Assessment of the impact of Hydration on the Incidence of Acute Kidney Injury (AKI) with Intravenous Acyclovir: A retrospective observation study

Assessment of the impact of Hydration on the Incidence of Acute Kidney Injury (AKI) with Intravenous Acyclovir: A retrospective observation study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Assessment of the impact of Hydration on the Incidence of Acute Kidney Injury (AKI) with Intravenous Acyclovir: A retrospective observation study Marwah Almuzaini, Rania Aljehani, Doaa Aljefri, Alaa Alahmadi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7515510/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Intravenous (IV) acyclovir use is associated with adverse events, including acute kidney injury (AKI). Hydration to increase the urine flow to prevent crystal precipitation is a strategy to prevent acyclovir-induced nephrotoxicity. To our knowledge, no study has compared the incidence of AKI among patients receiving IV acyclovir with proper hydration. We aimed to compare the incidence of AKI in patients who received IV acyclovir with or without hydration. Methods This was a retrospective, observational study at King Abdulaziz Medical City, Jeddah. Adult patients who received IV acyclovir from 2019–2022 were included. We compared the incidence of AKI between hydrated and nonhydrated patients and between patients who received adequate hydration and those who received inadequate hydration. Adequate hydration is defined as at least 1500 mL of IV fluid daily during the whole course of acyclovir. For descriptive univariate analysis, Fisher’s exact test and a t test were used. For potential differences in AKI status, we used multiple binary logistic and multiple logistic regression models through SAS 9.4. The two-sided statistical significance level was set at P < 0.05. Results A list of 281 patients was generated. Two hundred and one patients were eligible, 33 of whom had repeated courses. Two hundred sixty-six treatment courses were included in the final analysis. The baseline characteristics were similar between the two groups. The estimated incidence of AKI was 11.6% in the hydrated group vs. 18.8% in the nonhydrated group, with no statistically significant difference between the two groups (P = 0.39). According to the multiple logistic regression model, there was no statistically significant difference in the odds of AKI between patients who received adequate hydration and those who received inadequate hydration (OR = 0.81, 95% CI (0.31–2.17)). There was a statistically significant increase in the odds of anuria (OR = 3.64, 95% CI (1.02–13.01)) and the serum creatinine level (OR = 1.06, 95% CI (1.001, 1.12)). Conclusions Fewer AKIs trend among hydrated patients than among nonhydrated patients was detected. Additionally, inadequate hydration with IV acyclovir resulted in an increase in serum creatinine and anuria. Maintaining continuous daily hydration could be the key to preventing acyclovir-induced nephrotoxicity. acyclovir intravenous acyclovir nephrotoxicity/acyclovir acute kidney injury/acyclovir intravenous hydration/acyclovir Figures Figure 1 Figure 2 Background Acyclovir is widely used to treat different viral infections, including herpes simplex and herpes booster infections (Tyring, S. K et al., 2000, Beutner KR, et al., 1995). Despite its efficacy, there are several adverse effects associated with the use of intravenous (IV) acyclovir, including but not limited to nausea, vomiting, headache, increased blood urea nitrogen (BUN) and serum creatinine (SCr) levels and acute kidney injury (AKI) (Beutner KR, et al., 1995; Bean B, et al., 1985). IV acyclovir can cause AKI within 1–4 days after starting IV acyclovir via precipitation of the drug particles in renal tubules because acyclovir is poorly soluble in urine; thus, renal tubular obstruction can occur (Lee, Eun Ju, et al., 2015, Perazella, et al., 2005, Sawyer, M. H., et al, 1988). There are several risk factors associated with renal impairment, including the presence of other comorbidities, such as diabetes mellitus or underlying renal impairment; a high dose of acyclovir; a rapid rate of infusion; severe volume depletion; and the use of other nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), vancomycin, and