I would like to tell you something…Will you listen to me…?

Hanan Fathy
Pediatric Nephrology Unit

University Of Alexandria


• Excretion • Homeostasis • Osmoregulation • Regulation of salts in the body • Regulation of pH • Production of a hormone (EPO) .


• 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 .

Renal injury Results from • • • • Hemodynamic changes Direct injury to cells and tissue Inflammatory tissue injury Obstruction of renal excretion .

Acute renal failure Acute kidney injury Biochemical test Biomarkers .


Sudden causes affecting Renal Perfusion Called Pre-renal Parenchymal Structures Induce GFR Parenchymatous (intrinsic) Urine output Post-renal ARF .

.• One of the most striking characteristics of the renal circulation is the ability of the kidney to maintain a constant renal blood flow (RBF) and glomerular filtration rate (GFR) as renal perfusion pressure is altered. Thus “renal protection” is lost when “renal autoregulation” fails.


Tacrolimus ACE inhibitors NSAIDS Radiocontrast Amphotericin B Aminoglycosides Sepsis Small-vessel Renal Vascular Disease Vasculitis Atheroemboli Thrombotic Microangiopathies Transplant Rejection Hepatorenal Syndrome Ischemic Acute Kidney Injury .Conditions that Lead to Pre-renal Azotemia-Ischemic AKI Intravascular Volume Depletion Large-vessel Renal Vascular Disease Decreased Effective Circulating Volume CHF Cirrhosis Nephrosis Generalized or Localized Reduction in Renal Blood Flow Renal Artery Thrombosis Renal Artery Embolism Renal Artery Stenosis or Crossclamping Medications CYA.

with normal gestational age. Two days before admittance. the child was hospitalized in another pediatric department for bronchopneumonia being treated with association of antibiotics. 2 months breast feeding and then artificial feeding with cow milk. Family history revealed young and apparently healthy parents. a suspicion of polycystic kidney was established. Based on an ultrasound examination. Was admitted to the hospital for: Fever and vomiting. Birth weigh 3300g. He was the third child. .A 6-month old infant. No information regarding diuresis before admittance was available.

5mEq/l. uric acid=9.. bad general state. severe pallor.4mg%. . albuminura. leucocytouria. fever (T=390C). urea=178mg%.Clinical examination showed an infant with 3850g. creatinine=1.07. warm extremities.7mg%. Uroculture with E. U/S bilateral hydroureteronephrosis. enlarged abdomen. Hb=6.7mmol/l. K=6. Na=146→135→119mEq/l. no appetite. Coli>100. liver with inferior margin 2 cm below the right rib.000/ml. Biologic tests showed: Oligo-anuria was present during the entire evolution.6g%. ph=7. BE=-19.

3. to acute renal failure. 2. and the rapid evolution of pyelonephritis . ambiguous results at ultrasound examinations.in the absence of therapy. The delayed diagnosis was determined by multiple factors: few clinical signs at the domicile.• Conclusions: 1. Voiding urogram performed in due time would have been allow a timely diagnosis and a appropriate treatment . The case represents a diagnosis error.


an infusion of vasoactive drugs (dopamine 6 mcg/kg/minute. transferred from the neonatal unit on the ninth day after the surgical correction of Fallot's tetralogy and pulmonary atresia. In order to decrease the doses of intravenous vasoactive drugs.6 mmol/L and chloride 96 mmol/L. . the infant required mechanical ventilation.5 kg.8 g/dL.5 mg/dL. dobutamine 10 mcg/kg/minute and milrinone 0. there was marked generalized edema.4 mg/kg/hour. prescribing a dose of digoxin of 10 mcg/kg enterally. The patient had received treatment with vancomycin and amikacin up to 2 days earlier. • On admission to the pediatric intensive care unit. • On examination.• A 20-day-old male infant with a body weight of 2. albumin 2. urea 75 mg/dL. The initial blood tests revealed a creatinine level of 0.5 mcg/kg/minute) and furosemide in a continuous infusion of 0. sodium 132 mmol/L. • It was decided to administer digitalis to the patient. potassium 4.

• Four hours after the administration of the drug. on persistence of the oliguria. the infusion of furosemide was increased from 0. indomethacin had been prescribed at a dose of 25 mg (10 mg/kg).5 to 15 mcg/kg/minute in order to raise the mean blood pressure and improve renal perfusion. There were no neurological clinical symptoms or alterations in the cerebral echography that suggested cerebral edema. lactate 1. The urinalysis was normal. with a fall in diuresis from 4 to 1. volume expansion was performed with 5% albumin (20 mL/kg). Intravenous sodium replacement was started according to the equation (135 .4 to 1 mg/kg/hour.121) × 0. which is 50 to 100 times higher than the therapeutic dose. • Initially. . to exclude hypovolemia. Instead of digoxin.5 mL/kg/hour. Blood tests revealed a rise in creatinine to 0.1 mmol/L. though no improvement in the diuresis was achieved.7 mg/dL and in urea to 89 mg/dL and a fall in sodium to 121 mmol/L.6 × weight (kg) in 24 hours and the dose of dopamine was increased from 7. • Subsequently. and with no change in the hemodynamic situation (blood pressure 65/40 mmHg. heart rate 140 bpm). • The medication chart was reviewed and the error was detected. the child presented with progressive oliguria.

• What are risk factors of this patient developing acute renal failure? • What are the possible preventable human errors? .

Decreased Effect Renal Blood Flow Sepsis Systemic inflammation Impaired cardiac output

Nephrotoxins Aminoglycosides Amphotericin Foscarnet Rhabdomyolysis Iodinated radiocontrast

Pre-renal Azotemia Nephrotoxic tubular injury

Ischemic tubular injury

Acute tubular necrosis




Tissue Hypoxia Inflammation

Multi Organ Failure

Pediatrics 2003. Shock reversal resulted in 96% survival versus 63% survival among patients who remained in persistent shock state.Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome A. 112: 793-799 . Han YY et al. B. Resuscitation consistent with the new ACCM-PALS Guidelines resulted in 92% survival versus 62% survival among patients who did not receive resuscitation consistent with the new ACCM-PALS Guidelines.

. Prefer the lung to the kidneys do not fill the kidneys A threshold may–exist beyond which the perceivedand flood the lungs benefit of additional fluid therapy after resuscitation may be detrimental.A common adverse consequence of fluid resuscitation is ‘fluid overload’ and pulmonary oedema leading to a significant reduction in lung Organ preference function and oxygenation. A positive cumulative fluid balance has been shown in several studies to independently predict hospital morbidity and mortality.


Follow-up of these patients is recommended. Sepsis is a frequent cause of AKI in children.  Genetic risk factors may be involved in the individual susceptibility to septic AKI .  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.

NEJM 2004. 351: 159-69 .Methods of Attenuating or Preventing 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.

• Early recognition and timely mangement of shock . • Early recognition and aggressive management of sepsis.• Ensure adequate renal perfusion. • Avoid / minimize use of nephrotoxic drugs including radio contrast.

• • • • Blood pressure Intravascular volume Cardiac output Other markers of perfusion .


No drug produces a single effect!!! .

6 (1.1 to 2. Journal of Pediatrics.4 to 8.5) 1.Characteristic Age 0 to 3 years Male 1 to 4 additional meds 5 or more additional meds No clinic visit Odds Ratio (95 CI)* 1.4 (1.3 to 2.6) McPhillips et al.0) 1.0) 3.0 to 2. 2005 .8 (1.4 (1.1 to 2.7 (1.4) 1.

Lack of guidelines regarding use of adult dosing regimens . Lack of standardization of recommended doses 4.1. Off-label medication use is common 3. Pediatric prescribing is complex 2.

• 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 .

