Acute Renal Failure- Etiology and Pathophysiology - PowerPoint Presentation

Slide1

Acute Renal Failure- Etiology and Pathophysiology

Dr. Mohd. Aslam

Slide2

Anatomy

Slide3

Basic Renal Physiology

Nephron

is the functional unit of the kidney

Capable of forming urine, has two major

components:– Glomerulus– Tubule:• proximal• loop of Henle• Distal• collecting

Slide4

Outline

Definition of ARF

Epidemiology

Etiology of ARF

Pathophysiology

Management of ARF– Diagnosis of ARF– Treatment of ARF

Slide5

DEFINITION:

AKI 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 Acute Renal Failure should now be restricted to patients who have AKI and “need renal replacement therapy”The kidneys receives 20% of the cardiac output

Slide6

‘ACUTE KIDNEY INJURY’

Abrupt reduction [<48 hrs] in kidney function, defined as an absolute increase in

S.creatinine

of ≥0.3 mg/

dL.A percentage increase in S.creatinine of ≥ 50% [1.5 fold from baseline] or a reduction in urine output– documented oliguria of < 0.5 ml/kg/hr, for more than six hours.

Slide7

Epidemiology

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 sepsis35–45% in those without

Slide8

AKI: Urine Volume

•

Anuria

(< 100 ml/24h)

– Acute bilateral arterial or venous occlusion

– Bilateral cortical necrosis– Acute necrotizing glomerulonephritis– Obstruction (complete)• Oliguria (100-500 ml/24h)

– Pre-renal

azotemia

– ATN

• Non-

Oliguria

(> 500 ml/24h)

– ATN

– Obstruction (partial)

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Classification provides:

– Information on etiology of ARF

– Information on prognosis

– Directs appropriate therapy

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Staging

Slide11

Staging

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RISK FACTORS

Advanced age, older than 75 years

Atherosclerosis

Diabetes

HTN

Heart failureLiver diseasePersons with Kidney diseases e.g. preexisting chronic kidney diseasesepsis.Exposed to contrast agents or undergoing cardiac surgery.

Slide13

CAUSES OF ACUTE KIDNEY INJURY

Slide14

Pre-renal causes of AKI

Volume depletion

• Renal losses (diuretics,

polyuria

)

• GI losses (vomiting, diarrhea)• Hemorrhage• PancreatitisDecreased cardiac output• Heart failure• Pulmonary embolus• Acute myocardial infarction• Severe valvular

heart disease

Slide15

Post-renal causes of AKI

Ureteric

obstruction

• Stone disease

• Tumor

• Ligation during pelvic surgeryBladder neck obstruction• BPH• Cancer of the prostate• Drugs (Tricyclic antidepressants, ganglion blockers)• Bladder tumor

• Stone disease, hemorrhage/clot

Urethral obstruction (strictures, tumor)

Slide16

Renal Causes of AKI

:

• Large Vascular

• Small vascular and

Glomerular• Interstitial nephritis• Acute tubular necrosis

Slide17

Renal Causes of AKI

Large Vascular

:

•

Renovascular disease + ACEI• Renal artery thrombosis/dissection• Cholesterol emboli (recent Cardiac cath/aortic surgery)• Renal vein Thrombosis (hypercoagulable

,

Nephrotic

)

Slide18

Acute Glomerulonephritis (GN) / Small

vascular

•

Anti–GBM disease (

Goodpasture

syndrome)• ANCA-associated GN (Wegener granulomatosis, microscopic polyangiitis)• Immune

complex

GN (lupus,

cryoglobulinemia

, primary MPGN)

•

IgA

nephropathy

• HUS/TTP

• Malignant hypertension

Slide19

Tubular

• Ischemic

• Toxic

–

Heme

pigment (rhabdomyolysis, intravascular hemolysis)– Crystals (tumor lysis syndrome, ethylene glycol poisoning, methotrexate)

– Drugs (

aminoglycosides

, lithium,

amphotericin

B,

radiocontrast

agents)

Slide20

Interstitial

•

Drugs (

penicillins

, NSAIDs,

allopurinol, rifampin, sulfonamides)• Infection (pyelonephritis, viral nephritis)• Systemic disease (Sjogren syndrome,

sarcoid

,

lupus, lymphoma )

Slide21

Pathophysiology

•

Increase in

NaCl

delivered to macula

densa. Damage to proximal tubule cells increases NaCl delivery to distal nephron. This causes disruption of feedback mechanism.• Obstruction of tubular lumen.

