how to prevent renal injury
TRANSCRIPT
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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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1. Fever is a symptom not a disease
2. A child can have meningitis with a low
fever or a viral URTI with a high fever
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1. Fever is a symptom not a disease
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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1. Fever is a symptom not a disease
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-InflammatoryDrugs (NSAIDs)
Nonsteroidal Anti Inflammatory
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Nonsteroidal Anti-InflammatoryDrugs (NSAIDs)
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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