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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 7  |  Issue : 2  |  Page : 44-47

Analysis of creatinine clearance in patients on antimicrobial and analgesic therapy


1 Department of Pharmacology, Tagore Medical College and Hospital, Chennai, Tamil Nadu, India
2 Department of Community Medicine, Tagore Medical College and Hospital, Chennai, Tamil Nadu, India
3 IV Year M.B.,B.S, Tagore Medical College and Hospital, Chennai, Tamil Nadu, India

Date of Submission17-Jan-2019
Date of Decision27-May-2019
Date of Acceptance09-Jun-2019
Date of Web Publication02-Jan-2020

Correspondence Address:
Dr. Arvinth Arthanareeswaran
Department of Pharmacology, Tagore Medical College and Hospital, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JIHS.JIHS_3_19

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  Abstract 


Background: Nephrotoxicity has become increasingly common due to indiscriminate use of drugs. Analgesic nephropathy is a unique drug-induced kidney disease which is characterized by renal papillary necrosis and interstitial nephritis resulting from prolonged excessive consumption of combination antipyretic analgesics. This study was done to assess the renal work load in hospitalized patients taking analgesics and antimicrobial medication by creatinine clearance and to find their consequences. Aim and Objectives: (1) To determine the proportion of participants having altered creatinine clearance. (2) To compare the creatinine clearance among the hospitalised patients on treatment with antimicrobials and analgesics. Materials and Methods: It was a cross sectional observational study in which 1200 patients were enrolled, divided into 2 groups, with Group A: Comprising of those under antibiotic treatment; with Group B: Comprising of those under analgesic treatment. Creatinine clearance was calculated by Modification of Diet in Renal Disease (MDRD) equation and CKD-EPI equation. Observation and Results: On analyzing the drugs causing renal impairment out of 1200 participants, it was found that among analgesics diclofenac (52%) and among antibiotics, aminoglycosides (61%), were more commonly resulting in renal dysfunction. Conclusion: According to the present study, it is clear that precaution has to be taken before initiating antimicrobials and analgesic therapy, as they are often nephrotoxic.

Keywords: Antimicrobial and analgesic drugs, creatinine clearance, nephrotoxicity


How to cite this article:
Vivekkumar S P, Arthanareeswaran A, Suganya E S, Narayanan AS. Analysis of creatinine clearance in patients on antimicrobial and analgesic therapy. J Integr Health Sci 2019;7:44-7

How to cite this URL:
Vivekkumar S P, Arthanareeswaran A, Suganya E S, Narayanan AS. Analysis of creatinine clearance in patients on antimicrobial and analgesic therapy. J Integr Health Sci [serial online] 2019 [cited 2020 Apr 4];7:44-7. Available from: http://www.jihs.in/text.asp?2019/7/2/44/274530




  Introduction Top


People prefer to take medications such as tablets and syrups even for a simple illness, which is self-limiting. Kidneys play an important role in drug excretion. Drug excretion is the process of elimination of systemically absorbed drug in urine, feces, saliva, etc.[1] Clearance is defined as the volume of plasma cleared completely of a substance per unit time. Clearance test is used to access the glomerular function of the kidney.[2] Creatinine is an endogenous compound which is a product of creatine phosphate degradation, in a spontaneous and nonenzymatic reaction.[3]

Nephrotoxicity has become increasingly common due to indiscriminate use of drugs such as aminoglycosides.[4] People are utilizing antimicrobial and analgesic drugs to get relief even in the absence of doctor's prescription. It increases the kidney's workload and may lead to kidney failure along with drug resistance. Antimicrobials are the drugs designed to kill or inhibit the pathogens.[2] These are drugs which particularly affects the proximal convoluted tubule epithelial cells due to selective endocytosis and accumulation of aminoglycosides through the multiligand receptor megalin.[5] Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious and have a wide margin of safety. However, they do have potentially serious side effects that can occur even when they are taken in appropriate doses, and the impetus for the development of new NSAIDs has arisen from the desire to produce agents with reduced potential for adverse effects. NSAIDs are group of analgesics that nonselectively inhibit the cyclooxygenase (COX) enzymes.[6] These enzymes play a role in renal hemodynamics, glomerular filtration rate (GFR), and salt and water excretion.[7] Thus, by inhibiting the COX enzymes, NSAIDs alter the creatinine clearance. Analgesic nephropathy is a unique drug-induced kidney disease which is characterized by renal papillary necrosis and interstitial nephritis resulting from prolonged excessive consumption of combination of antipyretic analgesics. Combination of analgesic agents is also causally associated with renal disease. In general, the kidney has a large capacity to compensate for tubular insults so that an ongoing cell death process may remain undetected by functional explorations. The demonstration of tubular cells undergoes a marked proliferative response, even after low-dose treatments with aminoglycosides, and has shed a new light on the significance of the so-called nontoxic alterations, which is seen under many states. A major difficulty and a point of much confusion have been still in ascertainment of which changes, among the numerous ones described above, are truly responsible for toxicity. There is partly a lack of unambiguous knowledge in this area which has prevented the launching of large-scale programs aimed at designing or screening new aminoglycosides on a rational basis. The goal of reducing or protecting against aminoglycoside nephrotoxicity has drawn much effort and attention over the past decade. This study is to assess the renal workload in hospitalized patients taking analgesics and antimicrobial medication by creatinine clearance and to find their consequences.

