drug induced renal diseases 24-11-09

7/29/2019 Drug Induced Renal Diseases 24-11-09

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ByB. Shalini

(M.Pharm pharmacy practice 1st year)

Under the guidance ofNeelakant Reddy Patil

M.Pharm


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Drug induced renal failure is a condition inwhich kidneys fail to function adequatelycausing a large number of other medicalproblems due to drug toxicity.

Drug induced renal disease occurs inpatients taking drugs and diagnosticagents.

This type of disorder can be seen in bothin-patients and out-patients.


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According to a study, it has been found that29% of acute renal failure (ARF) cases werecontributed by drug toxicity.

Most of the ARF-DI cases was found onthose patients who were taking moreNSAIDS and antibiotics.

In some cases the cause of ACEI leaded to

the formation of ARF-DI.


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Toxins and drugs can produce renal injury in 3ways:-

1. They trigger interstitial immunologic reaction byhypersensitive nephritis induced drugs.

2. They cause acute renal failure.3. They cause subtle but cumulative injury to tubule

that make years to manifest resulting to chronicinsufficiency.

The last defined one is one of the most chronicbut clinically unrecognizable until significant

damage to renal system has occurred.


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There are 4 types of drug induced renalfailures:

1. Hemodynamic renal failure

2.

Tubular epithelial cell injury3. Crystal nephropathy

4. Osmotic nephrosis


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This type of renal failure is occurred due tothe over consumption of

NSAIDS (including COX2 inhibitors)

ACE-i Angiotensin-2 receptor blockers (ARB).


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The most common type of NSAID-inducedacute renal failure results from decreasedsynthesis of renal vasodilatorprostaglandins, which can lead to reduced

renal blood flow and reduced glomerularfiltration.

The reduction in sodium excretion thatfollows the reduction in renal prostaglandin

synthesis can lead to elevation of systemicblood pressure, especially in elderlypatients.


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In one study, ibuprofen, piroxicam, andsulindac all reduced urinary sodium in bothyoung and elderly patients independent oftheir renal function.

The recognized risk factors for NSAID

induced prerenal acute renal failure areimpaired renal function, hypovolemia, congestiveheart failure, cirrhosis, sodium and waterdepletion, anesthesia, advanced age, renal

transplantation, and use of other drugs such asACE inhibitors.


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It was initially hoped that the COX-2inhibitors such as celecoxib and rofecoxibwould be less nephrotoxic than regularNSAIDs.

Perazella et al (reference) recently reported theoccurrence of renal failure after therapy with COX-2inhibitors.


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ACE inhibitors are a double edge sword, asthey can also cause renal failure underpeculiar circumstances.

After ACE inhibitors were introduced, functionalacute renal failure was reported in patients with

renal artery stenosis (narrowing of renal artery)receiving these drugs.


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In some patients with renal artery stenosis,glomerular filtration may be critically

dependent on the efferent arteriolar effectsof angiotensin-2.

In these patients, acute renal failureresults from loss of postglomerular

efferent arteriolar vascular tone and isreversible if the drug is withdrawn.

The pretreatment glomerular filtrationrate is the single best predictor of acute

renal failure resulting from the use of ACEinhibitors.


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Angiotensin II receptor blockers (ARBs) (ex:-losartan, valsartan) reduce blood pressure toa degree comparable to that achieved withACE inhibitors, and like ACE inhibitors, they

reduce proteinuria to a degree greater thanwould be expected from blood pressurereduction alone.


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This cell injury is due to the formation ofischemic condition in the kidneys due toless amount of oxygen supply to thenephrons, this is due to the storage of moreATP for the metabolism of drug.

Certain anti HIV drugs like cidofovirphosphocoline (anti viral) interferes with thenormal synthesis and/or degradation of

membrane phospholipids, resulting inproximal tubular injury and in extremecases, cell necrosis.


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Radio contrast media and cytotoxic agents

(ex:- doxorubicin, daunorubicin, vincaalkaloids) also leads to tubular injury. Itcauses pre existing renal insufficiency.

Renal failure due to amino glycosides (used

to treat anti bacterial infections) is occurredin continued therapy by injuring the tubularepithelial with the tubular lumen and backleak of the glomerular filtrate.

This condition leads to decreasedglomerular filtration.


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Aminoglycoside antibiotics, used in severegram-negative sepsis, cause nephrotoxicityin 10% to 20% of therapeutic courses.

Binding of these drugs to the proximal tubule dependson amino groups in each aminoglycoside agent.

Gentamicin is the most nephrotoxic of

the aminoglycosides, followed in descending order bytobramycin, amikacin, netilmicin, and streptomycin.


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Deposition of crystals in the kidneys cancause renal failure. The renal injury occursfrom crystals because of their relativeinsolubility in human urine.

A number of routinely prescribed medicationscause crystal-induced renal disease, termed

crystal nephropathy.


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The following drugs causes crystalnephropathy:-

Acyclovir (anti viral used to treat herpesinfection)

Sulphonamides (antibiotics used to treatbacterial infections) (ex:-sulphamethoxazole)

Methotrexate (anti metabolite used to treat

psoriasis, rheumatoid arthritis) Indinavir (anti retroviral)


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Rectangular indinavir crystals in urinary

sediment on light microscopy.


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Induction of cell swelling and vacuolization(causing disruption of cellular integrity) aswell as tubular luminal occlusion fromswollen tubular cells are the mechanismsthought to underlie the development ofrenal failure.

The cause for the osmotic nephrosis are:-

Intravenous immune globulin.Hydroxyethyl starch .


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Although increased levels of BUN andcreatinine are the hallmarks of renal failure,

the rate of rise is dependent on the degree ofrenal insult as well as protein intake withrespect to BUN (blood urea nitrogen).

The ratio of BUN to creatinine is an importantfinding because the ratio can exceed 20:1 inconditions in which enhanced reabsorptionof urea is favored for renal failure.

Assuming no renal function, the rise in BUNover 24hrs can be roughly predicted usingthe following formula:24-hour protein intake in milligrams X 0.16 by total body water in mg/dL added to theBUN value.

Assuming renal function, rise in creatininecan be predicted.


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Herbal medicines use has been suggested tocause 35% of all cases of acute renal failure insome African countries.

Several reports documented rapidly progressivekidney failure leading to end-stage renal diseasein women who had taken diet pills that containedChinese herbs.

This so-called Chinese herb nephropathy wascharacterized by an extensive fibrosis of the renalinterstitium.


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Cocaine abuse can induce several forms ofrenal damage, including acute tubularnecrosis due to rhabdomyolysis.

It can also cause accelerated or malignanthypertension, renal failure, and allergic

interstitial nephritis (probably mediated byadditives in the crack formulation of cocaine).


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Findings of granular muddy-brown castsare suggestive of tubular necrosis. Thepresence of tubular cells or tubular cellcasts also supports the diagnosis of ATN(acute tubular necrosis). Often oxalate

crystals are observed in cases of ATN. Reddish brown colored urine suggests the

presence of myoglobin or hemoglobin,especially in the setting of a positive

dipstick for heme and no RBCs in themicroscopic examination.


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FEurea (fractional excretion of urea) iscalculated for the identification of renalfunction in case of drug induced renal

failure as its concentration wont getdisturbed in administration of diuretics.

FEurea is calculated as:-

FEurea = (Uurea/Purea)orFEurea= (Ucr/Pcr) 100

U urea=urine ureaP urea=plasma ureaU cr=urine creatinineP cr=plasma creatinine


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drug induced renal diseases 24-11-09

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