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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 7  |  Issue : 5  |  Page : 282-284

Acyclovir crystalluria: The utility of bedside urine routine microscopic examination


Department of Pediatrics, Division of Pediatric Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Date of Submission25-May-2020
Date of Decision06-Jul-2020
Date of Acceptance11-Jul-2020
Date of Web Publication14-Sep-2020

Correspondence Address:
Dr. Ramachandran Rameshkumar
Department of Pediatrics, Division of Pediatric Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcc.jpcc_90_20

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  Abstract 


Acyclovir, an acyclic nucleoside, is commonly used for the treatment of viral infections. Acyclovir is well tolerated in children. However, severe nephrotoxicity has been shown to occur in some children. One of the mechanisms for acyclovir-induced nephrotoxicity is acyclovir-induced crystalluria. Prompt attention to urine microscopy examination can help avoid drug-induced nephrotoxicity. Here, we report a case of a seven-year-old febrile comatose child who received intravenous empirical acyclovir therapy and developed cloudy urine. Bedside urine microscopic examination shows fine-needle-shaped crystal. The urine was cleared within 12 h of stopping the acyclovir and adequate intravascular hydration. A child recovered without evidence of acute kidney injury.

Keywords: Acyclovir, children, complications, crystalluria, microscopy, urine examination


How to cite this article:
Jain P, Rameshkumar R, Satheesh P, Mahadevan S. Acyclovir crystalluria: The utility of bedside urine routine microscopic examination. J Pediatr Crit Care 2020;7:282-4

How to cite this URL:
Jain P, Rameshkumar R, Satheesh P, Mahadevan S. Acyclovir crystalluria: The utility of bedside urine routine microscopic examination. J Pediatr Crit Care [serial online] 2020 [cited 2020 Sep 26];7:282-4. Available from: http://www.jpcc.org.in/text.asp?2020/7/5/282/295027




  Introduction Top


Urine microscopy is a low-cost investigation that can provide useful and relevant information in a broad spectrum of clinical situations.[1] The presence of crystals in urine is a common finding in the routine examination of urine. A variety of drugs sulphadiazine, acyclovir, triamterene, piridoxilate, and primidone may cause crystalluria. Although acyclovir is well tolerated, it may lead to severe nephrotoxicity.[2] Acyclovir crystalluria is an uncommon side effect of the commonly used drug. Timely detection of acute kidney injury (AKI) and prompt intervention is necessary to prevent morbidity. Prompt attention to urine microscopy observation can help to avoid drug-associated renal toxicity. We highlighted the utility of art and science of urine microscopic examination in a report of the seven-year-old febrile comatose child who developed acyclovir-induced crystalluria.


  Case Report Top


A seven-year-old developmentally normal boy with no significant history was brought to the emergency department with a history of fever for the past three days and altered sensorium for one day. There was no history of seizures, jaundice, or recent vaccination. Examination findings were terminal neck rigidity, and upper motor neuron signs but no papilledema. The provisional diagnosis of acute febrile encephalopathy was considered. The child was managed with supportive care, osmotherapy (3%-saline), and intravenous antimicrobials (ceftriaxone, 50 mg/kg/dose every 12 h and acyclovir, 10 mg/kg/dose every 8 h over 1-h infusion). The lumbar puncture was done after finding an unremarkable study of contrast-enhanced computer tomographyof the head examination. The child was on mechanical ventilation for three days for disordered control of breathing.

On the day three of stay, his urine changed to cloudy appearance. His serum creatinine levels were within the normal range (0.6 mg/dL). The specific gravity of urine was 1.020. Microscopy of urinary sediment revealed abundant, colorless, transparent, and fine-needle-shaped crystals [Figure 1]. The macroscopic and microscopic picture of urine suggested acyclovir-induced crystalluria is the most likely diagnosis. The drug was stopped, and adequate hydration ensured to maintain adequate urine output. Renal function and urine output were normal during the stay. Urine was clear of crystals within 12 h. Cerebrospinal fluid (CSF) examination showed hypoglycorrhachia (CSF sugar 38 mg/dL and blood sugar 84 mg/dL), the protein of 75 mg/dL and 60 cells with 80% neutrophils. Since the CSF picture suggestive of pyogenic meningitis and polymerase chain reaction for herpes virus in CSF was negative, acyclovir was not restarted.
Figure 1: Multiple needle-shaped crystals observed under light microscopy

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  Discussion Top


The urine microscopy is one of the few tests which can be done at the bedside and at a low cost. A variety of drugs such as triamterene, sulphadiazine, acyclovir, piridoxilate, and primidone may cause transient crystalluria.[3] Factors leading to precipitation of crystals within renal tubular lumen are an overdose, dehydration, and hypoalbuminemia.[4]

The incidence of acyclovir-induced renal impairment has been reported to be 16% in adults.[5] Acyclovir crystals are birefringent and needle-shaped[3] [Figure 1], and the abundance of these crystals give urine a silky and opalescent macroscopic appearance. Needle-shaped crystals are not unique to acyclovir drug. Endogenous causes of needle-shaped crystals are uric acid, calcium phosphate, tyrosine, and bilirubin crystals, whereas drug-related needle-shaped crystals are formed by acyclovir, atazanavir, ciprofloxacin, and amoxicillin.[6] As laboratory technicians do not have access to medical records, timely reporting of moderate to abundant crystalluria to clinician is of paramount importance to raise concern for the risk of acute kidney injury (AKI). Therefore, long needle-shaped crystals, with bright birefringence under polarized light microscopy that readily dissolve with the addition of saline, acid, or base in the urine of patients receiving acyclovir intravenously is most likely due to acyclovir crystalluria.

