Prof & HOD Dr K A S MurthyChair person Dr Ashok P

Guest Dr Kiran.KK

Presenter Dr VamsaVardhan P

What is AKI

AKI is defined as -

Increase in Serum Cr by 0.3 mg/dl within 48 hours

OR

Increase in Serum Cr to 1.5 times of baseline, which is known or presumed to have occurred within the prior 7 days

OR

Urine volume <0.5 ml/kg/h for 6 hours.

AKIN Criteria

RIFLE Criteria

Why do we care about AKI

Epidemiology

• It occurs in

– 5% of all hospitalized patients and

– 35% of those in intensive care units

• Mortality is high:

• up to 75–90% in patients with sepsis

• 35–45% in those without sepsis

Etiology

Conceptual model for AKI

Kidney International Supplements (2012) 2, 19–36

Natural history of AKI

Kidney International Supplements (2012) 2, 19–36

(8-22%)

(2-8%)

c/f

Asymptomatic

elevations in the plasma creatinine

abnormalities on urinalysis

Signs and symptoms resulting from loss of kidney function:

decreased or no urine output, flank pain, edema, hypertension, or discolored urine

Cont… Symptoms and/or signs of renal failure:

weakness and

easy fatiguability (from anemia),

anorexia,

vomiting, mental status changes or

Seizures

edema

Systemic symptoms and findings:

fever

arthralgias,

pulmonary lesions

Diagnosis

Detailed history

Blood urea nitrogen and serum creatinine

CBC, peripheral smear, and serology

Urinalysis

Urine electrolytes

U/S kidneys

Serology: ANA,ANCA, Anti DNA, HBV, HCV, Anti GBM,

cryoglobulin, CK, urinary Myoglobulin

Differences between AKI & CKD

AKI CKD

Urine analysis

Urine analysis

Unremarkable in pre and post renal causes

Differentiates ATN vs. AIN. vs. AGN

Muddy brown casts in ATN

WBC casts in AIN (few rbc can +)

RBC casts in AGN (few wbc can +)

Hansel stain for Eosinophils - AIN

Urine output

An acute reduction in urine output (oliguria - <400 mL/24 h & Anuria - <100ml/24 hr) usually denotes more significant AKI (i.e., lower GFR).

An Oliguria is associated with worse clinical outcomes.

Non oliguric AKI seen in nephrogenic DI which is characteristic of longstanding urinary tract obstruction, tubulointerstitial disease, or nephrotoxicity from cisplatin or aminoglycosides .

Urine output cont..

Complete anuria (<100 ml/day )early in the course of AKI is uncommon except

1) Hypovolemic shock

2) complete urinary tract obstruction,

3) renal artery occlusion,

4) overwhelming septic shock,

5) severe ischemia (often with cortical necrosis),

6) severe proliferative glomerulonephritis or vasculitis.

Urine colour (haematuria)

Red or brown urine may be seen with or without gross hematuria.

If the color persists after centrifugation, then its pigment nephropathy(rhabdomyolysis or hemolysis)

Endogenous Drugs Food substances

1) RBC2) Hb3) MYOGLOBIN4) BILIRUBIN5) MELANIN6) PORPHYRIN

1) CHLOROQUINE2) QUININE3) RIFAMPICIN4) SULPHONAMIDES5) LEVODOPA6) METHYLDOPA7) NITROFURANTOIN8) PHENOPHTHALEIN9) PHENYTOIN10) METRANIDAZOLE

1) BEETROOT2) BLACK BERRIES3) BLUE BERRIES4) FAVA BEANS5) ARTIFICIAL FOOD

COLOURING

Glomerular / Urologic bleeding

Glomerular Non glomerular/Urologic

Urine colour Dark red /cola coloured /smoky

Bright red

clots - +

proteinuria + -

RBC morphology Dysmorphic Isomorphic

HTN & Edema + -

Renal function Decreased normal

URTI + -

Fever ,rash + -

Urinary voiding sym - +

trauma - +

Flank pain - +

CBC

Anemia is common in AKI and is usually multifactorial in origin.

Severe anemia in the absence of bleeding

Hemolysis,

Multiple myeloma

Thrombotic microangiopathy

Collagen vascular disorders

(Thrombocytopenia, schistocytes on peripheral blood smear, elevated LDH & low haptoglobin content)

Cont..

Peripheral eosinophilia -

Interstitial nephritis

Atheroembolic disease

Polyarteritis nodosa

Churg-Strauss vasculitis

Dyselectrolytemia:hyperkalemia &hyperphosphatemia

Creatinine Phosphokinase increase – Rhabdomyolysis

Uric acid increase - TLS & Rhabdomyolysis

Renal failure indices

PreRenal ATN

Specific gravity > 1.020 < 1.010

Urine osmolality (mOsm/kg) > 500 < 350

U osm/P osm > 1.3 < 1.1

Urinary Na < 20 > 40

U/P urea nitrogen > 8 < 3

U/P creatinine 40 < 20

FENa(%) < 1 > 1

RFI (renal failure index) < 1 > 1

FEurea (%) < 35 > 35

FENa :

UNa x Pna

FENa = ————— x 100PNa x UCr

FENa < 1% (Pre-renal state)

May be low in selected intrinsic cause

Contrast nephropathy

Acute GN

Myoglobin induced ATN

FENa > 1% (intrinsic cause of ARF)

BUN/Cr helpful in classifying cause of ARF

ratio> 20:1 suggests prerenal cause like catebolic states, GIB , steroids , hypovolemia.

Radiologic evaluation

Imaging with USG – PVR / CT KUB – post renal AKI .

(dilatation of pelvicalyceal system & HUN )

Simple bladder catheterization can rule out urethral obstruction.

Obstruction can be present without radiologic abnormalities in the setting of retroperitoneal fibrosis, encasement with tumor, and also early in the course of obstruction.

Antegrade or Retrograde pyelography – high index of suspicion of obstruction with normal imaging.

Renal scan - assessing kidney size & echogenicity

- AKI vs CKD

Large kidney in CKD :-

1) Diabetic nephropathy,

2) HIV-associated nephropathy, 3) Infiltrative diseases,

4) AIN (occassionally)

5) ADPKD

Renal vessel doppler .

MRI- gadolinium scan helpful ,but disadvantage of nephrogenic fibrosis especially seen in oliguric AKI in end stage(dialysis dependent).

Anion gap

The anion gap may be increased with any cause of uremia due to retention of anions such as phosphate, hippurate, sulfate & urate.

The co-occurrence of an increased anion gap and an osmolal gap- ethylene glycol poisoning.

which also cause oxalate crystalluria.

Low anion gap - multiple myeloma

(unmeasured cationic proteins)

Glomerulonephritis and Vasculitis (Intrinsic causes)

a) Depressed complement levels

b) High titers of Antinuclear antibodies (ANAs),

c) Antineutrophilic cytoplasmic antibodies (ANCAs),

d) Antiglomerular basement membrane (AGBM) antibodies

e) Cryoglobulins

Complement levels in Acute Nephritic syndrome – Low C3 & C4

Systemic causes Renal localized causes

1) SLE

2) Cryoglobulinemia(Hep C )

3) Bacterial endocarditis

4) Shunt Nephritis

1) Acute PSGN (low C3 & Normal C4)

2) MPGN – type 1 (low C3 & C4)

3) MPGN – type 2 (low C3 & normal C4)

Acute nephritis –Normal Complement

Systemic Renal

1) PAN

2) HSP

3) Goodpasture’s syndrome

4) Wegener’s granulomatosis

5) Hypersensitivity vasculitis

1) IgA nephropathy

2) RPGN

3) Anti GBM localised to kidney

4) Pauci-immuen GN (kidney localised)

Kidney biopsy indications

1) Unexplained AKI.

2) Even in prerenal AKI >1 m duration

3) Rapidly progressive AKI

4) Dialysis dependent AKI

5) AKI – systemic disease / glomerular etiology

6) Significant proteinuria (> 1g/24 hr)

7) Microscopic hematuria with any degree of proteinuria

S.E :- Risk of bleeding in patients with thrombocytopenia or coagulopathy.

Contraindication for P/C renal biopsy

Absolute Relative

a) Uncontrolled Htn

b) Bleeding diathesis

c) Widespread cystic disease / renal malignancy

d) Hydronephrosis

e) Uncooperative pt

a) Single kidney

b) Antiplatelet / Anticoagulant therapy

c) Anatomic abnormalities

d) Small kidney’s

e) Active urinary/ local skin sepsis

f) Obesity

Biomarkers

BUN and creatinine are functional biomarkers of glomerular filtration rather than tissue injury and, therefore, it is suboptimal for the diagnosis of actual parenchymal kidney injury.

Kidney injury molecule-1 (KIM-1) is a type 1 transmembrane protein that is abundantly expressed in PCT injured by ischemia or nephrotoxins such as cisplatin.

KIM-1 is not expressed in appreciable quantities in the absence of tubular injury or in extrarenal tissues.

(KIM-1’s - phagocytic properties to tubular cells.)

