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Sidda Rama R et al / Int. J. of Pharmacology and Clin. Res. Vol-1(1) 2017 [08-10]
www.ijpcr.net
8
IJPCR |Volume 1 | Issue 1 | Jan – Jun- 2017
www.ijpcr.net
Case Report Clinical Research
Rare case report on Amikacin induced Nephrotic syndrome
Dr. Sreedhar Reddy1
, R Sidda Rama2*
, P Gowtham2
, Gangula Amareswara Reddy2
, K
Venkata Sankar Reddy3
, R.Rohith3
, P Chandrakanth3
1
Assistant Professor, Department of Pediatrics, RIMS, Kadapa, India - 516003
2
Pharm D, P Rami Reddy Memorial College of Pharmacy, Kadapa, India - 516003
3
Pharm D, Annamacharya College of Pharmacy, Rajampet, India - 516115
*Corresponding author: R Sidda Rama
Email Id: siddaramapharmd22@gmail.com
ABSTRACT
Nephrotic syndrome is a collection of symptoms due to the many nephrotic drugs and some diseases effecting to the kidney
characterized by hypo proteinaemia, hyper cholesterolaemia, generalized edema and heavy proteinuria. Amikacin is the
antibiotic which is used in treating many infectious diseases in children. It is having many side effects like nephrotoxicity,
hypersensitivity reactions and Ototoxicity etc. The therapeutic dose of amikacin also leads to the nephrotoxicity in the
childrens due to the pharmacokinetic and pharmacodynamic changes. Here in this case report a 10 years old female child was
presented with facial puffiness, generalized edema, increased total cholesterol, decreased serum albumin and urine output due
the usage of amikacin.
Keywords: Amikacin, Nephrotic syndrome, Facial puffiness, Edema, Decreased serum albumin, ADR analysis.
INTRODUCTION
Nephrotic syndrome is a group of symptoms that
include protein in the urine, low blood protein levels,
high cholesterol levels, high triglyceride levels,
and swelling. Common symptoms of this includes:
Swelling (edema) in the face and around the eyes
(facial swelling) in the arms and legs, especially in the
feet and ankles In the belly area (swollen abdomen)
Other symptoms include: Poor appetite and weight gain
(unintentional) from fluid retention [1]. The patients
with nephrotic syndrome will be having a major side
effect of Acute Renal Failure. Nephrotoxicity leads to
Acute Renal Failure. Nephrotoxicity is a major adverse
effect of many drugs hence it is difficult to identify the
causative drug since in many cases, multiple drugs are
administered to a patient simultaneously [2]. Many
reports are available with drug induced nephrotoxicity
[2, 3] and use of Amikacin mostly causes
Nephrotoxicity. Amikacin falls under the category of
“aminoglycoside antibiotic”. It plays an important role
in the treatment of life-threatening infections;
especially for treating infections in children hence it
requires a dose adjustment. Children are more
susceptible to the complications of this category of
ISSN:2521-2206
International Journal of Pharmacology and
Clinical Research (IJPCR)
Sidda Rama R et al / Int. J. of Pharmacology and Clin. Res. Vol-1(1) 2017 [08-10]
www.ijpcr.net
9
drugs due to their pharmacokinetic and
pharmacodynamic differences [4].
CASE REPORT
A 10 years old female child was admitted in PICU
with the complaints of cold, cough and fever since 1
week. No history of similar complaints in the past.
Birth history of the patient was found to be normal
vaginal delivery, no history of neonatal jaundice and
birth asphyroxia. Development of the child is
appropriate for the age. On general examination the
patient was conscious and coherent. Her vitals were
found to be BP – 80/70 mm of Hg, PR – 80 bpm and
systemic examination were found to be CVS – S1S2 +,
CNS – NAD, RS – BLAE+, P/A – Soft. Clinical
evaluation was done and patient was treated
symptomatically on day 1 with parenteral antibiotics
(Amikacin 90mg IV BD), parenteral anti ulcer drug –
Pantoprazole 30 mg IV BD, and oral antipyretic drug –
Paracetamol 250 mg. On day 2, 3 &4 she was treated
with same medications. On day 5 patients complained
of Facial puffiness, pedal edema (Fig. 1), shortness of
breath and abdominal pain.
Fig.1: Facial puffiness and Pedal edema
After the symptoms laboratory examinations shows
Serum albumin – 1.7 g/dl, Total cholesterol – 369
mg/dl, urine examination showed that the patient has
proteinuria, decreased urine output and glycosuria.