The acyclovir can cause crystalluria though it is an uncommon side effect of commonly used drugs.[7] The occurrence of acyclovir-induced crystalluria increases when high dosages are given intravenously, and when accorded to dehydrated patients.[5] Additional risk factors are preexisting AKI, concurrent administration of nephrotoxic agents, and rapid intravenous infusion.[4] In the index case, acyclovir dose and duration of infusion were as per standard recommendations. The identifiable risk factor in the index case is restricted maintenance fluid (80% of daily requirement) and coadministration of ceftriaxone as a combination of ceftriaxone and acyclovir may result in nephrotoxicity. Vomiero et al. reported that a combination of ceftriaxone and acyclovir resulted in an increased incidence of renal impairment as compared to monotherapy in meningoencephalitis cases. However, they did not find evidence of crystalluria in their cases.[8]

Drug-induced crystalluria may be asymptomatic or in association with erythrocyturia or leukocyturia.[1] In the index case, crystalluria led to cloudy urine. The primary mechanism of acyclovir-induced nephrotoxicity is thought to be because of crystalluria.[5],[9],[10] However, clinical evidence of nephrotoxicity in the absence of crystal formation suggests that acyclovir may cause direct insult to renal tubular cells. Gunness et al. reported that renal biopsies from the patients receiving acyclovir demonstrated flattened vacuolated, bulging epithelial cells, and no evidence of crystals.[2]

Treatment of acyclovir nephrotoxicity is mainly supportive and modification of drug or discontinuation in addition to maintaining a high urinary flow rate with intravenous fluids and furosemide.[4] In the index case, the drug was stopped and good urine output was achieved with adequate hydration. Subsequently, urine was clear of crystals within 12 h, and renal function tests were also within the normal range.


  Conclusion Top


This case highlights the utility of art and science of urine microscopy. Acyclovir is recommended mainly for acute meningoencephalitis in tropical countries. Hence, daily microscopic examination of urine in patients who were receiving Acyclovir may help in early detection of crystalluria, and necessary intervention can be done accordingly. The low-cost investigation and feasibility to perform bedside, it should be more widely used by clinicians. In the clinical context, timely recognition and prompt intervention can prevent drug-induced kidney injury.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given their consent for images and other clinical information to be reported in the journal. The patient's parents understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgment

We would like to acknowledge the parents of index patient for giving the consent for publication of their child data in a medical journal and the contribution of Mrs. S. Raja Deepa B. Com, MCA (Jawaharlal Institute of Postgraduate Medical Education and Research Campus, Puducherry, India) for grammar correction/manuscript review.

Financial support and sponsorship

Supported, in part, by the institutional and departmental fund.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Fogazzi GB, Garigali G. The clinical art and science of urine microscopy. Curr Opin Nephrol Hypertens 2003;12:625-32.  Back to cited text no. 1
    
2.
Gunness P, Aleksa K, Bend J, Koren G. Acyclovir-induced nephrotoxicity: The role of the acyclovir aldehyde metabolite. Transl Res 2011;158:290-301.  Back to cited text no. 2
    
3.
Fogazzi GB. Crystalluria: A neglected aspect of urinary sediment analysis. Nephrol Dial Transplant 1996;11:379-87.  Back to cited text no. 3
    
4.
Fleischer R, Johnson M. Acyclovir nephrotoxicity: a case report highlighting the importance of prevention, detection, and treatment of acyclovir-induced nephropathy. Case Rep Med 2010;2010:602783.  Back to cited text no. 4
    
5.
Brigden D, Rosling AE, Woods NC. Renal function after acyclovir intravenous injection. Am J Med 1982;73:182-5.  Back to cited text no. 5
    
6.
Cavanaugh C, Perazella MA. Urine sediment examination in the diagnosis and management of kidney disease: Core curriculum 2019. Am J Kidney Dis 2019;73:258-72.  Back to cited text no. 6
    
7.
Lyon AW, Mansoor A, Trotter MJ. Urinary gems: Acyclovir crystalluria. Arch Pathol Lab Med 2002;126:753-4.  Back to cited text no. 7
    
8.
Vomiero G, Carpenter B, Robb I, Filler G. Combination of ceftriaxone and acyclovir-An underestimated nephrotoxic potential? Pediatr Nephrol 2002;17:633-7.  Back to cited text no. 8
    
9.
Mason WJ, Nickols HH. Images in clinical medicine. Crystalluria from acyclovir use. N Engl J Med 2008;358:e14.  Back to cited text no. 9
    
10.
Peterslund NA, Larsen ML, Mygind H. Acyclovir crystalluria. Scand J Infect Dis 1988;20:225-8.  Back to cited text no. 10
    


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