Aim and objectives

The aim and objectives of this study are as follows:

  1. To determine the proportion of participants having altered creatinine clearance
  2. To compare the creatinine clearance among the hospitalized patients on treatment with antimicrobials and analgesics.



  Materials and Methods Top


The study was conducted in the wards of different specialties, Tagore Medical College and Hospital, Chennai.

Study design

Study design involves the cross-sectional observational study.

Duration of study

The study duration was 2 months.

The study was conducted after getting approval from the Institutional Ethics Committee. One thousand and two hundred patients were enrolled and divided into two groups, with Group A comprising those under antibiotic treatment and Group B comprising those under analgesic treatment. In this study, after fulfilling the following selection criteria, informed written consent was obtained in English or vernacular language from each patient.

Selection criteria

Inclusion criteria

  • Patients receiving antimicrobial and analgesic agents
  • Both men and women
  • Age >or = 18 years
  • Patients hospitalized for >3 days were included in the study.


Exclusion criteria

  • Patients with diabetic ketoacidosis
  • Patients with collagen vascular diseases include rheumatoid arthritis and systemic lupus erythematosus
  • Pregnant women
  • Severe illness (septicemia and cardiac failure)
  • Patients who are not willing to participate in the study
  • Patients with moderate-and-severe dehydration were excluded from the study.


Demographic profile includes age, sex, weight, and occupation, and address will also be obtained. Clinical profile, including medical history, drug history, personal history, and family history, was asked from the patient while interviewing. Details, including present diagnosis and treatment, was also recorded. A volume of 2 ml of venous blood had been taken by venipuncture before and after treatment and sent to the biochemistry laboratory for estimating serum creatinine. For calculating creatinine clearance, modification of diet in renal disease (MDRD) equation and CKD-EPI equation will be used and values were tabulated.[8]


  Observation and Results Top


Of 1200 participants enrolled, most of them were in the age group of 25–35 years (27.5%) followed by 56–65 years aged participants (26.6%). The mean ± 2 SD is 47.8 ± 12 years [Table 1]. Among the participants, 52.5% of them were male [Figure 1].
Table 1: Distribution of the study participants based on the age of the participants (n=1200)

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Figure 1: Distribution of study participants according to their sex (n = 1200)

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Of 600 participants, on antibiotic treatment, majority (35%) of them were taking metronidazole [Table 2] and among those treated with analgesics, most of them (46.6%) were taking diclofenac [Table 3].
Table 2: Distribution of the study participants based on antimicrobial used in treatment (n=600)

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Table 3: Distribution of the study participants based on analgesic used in treatment (n=600)

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Independent t-test was carried out to determine the significance in the difference between the creatinine values of Group A and Group B; it was found statistically insignificant having a P > 0.05.

Creatinine clearance was determined using the MDRD equation and the CKD-EPI equation.

Decreased creatinine clearance was noted to be 6% [Figure 2] among those treated with analgesics and 4% [Figure 3] among those treated with antibiotics.
Figure 2: Distribution of patients on analgesic treatment based on creatinine clearance (n = 600)

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Figure 3: Distribution of patients on antibiotic treatment based on creatinine clearance (n = 600)

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On analyzing the drugs causing renal impairment, it was found that among analgesics, 52% of diclofenac [Figure 4] and among antibiotics, 61% of aminoglycosides [Figure 5] were more commonly resulting in renal dysfunction.
Figure 4: Proportion of analgesics causing impaired renal function, based on creatinine clearance (n = 36)

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Figure 5: Proportion of antimicrobials causing impaired renal function bases on creatinine clearance (n = 25)

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  Discussion Top


Renal toxicity due to medication has been increasing in the past few decades. The main reason being irrational prescriptions of renal toxic drugs are highly prevalent due to the countermedication practices.

In order to determine the effect on kidney function due to intake of antimicrobials and analgesics, creatinine clearance values are compared in the present study between the two groups. Imai E et al.[9] in their study titled “Estimation of GFR by the MDRD study equation modified for Japanese patients with CKD,” stated that GFR estimation is crucial to determine the kidney function and also to assess the progression of treatment in CKD patients.

