3. DRUGS AND TOXINS
ASSOCIATED WITH KIDNEY
• INTRODUCTION:
Kidney, an excretory organ which plays a
major role in homeostasis of the body.
• By excreting water and electrolytes through
urine, kidney plays a major role in
homeostatsis.
4. STRUCTURE OF KIDNEY
Kidneys are pair of excretory organ situated
on the posterior abdominal wall behind the
peritoneum.
Each kidney is a bean shaped and is
surrounded by a fibrous fatty and a fascial
capsule.
It has an outer cortex, inner medulla and renal
sinus.
6. NEPHRON
It is the structural and functional unit of
kidney.
Each kidney has 1 to 1.3 billion nephrons.
It has 2 parts: renal corpuscle and renal tubule.
Renal corpuscle consist of glomerulus and
bowman’s capsule.
Renal tubule consist of proximal convoulted
tubule, loop of henle and distal convoultd
tubule.
9. ACUTE RENAL FAILURE
ARF is a “sudden reduction in the Glomerular
Filtration Rate(GRF) that is expressed
clinically as the retention of nitrogenous waste
products (urea, creatinine) in the blood”.
The accumulation of these waste products is
termed as azotemia.
13. ARF is also clinically described as
Anuria – no urine output or less than 100ml/
24 hours
Oliguria - <400ml urine output/ 24 hours
Polyuria/ Non oliguria - >400ml urine output /
24 hours.
Anuria is uncommon and suggests either
complete obstruction or a major vascular event
such as renal infraction, high grade ischemic
acute tubular necrosis (ATN).
14. Non oliguric ARF is common in intra renal
ARF.
Oliguric more commonly characterizes
obstruction and pre-renal azotemia.
15. PRE-RENAL ACUTE FAILURE
• Pre-renal abnormalities are the physiologic
response that leads to decreased kidney
function (i.e. GFR).
• Elevated blood urea nitrogen (BUN) &
creatinine due decreased perfusion of the
kidney. Decreased perfusion of kidney which
may be due to ↓se
Consequence of inadequate volume blood
Inadequate cardiac output due to impaired MI
Marked vasodilation as may occur with
sepsis(severe infection).
16. INTRARENAL OR INTRINSIC ACUTE
RENAL FAILURE
• Intrinsic ARF can be categorized anatomically by
the area of the kidney parenchyma involved:
vascular, glomerular, tubular or intersititial areas.
• The decrement in GRF is directly proportional to
the kidney damage.
Acute tubular necrosis (ATN) is the death
of tubular cells, which may result when tubular
cells do not get enough oxygen (ischemic ATN) or
when they have been exposed to a toxic drug.
17. CAUSES
• Hypotension
• Obstetric (birth-related) complications
• Obstructive jaundice
• Sepsis (infection in the blood or tissues)
• Surgery
Use of drugs such as
Aminoglycosides,
Amphotericin B,
Cisplatin,
Radioisotopes.
18. ACUTE INTERSTITIAL NEPHRITIS
• The interstitium is the tissue that surrounds and imbeds the
glomeruli and tubules within the kidneys.
• AIN is rapidly developing inflammation that occurs
within the interstitium which results in reduced GFR and
renal flow.
CAUSES
Mainly due to antibiotics and NSAIDs such as
Ibuprofen,
Cephatholin,
Cimetidine
Cyclosporine,
Methicillin,
Penicillins.
19. POST RENAL ACUTE RENAL FAILURE
Post renal ARF is caused by an acute
obstruction that affects the normal flow of
urine out of both kidneys. The blockage causes
pressure to build in all of the renal nephrons.
The excessive fluid pressure ultimately causes
the nephrons to shut down.
The degree of renal failure corresponds
directly with the degree of obstruction.
20. CAUSES
Drugs that cause Post renal ARF are
Acyclovir,
Methotrexate,
Indinavir,
Sulfadiazine.
22. CHRONIC KIDNEY DISEASE
• Chronic renal failure (CRF) or kidney failure
is the progressive loss of kidney function.
• CKD caused by drugs is usually manifested
tubulointerstitial injury.
