxic potential (for example, NSAIDs,

ACEI)

• Use of iodinated contrast agents within past week

• Oliguria

• Liver disease /jaundice

• Limited access to fluids, e.g. via neurological impairment

• Deteriorating early warning scores

• Symptoms or history of urological obstruction

DIAGNOSTIC EVALUATION OF AKI

STEP 1-History of the patient & Clinical

exam

STEP 2- Investigations

Urinalysis/Haematological

investigations/Radiology & imaging

modalities

STEP 3- Selected therapeutic trials

STEP 4-Renal biopsy (in certain situations)

URINALYSIS IN AKI

PRE RENAL VS INTRINSIC RENAL

RADIOLOGY

Renal ultrasound /CT(useful for obstructive forms/post renal AKI & acute vs CKD)

Doppler scans(to assess renal blood flow) Anterograde/retrograde Pyelography-in

doughtful cases Nuclear imaging studies :

DMSA: anatomy.DTPA and MAG3: renal function,urinaryexcretion and upper tract outflow ect…

(MRI with Gd enhancement is better avoided to prevent NSF in ESRF)

HAEMATOLOGY

FBC/CBC &PBF-for diagnostic clues

BU/BUN & S.Cr-markers of glomerular filtration

U&E’s/S.Ca/S.PO4

Coagulation profile

ABG-anian gap –high in any cause of uraemia/low in MM

CPK/Myoglobinuria/uric acid - rhabdomyalysis

Immunological assays-compliments/ANA/ANCA/AGBM/cryoglobulins-in GN & vasculitides

Virological markers

NOVEL BIOMARKERS-eairly & accurate diagnosis

NOVEL BIOMARKERS OF AKI-RATIONALE

IMPORTANT BIOMARKERS….RELEASED AS A

RESULT OF KIDNEY INJURY!!!!

Kidney injury molecule-1 (KIM-1)

Neutrophil gelatinase associated lipocalin(NGAL)

Cystatin –C

Interleukin -18

Clusterin

Osteopontin

Cysteine rich protein (CYR 61) ect…

CYSTATIN-C

Superior to serum creatinine, as a surrogate

marker of early and subtle changes of kidney

function.

Identifies kidney injury while creatinine levels

remain in the normal range.

Allows detection of AKI, 24-48 hours earlier

than serum creatinine !

KIM-1

KIM-1 is a type 1 trans-membrane

glycoprotein

Served as a marker of severity of AKI

Can be used to predict adverse outcomes in

hospitalized patients better than

conventionally used severity markers.

NGAL

Highly up regulated after inflammation and

kidney injury and can be detected in the

plasma and urine within 2 hours of

cardiopulmonary bypass–associated AKI.

Considered equivalent to troponin in acute

coronary syndrome.

RENAL BIOPSY IN DIGNOSIS OF AKI

Considered when pre /post renal

azotemia,ischaemic/nephrotoxic AKI are

unlikely

Suspicion of-GN/vasculitides /TIN/myeloma

kidney/HUS&TTP

Definitive diagnosis & prognostication of AKI

Organ/life threatening bleeding may occur

with coagulopathy/thrombocytopenia!

MANAGEMENT OF AKI-PRIORITIES

Evaluate promptly to determine the cause

Monitor the patient with S.cr/BU daily basis &

UOP frequently

Manage according to the cause and stage of

AKI

Evaluate patients at 3 months for resolution

or worsening of preexisting CKD

AKI STAGES

TREATMENT & PREVENTION OF AKI

Management of the specific cause

Management of hypotension & shock-optimizing haemodynamics with fluid resuscitation & vasopressors

Treatment if infection/concurrent sepsis

Glycaemic control & nutritional support

Elimination of nephrotoxic medication

Use of diuretics

Vasodilator therapy

Growth factor intervention

Role of erythropoitein

RRT

HYPOTENTION /SHOCK-WHICH FLUID & HOW

MUCH? KDIGO recommends using isotonic crystalloids(0.9%

saline/Hartmann’s) rather than colloids (albumin or starches) .

(increased risk of AKI with use of high molecular weight starches in severe sepsis-Lancet 2001; 357:911-6)

Colloids- in some patients to avoid excessive fluidadministration in patients requiring large volume resuscitation, or

in specific patient subsets (e.g., a cirrhotic patient with spontaneous peritonitis, or in burns).

Colloids- 4%Albumin is renoprotective and Hyperoncotic starch shows nephro- toxicity.

There is no benefit of using colloids over crystalloids in managing AKI in terms of survival or need/duration of RRT.

VASOPRESSORS/INOTROPES

To those who refractory to fluids to maintain renal perfusion

Norepinephrine ,vasopressin

Useful in septic shock/burns/liver failure

Appropriate use of vasoactive agents can improve kidney perfusion in volume resuscitated patients with vasomotor shock.

KDIGO recommends not to use low-dose dopamine to prevent or treat AKI/doesn’t provide any benefit in preventing or eairytreatment of AKI. (1A)

GLYCAEMIC CONTROL/NUTRITION

Target glycaemic control

Plasma glucose- 80-110 mg/dl

Intense glycaemic control increases

mortality & doesn’t delay RRT.

Total calorie intake – 20-30 Kcal/Kg

Protein intake – 0.8-1.0 g/Kg/day-non catabolic

- 1.0-1.5 g/Kg/day-catabolic

state

ROLE OF DIURETICS (FRUSEMIDE)

No evidence to reduce incidence or severity of AKI

Indicated only in volume over load states!

Diuretics only converts oliguric to non oliguricrenal faliure!

It promotes eairly diuresis but no effects on survival!

Increased the risk of AKI when given to contrast induced AKI.

ROLE OF VASODILATOR THERAPHY IN AKI

Low dose dopamine –NO

BENEFIT/NEGATIVE RESULTS UN

VARIOUS STUDIES!

Fenoldopen (pure dopamine type-1 receptor

agonist/without systemic adrenergic

stimulation)- NOT USEFUL!

ANP-NOT USEFUL!

GROWTH FACTOR INTERVENTION IN AKI

• Recombinant human IGF-1 -peptide with renal

vasodilatory/mitogenic and anabolic properties.

• KDIGO Work Group recommends against its

use in patients with AKI!

ROLE OF EPO IN PREVENTION OF AKI

Recent animal studies suggest a potential clinical benefit of

erythropoietin in AKI.

• The renoprotective action of Epo may be related to

pleomorphic properties including antiapoptotic and

antioxidative effects, stimulation of cell proliferation, and

stem-cell mobilization.

• Although one recent RCT in the prevention of human AKI

was negative, the usefulness of erythropoietin in human AKI

should be further tested in RCTs.

• NOT USEFUL IN PREVENTING AKI IN HUMAN

ROLE OF RRT IN AKI Established oligo-anuric AKI/do not respond to initial

management

HD/PD/CRRT(CVVH-continuous veno-venous haemofiltration/CVVD/CVVHD ect

Indications or RRT- 1. Hyperkakaemia refractory to medication

2. Persisting anuria/oliguria despite adequate fluid resusitation

3. Fluid overload refractory to diuretics

4. Refractory metabolic acidosis

5. Uraemicsyndrome/ complications-encephalopathy/pericarditis/vomiting

6. Poisoining-lithium/salicylates

7.Trends of S.Cr/BU levels-there is no definite level!

SUMMARY

AKI is common & often preventable!

Associated with increase in morbidity & mortality world wide.

Many patients respond to simple measures if act accordingly.

Novel staging systems, biomarkers, therapeutic modalities are implemented for better evaluation& management of patients with AKI.

Timely RRT may improve the survival!

THANK YOU!