acte kidney injury-advances in diagnosis & management
TRANSCRIPT
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!