Nephrotoxins

1. PRESENTATION ON NEPHROTOXINS
BY
UGWU ANTHONY CHUKWUEBUKA
PRESENTED TO THE DEPARTMENT OF PHARMACY,
FEDERAL MEDICAL CENTER KEFFI
ON 10TH JUNE 2022.

2. GROUP MEMBERS
 PRECEPTOR: DR (Pharm) Rabiu Tanko
 SUPERVISORS:
Pharm Esther Onumonu
Pharm Patience Affiku
Pharm Song Gam Jong
 MEMBER INTERNS:
Pharm Mohammed Jibrin Mohammed
Pharm Azih Cynthia Nneka.

3. OUTLINE
 BACKGROUND
 NEPHROTOXIC DRUGS
 MECHANISM OF DRUG NEPHROTOXICITY
 METALIC NEPHROTOXINS
 NEPHROTOXIC HERBS AND FRUITS
 RISK FACTORS
 PREVENTION
 RESEARCH RESULTS
 ROLES OF PHARMACISTS
 CONCLUSION AND
 REFERENCES

4. BACKGROUND
 The kidney is one of a pair of organs in the
abdomen.
 It have the functions of removing waste and extra
water from the blood (as urine)and maintain salt
balance.
 The kidney also make hormones that help control
BP and stimulate bone marrow to make red blood
cells.

5. CONTINUE
 Toxins are substances created by plants and
animals that are poisonous to humans.
 They may also include some medicines that are
helpful in small doses, but poisonous in large
amounts.

6. CONTINUE…….
 Nephrotoxins are substances exhibiting
nephrotoxicity.
 And Nephrotoxicity is the poisonous or toxic
effect of some substances to the kidney.
 Nephrotoxicity should not be confused with some
medications predominantly excreted from the
kidney, needing their doses adjusted in cases of
decreased kidney function.

7. CONT……………………..
 Exposure to chemical reagents like ethylene
glycol, carbon tetrachloride, sodium oxalate and
heavy metals such as cadmium, mercury, arsenic
and lead also induces nephrotoxicity.
 Toxic effects of these substance may be direct or
mediate indirectly through immunological
mechanisms.
 Prompt recognition of the disease and cessation
of responsible substances and drugs are usually
the only necessary therapy.

8. HIGHLIGHTS

9. EXAMPLES OF NEPHROTOXINS
 Chemotherapeutic drugs
 Drugs of abuse eg, cocaine, heroin and
amphetamine
 Antibiotics like the aminoglycosides, B-lactam
antibiotic, amphotericin B
 NSAIDs
 ACEIs
 Industrial chemicals
 Heavy metals like arsenic, cadmium and mercury.
 Herbal medicines like Lawsonia intermis etc.

10. NEPHROTOXIC DRUGS
 The most common nephrotoxic drugs are:
 Aminoglycosides (Neomycin, gentamicin,
amikacin, tobramycin, streptomycin)
 Cisplatin
 Amphotericin B
 B-lactam antibiotics
 NSAIDs

12. MECHANISM OF DRUG NEPHROTOXICITY
 BASED ON THE HISTOLOGICAL COMPONENT OF
THE KIDNEY AFFECTED;
 1. Tubular Epithelial Injury Via Intracellular
Accumulation.
 These drugs accumulate in the intracellular
spaces leading to injury in the epithelial tubules.
 Examples are amphotericin B, aminoglycosides,
cisplatin, carboplatin, tenofovir, adenofovir,

13. Mechanism of drug nephrotoxicity cont…
 2. Tubular Obstruction By Crystals And Casts
Containing Drugs And Their Metabolites.
 These drugs and their metabolites form crystals
and casts which obstructs the tubules.
 Examples are sulfadiazine, methotrexate,
triamterene, vancomycin, ciprofloxacin.

14. Mechanism of drug nephrotoxicity cont…
 3. Interstitial Nephritis
 These drugs causes the spaces between small
tubules inside the kidney to become inflamed
thereby reducing the ability of the kidney to filter
properly.
 Examples are NSAIDs, Proton pump inhibitors,
penicillin, phenytoin, allopurinol, carbamazepine.

15. INDIRECT WAYS NSAIDs, ACEIs and
AMINOGLYCOSIDES CAUSE NEPHROTOXICITY
 NSAIDs block the renal prostaglandins (by inhibiting
both COX I AND COX II) which are the natural
chemicals that dilate blood vessels (Afferent
arterioles) and allow oxygen to reach the kidney to
keep them alive and healthy.
 They also decrease the GRF by constricting the
afferent arterioles

16. NSAID NEPHROTOXICITY

17. CONT…………………….
 Naproxen is found to be the most nephrotoxic
NSAID while Sulindac has been hypothesized to
have decreased renal effect due to its decreased
COX inhibition and rapid renal metabolism
compared to other NSAIDs.
 ACE inhibitors depress angiotensin II and thus
inhibit angiotensin II mediated vasoconstriction of
the efferent tubules. This lowers glomerular
filtration pressure and decreases the glomerular
filtration rate.

18. ACEI NEPHROTOXICITY

19. Dosage Adjustment of ACEIs in patients
with CKD.
DRUG DOSAGE PERCENTAGE OF USUAL DOSAGE BASED ON
GFR(Ml/min/1.73m2)
>50 10-50 <10
Lisinopril 5-10mg 100% 50-75% 25-50%
Ramipril 5-10mg 100% 50-75% 25-50%
Enalapril 5-10mg b.d 100% 75-100% 50%

20. CONTINUE……….
 For Aminoglycosides, a small but sizable
proportion of the administered dose is retained in
the epithelial cells, lining the proximal tubules
after glomerular filtration, leading to rise in serum
creatinine and decreased glomerular filtration rate.