B-lactam antibiotics (Perazella, et al., 2005; Schetz, M., et al., 2005, Lee Eun Ju, et al., 2018). There are general strategies used to prevent drug-induced nephrotoxicity, including identifying all risk factors before initiating therapy, minimizing the use of other nephrotoxic medications, and ensuring adequate hydration by using isotonic fluids to increase the urine flow rate to prevent precipitation of the crystals and prevent the obstruction of tubules (Guo, X., et al., 2002, Lee, Eun Ju, et al., 2018). One retrospective observational study compared changes in BUN, SCr and estimated glomerular filtration rates as parameters of kidney function in patients who received IV acyclovir and reported that kidney parameters changed in patients who did not receive IV hydration or who were hydrated less than 2 liters (Kim, S., et al., 2015). To our knowledge, no study has compared the incidence of AKI among patients receiving IV acyclovir with proper hydration. Therefore, we aimed to compare the incidence of AKI in patients who received IV acyclovir with or without hydration. Additionally, we will assess the impact of adequate and inadequate hydration on SCr, BUN and urine output. Methods Study design and setting: This was a retrospective, observational single-center study conducted at King Abdulaziz Medical City (KAMC) in Jeddah. Data were collected from December 2019 to February 2022. Data were retrieved from an in-house built Hospital Information System (BESTCare2.0A). The system is a fully integrated healthcare electronic system that executes multiple functions like Electronic Health Record (EHR), Computerized Physician's Order Entry (CPOE), pharmacy, laboratory and radiology services, …. Study population: Adult patients (aged ≥ 18 years) who required hospital admission and received IV acyclovir for at least 2 doses. Patients who had received dialysis in the prior 120 days and patients in the intensive care unit (ICU) were excluded. Only patients with complete details on dosing and kidney function will be included. Different qualitative and quantitative data for the study population were collected from the Electronic Health Records (EHR): demographic data, laboratory tests (SCr & BUN), urine output, acyclovir dose, hydration status, type of hydration, volume of hydration, and other nephrotoxic medications (NSAIDs, ACEIs/ARBs, vancomycin, B-lactam antibiotics, and aminoglycosides) Ethical approval: The study received approval from the institutional review board of the King Abdullah International Medical Research Center (KAIMRC), Saudi Arabia, IRB approval number (IRB/1117/22), approved study number (NRJ22J/065/04) in June 2022. The study adhered to the principles outlined in the Declaration of Helsinki as well as both national and institutional standards. In consideration of the study's retrospective observation design that didn’t interfere with patient care at any level, and in accordance with institutional/national guidelines, written informed consent was not required. Definitions AKI was determined on the basis of the Kidney Disease Improving Global Outcomes (KDIGO 2012) criteria: an increase in serum creatinine of ≥ 0.3 mg/dL (≥ 26.5 mmol/L) within 48 hours. The increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days. The urine volume was < 0.5 mL/kg/hour for 6 hours. Adequate hydration is defined as receiving continuous hydration daily during the whole course of acyclovir, including any type of intravenous fluid with at least 1500 mL. A volume of less than 1500 mL may be acceptable if the patient’s medical condition requires fluid restriction, for example, for patients who have heart failure and edema. Statistical analysis A list of patients who received IV acyclovir generated in an Excel sheet. Patient demographic data and laboratory test data were extracted from the patients’ electronic medical records. The laboratory tests included the collection of SCr and BUN and reported their baseline and peak values during the administration of IV acyclovir. Descriptive statistical analysis is presented, depicting categorical outcomes through frequencies and percentages, whereas continuous outcomes are represented as the means with standard deviations (SDs). Univariate descriptive analysis, the chi-square test and Fisher's exact test were used for categorical variables, whereas the t test was used for normally distributed numeric variables. To assess potential differences in acute kidney status between patients with and without hydration, a multiple binary logistic regression model was applied. To improve the regression model, a forward stepwise selection model technique has been used to select significant predictors (McCarthy RV, et al., 2022). Only significant predictors with specified significant level remain in the final model. For further model selection step, we also used the area under the curve to assure the specificity and sensitivity of our selected model. The threshold for statistical significance was set at P<0.05 (two-sided). All analyses were executed via SAS 9.4(McCarthy RV, et al., 2022). Results Among the 281 screened patients, 201 were included; of those patients, 33 had repeated courses, so 266 courses were assessed for primary and secondary outcomes. The reasons for excluding the remaining 80 participants are shown in Figure 1. Two hundred fifty patients received hydration, while 16 patients did not receive hydration. Table 1 summarizes the demographic data and baseline characteristics of the participants. The baseline characteristics of the two groups were similar. The mean age of the patients in the hydrated group was 47 years, whereas that in the nonhydrated group was 52 years. In total, 152 (60.8%) out of 250 patients in the hydrated group had underlying diseases (i.e., diabetes, hypertension, diarrhea, heart failure, and chronic kidney disease), and 13 (81.25%) out of 16 patients in the nonhydrated group had other comorbidities. Eighty-eight percent of the hydrated patients received other nephrotoxic medications (i.e., nonsteroidal anti-inflammatory drugs, vancomycin, aminoglycoside, beta-lactam, amphotericin, trimethoprim sulfamethoxazole, colistin, and radiocontrast dye), whereas 94% of the nonhydrated patients did. Most of the patients in both groups received the appropriate dose of IV acyclovir (68%), with 171 patients in the hydrated group and 11 patients in the nonhydrated group. Patients who received hydration had a mean duration of 8.9 days of acyclovir treatment, whereas nonhydrated patients had a mean duration of 5.8 days of acyclovir treatment. The mean baseline BUN and SCr levels were relatively similar in both groups. Table 1 . Baseline characteristics of patients administered acyclovir with and without hydration (univariate analysis). Baseline Characteristics Hydration group, N(%) 1, 250 (93.98) No Hydration N(%), 16 (6.02) P value 4 Age (year) Mean/median/standard deviation 47/ 45/18.98 52/ 51/17.84 0.83 Male 121 (48.4) 10 (62.5) 0.39 Body Mass Index (BMI) (kg/m 2) Mean/median/Standard deviation 25.74/ 25.26/6.07 28.25/ 27.71 /6.21 0.81 Comorbidities 2 152 (60.8) 13 (81.25) 0.1 Nephrotoxic Medications 3 220 (88.00) 15 (93.75) 0.84 Serum creatinine level (baseline) Mean/median/standard deviation 72.98/60 /50.11 84.68/69 /34.47 0.34 Blood urea nitrogen (baseline) Mean/median/standard deviation 5.29/4 /4.66 4.98/4.3 /2.23 0.002 Appropriate dose 171 (68.4) 11 (68.75) 0.97 Duration of Acyclovir (days) Mean/median/standard deviation 8.91/7 /7.56 5.81/4 /5.64 0.19 Number of acyclovir courses/patient Mean/median/standard deviation 2.05/1 /1.71 1.25/1 /0.57 <0.0001 1 N (%) frequency and percentage 2 Diabetes, hypertension, diarrhea, heart failure, and chronic kidney disease, allergies 3 Nonsteroidal anti-inflammatory drug, Vancomycin, Aminoglycoside, Beta-lactam, Amphotericin, trimethoprim sulfamethoxazole, Colistin, radiocontrast dye 4 chi-square test, fisher exact test, and t-test when appropriate Table 3 . Multiple logistic regression model to examine differences between patients with and without adequate hydration Adequate hydration (no vs yes) 2 P 1 Odds ratio (OR) Confidence interval (CI) Age 1.00 (0.98, 1,09) 0.96 Gender Male 0.78 (0.4, 1.41) 0.41 Female Reference group Reference group Body Mass Index (BMI) 0.6 1.01 (0.96, 1.06) Comorbidity 0.83 Yes 0.93 (0.17, 1.83) No Reference group Reference group Medication given 0.71 Yes 1.18 (0.47, 2.99) No Reference group Reference group Anuria 0.04 Yes 3.64 (1.02, 13.01) No Reference group Reference group Appropriate does 0.68 Yes 1.14 (0.59, 2.22) No Reference group Reference group Acute Kindy disease 0.68 Yes 0.81 (0.31, 2.17) No Reference group Reference group Serum creatine level (day peak) 2 0.04 1.06 (1.001, 1.12) Blood urea nitrogen (baseline) 1.02 (0.94, 1.1) 0.62 Serum creatine level (after 48 hours) 0.63 (0.24, 1.65) 0.34 1 adjusted binary logistic regression model with including significant predictors for hydration. 