• The kidneys attempt to compensate for renal
damage by hyperfiltration (excessive straining
of the blood) within the remaining functional
nephrons. Over time, hyperfiltration causes
further loss of function.
26. NEPHROTIC SYNDROME
Nephrotic syndrome is kidney disease with
proteinuria, hypoalbuminemia, and edema.
Nephrotic-range proteinuria is 3 grams per day
or more.
It is usually caused due to damage of cluster of
small blood vessels in the kidney.
27.
28. CAUSES
• There are many specific causes of nephrotic syndrome.
These include kidney diseases such as minimal-change
nephropathy, and membranous nephropathy.
• Nephrotic syndrome can also result from systemic
diseases that affect other organs in addition to the
kidneys, such as diabetes, amyloidosis, and lupus
erythematosus.
• Infection is a major concern in nephrotic syndrome;
patients have an increased susceptibility to infection
with Streptococcus pneumoniae, Haemophilus
influenzae, Escherichia coli, and other gram-negative
organisms.
30. NSAIDS
• NSAIDs are non-steroidal anti-inflammatory
drugs, also known as NAIDs, non-steroidal anti-
inflammatory agents/analgesics (NSAIAs) or
non-steroidal anti-inflammatory medicines
(NSAIMs).
• They are medications with analgesic (pain
reducing), antipyretic (fever reducing) effects. In
higher doses they also have anti-inflammatory
effects - they reduce inflammation (swelling).
31. NSAIDS DRUGS
The most common NSAIDs are
Aspirin
Ibuprofen
Naproxen
Diclofenac
Melaoxicam
34. ACTION OF NSAIDS
• Prostaglandins - These are hormone-like
substances that participate in a wide range of
body functions, one of which causes pain and
inflammation.
• NSAIDs prevent the COX enzymes from
releasing the prostaglandin chemicals responsible
for inflammation and pain.
• COX-2 enzymes cause inflammation and pain in
the body. NSAID medications were created that
inhibited the COX-2 enzyme.
35.
36. SIDE EFECTS
Cardiovascular system
Blood pressure may rise with use of NSAIDs.
Control of treated hypertension may be adversely affected
by the addition of either selective or nonselective NSAIDs.
Gastrointestinal system
Short-term use of NSAIDs can cause stomach
upset (dyspepsia). Long-term use of NSAIDs, especially at
high doses, can lead to peptic ulcer disease and bleeding
from the stomach.
Liver toxicity
Long-term use of NSAIDs, especially at high
doses, can rarely harm the liver. Monitoring the liver
function with blood tests may be recommended in some
cases.
37. SIDE EFFECTS
Kidney toxicity
Use of NSAIDs, even for a short period
of time, can harm the kidneys. This is
especially true in people with underlying
kidney disease. The blood pressure and kidney
function should be monitored at least once per
year but may need to be checked more often,
depending on a person’s medical conditions.
38. EFFECT ON KIDNEY
• All non-steroidal anti-inflammatory drugs
(NSAIDs) have been associated with the
development of acute kidney injury.
• NSAIDs and Acute Kidney Injury
• NSAIDs can cause two different forms of acute
kidney injury.
• Haemodynamically mediated (eg, pre-renal injury
and/or acute tubular necrosis).
• Immune mediated (eg, acute interstitial nephritis).
39. NSAID INDUCED ARF
• NSAIDs reversibly inhibit the production of renal
prostaglandins via their inhibition of COX-1 and COX-
2. Maximal inhibition occurs at steady state plasma
concentrations (usually 3–7 days).
• Renal prostaglandins cause dilatation of the renal
afferent arteriole. This mechanism is important for
maintaining GFR when renal blood flow is reduced (ie,
not in young, healthy people).
• Therefore, NSAID use is likely to have a greater effect
on renal function in patients with other risk factors.
• It is unclear how NSAIDs induce acute interstitial
nephritis.
40. AMPHOTERICIN B
Amphotericin B is an antifungal drug often
used intravenously for systemic fungal
infections.
It is the only effective treatment for some
fungal infections.