Proximal convoluted tubule (s1/s2 segment) Aminoglycoside Cephaloridine Cadmium Cl K dichromate Glomeruli Interferon-α Gold Penicillamine Renal vessel NSAIDs ACE Inhibitor Cyclosporin A Interstitium Cephalosporin Pappillae Phenacetin Cadmium NSAIDs .

return to baseline. . pallillaly necrosis or prolonged proteinuria.• • • • • Acute renal failure Chronic renal failure Nephrotic syndrome (Acute/Chronic) Fluid and Electrolyte disturbances Acid-base disorders • Most episodes of drug-induced renal disorders are reversible discontinue drug  renal fn. • Chronic renal injury (due to medication)  Chronic tubulointerstitial inflammation.


Amikacin Gentamicin Neomicin Netilmicin Kanamicin Streptomycin Tobramycin [AMIKIN ®] [GARAMYCIN ®] [NETROMYCIN ®] [KANTREX ®] [TOBREX. NEBCIN ®] .

Lysosomal overload • Inhibition of intralysosomal phospholipase activity • Intralysosomal phospholipidosis • Altered phosholipase signalling mechanisms • PROXIMAL TUBULE NECROSIS .


•Recent previous AMG therapy Related to synergistic nephrotoxicity AMG combination with •Cyclosporin •Amphotericin B •Vancomycin •Diuretics Irreversible Damage! .Related to AMG dosing •Large total cumulative dose Related to Predisposing condition in the patient •Preexisting renal insufficiency •Increased age •Poor nutrition •Shock •Gram negative bactermia •Liver disease •Hypoalbuminemis •Obstructive jaundice •K+ or Mg++ deficiency •Prolong therapy •High peak or trough conc.

concomitant therapy with other nephrotoxic drugs •Limit total dose Management •Monitor Scr.Prevention •Switching to alternative antibiotics •Avoid volume depletion. •Decreasing the frequency of AMG dosing to at least daily (as direct by renal clearance) . concentration. renal fn and electrolytes •Discontinue AMG if changes are seen.



Fever is a symptom not a disease .1.

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 .

1. The difference is in how sick the child is!! . 2. Fever is a symptom not a disease A child can have meningitis with a low fever or a viral upper respiratory tract infection with a high fever 3.

MINIMAL CLOTHES & COOL ENVIRONMENT 5.1. 2. 3. FLUIDS . Fever is a symptom not a disease A child can have meningitis with a low fever or a viral upper respiratory tract infection with a high fever The difference is in how sick the child is!! 4.


Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) • Hemodynamically. Hyperkalemia. Hypertension .Induced ARF • Acute Interstitial Nephropathy + Proteinuria • Papillary necrosis and chronic renal failure (Analgesic nephropathy) • Salt and water retention.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) • Papillary necrosis .

 Cirrhosis.  Hypercalcemia. diarrhea. diuretics) .  Congestive Heart Failure.  Volume depletion (vomiting.Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Patients at risk:  Preexisting renal disease (glomerular disease nephrotic syndrome .lupus).



protease inhibitor) • Methotrexate (antineoplastic agent.• Acyclovir (antiviral agent ) • Indinavir (antiretroviral agent. antimetabolite) • Sulfonamide antibiotics • Triamterene .

Ann Intern Med 128-321 .Sulfonamide crystals Indinavir sulfate urinary crystals Gagnon et al. 1998.

• Monitor therapy if toxicity is occurs. . • Use the lowest dose and shortest course of therapy that is efficacious. • Monitor appropriately for potential toxicity.• Know the potential nephrotoxicity of drug and therapeutic pharmacologic agents. • Consider alternative diagnostic and therapeutic approaches. • Compare the potential risks and expected benefits for each course of treatment.

5. 7. Treat infection. Recognise and assess the patient at risk Avoid nephrotoxic agents Maintain effective circulatory volume Recognise and treat hypoxia Early recognition of rising BUN and Cr. 2. 4. perfusion pressure and GFR . avoid nosocomial infection Pharmacological manipulation to maintain RBF. 6. 3.1.

Awareness of signs and symptoms of different renal diseases for early detection and timely referral. Spread of health education information to parents as regards what is normal and what is abnormal concerning their children's renal system.8. 10. Timely referral to a pediatric nephrologist in cases with suspected renal disease or insult . 9.