2 “adequate hydration” is the reference group in the model. Abbreviations: AKI: Acute Kidney Injury; BUN: blood urea nitrogen, CI: Confidence interval; SCr: serum creatinine (SCr), IV: intravenous, OR: Odds ratio The estimated incidence of AKI was 11.6% in the hydrated group versus 18.8% in the nonhydrated group, with no statistically significant difference between the two groups (P=0.39). See table 2. According to the multiple logistic regression model, there was a 19% lower odds of AKI in patients who received adequate hydration than in those who received inadequate hydration, but this difference was not statistically significant (OR= 0.81, 95% CI (0.31–2.17)). The model performance is shown in figure 2. We assessed the impact inadequate hydration on SCr, BUN and urine output compared to patients who received adequate hydration. A statistically significant increase in the odds of anuria (OR= 3.64, 95% CI (1.02 - 13.01)) and the serum creatinine level (OR= 1.06, 95% CI (1.001, 1.12)) was reported as summarized in table 3. Table 2 . Primary outcome. P value No Hydration, N (%) 16 (6.02) Hydration group, N (%) 250 (93.98) 0.39 3 (18.75) 29 (11.6) Incidence of AKI in patients who received IV Acyclovir with hydration versus no hydration, N (%) Roc curve or also called the area under the curve is a metrics to evaluate the model’s performance, the closer to 1 the better is the model. The more that the ROC curve hugs the top left corner of the plot, the better the model does at classifying the data into categories. Roc curve is also a plot that displays the sensitivity and specificity of a logistic regression model. In our analysis, we compared different logistic regression models, and the existed one is the best fit with AUC of 0.76. Discussion In this retrospective observational study, the incidence of acute kidney injury was greater among patients who received IV acyclovir and who were nonhydrated or did not receive adequate hydration; however, the differences were not statistically significant. Anuria and elevated serum creatinine were significantly greater among patients who received inadequate hydration. Acyclovir-induced acute kidney injury has been well documented and is most likely due to crystal precipitation. In our cohort, the dose was considered appropriate if it was dosed maximally at 10 mg/kg on the basis of actual body weight (ABW) (BMI < 30 kg/m2) or if (ABW 30 kg/m2), with adjustment of the frequency on the basis of creatinine clearance. In the present study, the failure to detect differences in AKI between the two groups could be attributed to the small number of patients who did not receive hydration and the low incidence of AKI in our sample. Moreover, the relatively small incidence of AKI could be related to the preparation of IV acyclovir at our institution. Most treatment doses of acyclovir are prepared in at least 250 mL of suitable fluid. Although one retrospective study revealed that the preparation of acyclovir at 250 mL was not associated with a significant decrease in the incidence of AKI, it was associated with a significant decrease in the doubling of serum creatinine. (Dubrofsky, L., et al. 2016) Our findings highlight the importance of maintaining daily continuous hydration in patients who receive IV acyclovir to prevent acyclovir-associated kidney injury. Our results are in line with those of published studies (Guo, X., et al., 2002; Lee, Eun Ju, et al., 2018; Kim, S., et al., 2015). However, the present study has several limitations. First, this was a single-center retrospective study, and we did not have the opportunity to standardize the amount of IV fluid used. Second, the number of patients who were compared in the study was relatively small. Third, there is no established literature definition