Drug induced kidney diseases

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DRUG INDUCED KIDNEY DISEASES:

By Dr. Siva R Challa KVSR Siddhartha College of Pharmaceutical Sciences DRUG INDUCED KIDNEY DISEASES

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Classification of drug induced renal diseases:

Classification of drug induced renal diseases 3

Drug induced Hemodynamic acute renal failure: NSAIDS & COXIBS :

Drug induced Hemodynamic acute renal failure: NSAIDS & COXIBS 4

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NSAID/COXIB induced hemodynamic renal failure:

NSAID/COXIB induced hemodynamic renal failure NSAIDS causes hemodynamic acute renal failure due to inhibition of the synthesis of vasodilatory prostaglandins which are mainly contributing the vasodilation of afferent arterioles for normal maintenance of GFR) COX-2 inhibitors celecoxib and rofecoxib are causing hemodynamic renal failure because COX-2 isoform facilitates synthesis of vasodilatory PGs that are required to maintain the normal renal blood flow and GFR in clinical diseases like volume contraction and chronic kidney disease. 6

NSAID/COXIB induced hemodynamic renal failure:

NSAID/COXIB induced hemodynamic renal failure Use with caution in CKD (grade 3 or greater) Inhibit renal vasodilatory prostaglandins E2 & I2 Produced by COX-2 Reversible reduction in GFR Higher risk if intravascular volume depletion Management: D/C drug, use alternate analgesia Hypertension Edema, sodium and water retention Mean increase SBP 5 mm Hg 7

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Excess ATII effects on efferent arteriole leads to proteinuria as it was seen in diabetic nephropathy:

Excess ATII effects on efferent arteriole leads to proteinuria as it was seen in diabetic nephropathy 9

Reno protective properties of ACEI/ARB to minimize the proteinuria in diabetic nephropathy:

Reno protective properties of ACEI/ARB to minimize the proteinuria in diabetic nephropathy 10

Risk Factors for ARF with ACEI/ARB:

Risk Factors for ARF with ACEI/ARB Decreased intravascular volume (dehydration, diuretic overuse, CHF, vomiting, diarrhea) Use of afferent vasoconstrictor agents (NSAIDs, cyclosporine, tacrolimus) Sepsis Renal-artery stenosis Polycystic kidney disease 11

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Statins induced rhabdomyolysis and obstruction of myoglobulin in glomerulus causes decreased in GFR and in turn leads to renal failure 13

Drug induced acute renal failure : INTRINSIC:

Drug induced acute renal failure : INTRINSIC Drug induced Acute Interstitial Nephritis (AIN) Drug induced Acute Tubular Necrosis (ATN) Drug induced osmotic nephrosis 14

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Drug induced Acute Interstitial Nephritis :

Drug induced Acute Interstitial Nephritis 16

Drug induced Acute Tubular Necrosis :

Drug induced Acute Tubular Necrosis 17

Drug induced Acute Tubular Necrosis :

Drug induced Acute Tubular Necrosis 18

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Drug induced Acute interstitial Nephritis (AIN):

Drug induced Acute interstitial Nephritis (AIN) Following classes of drugs causes AIN Beta-lactam antibiotics (Mainly cephalosorins) Other antibiotics like sulofanmides, rifampicin, vancomycin, ciprofloxacin etc. Non-steroidal anti-inflammatory drugs Phenytoin Diuretics (Furosemide and thiazides) 20

Drug induced Acute interstitial Nephritis (AIN):

Drug induced Acute interstitial Nephritis (AIN) AIN caused by beta- lactam and sulfa based antibiotics is characterized by systemic signs of hypersensitivity reactions including Fever (87% patients) Eosinophilia (79% patients) Skin rash (24% patients) Whereas NSAID induced AIN does not manifest these systemic signs of hypersensitivity. 21

Drug induced Acute interstitial Nephritis (AIN):