Culture report (urine sample) has shown negative for
bacterial growth. Blood profile shows Hb – 12g%, TC
– 9000 cells/cumm, Differential count: P – 50%, L –
40%, E – 2%. Liver function tests shows Total
bilurubin – 0.2 mg/dl, indirect bilirubin – 0.3 mg dl and
SGOT – 17mg/dl. Ultra sound abdomen shows normal.
We the Pharm-D students intimated about the patient’s
condition and then the physician withdrawn the
suspected drug and then the patient’s laboratory results
are as follows
S.No Tests Values Reference values
1. Serum albumin 3.9 g/dl 3.5 – 5 g/dl
2. Total cholesterol 170 mgs/dl 150 – 200 mgs/dl
3. Urine Output 950 ml/day 800 – 2000 ml/day
ADR ANALYSIS
Causality assessment
The suspected drug causing “Nephrotic Syndrome”
is analysed by using Naranjo’s scale, WHO-UMC
scale, Karch & Lasagna scale shown in table-1, and
severity, predictability and preventability were shown
in table-2.
DE-Challenge
After causality assessment the suspected drug was
stopped and symptomatic treatment was given.
Sidda Rama R et al / Int. J. of Pharmacology and Clin. Res. Vol-1(1) 2017 [08-10]
www.ijpcr.net
10
Table 1: Causality assessment of suspected ADR
Sl.No Suspected drug Naranjo’s scale WHO-UMC Karch & Lasagna scale
1 Amikacin Probable Likely Probable
Table 2: Severity, Predictability and Preventability of suspected ADR
ADR Severity Predictability Preventability
Amikacin induced Nephrotoxicity Moderate level 4a Not Predictable Probably preventable
DISCUSSION
Aminoglycoside-induced nephrotoxicity is defined
by tubular necrosis, proliferation and apoptosis, basal
membrane disruption, mesangial cell contraction,
detected by a decrease in glomerular filtration [5].
Drug-induced nephrotoxicity symptoms are fever,
weight loss and anorexia nervosa. In this case patient
had manifestations consistent with the symptoms
mentioned above. The laboratory tests usually show
glycosuria, proteinuria, hypercholestemia and
decreased urine output [2-4]. Drugs that are associated
with nephrotoxicity include antibiotics,
anticonvulsants, NSAIDs and diuretics [6]. Incidence
of nephrotoxicity due to aminoglycosides has risen
from 2-3% in 1969 to 20% in the past decade. Despite
nephrotoxicity and ototoxicity, these drugs are still
being used in clinical practice because of the
antibacterial effect, low cost, and limited bacterial
resistance [7]. An increase in glomerular permeability
leads to albuminuria and eventually to
hypoalbuminemia. In turn, hypoalbuminemia lowers
the plasma colloid osmotic pressure, causing greater
transcapillary filtration of water throughout the body
and thus the development of edema. However, studies
of humans with tubular transport defects suggest that
the glomerular urinary space albumin concentration is
3.5 mg/L. With this concentration, and a normal daily
glomerular filtration rate (GFR) of 150 liters, one
would expect no more than 525 mg per day of albumin
in the final urine. Amounts above that level point to
glomerular disease [8].
CONCLUSION
Amikacin is the antibiotic which is used in treating
many infectious diseases in children. It is having many
side effects like nephrotoxicity, hypersensitivity
reactions and Ototoxicity etc. The therapeutic dose of
amikacin also leads to the nephrotoxicity in the
childrens due to the pharmacokinetic and
pharmacodynamic changes. Here in this case report a
10 years old female child was presented with facial
puffiness, generalized edema, increased total
cholesterol, decreased serum albumin and urine output
due the usage of amikacin.
REFERENCES
[1]. http://www.nlm.nih.gov/medlineplus/ency/article/000490.htm
[2]. Printza N, Koukourgianni F, Saleh T, Goga C, Papachristou F. Drug-induced interstitial nephritis in a child with
idiopathic nephrotic syndrome. Saudi J Kidney Dis Transpl 20(6), 2009, 1072-5.
[3]. Van der Meulen J, De Jong GM, Westenend PJ. Acute interstitial nephritis during rifampicin therapy can be a
paradoxical response: a case report. Cases J 3, 2009, 2:6643. doi:10.1186/1757-1626-0002-0000006643.
[4]. Vogelstein B, Kowarski A.A., Lietman P.S. The pharmacokinetics of amikacin in children. The Journal of pediatrics
91(2), 1977, 333-339.
[5]. Bennett WM, Wood CA, Houghton DC, Gilbert DN. Modification of experimental aminoglycoside nephrotoxicity.
American J of Kidney Dis 8, 1986, 292-6.
[6]. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nat Rev Nephrol 6(8), 2010, 461-70.
doi:10.1038/nrneph.2010.71.
[7]. Sandhu JS, Sehgal A, Gupta O and Singh A, Aminoglycoside nephrotoxicity revisited. J Indian Acad Clin Med 8(4),
2007, 331-333.
[8]. http://emedicine.medscape.com/article/244631-overview#a0104.

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Rare case report on amikacin induced nephrotic syndrome

  • 1. Sidda Rama R et al / Int. J. of Pharmacology and Clin. Res. Vol-1(1) 2017 [08-10] www.ijpcr.net 8 IJPCR |Volume 1 | Issue 1 | Jan – Jun- 2017 www.ijpcr.net Case Report Clinical Research Rare case report on Amikacin induced Nephrotic syndrome Dr. Sreedhar Reddy1 , R Sidda Rama2* , P Gowtham2 , Gangula Amareswara Reddy2 , K Venkata Sankar Reddy3 , R.Rohith3 , P Chandrakanth3 1 Assistant Professor, Department of Pediatrics, RIMS, Kadapa, India - 516003 2 Pharm D, P Rami Reddy Memorial College of Pharmacy, Kadapa, India - 516003 3 Pharm D, Annamacharya College of Pharmacy, Rajampet, India - 516115 *Corresponding author: R Sidda Rama Email Id: siddaramapharmd22@gmail.com ABSTRACT Nephrotic syndrome is a collection of symptoms due to the many nephrotic drugs and some diseases effecting to the kidney characterized by hypo proteinaemia, hyper cholesterolaemia, generalized edema and heavy proteinuria. Amikacin is the antibiotic which is used in treating many infectious diseases in children. It is having many side effects like nephrotoxicity, hypersensitivity reactions and Ototoxicity etc. The therapeutic dose of amikacin also leads to the nephrotoxicity in the childrens due to the pharmacokinetic and pharmacodynamic changes. Here in this case report a 10 years old female child was presented with facial puffiness, generalized edema, increased total cholesterol, decreased serum albumin and urine output due the usage of amikacin. Keywords: Amikacin, Nephrotic syndrome, Facial puffiness, Edema, Decreased serum albumin, ADR analysis. INTRODUCTION Nephrotic syndrome is a group of symptoms that include protein in the urine, low blood protein levels, high cholesterol levels, high triglyceride levels, and swelling. Common symptoms of this includes: Swelling (edema) in the face and around the eyes (facial swelling) in the arms and legs, especially in the feet and ankles In the belly area (swollen abdomen) Other symptoms include: Poor appetite and weight gain (unintentional) from fluid retention [1]. The patients with nephrotic syndrome will be having a major side effect of Acute Renal Failure. Nephrotoxicity leads to Acute Renal Failure. Nephrotoxicity is a major adverse effect of many drugs hence it is difficult to identify the causative drug since in many cases, multiple drugs are administered to a patient simultaneously [2]. Many reports are available with drug induced nephrotoxicity [2, 3] and use of Amikacin mostly causes Nephrotoxicity. Amikacin falls under the category of “aminoglycoside antibiotic”. It plays an important role in the treatment of life-threatening infections; especially for treating infections in children hence it requires a dose adjustment. Children are more susceptible to the complications of this category of ISSN:2521-2206 International Journal of Pharmacology and Clinical Research (IJPCR)
  • 2. Sidda Rama R et al / Int. J. of Pharmacology and Clin. Res. Vol-1(1) 2017 [08-10] www.ijpcr.net 9 drugs due to their pharmacokinetic and pharmacodynamic differences [4]. CASE REPORT A 10 years old female child was admitted in PICU with the complaints of cold, cough and fever since 1 week. No history of similar complaints in the past. Birth history of the patient was found to be normal vaginal delivery, no history of neonatal jaundice and birth asphyroxia. Development of the child is appropriate for the age. On general examination the patient was conscious and coherent. Her vitals were found to be BP – 80/70 mm of Hg, PR – 80 bpm and systemic examination were found to be CVS – S1S2 +, CNS – NAD, RS – BLAE+, P/A – Soft. Clinical evaluation was done and patient was treated symptomatically on day 1 with parenteral antibiotics (Amikacin 90mg IV BD), parenteral anti ulcer drug – Pantoprazole 30 mg IV BD, and oral antipyretic drug – Paracetamol 250 mg. On day 2, 3 &4 she was treated with same medications. On day 5 patients complained of Facial puffiness, pedal edema (Fig. 1), shortness of breath and abdominal pain. Fig.1: Facial puffiness and Pedal edema After the symptoms laboratory examinations shows Serum albumin – 1.7 g/dl, Total cholesterol – 369 mg/dl, urine examination showed that the patient has proteinuria, decreased urine output and glycosuria. Culture report (urine sample) has shown negative for bacterial growth. Blood profile shows Hb – 12g%, TC – 9000 cells/cumm, Differential count: P – 50%, L – 40%, E – 2%. Liver function tests shows Total bilurubin – 0.2 mg/dl, indirect bilirubin – 0.3 mg dl and SGOT – 17mg/dl. Ultra sound abdomen shows normal. We the Pharm-D students intimated about the patient’s condition and then the physician withdrawn the suspected drug and then the patient’s laboratory results are as follows S.No Tests Values Reference values 1. Serum albumin 3.9 g/dl 3.5 – 5 g/dl 2. Total cholesterol 170 mgs/dl 150 – 200 mgs/dl 3. Urine Output 950 ml/day 800 – 2000 ml/day ADR ANALYSIS Causality assessment The suspected drug causing “Nephrotic Syndrome” is analysed by using Naranjo’s scale, WHO-UMC scale, Karch & Lasagna scale shown in table-1, and severity, predictability and preventability were shown in table-2. DE-Challenge After causality assessment the suspected drug was stopped and symptomatic treatment was given.
