how to prevent renal injury

7/30/2019 How to Prevent Renal Injury

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I would like to tell you

somethingWill you listen to

me?


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Hanan Fathy

Pediatric Nephrology Unit

University Of Alexandria


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Excretion

Homeostasis

Osmoregulation Regulation of salts in the body

Regulation of pH

Production of a hormone (EPO)


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0.4% of body weight vs 25% of cardiac

output each minute

High metabolic demand

High oxygen consumption

High substrate delivery

High surface area

Glomerular basement membrane

Tubular microvilli


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Hemodynamic changes

Direct injury to cells and tissue

Inflammatory tissue injury Obstruction of renal excretion

Renal injury Results from


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Acute renal failure Acute kidney injury

Biochemical test Biomarkers


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Renal Perfusion

ParenchymalStructures

Urine output

Induce

GFR

Pre-renal

Parenchymatous(intrinsic)

Post-renal

Sudden causes

affecting

ARF

Called


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One of the most striking characteristics of therenal circulation is the ability of the kidney tomaintain a constant renal blood flow (RBF) andglomerular filtration rate (GFR) as renalperfusion pressure is altered.

Thus renal protection is lost when renal autoregulation fails.


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Conditions that Lead to Pre-renal Azotemia-Ischemic AKI

Generalizedor Localized Reduction in

Renal Blood Flow

IschemicAcute Kidney Injury

Intravascular Volume Depletion

Decreased Effective Circulating VolumeCHF Cirrhosis Nephrosis

Medications

CYA, TacrolimusACE inhibitors NSAIDS

Radiocontrast Amphotericin B

Aminoglycosides

Hepatorenal

Syndrome

Sepsis

Large-vessel Renal Vascular DiseaseRenal Artery Thrombosis

Renal Artery Embolism

Renal Artery Stenosis or Crossclamping

Small-vessel Renal Vascular Disease

Vasculitis Atheroemboli

Thrombotic Microangiopathies

Transplant Rejection


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A 6-month old infant, Was admitted to the hospital for:

Fever and vomiting.

Family history revealed young and apparently healthy parents.

He was the third child, with normal gestational age,

Birth weigh 3300g, 2 months breast feeding and then artificialfeeding with cow milk.

Two days before admittance, the child was hospitalized inanother pediatric department for bronchopneumonia beingtreated with association of antibiotics.

Based on an ultrasound examination, a suspicion of polycystickidney was established. No information regarding diuresisbefore admittance was available.


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Clinical examination showed an infant with 3850g,

fever (T=390C), bad general state, no appetite, severepallor, warm extremities, enlarged abdomen, liver withinferior margin 2 cm below the right rib..

Oligo-anuria was present during the entire evolution.Biologic tests showed:

Hb=6,6g%.

urea=178mg%.

creatinine=1,4mg%.

uric acid=9,7mg%.Na=146135119mEq/l.

K=6,5mEq/l.

ph=7,07.

BE=-19,7mmol/l.albuminura, leucocytouria,

Uroculture with E. Coli>100,000/ml.

U/S bilateral hydroureteronephrosis.


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Conclusions:

1. The case represents a diagnosis error.

2. The delayed diagnosis was determined by

multiple factors: few clinical signs at the

domicile, ambiguous results at ultrasound

examinations, and the rapid evolution ofpyelonephritis ,in the absence of therapy, to

acute renal failure.

3. Voiding urogram performed in due time would

have been allow a timely diagnosis and a

appropriate treatment


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A 20-day-old male infant with a body weight of 2.5 kg,transferred from the neonatal unit on the ninth day after thesurgical correction of Fallot's tetralogy and pulmonary atresia.

On admission to the pediatric intensive care unit, the infantrequired mechanical ventilation, an infusion of vasoactive drugs(dopamine 6 mcg/kg/minute, dobutamine 10 mcg/kg/minute andmilrinone 0.5 mcg/kg/minute) and furosemide in a continuousinfusion of 0.4 mg/kg/hour. The patient had received treatment

with vancomycin and amikacin up to 2 days earlier.

On examination, there was marked generalized edema. The initialblood tests revealed a creatinine level of 0.5 mg/dL, urea 75mg/dL, albumin 2.8 g/dL, sodium 132 mmol/L, potassium 4.6

mmol/L and chloride 96 mmol/L. In order to decrease the doses ofintravenous vasoactive drugs,

It was decided to administer digitalis to the patient, prescribing adose of digoxin of 10 mcg/kg enterally.