Casts clog the lumen. This will increase the tubular pressure and then GFR will fall.

•

Backleak

of fluid through the tubular basement membrane.

Slide22

Pathophysiology

It includes one of these 3 major patterns:

1)

Syndrome of acute nephritis

2)

Syndrome accompanying tubular pathologyOliguric phaseDiuretic phaseRecovery phase3) Pre – renal syndrome

Slide23

1)

Syndrome of acute nephritis

This is associated with

glomerulonephritis

Results in increase in

glomerular permeability and decrease in GFRCharacteristic features: mild proteinuria, haematuria,Oedema

Slide24

2)

Syndrome accompanying tubular pathology

ARF is caused by destruction of the tubular cells of the

nephron

Disease progresses in 3 stages:

a) Oliguria phaseLasts for 7-10 days with urine output less than 400 ml/dayLeads to azotaemia, metabolic acidosis, hyperkalaemia, hypernatraemia

and

hypervolaemia

Slide25

b

)

Diuretic phase

Healing of tubules results in improving urinary output

Effects: Dehydration & electrolyte imbalance

c) Recovery phaseFull recovery of tubular cells occurs in half cases while others terminate in deathTime period for recovery – Variable

Slide26

3)

Pre – renal syndrome

It occurs because of secondary disorders like

ischaemia

& not due to

glomerular or tubular damage.Causes of ischaemia: renal arterial obstruction, hypovolaemia, hypotension or cardiac insufficiency.Due to depressed renal blood flow, there is decrease in GFR causing oliguria, azotemia and edema

Slide27

Pre-renal AKI

• History

-- blood or volume loss

-- cardiac failure, arrhythmia,

(

cardiogenic shock)-- sepsis• Physical exam – focus on volume status– Vital signs – current and preceding the development of AKI– Neck veins, lungs, heart, mucous membranes and edema

Slide28

Sustained

prerenal

azotemia

is the main factor that predisposes patients to ischemia- induced ATN

Prerenal azotemia and ischemic tubular necrosis represent a continuum. Azotemia progresses to necrosis when blood flow is sufficiently compromised Most cases of ischemic AKI are reversible if the underlying cause is corrected.

Slide29

Renal or Intrinsic AKI

–

Glomerular

• History – systemic or primary kidney

• P/E – BP (usually hypertensive), edema

• BUN: creatinine ratio: preserved• Urine analysis : + protein, RBCs +• Often require kidney biopsy

Slide30

Renal or Intrinsic AKI

– Interstitial

History – exposure to medications usually 7- 14 days earlier-

penicillins

,

cephalosporins, dilantinP/E – maculopapular erythematous skin rash, 1/3 have fever,

arthralgias

BUN:creatinine

ratio: 10-20:1

•Urine analysis: + protein

WBCs, WBC casts,

eosinophils

Slide31

Renal or Intrinsic

ATN – Acute Tubular Necrosis

• The most common type of hospital-acquired ARF

• May be

1) ischemic or

2) nephrotoxic • Most common ATN is ischemic, most often due to a prolonged pre-renal state (prolonged reduced renal perfusion)

Slide32

Acute Tubular Necrosis

History – prolonged pre-renal state

Exposure to

nephrotoxin

Aminoglycoside

antibioticsEthylene glycolPigments (myoglobin, hemoglobin)• P/E – assess volume status (to exclude prerenal AKI)

Slide33

Contrast-Induced AKI

Prevalence:

• Less than 1% in patients with normal renal function

• Increases significantly with renal insufficiency

Risk factors:

• Renal insufficiency• Diabetes mellitus• Multiple myeloma• High osmolar (ionic) contrast media• Contrast medium volume

Slide34

Contrast-induced AKI

Clinical Characteristics:

• Onset - 24 to 48 hrs after exposure

• Duration - 5 to 7 days

• Non-

oliguric (majority)• Dialysis - rarely needed• Urinary sediment - variable• FENa: Low

Slide35

Post-Renal AKI

•

History – symptoms (frequency, hesitancy, etc)