  • 3. Sidda Rama R et al / Int. J. of Pharmacology and Clin. Res. Vol-1(1) 2017 [08-10] www.ijpcr.net 10 Table 1: Causality assessment of suspected ADR Sl.No Suspected drug Naranjo’s scale WHO-UMC Karch & Lasagna scale 1 Amikacin Probable Likely Probable Table 2: Severity, Predictability and Preventability of suspected ADR ADR Severity Predictability Preventability Amikacin induced Nephrotoxicity Moderate level 4a Not Predictable Probably preventable DISCUSSION Aminoglycoside-induced nephrotoxicity is defined by tubular necrosis, proliferation and apoptosis, basal membrane disruption, mesangial cell contraction, detected by a decrease in glomerular filtration [5]. Drug-induced nephrotoxicity symptoms are fever, weight loss and anorexia nervosa. In this case patient had manifestations consistent with the symptoms mentioned above. The laboratory tests usually show glycosuria, proteinuria, hypercholestemia and decreased urine output [2-4]. Drugs that are associated with nephrotoxicity include antibiotics, anticonvulsants, NSAIDs and diuretics [6]. Incidence of nephrotoxicity due to aminoglycosides has risen from 2-3% in 1969 to 20% in the past decade. Despite nephrotoxicity and ototoxicity, these drugs are still being used in clinical practice because of the antibacterial effect, low cost, and limited bacterial resistance [7]. An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema. However, studies of humans with tubular transport defects suggest that the glomerular urinary space albumin concentration is 3.5 mg/L. With this concentration, and a normal daily glomerular filtration rate (GFR) of 150 liters, one would expect no more than 525 mg per day of albumin in the final urine. Amounts above that level point to glomerular disease [8]. CONCLUSION Amikacin is the antibiotic which is used in treating many infectious diseases in children. It is having many side effects like nephrotoxicity, hypersensitivity reactions and Ototoxicity etc. The therapeutic dose of amikacin also leads to the nephrotoxicity in the childrens due to the pharmacokinetic and pharmacodynamic changes. Here in this case report a 10 years old female child was presented with facial puffiness, generalized edema, increased total cholesterol, decreased serum albumin and urine output due the usage of amikacin. REFERENCES [1]. http://www.nlm.nih.gov/medlineplus/ency/article/000490.htm [2]. Printza N, Koukourgianni F, Saleh T, Goga C, Papachristou F. Drug-induced interstitial nephritis in a child with idiopathic nephrotic syndrome. Saudi J Kidney Dis Transpl 20(6), 2009, 1072-5. [3]. Van der Meulen J, De Jong GM, Westenend PJ. Acute interstitial nephritis during rifampicin therapy can be a paradoxical response: a case report. Cases J 3, 2009, 2:6643. doi:10.1186/1757-1626-0002-0000006643. [4]. Vogelstein B, Kowarski A.A., Lietman P.S. The pharmacokinetics of amikacin in children. The Journal of pediatrics 91(2), 1977, 333-339. [5]. Bennett WM, Wood CA, Houghton DC, Gilbert DN. Modification of experimental aminoglycoside nephrotoxicity. American J of Kidney Dis 8, 1986, 292-6. [6]. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nat Rev Nephrol 6(8), 2010, 461-70. doi:10.1038/nrneph.2010.71. [7]. Sandhu JS, Sehgal A, Gupta O and Singh A, Aminoglycoside nephrotoxicity revisited. J Indian Acad Clin Med 8(4), 2007, 331-333. [8]. http://emedicine.medscape.com/article/244631-overview#a0104.