Neutrophil gelatinase associated lipocalin ( NGAL , also known as lipocalin-2 or siderocalin) .

NGAL was first discovered as a protein in granules of human neutrophils.

NGAL can bind to iron siderophore complexes and may have tissue-protective effects in the proximal tubule.

NGAL is highly upregulated after inflammation and kidney injury and can be detected in the plasma and urine within 2 hours of cardiopulmonary bypass –associated AKI.

Novel biomarker

Complications of AKI

1) Uraemia

2) Hyper / hypovolemia

3) Hyponatremia

4) Hyperkalemia

5) Hyperphosphatemia / hypocalcemia

6) Metabolic acidosis

7) Bleeding

8) Infection risk

9) Cardiac –pericarditis, arrhythmia &pericardial effusion

10) Malnutrition

ATN

Most common cause of intrinsic cause of ARF

Often multifactorial

Ischemic ATN:

Hypotension, sepsis, prolonged pre-renal state

Nephrotoxic ATN:

Contrast, Antibiotics, Heme proteins

ATN

Diagnose by history, FENa (>2%)

sediment with coarse granular casts, RTE cells

Treatment is supportive care.

Maintenance of euvolemia (with judicious use of diuretics, IVF, as necessary)

Avoidance of hypotension

Avoidance of nephrotoxic medications (including NSAIDs and ACE-I) when possible

Dialysis, if necessary

80% will recover, if initial insult can be reversed

Contrast induced nephropathy

Most cases of Contrast induced nephropathy

manifested as an asymptomatic , transient decrease in

renal function & nonoliguric.

CI-AKI - an increase in SCr by 425% or 0.5 mg/dl occurring within 72 hours after contrast medium

administration, in the absence of an alternative

etiology for the decrease in kidney function.

Nonoliguric variant creatinine levels usually peaks @ 3-5 days & returns to normal @ 10-14 days.

Oliguric variant creatinine levels peaks @ 5-10 days & returns to normal @ 14-21 days.(may need dialysis)

Risk Factors:

CKD, Hypovolemia ,DM – nephropathy, CHF, Advancing age, ongoing treament with nephrotoxic drugs, multiple myeloma, hepatic failure, prior load contras with in 48-72 hr & use of diuretics etc .

Rx/Prevention:

Crystalloids 1ml/kg/hr , 12 hours pre & post study

(0.5-1 lt)

N-acetyl cystein 600 BID pre & post (4 doses)

Adenosine antagonist (theophylline 200mg IV single dose 30 min prior to study),

Nahco3 infusion

dopamine agonist(fenoldopam)

Statins 80mg/day

Kidney International Supplements (2012) 2, 69–88

Rhabdomyolysis

Common after trauma (“crush injuries”), seizures, burns,

limb ischemia occasionally after IABP or

cardiopulmonary bypass.

Diagnose with serum CK (usu. > 10,000), urine dipstick

(+) for blood, without RBCs on microscopy, pigmented

granular casts

Treatment is largely supportive care (IV Fluids).

Acute GN

Rare in the hospitalized patient

Diagnose by history, hematuria, RBC casts, proteinuria (usually non-nephrotic range), low serum complement

RPGN often associated with anti-GBM or ANCA

Usually will need to perform renal biopsy

Atheroembolic AKI

Associated with emboli of fragments of atherosclerotic

plaque from aorta and other large arteries.

Diagnose by history, physical findings (evidence of other

embolic phenomena--CVA, ischemic digits, “blue toe”

syndrome, etc), low serum C3 and C4, peripheral

eosinophilia, eosinophiluria, rarely WBC casts.

Commonly occur after intravascular procedures or

cannulation (cardiac cath, CABG, AAA repair, etc.)

AIN

Usually drug induced

methicillin, rifampin, NSAIDS

Develops 3-7 days after exposure

Fever, Rash , and eosinophilia common

Usually Non-oliguric AKI

U/A reveals WBC, WBC casts, + Hansel stain

Often resolves spontaneously

Steroids may be beneficial ( if Scr>2.5 mg/dl)

Treatment

Optimization of hemodynamic and volume status

Avoidance of further renal insults

Optimization of nutrition

If necessary, institution of renal replacement therapy

Indication for RRT

1) Symptoms of uremia ( encephalopathy..,)

2) Uremic pericarditis

3) Refractory volume over load

4) Refractory hyperkalemia

5) Refractory metabolic acidosis

Reference

Harrison’s internal medicine 18th edition

Brenner & Rector’s 9th edition

CMDT 2013

KDIGO clinical practice guidelines for AKI .

(JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY -

2012)

Thank you