for adequate hydration, so we set our specific definition by considering the hydration status of those patients. Conclusion The present study highlights that maintaining continuous daily hydration may be essential for preventing acyclovir-induced nephrotoxicity. Although there was no statistically significant difference in the overall incidence of AKI between hydrated and nonhydrated patients, our findings showed that inadequate hydration during IV acyclovir administration led to a statistically significant increase in serum creatinine levels and cases of anuria. Abbreviations ABW Actual Body Weight ACEIs Angiotensin Converting Enzyme Inhibitors AdjBW Adjusted Body Weight AKI Acute Kidney Injury ARBs Angiotensin Receptor Blockers BMI Body Mass Index BUN Blood Urea Nitrogen CI Confidence interval IV Intravenous NSAIDs None Steroidal Anti-inflammatory Drugs OR Odd’s Ratio SCr Serum Creatinine Declarations Ethics approval and consent to participate: The study received approval from the institutional review board of the King Abdullah International Medical Research Center, Saudi Arabia (IRB/1117/22), in June 2022. The study adhered to the principles outlined in the Declaration of Helsinki as well as both national and institutional standards. In consideration of the study's retrospective design, and no active intervention or interference with regular patient care, informed consent was not obtained from the participants. Consent for publication: Not applicable Availability of data and materials: Data were retrieved from an in-house built Hospital Information System. The system is a fully integrated healthcare electronic system that executes multiple functions like Electronic Health Record (EHR), Computerized Physician's Order Entry (CPOE), pharmacy, laboratory and radiology services, …. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests Funding: We received no fund for this research paper Authors' contributions MA worked on data collection, and started initial manuscript writing RA is the idea owner, revised the manuscript DA Participated in framing the final idea, revised the manuscript AA Participated in data collection and revised the manuscript MR did the statistical data analysis, participated in writing the statistical part of the manuscript EY Participated in framing the idea, helped in data analysis, did the final manuscript revision Acknowledgements: Not applicable References Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39(7):1546–53. Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000;9(9):863. Bean B, Braun C, Balfour JRH. Acyclovir therapy for acute herpes zoster. Lancet. 1982;320(8290):118–21. Bean B, Aeppli D. Adverse effects of high-dose intravenous acyclovir in ambulatory patients with acute herpes zoster. J Infect Dis. 1985;151(2):362–5. Lee EJ, Jang HN, Cho HS, Bae E, Lee TW, Chang SH, Park DJ. The incidence, risk factors, and clinical outcomes of acute kidney injury (staged using the RIFLE classification) associated with intravenous acyclovir administration. Ren Fail. 2018;40(1):687–92. Perazella MA. Drug-induced nephropathy: an update. Exp Opin Drug Saf. 2005;4(4):689–706. Kim S, Byun Y. Comparison of renal function indicators according to hydration volume in patients receiving intravenous acyclovir with CNS infection. Biol Res Nurs. 2015;17(1):55–61. Schetz M, Dasta J, Goldstein S, Golper T. Drug-induced acute kidney injury. Curr Opin Crit Care. 2005;11(6):555–65. Guo X, Nzerue C. How to prevent, recognize, and treat drug-induced nephrotoxicity. Cleve Clin J Med. 2002;69(4):289–90. Raschilas F, Wolff M, Delatour F, Chaffaut C, De Broucker T, Chevret S, Lebon P, Canton P, Rozenberg F. Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis. 2002;35(3):254–60. Sawyer MH, Webb DE, Balow JE, Straus SE. Acyclovir-induced renal failure: clinical course and histology. Am J Med. 1988;84(6):1067–71. McCarthy RV, McCarthy MM, Ceccucci W, McCarthy RV, McCarthy MM, Ceccucci W. Predictive models using regression. Appl Predictive Analytics: Finding Value Data. 2022:87–121. Kim S, Byun Y. Comparison of renal function indicators according to hydration volume in patients receiving intravenous acyclovir with CNS infection. Biol Res Nurs. 2015;17(1):55–61. Dubrofsky L, Kerzner RS, