Dr S. Karthikeyan,

Prof P. Vijayaraghavan’s Unit

Stanley Medical College

Definition ARF is a sudden and usually reversible decrease in

the glomerular filtration rate (GFR) occurring over a period of hours to days

.The term “Acute Kidney Injury” now replaces the

term ARF; the term ARF should now be restricted to patients who have AKI and “need renal replacement therapy”.

Acute kidney injury classification -ADQI

RIFLE criteria

Serum Creatinine as a marker for AKI and GFR

Normal S.Creatinine is 0.6-1.2mg/dl and is the most commonly used parameter to assess renal function.

Unfortunately the correlation between S.Creatinine concentration and GFR may be confounded by several factors.

Ser

um

Cre

atin

ine

(mg

/dl)

GFR (ml/min per 1.73m2)

1.0

0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

40 60 80 100 120 140 160 180200

There is abrupt drop in GFR but the S.Cr. does not start going up for 24 or 36 hours after the acute insult .

40

80

0

GFR(mL/min)

0 7 14 21 28

4

Days

2

0

6

Serum Creatinine(mg/dL)

Relationship between GFR and serum creatinine in ARF

Creatinine is not an ideal marker

1. Creatinine excretion is dependent on renal factors independent of function:Certain medications such as cimetidine and

trimethoprim interfere with proximal tubular creatinine secretion and may cause rise in S. creatinine without fall in GFR.

2. S.Creatinine is dependent on nonrenal factors independent of renal functionS.Creatinine is dependent on muscle mass,

infection, volume of distribution, age, gender, race, body habitus, diet, presence of amputations.

Eg. S. Creatinine of 1.2mg/dl in a 40kg elderly signifies severe reduction of GFR while the same value in a 100kg represents a normal renal function

3. Creatinine production and excretion must be in a steady state before creatinine may be used in any formula for the estimation of GFR.

NEW MARKERCystatin C –protein

Produced by nucleated cells

Filtered and completely reabsorbed

Changes in serum levels occur sooner

NOVEL BIOMARKERS1. IL- 18

2.KIM-1

3.Gro α/KC

4.NGAL-neutrophil gelatinase associated lipocalin

5.NHE-3

Spectrum of AKIPrerenal : renal hypoperfusion

Renal (Intrinsic) :GlomerularTubularVascular Interstitial

Post renal: obstruction

InjuryInjury

Generalized or localized reduction in RBF

HaemorrhageHaemorrhageVolume depletionVolume depletion

( vomiting,( vomiting,diarrhoea,diarrhoea,

inappropriate inappropriate diuresis, burns)diuresis, burns)

Cardiogenic shockCardiogenic shockDistributive Distributive shockshock

(sepsis, (sepsis, anaphylaxis)anaphylaxis)

Cardiac failureCardiac failureHepatic cirrhosisHepatic cirrhosis

Nephrotic syndromeNephrotic syndrome

NSAIDs NSAIDs ACEI / ARBsACEI / ARBs

AAAAAARAS /occlusionRAS /occlusion

Reduced GFR

PRE-RENAL (Hemodynamic) AKI

PRERENAL AKI

Pre renal AKI characteristics:Decreased RBF and GFR

Increased Na and H2O reabsorption

Oliguria

High Uosm (>500), low UNa ( FeNa <1%)

Elevated BUN / S.Cr. Ratio

Bland urinary sediments

TubularTubularGlomerularGlomerular VascularVascularInterstitialInterstitial

ATNATN

Ischemia (50%)Ischemia (50%)Toxins (30%)Toxins (30%)

Ac. Interstitial Ac. Interstitial nephritisnephritis

Drug inducedDrug induced - - NSAIDs,NSAIDs,

antibioticsantibioticsInfiltrative -Infiltrative -lymphomalymphoma

Granulomatous- Granulomatous- sarcoidosis, sarcoidosis, tuberculosistuberculosis

Infection relatedInfection related - - post-infective, post-infective, pyelonephritispyelonephritis

Vascular Vascular occlusionsocclusions

- - Renal artery Renal artery occlusion occlusion

- Renal vein - Renal vein thrombosisthrombosis

- Cholesterol - Cholesterol emboliemboli

Ac.GN Ac.GN

–post-infectious,post-infectious,– SLE,SLE,–ANCA associated,ANCA associated,–anti-GBM diseaseanti-GBM disease–Henoch-Schönlein Henoch-Schönlein purpurapurpura–Cryoglobulinaemia,Cryoglobulinaemia,–Thrombotic Thrombotic microangiopathy microangiopathy

•TTPTTP•HUSHUS

5%5%

85%85%

8 -12%8 -12%

< 2%< 2%

ATN

CAUSES:

1.Ischemia

2.Infection with or without sepsis

3.Toxins –exogenous- radiocontrast,ampho-B

aminoglycosides

-endogenous-rhabdomyolysis,

hemolysis

ATN cont…. Common sites –

S3 segment of the proximal tubule

Thick ascending limb (more glycolytic machinery for ATP synthesis)

Medullary blood flow -- 10% to 15% of total RBF

Relative hypoxia in the outer medulla ;

PaO2 50 mm of

Hg

PaO2 20 mm of

Hg

10 mm of Hg

PaO2

Phases of ATN Initiation : - hours to days GFR declines Extension :- continuing ischemic injury and

inflammation GFR low Maintenance:- 1-2 weeks GFR stabilises uremic complications may arise Recovery :- GFR rises

ATN characteristics:Decreased GFR, Oliguria

Decreased Na reabsorption

Low Uosm (< 350), High UNa (FeNa >1%)

Elevated BUN / S.Cr.

Urinary sediments- Muddy pigmented granular casts

Intra-luminalIntra-luminal•Stone,Stone,•Blood clots, Blood clots, •Papillary Papillary necrosisnecrosis

•Pelvic Pelvic malignanciesmalignancies•Prolapsed uterusProlapsed uterus•Retroperitoneal Retroperitoneal fibrosisfibrosis

IntrinsicIntrinsic

Intra-mural Intra-mural •Urethral stricture, Urethral stricture, •BPH, BPH, •Carcinoma prostate,Carcinoma prostate,• Bladder tumour,Bladder tumour,• Radiation fibrosisRadiation fibrosis

ExtrinsicExtrinsic

Post-renal Urinary outflow tract obstruction

ComplicationsMETABOLIC:

hyperkalemia, hyponatremia,

hypocalcemia, hyperphosphatemia,

hyperuricemia, metabolic acidosisCVS:

pericarditis/effusion , hypertension ,MI,

arrhythmias, pulmonary edemaGIT:

nausea, vomiting, malnutrition ,GI hemorrhage

CNS:

asterixis ,mental changes ,seizures

INFECTIONS:

pneumonia ,sepsis

Approach to a patient with AKI

Differentiate acute or chronic renal failure

Distinguishing between acute and chronic renal

failure is important, as the approach to these

patients differs greatly.

Factors that suggest chronicity :

Long duration of symptoms,

Absence of acute illness, anaemia,

hyperphosphatemia, and hypocalcaemia,

Previous Serum creatinine measurements

Small kidneys on ultrasound (except for in -Diabetes, PCKD, Urinary Tract Obstruction)

Exclude obstruction

Urological evaluation

Renal stones,

Symptoms of bladder outflow obstruction- Prostate

enlargement Prolapsed uterus

A palpable bladder.

CONTD ...

X-ray KUB

Renal ultrasonography – detect dilatation of the renal

pelvis and calyces

CT Scan

Evidence of renal parenchymal disease

(other than ATN)

History and examination (systemic features)

Urine dipstick

Urine microscopy (red cells, red cell casts,

eosinophils, proteinuria)

Signs of major “vascular occlusion”

Loin pain

Macroscopic haematuria

Anuria

Renal asymmetry

Assess the volume status of the patient:

Pulse,

JVP,

postural blood pressure,

daily weights,

fluid balance/fluid challenge

INVESTIGATIONS BiochemistryBlood urea, creatinine,

electrolytes,

Blood gas analysis.

Urine osmolality/sodium

Sr.Creatine kinase, myoglobin in urine

Markedly elevated CK and myoglobinuria suggests rhabdomyolysis

Serum immunoglobulins, serum protein electrophoresis, Bence Jones proteinuria

Monoclonal band on serum protein

electrophoresis, and Bence Jones proteinuria suggest multiple myeloma

Urine analysis:

Dipstick for blood, protein - Suggests a renal inflammatory process

Microscopy for cells, casts, crystals

RBC s Present in glomerulonephritis , vasculitis , HUS TTP scleroderma crisis

Casts:Hyaline –prerenal ARF

Granular –ATN (muddy brown)

Red blood cell casts –glomerulonephritis,vasculitis

malignant hypertension

WBC casts- AIN, pyelonephritis ,leukemic or

lymphomatous infiltrates

Crystals Urate crystals – acute urate nephropathy

Oxalate crystals –ethylene glycol ingestion /acyclovir/

indinavir

Eosinophiluria > 5 % of WBC s AIN ,atherothrombotic

disease

HaematologyFull blood count, blood film:

Eosinophilia may be present in acute interstitial nephritis,

cholesterol embolization, or vasculitis (CSS)

Thrombocytopenia and red cell fragments suggest thrombotic microangiopathy –TTP, HUS

Coagulation studies Disseminated intravascular coagulation associated

with sepsis

ImmunologyAntinuclear antibody (ANA) , Anti-double

stranded (ds) antibody - ANA positive in SLE and other autoimmune

disorders;DNA antibodies anti-ds DNA antibodies more specific for SLE

C3 & C4 complement concentrations-Low in SLE, acute post infectious

glomerulonephritis, CryoglobulinemiaASO and anti-DNAse B titres

High after streptococcal infection

Immunology...ANCA

p-ANCA - Anti PR3 antibodies c-ANCA - Anti MPO antibodies

Associated with systemic vasculitis - Wegener’s granulomatosis; CSS, Microscopic polyangiitis.

AntiGBM antibodies Present in Goodpasture’s disease

SerologyHepatitis B and C, HIV serology

Important implications for infection control within dialysis area

RadiologyRenal ultrasonography

For renal size, symmetry, evidence of obstruction

Management principles in ARF

Identify and correct pre-renal and post-renal factors

Optimise cardiac output and RBF :

Stop/adjust the dose of nephrotoxic drugs (ACEI, ARBs,

NSAIDs)

Management principles...

Accurately monitor fluid balance and daily body weight

Identify and treat acute complications

Hyperkalaemia,hypertensionAcidosis,Pulmonary oedema

Management of complications Volume overload –salt restriction < 1 – 1.5 g/d water restriction -< 1

litre /d diuretics

Hyponatremia –restriction of oral & intravenous fluids

Hyperkalemia – K binding resins ,glucose + insulin

Ca gluconate ,soda bicarb.Metabolic acidosis – soda bicarb ., if < 15 meq Hyperphosphatemia – PO4 binders –sevalamer

Contd….Hypocalcemia –calcium carbonate

Nutrition –restriction of dietary protein < 0.8 g/kg /d

calories – 25-30 kcal / d enteral nutrition preferred

Contd …

Identify and aggressively treat infection;

Minimise indwelling lines

Identify and treat bleeding tendency:

Prophylaxis - proton pump inhibitor or H2 antagonist, transfuse if required

Absolute indication for dialysis Evidence of uremia ;

Intractable volume overload

Hyperkalemia

Severe metabolic acidosis refractory to medical

measures

Thank you Thank you