- carcinoma, DM, stones, medications

• P/E – distended bladder, prostatic enlargement, pelvic masses , lymph nodes

• Laboratory studies-- elevated BUN:creat ratio -- unremarkable urine sediment -- variable urine chemistries• Renal ultrasound – hydronephrosis

Slide36

Rhabdomyolytic

ARF

•

Diagnose with ­ serum CPK (usu. > 10,000), urine dipstick (+) for blood, without RBCs on microscopy, pigmented granular casts

• Common after trauma (“crush injuries”), seizures, burns, limb ischemia occasionally after IABP or cardiopulmonary bypass

• Treatment is largely supportive care.• Alkalinization of urine

Slide37

Atheroembolic

ARF

•

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), low serum C3 and C4, peripheral

eosinophilia, eosinophiluria• Commonly occur after intravascular procedures or cannulation ( CABG, AAA repair, etc.)

Slide38

Clinical features

•

Signs and symptoms resulting from loss of kidney function:

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

• Asymptomatic

– elevations in the plasma creatinine– abnormalities on urinalysis

Slide39

Clinical features

•

Symptoms and/or signs of renal failure:

– weakness and easy

fatiguability

– Anorexia, vomiting– Seizures, mental status changes – Edema• Systemic symptoms and findings:– Fever, Shortness of breath –

Arthralgias

, Anorexia,

Pruritus

Slide40

Complications

Hyperuricemia

,

Hyperkalemia

, Metabolic acidosis

Infection- pneumonia, sepsisGIT- nausea, vomiting, malnutrition, GIT bleedingCNS- asterixis, mental changes, seizuresAnaemia, bleedingHyperphosphatemia

,

hypocalcemia

Cardio- Pulmonary complications

Slide41

Acute Renal Failure- Diagnosis and Management

Slide42

Differential diagnosis of acute renal failure

Slide43

Pre-renal AKI

•

Laboratory studies:

–

BUN:creatinine

ratio – elevated in pre-renal; >20:1– Urine sediment: hyaline and fine granular casts– Urine Specific gravity: high– Urine dipstick: negative (no blood or protein)– Urinary to plasma creatinine ratio: high– Urinary Na: low– FENa: low

Slide44

Renal or Intrinsic

ATN – Acute Tubular Necrosis

•

BUN:creatinine

ratio: preserved (10-20:1)

• Urine analysis : negative protein, blood-- granular casts (dirty brown casts)-- renal tubular epithelial cells• Urine chemistries – Urinary Na: high (>40 meq/L)

FENa

: high (>2%)

Urinary to plasma creatinine ratio: low

Slide45

Post-Renal AKI

• Laboratory studies--

elevated

BUN:creat

ratio

-- unremarkable urine sediment-- variable urine chemistries• Renal ultrasound – hydronephrosis• Treatment is to relieve the obstruction– Bladder catheterization– Nephrostomy tubes

Slide46

INVESTIGATIONS

Biochemistry:

Blood urea,

creatinine,

electrolytes,

Blood gas analysis.Urine osmolality/sodium/creatinine

Slide47

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.

Slide48

Slide49

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.

Slide50

2.S.Creatinine is dependent on

nonrenal

factors independent of renal function:

S.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 function3.Creatinine production and excretion must be in a steady state before creatinine may be used in any formula for the estimation of GFR.

Slide51

Fractional Excretion of Na

Since urinary indices depend on urine sodium concentration, they should be interpreted cautiously if the patient has received diuretic

Spot urine Na may be affected (raised) by diuretic use and baseline impaired kidney function (CKD where maximum urine Na

reabsorption

is impaired)

Fractional excretion of Na accounts for this by including creatinine: FeNa = (urine [Na] ÷ plasma [Na]) ÷ (urine creatinine ÷ plasma creatinine) X 100

Slide52

RENAL INDICES

Renal Failure Index (RFI):

RFI = urine [Na] ÷ urine creatinine /serum creatinine

Slide53

Slide54

Slide55

URINE ANALYSIS

•

Dipstick for blood, protein – Suggests a renal inflammatory process

• Microscopy may show cells, casts, crystals

Slide56

RBCs in Urine

Present in

glomerulonephritis

,

vasculitis

,HUS TTPscleroderma crisis

Slide57

URINARY CASTS

Hyaline –

prerenal

ARF

Granular –ATN (muddy brown)

