Presented By Dr / Said Said Elshama Nephrotoxicity Presented By Dr / Said Said Elshama

Learning objectives Nephrotoxicity definition . Mechanisms of nephrotoxicity. Drugs induced nephrotoxicity. Clinical picture of nephrotoxicity. Management of nephrotoxicity.

Definition Disturbance or harmful effect on the kidney. By introducing drugs or toxic substances into the body . .

Mechanisms of nephrotoxicity intraglomerular hemodynamic acute tubular cell necrosis Inflammation Rhabdomyolysis Crystal nephropathy Thrombotic microangiopathy

Intra-glomerular pressure GFR Intra-glomerular pressure Urine output Angiotensin 11- Mediated vasoconstriction of efferent arterioles (ACE inhibitors) Prostaglandin Mediated vasodilatation of afferent arterioles (NSAID)

Acute tubular cell necrosis Concentrating glomerular filtrate Reabsorbing glomerular filtrate Renal tubular cells Acute tubular cell necrosis Aminoglycosides Cisplatin

inflammation Glomerulonephritis Acute interstitial nephritis Chronic interstitial nephritis Ex. NSAID, rifampicin, vancomycin, antiviral inflammation

Ex . Acyclovir, ciprofloxacin Crystal nephropathy Ex . Acyclovir, ciprofloxacin Urinary pH Concentration of drug Volume depletion Renal insufficiency

Ex. Cocaine heroin , amphetamine Rhabdomyolysis Ex. Cocaine heroin , amphetamine Tubular obstruction Alteration in GFR Direct toxicity

Thrombotic Microangiopathy Immune mediated reaction Direct endothelial toxicity Thrombotic Microangiopathy Antiplatelets(cyclosporine)

Causes of nephrotoxicity Antibiotics Analgesics Heavy metals Contrast agents Anti cancer Solvents Herbicides and pesticides Overproduction of uric acid

Risk Factors Age Underlying kidney disease Severe dehydration Prolonged exposure to toxic agents heart failure Sepsis Renal insufficiency (GFR is less than 60 ml/m Overproduction uric acid disease Intravascular volume depletion

Factors affecting susceptibility of kidney to toxicants 1 High renal blood flow LL 2 Concentration of chemicals 3 Re-absorption and secretion of chemicals 4 Activation pro-toxicants to reactive

Common nephrotoxic drugs Non steroidal anti - inflammatory Aspirin- ibuprofen Aminogycosides Gentamycin Antibiotics Vancomycin Antiviral Acyclovir

Clinical picture Excess urea in the blood (azotemia) Anemia Acidosis Over hydration Hypertension Heamturia Pyuria Oliguria Seizures Coma

DIAGNOSIS Examination Urine analysis Renal functions tests History taking Examination Investigations Urine analysis Renal functions tests

Management Diagnosis Treatment Prevention History Examination Investigation Treatment Prevention

Treatment Stop the drug Remove the toxin Diuretics Chelation Hemodialysis Hemoperfusion

Prevention Adjust dose Assess renal function Avoid nephrotoxic combinations Correct risk factors Ensure adequate hydration Use non-nephrotoxic drugs

Questions Mechanism of gentamycin nephrotoxicity is intraglomerular hemodynamic acute tubular cell necrosis Inflammation Thrombotic microangiopathy Crystal nephropathy

Questions If patient has tobramycin nephrotoxicity, the first step of treatment is to:- Give excess fluid Slow the infusion rate Stop the medication Add antidote

Questions Antiprostaglandin activity of nephrotoxic drugs due to Vasodilatation of efferent arterioles Vasodilatation of afferent arterioles Vasoconstriction of afferent arterioles Vasoconstriction of efferent arterioles

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