DRUGS The common amphotericin b drugs are
o Fungilin
o Fungizone
o Abelcet
o AmBisome
o Fungisome
o Amphocil
o Amphotec
43. SIDE EFFECTS
Common side effects may include:
a reaction which may include fever
headaches and low blood pressure
kidney problems
Allergic symptoms including anaphylaxis may
occur.
44. EFFECT ON KIDNEY
This drug causes disturbances in both
glomerular and tubular function.
The drug binds to the membrane sterol in the
renal epithelial cells and altering its membrane
permeability.
This also causes enhanced cell death, calcium
channel blockage, etc.
45. AMINOGLYCOSIDES
• Aminoglycosides have long been important in the
treatment of serious gram negative infections.
• They have bactericidal activity against most gram
negative bacteria including Acinetobacter,
Enterobacter, Escherichia coli, Klebsiella,
Proteus and Shigella.
• They also act synergistically against gram
positive organisms such as Staphylococcus aureus
and Staphylococcus epidermidis.
46.
47. EFFECT ON KIDNEY
The drug after entering the luminal fluid of
proximal convoluted tubule, a small but
toxicologically important portion of the drug is
resorbed and stored in the cells.
This reacts with the negatively charged
phospoholipids binding site in the brush border.
This forms apical cytoplasmic vesicles called
endocytotic vesicles, which fuses with the
lysosomes.
48. EFFECT ON KIDNEY
The overall result is the accumulation of polar
phospholipids as “myleiod bodies”.
This leads to damage of cell organelle and
finally leads to cell death.
49.
50. ACE INHIBITORS
• An angiotensin-converting-enzyme inhibitor (ACE
inhibitor) is a pharmaceutical drug used primarily for
the treatment of hypertension (elevated blood pressure)
and congestive heart failure.
• This group of drugs cause relaxation of blood vessels,
as well as a decreased blood volume, which leads to
lower blood pressure and decreased oxygen demand
from the heart.
• They inhibit the angiotensin-converting enzyme, an
important component of the renin-angiotensin-
aldosterone system.
54. ACTION OF ACE INHIBITORS
• Angiotensin II is a very potent chemical produced by the body
that primarily circulates in the blood. It causes the muscles
surrounding blood vessels to contract, thereby narrowing
vessels.
• The narrowing of the vessels increases the pressure within the
vessels causing increases in blood pressure (hypertension).
• Angiotensin II is formed from angiotensin I in the blood by the
enzyme angiotensin converting enzyme (ACE). (Angiotensin I
in the blood is itself formed from angiotensinogen, a protein
produced by the liver and released into the body.)
• ACE inhibitors block ACE enzyme thereby decrease the
normal GFR rate.
55. EFFECT ON KIDNEY
Inhibition of ACE kinase –II results in
atleast two important effects:
a. Depletion of angiotensin II
b. Accumulation of bradykinin
56. LITHIUM MEDIATED acute
RENAL FAILURE
Lithium is currently a drug of choice for
treating persons with bipolar depression and is
widely used in this population.
• Lithium is completely absorbed by the GI tract.
The drug is not protein bound and is completely
filtered at the glomerulus. The majority of the
filtered load is reabsorbed by the proximal tubule,
but significant amounts are also absorbed in the
loop of Henle and the early distal nephron.
57. SIDE EFFECTS
• Confusion, poor memory, or lack of awareness
• Fainting
• Fast or slow heartbeat
• Frequent urination
• Increased thirst
• Irregular pulse
• Stiffness of the arms or legs
• Troubled breathing (especially during hard work
or exercise)
• Unusual tiredness or weakness
58. EFFECT ON KIDNEY
Lithium can affect renal function in several
ways.
Acutely and chronically, lithium salts produce a
natriuresis that is associated with an impaired
regulation of the expression of the epithelial
sodium channel in the cortical collecting tubule.
The most common complication of chronic
lithium therapy is nephrogenic diabetes insipidus.
59. PREVENTION
• Limiting accessibility to highly toxic
substances.
• Avoid culprit drugs
• Educate those prescribing and taking
medication about its side effects.
60. CONCLUSION
“ PREVENTION IS BETTER THAN CURE”.
Therefore one should take care of their health
in order to lead a health and a contended life.