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Four hours after the administration of the drug, the child presented withprogressive oliguria, with a fall in diuresis from 4 to 1.5 mL/kg/hour, and withno change in the hemodynamic situation (blood pressure 65/40 mmHg, lactate1.1 mmol/L, heart rate 140 bpm). Blood tests revealed a rise in creatinine to

0.7 mg/dL and in urea to 89 mg/dL and a fall in sodium to 121 mmol/L. Therewere no neurological clinical symptoms or alterations in the cerebralechography that suggested cerebral edema. The urinalysis was normal.

Initially, to exclude hypovolemia, volume expansion was performed with 5%albumin (20 mL/kg). Intravenous sodium replacement was started accordingto the equation (135 - 121) 0.6 weight (kg) in 24 hours and the dose ofdopamine was increased from 7.5 to 15 mcg/kg/minute in order to raise themean blood pressure and improve renal perfusion.

Subsequently, on persistence of the oliguria, the infusion of furosemide wasincreased from 0.4 to 1 mg/kg/hour, though no improvement in the diuresiswas achieved.

The medication chart was reviewed and the error was detected. Instead ofdigoxin, indomethacin had been prescribed at a dose of 25 mg (10 mg/kg),which is 50 to 100 times higher than the therapeutic dose.


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What are risk factors of this patient

developing acute renal failure?

What are the possible preventable

human errors?


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Decreased Effect Renal Blood FlowSepsisSystemic inflammationImpaired cardiac output

NephrotoxinsAminoglycosidesAmphotericinFoscarnetRhabdomyolysisIodinated radiocontrast

Pre-renal Azotemia

Acute tubular necrosis

Nephrotoxic tubular injuryIschemic tubular injury


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Tissue

Hypoxia

Inflammation

Volume

Perfusion

Micro-

circulation

Multi Organ Failure


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A, Shock reversal resulted in96% survival versus 63%survival among patients whoremained in persistent shock

state.

B, Resuscitation consistent withthe newACCM-PALS Guidelinesresulted in 92% survival versus62% survival among patients

who did not receiveresuscitation consistent withthe newACCM-PALSGuidelines.

Early reversal of pediatric-neonatal septic shock bycommunity physicians is associated with improvedoutcome

Han YY et al. Pediatrics 2003; 112: 793-799


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Organ preference

Prefer the lung to the

kidneysdo not fill the kidneys

and flood the lungs

A common adverse consequence of fluidresuscitation is fluid overload and pulmonaryoedema leading to a significant reduction in lungfunction and oxygenation.

A threshold may exist beyond which theperceived benefit of additional fluid therapy afterresuscitation may be detrimental.

A positive cumulative fluid balance has beenshown in several studies to independentlypredict hospital morbidity and mortality.


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Sepsis is a frequent cause of AKI in children.

Sepsis increases the mortality of AKI

AKI increases the mortality of sepsis

More than half of children with septic AKI presents renal

dysfunction at discharge and 1/3 develops abnormalities in the

long term. Follow-up of these patients is recommended.

Genetic risk factors may be involved in the individual

susceptibility to septic AKI


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Methods of Attenuating orPreventing Sepsis-Related Acute

Renal Failure

Arginine vasopressin

Hydrocortisone

Early directed resuscitation

Maintenance of blood glucose< 145 mg/dl (8.0 mmol/l)

Activated protein C

Schrier RW et al. NEJM 2004; 351:159-69
http://content.nejm.org.bibliosan.cilea.it/content/vol351/issue2/images/large/10f4.jpeghttp://content.nejm.org.bibliosan.cilea.it/content/vol351/issue2/images/large/10f4.jpeg


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Ensure adequate renal perfusion.

Avoid / minimize use of nephrotoxic drugs

including radio contrast.

Early recognition and aggressive managementof sepsis.

Early recognition and timely mangement ofshock


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Blood pressure

Intravascular volume

Cardiac output Other markers of perfusion


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No drug produces

a single effect!!!


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Characteristic Odds Ratio (95CI)*

Age 0 to 3 years 1.6 (1.1 to 2.5)

Male 1.7 (1.1 to 2.4)1 to 4 additional meds 1.4 (1.0 to 2.0)

5 or more additional

meds

3.4 (1.4 to 8.0)

No clinic visit 1.8 (1.3 to 2.6)

McPhillips et al,Journal of Pediatrics, 2005


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1. Pediatric prescribing is complex

2. Off-label medication use is common

3. Lack of standardization of recommended doses

4. Lack of guidelines regarding use of adult dosing

regimens


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Radiocontrast Agents Aminoglycosides

Nonsteroidal Anti-Inflammatory Drugs (NAIDs)

Angiotensin-Converting Enzyme Inhibitors (ACEIs)

Lithium

Crystal-Induced Acute Renal Failure

Calcineurin inhibitors (Cyclosporine, Tacrolimus)

Amphothericin B

Chemotherapy


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Proximal convoluted tubule (s1/s2 segment)Aminoglycoside

Cephaloridine

Cadmium Cl

K dichromate

Renal vesselNSAIDs

ACE Inhibitor

Cyclosporin A

PappillaePhenacetin

InterstitiumCephalosporin

Cadmium

NSAIDs

GlomeruliInterferon-

Gold

Penicillamine


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Amikacin [AMIKIN ]

Gentamicin [GARAMYCIN ]Neomicin

Netilmicin [NETROMYCIN ]

Kanamicin [KANTREX

]Streptomycin

Tobramycin [TOBREX, NEBCIN ]


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Lysosomal overload Inhibition of intralysosomal phospholipase activity

Intralysosomal phospholipidosis

Altered phosholipase signalling mechanisms

PROXIMAL TUBULE NECROSIS


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Related to AMG dosingLarge total cumulative dose

Prolong therapy

High peak or trough conc.

Recent previous AMG therapy

Related to Predisposing condition

in the patientPreexisting renal insufficiency

Increased age

Poor nutrition

Shock

Gram negative bactermia

Liver disease

Hypoalbuminemis

Obstructive jaundice

K+ or Mg++ deficiency

Related to synergisticnephrotoxicity

AMG combination with

CyclosporinAmphotericin B

Vancomycin

DiureticsIrreversible Damage!


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Prevention

Switching to alternativeantibiotics

Avoid volume depletion,concomitant therapy withother nephrotoxic drugs

Limit total dose

Decreasing the frequencyof AMG dosing to at leastdaily (as direct by renalclearance)

Management

Monitor Scr, concentration,renal fn and electrolytes

Discontinue AMG ifchanges are seen.


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1. Fever is a symptom not a disease


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2. A child can have meningitis with a low

fever or a viral URTI with a high fever


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2. A child can have meningitis with a low fever or a viral

upper respiratory tract infection with a high fever

3. The difference is in how sick the child is!!


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2. A child can have meningitis with a low fever or a viralupper respiratory tract infection with a high fever

3. The difference is in how sick the child is!!

4. MINIMAL CLOTHES &

COOL ENVIRONMENT

5. FLUIDS


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N t id l A ti I fl t


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Hemodynamically- Induced ARF

Acute Interstitial Nephropathy +Proteinuria

Papillary necrosis and chronic renal

failure (Analgesic nephropathy)

Salt and water retention; Hyperkalemia;Hypertension

Nonsteroidal Anti-InflammatoryDrugs (NSAIDs)


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Papillary necrosis


Nonsteroidal Anti Inflammatory


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Patients at risk: Preexisting renal disease (glomerular disease

nephrotic syndrome ,lupus);

Hypercalcemia;

Congestive Heart Failure,

Cirrhosis,

Volume depletion (vomiting, diarrhea, diuretics)


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Acyclovir (antiviral agent )

Indinavir (antiretroviral agent, protease

inhibitor)

Methotrexate (antineoplastic agent,

antimetabolite) Sulfonamide antibiotics

Triamterene


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Know the potential nephrotoxicity of drug and therapeutic

pharmacologic agents.

Compare the potential risks and expected benefits for eachcourse of treatment.

Consider alternative diagnostic and therapeutic approaches.

Use the lowest dose and shortest course of therapy that isefficacious.

Monitor appropriately for potential toxicity.

Monitor therapy if toxicity is occurs.


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1. Recognise and assess the patient at risk

2. Avoid nephrotoxic agents

3. Maintain effective circulatory volume

4. Recognise and treat hypoxia

5. Early recognition of rising BUN and Cr.

6. Treat infection, avoid nosocomial infection

7. Pharmacological manipulation to maintain RBF,perfusion pressure and GFR


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8. Awareness of signs and symptoms of different renaldiseases for early detection and timely referral.

9. Spread of health education information to parents as

regards what is normal and what is abnormalconcerning their children's renal system.

10. Timely referral to a pediatric nephrologist in caseswith suspected renal disease or insult


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how to prevent renal injury

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