21. AMINOGLYCOSIDES NEPHROTOXICITY

22. CONTINUE…………
 FROM MOST TOXIC TO LEAST TOXIC
AMINOGLYCOSIDES;
 Neomycin > Gentamycin > Tobramycin > Amikacin
> Netilmicin > Streptomycin.

24. METALIC NEPHROTOXINS
 Heavy metals such as Arsenic, Cadmium, lead and
mercury causes nephrotoxicity at high exposure
levels.
 The kidney is the first target organ of heavy metal
toxicity due to its capacity to reabsorb and
accumulate divalent metals.
 Nephrotoxicity of these metals is due to the fact
that urinary elimination is a main route of
excretion, and the proximal tubules are especially
sensitive due to their reabsorption activities.

25. NEPHROTOXIC HERBS
 The herbal medicines most commonly associated
with nephrotoxicity are;
 Dioscorea quinquelaba
 Lawsonia intermis
 Tamandus indica (Tamarind)
 Artemisia herba-alba
 Khaya senegalensis (Mahogany)
 Cape aloes
 Adansonia digitate L. (Baobab)

27. Commonly known as Baobab (kuka in Hausa). The powder
contains more than 6times the amount of potassium in
banana
Adansonia digitate L

28. Tamarindus indica
Commonly known as Tamarind (Tsamiya in Hausa). It can
damage the kidney and nervous system. Tamarind candy was
cited as a cause of lead poisoning by CDCP in 1999.

29. NEPHROTOXIC FRUITS
 Nutrients are concentrated when fruits are dried.
 Hence, the potassium content of dried fruits like
dates, prunes and raisins are extremely high and
should be avoided in renal diet.
 Impaired kidneys build up potassium in the blood,
resulting in serious heart problems.

30. CONTINUE………………..
 A kidney friendly diet usually limits sodium to
under 2300mg per day as well as potassium and
phosphorous to less than 2000mg/day and
1000mg/day respectively

31. NEPHROTOXIC FRUITS CONT……..
 Examples of fruits with high potassium content
are; bananas, potatoes, avocados, melons,
tomatoes, oranges.
 One cup, 240ml of orange juice contains 473mg of
potassium.

32. CONTINUE……
 One cup of tomato sauce can contain up to 900mg
of potassium
 Four dates provide 664mg of potassium
 One average sized avocado provides 690mg of K.

33. RISK FACTOR OF NEPHROTOXICITY
 Age above 60
 Patient already suffering from renal insufficiency
 Patients with Sepsis, Heart failure and diabetes
 Patients with dehydration and extracellular volume
depletion
 Increased uric acid level or hyper uricemia

34. HOW TO PREVENT NEPHROTOXICITY
 Limit intake of NSAIDs of painkillers
 Use alternative drugs which are non-nephrotoxic
drugs
 Monitor renal function during therapy and adjust
dosage of drug depending on the vital signs

35. CONTINUE……
 Be aware of patient risk factors and avoid drugs
which could cause nephrotoxicity
 Modification of diet according to the renal function
 Adequate hydration and treatment of underlying
acute and chronic diseases.

36. ASSESSMENT OF THE KNOWLEDGE OF THE
NEPHROTOXIC EFFECTS OF NSAIDs AMONG
DRIVERS AND PASSENGERS AT KEFFI PARK
 A total of 56 persons were interviewed and
counselled on the nephrotoxicity of NSAIDs.
 91% of the respondents agreed to have used pain
killers before
 61% were able to identify the names of the pain
killers they had used.

37. CONTINUE………….
 46% of the respondents obtain their pain killer
drugs from Chemists, 27% from pharmacies, 5%
from hospitals and 5% depends solely on herbal
medicines.
 29% of the respondents combine more than one
NSAIDs at the same time.

38. CONTINUE………….
 9% of the respondents think that these NSAIDS
have some effect to the kidney but were not able
to identify the possible effects they could have.
 5% think they have absolutely no effect to the
kidney and finally
 86% do not know whether they have effect on the
kidney or not.

39. ROLE OF THE PHARMACIST
 From this study, it is obvious that a good number
of the respondents misuse NSAIDs and are not
even aware of the nephrotoxic effect of these
NSAIDs.
 It is the role of the pharmacist to educate our
patients on the nephrotoxic effects of these
drugs, fruits and herbs and adjust the doses in
cases of kidney impairments.

40. CONCLUSION
 Nephrotoxins are substances that have tendencies
of causing injury to the kidney, ranging from
drugs, chemicals, fruits, heavy metals, herbs to
cosmetics. These substances have different
mechanisms of which they exert their nephrotoxic
effects and their nephrotoxic effects can be
tackled by early identification and
discontinuation.

41. REFERENCES
 Jayashree T. ‘Diagnosis, treatment and prevention
of nephrotoxicity’ medindia= Jan 12, 2019
 Marwa S. et al ‘Nephrotoxicity: Role and
significance of renal biomarkers in the early
detection of acute renal injury’
J.Adv.Pharm.Technol.Res. June 2019.
 Cynthia A. ‘Drug induced nephrotoxicity’ American
Family Physicians, 2022.
 Wikipedia.org/nephrotoxicity
 Kim SY, Moon A. Drug-induced nephrotoxicity and
its biomarkers. Biomol Ther (Seoul) 2012;20:268-
72.

42. THANK YOU FOR LISTENING