AIN caused by beta- lactam and sulfa based antibiotics is usually begins 2 weeks after drug exposure but may occur sooner if patient has been previously sensitized to the same or a chemically similar agent. In contrast, NSAIDS causes AIN only after 1 year treatment. Usually, AIN caused by beta- lactam and sulfa based antibiotics is mediated by cell mediated immunity except in case of methicillin induced AIN, where humoral immunity plays an important role. Drug induced Acute interstitial Nephritis (AIN) 22

Drug induced Acute interstitial Nephritis (AIN):

Pathological findings in AIN include Interstitial inflammation Edema Tubelitis Importantly, interstitial granulomas are commonly seen in AIN and may represent the predominant injury (known as “granulomatous interstitial nephritis” Drug induced Acute interstitial Nephritis (AIN) 23

Drug induced Toxic Acute Tubular Necrosis (ATN):

Drug induced Toxic Acute Tubular Necrosis (ATN) The following drugs causes Toxic ATN Amino glycoside antibiotics Amphotericin B Cisplatin Anaesthetic agents (methoxyflurane) Calcineurin inhibitors Mannitol Radio contrast media 24

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Granular casts in the urine:

Granular casts in the urine 26

Drug induced Toxic Acute Tubular Necrosis (ATN):

Drug induced Toxic Acute Tubular Necrosis (ATN) Patients with Toxic ATN present with Acute renal failure that may be olguric and/or require dialysis. Tubular injury is often accompanied by increased fractional excretion of sodium (Fe Na). majority of the cases of ATN will recover following discontinuation of the drug and institution of supportive measures. 27

Drug induced Toxic Acute Tubular Necrosis (ATN):

Drug induced Toxic Acute Tubular Necrosis (ATN) Aminoglycoside nephrotoxicity involves disruption of membrane structure and function and alterations in membrane permeability, which leads to inhibition of lysosomal phospholipases, lysosomal rupture and cytoplasmic release of lysosomal acid hydrolases. Cisplatin induced is ATN is thought to involve oxygen free radical formation, reduction in renal perfusion and disruption of DNA and RNA synthesis. Mechanism of Amphotericin caused ATN are vasoconstriction and modifications of cell membrane integrity and permeability. 28

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Drug induced Ischemic Acute Tubular Necrosis (ATN):

Drug induced Ischemic Acute Tubular Necrosis (ATN) Prostaglandin mediated vasodilation plays an important autoregulatory role in the maintenance of renal perfusion. In the setting of effective volume depletion (eg. Congestive heart failure, cirrhosis or chronic kidney disease etc.), NSAID use can attenuate prostaglandin mediated vasodilation and precipitate hemodynamically mediated acute renal failure. Renal biopsy findings resemble ischemic ATN are the most common renal injuries following NSAID use. 33

Drug induced Osmotic nephrosis:

Drug induced Osmotic nephrosis High doses of mannitol , immunoglobulins , dextrans and starches are nephrotoxic Direct effect on glomerular filtration or the uptake of these large molecules by pinocytosis into the proximal tubule sucrose-based IVIG: The renal failure began from 1 to 10 days after therapy 34

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Drug induced Osmotic nephrosis 35

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Nephrotic syndrome:

Nephrotic syndrome Abnormal amounts of protein in the urine Drugs : NSAIDs, penicillamine and gold damage the glomerulus and alter the ability of the glomerulus to prevent protein from being filtered Stopping the drug may resolve the damage to the glomerulus 41

Drug induced Pseudo-Renal Failure :

Drug induced Pseudo-Renal Failure ↑ BUN due to protein catabolism Steroids, tetracyclines ↑ SCr due to competitive inhibition of creatinine secretion Trimethoprim, Cimetidine, Triamterene With Trimethoprim 15-35% rise SCr fully expressed after 3 days More sig in pts with pre-existing renal dysfunction Can occur with normal doses Completely reversible when drug is discontinued 42

Thank You :

Thank You 43

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