Red blood cell casts –glomerulonephritis,vasculitis malignant hypertensionWBC casts- AIN, pyelonephritis ,leukemic or lymphomatous infiltrates

Slide58

Crystals

•

Urate

crystals – acute

urate

nephropathy• Oxalate crystals –ethylene glycol ingestion /acyclovir/ indinavir• Eosinophiluria --> > 5 % of WBC s AIN ,atherothrombotic disease

Slide59

Haematology

•

Full 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

Slide60

Immunology

Antinuclear antibody (ANA) , Anti-double stranded (

ds

) antibody -

ANA positive in SLE and other autoimmune

disorders;DNA antibodies anti-ds DNA antibodies more specific for SLEC3 & C4 complement concentrations-Low in SLE, acute post infectious glomerulonephritis,

Cryoglobulinemia

ASO and anti-

DNAse

B

titres

High after streptococcal infection

Slide61

Immunology

ANCA:

• p-ANCA - Anti PR3 antibodies

• c-ANCA - Anti MPO antibodies

– Associated with systemic

vasculitis - Wegener’s granulomatosis; Microscopic polyangiitis.AntiGBM antibodies:– Present in

Goodpasture’s

disease

Slide62

Serology

•

Hepatitis B and C, HIV serology

Slide63

Radiology

•

Renal

ultrasonography

: For renal size, symmetry, evidence of obstruction

• Pyelography : localization• MRA/ Doppler US : arterial /venous obstruction

Slide64

NEW MARKER

Cystatin

C –protein

Produced by nucleated cells

Filtered and completely reabsorbed

Changes in serum levels occur sooner

Slide65

NOVEL BIOMARKERS

1.

IL- 18

2. KIM-1

3.

Gro α/KC4. NGAL-neutrophil gelatinase associated lipocalin5. NHE-3 -Sodium–hydrogen

antiporter

3

Slide66

AKI: PREVENTION

Recognize patients at risk (postoperative states, cardiac surgery, septic shock)

Prevent progression from

prerenal

to renal

Preserve renal perfusion(isovolemia, cardiac output, normal blood pressure)Avoid nephrotoxins (aminoglycosides, NSAIDS, amphotericin)

Slide67

GENERAL PROTOCOL FOR

MANAGEMENT OF AKI

•

Treat the underlying disease

• Strictly monitor intake and output (weight, urine output, insensible losses, IVF)

• Monitor serum electrolytes• Adjust medication dosages according to GFR• Avoid highly nephrotoxic drugs• Attempt to convert

oliguric

to non-

oliguric

renal failure (

furosemide

)

Slide68

FLUID THERAPY

If patient is fluid overloaded:

• Fluid restriction (insensible losses)

• Attempt

furosemide

1-2 mg/kg• Renal replacement therapyIf patient is dehydrated:• Restore intravascular volume first• Then treat as euvolemic

If patient is

euvolemic

:

• Restrict to insensible losses (30-35 ml/100kcal/24 hours) +

other

losses

(urine,

chest

tubes,

etc

)

Slide69

SODIUM

•

Most patients have

dilutional

hyponatremia which should be treated with fluid restriction• Severe hyponatremia (Na< 125 mEq/L) : dialysis or hemofiltration

Slide70

POTASSIUM

•

Oliguric

renal failure is often complicated by

hyperkalemia

, increasing the risk of cardiac arrhythmias• Treatment of hyperkalemia:– sodium bicarbonate (1-2 mEq/kg)– insulin + hypertonic dextrose– sodium polystyrene : 1 gm/kg (

Hypernatremia

and hypertension are potential complications)

– dialysis

Slide71

Slide72

MANAGEMENT OF AKI

Metabolic acidosis – soda

bicarb

., if < 15

meq

Hyperphosphatemia – PO4 binders –sevalamerHypocalcemia –calcium carbonateNutrition –restriction of dietary protein < 0.8 g/kg /d, calories – 25-30 kcal /kg/d, enteral nutrition preferred

Slide73

Contrast-induced AKI

Prophylatic

Strategies:

• Use I.V. contrast only when necessary

• Hydration

• Minimize contrast volume• Low-osmolar (nonionic) contrast media

Slide74

Acute Tubular Necrosis

•

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

Slide75

Hemoglobinuria

+

Myoglobinuria

:

Hemoglobinuria

: Transfusion reactions, HUS (hemolytic uremic syndrome), ECMO (extracorporeal membrane oxygenation)Myoglobinuria: Crush injuries, rhabdomyolysisurine (+) blood but (-) red blood cells

Increase CPK and K+

Treatment:

Aggressive hydration + urine

alkalinization

Mannitol

/

furosemide

Slide76

NURSING MANAGEMENT

Excess fluid volume related to decreased

Glomerular

filtration rate and sodium retention

Risk for infection related to alterations in the immune system and host defenses

Imbalanced nutrition: less than body requirementsRisk for injury related to GI bleedingSleep pattern disturbances related to disease conditionProviding skin careProviding support

Slide77

Criteria for Initiation of RRT

Anuria

Oliguria

Pulmonary edema

Hyperkalemia

>6.5mmol/LSevere acidemia <7.2Uremic encephalopathyUremic pericarditis

Slide78

Therapy

Renal replacement therapy

Furosemide

Dopamine

Fenoldapam

hANP (Anaritide)

Slide79

Diagnosis

History collection.

Physical examination.

1.

Asterixis

and myoclonus2. Peripheral edema (if volume overload is present)3. Pulmonary rales (if volume overload is present)4. Elevated right atrial pressure (if volume overload is present)

Slide80

Identification of precipitating cause.

Serum creatinine and BUN level .(n 7-18mg/dl)

Serum electrolytes.

Urine analysis.

Renal bladder ultra sound.

Renal scan.CT scans and MRI scan (to identify lesion and masses)The urine will be examined under a microscope.Biopsy.

Slide81

GENERAL PROTOCOL FOR

MANAGEMENT

Treat the underlying disease

strictly monitor intake and output (weight, urine

output, insensible losses, IVF)

Monitor serum electrolytes Adjust medication dosages according to GFR Avoid highly nephrotoxic drugs Attempt to convert oliguric to non-

oliguric

renal failure (

furosemide

x 3)

Slide82

Acute Renal Failure:

Treatment

•

Water and sodium restriction

• Protein restriction

• Potassium and phosphate restriction• Adjust medication dosages• Avoidance of further insults– BP support–

Nephrotoxins

Slide83

Treatment of ARF

Based on type/etiology of AKI (acute kidney injury) i.e., pre-renal, post-renal, or intrinsic renal initially

– Pre-renal – volume, improve renal perfusion

– Post-renal – relieve obstruction

– Intrinsic –

glomerular, tubular, interstitial, vascular (depends on type)• Follow clinically; attention to volume status, avoid additional insults; treat complications of ARF

Slide84

Acute Renal Failure

Diagnostic Tools

History and Physical examination

• Blood tests : CBC, BUN/creatinine, electrolytes, uric acid, PT/PTT, CK

• Urinary sediment

• Urinary indices– Urine volume– Urine electrolytes• Radiologic studies– Renal ultrasound (useful for obstructive forms)

– Doppler (to assess renal blood flow)

• Nuclear Medicine Scans

– DMSA: anatomy

– DTPA and MAG3: renal function, urinary

– Excretion and upper tract outflow

Slide85

Prevention

A careful history(

nephrotoxic

antibiotic agent

aminoglycosides

, gentamycin, tobramycin, etc.)blood tests and urinalysisDrink enough fluidsDifficulties urinating or blood in the urine should prompt a visitTreat hypotension promptly.

Prevent and treat infections promptly.

Pay special attention to wound, burns and other precursors of sepsis.

Slide86

ARF -- Summary

Dx

AKI by falling GFR [rising BUN and creatinine]

Classify into pre-renal, renal, or

postrenal

by history, PE, BUN:creat ratio, urine analysis

Slide87

ARF – Summary (cont…)

•

Sometimes also need urine chemistries [urine Na,

FxExNa

and/or

FxExurea] to distinguish pre-renal from ATN• Sometimes need renal ultrasound to verify obstruction [post-renal ARF]• Rarely need other studies, esp to dx type of intrinsic ARF [e.g., kidney biopsy: GN

vs

interstitial nephritis

vs

ATN]

Slide88

ARF – Summary (cont…)

•

Distinguishing the types of intrinsic ARF usually depends on history, PE,

urine analysis

– Vascular – large or small vessels

– Tubular = ATN– Interstitial = AIN– Glomerular = acute GN

Slide89

THANK YOU