In the present study, the reduced creatinine clearance was seen in both the groups, i.e., the group on analgesic and the group on antibiotic therapy, respectively. The proportion of participants with reduced creatinine clearance was higher among those taking analgesics comparing those on antibiotic treatment. Humes[10] reported in his study that increasing creatinine level will be evident due to antibiotic induced nephrotoxicity.

The study used the CKD-EPI method and MDRD method for determining the creatinine clearance. Michels et al.[11] inferred CKD-EPI equation as a better method in determining the creatinine clearance.

In a retrospective cohort study, children have developed altered renal function associated with nephron toxins exposure (≥3 days of aminoglycosides) having a relative risk of 3.84.[12] The present study finding also inferred that the aminoglycosides have been the major drug causing reduction in creatinine clearance among the antibiotic group.

Kaloyanides et al., in their study, stated that aminoglycoside nephrotoxicity is characterized by heterogeneity of renal functional adjustments. As early as 24 h after a single therapeutic dose of aminoglycoside, the urinary excretion of a variety of brush border membrane enzymes increases and progressively rises as therapy continues.[13]

Bonventre et al.[14] in their study on drug-induced nephrotoxicity and its biomarkers have found out that NSAID affects the glomerulus, and hence, responsible for nephrotoxicity; the biomarker for the NSAID-induced nephrotoxicity is proteinuria. Early diagnosis of drug-induced nephrotoxicity would be advantageous to reduce the economic costs losses during safety inspection of new drugs and also it avoids major drug-induced complications.[15]

Limitations of the present study are that the study when done as a prospective study must have been of more value as it also determines the degree of severity of adverse effect on analgesics and antibiotic therapy. Patients who warrant chronic therapy with these agents should be closely monitored for any early signs of kidney injury. Early detection and removal of the offending agent could halt or even reverse drug-induced kidney injury. There is a pressing need for multicenter clinical trials to assess the true incidence of these problems.


  Conclusion Top


According to the present study, it is clear that precaution has to be taken before initiating antimicrobials and analgesic therapy, as they are often nephrotoxic. Continuing medical education of the physicians is mandatory for quality improvement in patients with impaired renal function. Depending on the group of drug, age, and renal function, physician has to decide whether dose reduction or contraindications of drug in particular disease have to be done.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tripathi KD. Essentials of Medical Pharmacology. 7th ed, Vol. 27. New Delhi: Jaypee Brothers Medical Publishers; 2013. p. 688.  Back to cited text no. 1
    
2.
Kampmann JP, Hansen JM. Medical department p, Bispebjerg hospital and medical endocrinological department f, Herlev hospital, Bispebjergbakke 23. Dk-2400 Copenhagennv, Denmark. Glomerular filtration rate and creatinine clearance. Br J Clin Pharmac 1981;12:7-14.  Back to cited text no. 2
    
3.
Vasudevan DM, Sreekumari S, Vaidyanathan K. Textbook of Biochemistry for Medical Students. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 2013. p. 211.  Back to cited text no. 3
    
4.
Gentamicin Side Effects. Available from: https://www.drugs.com/sfx/gentamicin-side-effects.html. [Last accessed on 2017 Jan 17].  Back to cited text no. 4
    
5.
McWilliam SJ, Antoine DJ, Smyth RL, Pirmohamed M. Aminoglycoside-induced nephrotoxicity in children. Pediatr Nephrol 2017;32:2015-25.  Back to cited text no. 5
    
6.
Hörl WH. Nonsteroidal anti-inflammatory drugs and the kidney. Pharmaceuticals (Basel) 2010;3:2291-321.  Back to cited text no. 6
    
7.
Weir MR. Renal effects of nonselective NSAIDs and coxibs. Cleve Clin J Med 2002;69 Suppl 1:SI53-8.  Back to cited text no. 7
    
8.
Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, et al. Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007;53:766-72.  Back to cited text no. 8
    
9.
Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, et al. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol 2007;11:41-50.  Back to cited text no. 9
    
10.
Humes D. Aminoglycoside nephrotoxicity. Kidney Int 1988;33:900-11.  Back to cited text no. 10
    
11.
Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT, et al. Performance of the cockcroft-gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol 2010;5:1003-9.  Back to cited text no. 11
    
12.
Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs:physiologic foundations and clinical implications. Am J Med 1999;106(5B):135-245.  Back to cited text no. 12
    
13.
Mathiesen ER, Hommel E, Olsen UB, Parving HH. Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient diabetic nephropathy. Diabet Med 1988;5:145-9.  Back to cited text no. 13
    
14.
Bonventre JV, Vaidya VS, Schmouder R, Feig P, Dieterle F. Next-generation biomarkers for detecting kidney toxicity. Nat Biotechnol 2010;28:436-40.  Back to cited text no. 14
    
15.
Kim SY, Moon A. Drug-induced nephrotoxicity and its biomarkers. Biomol Ther (Seoul) 2012;20:268-72.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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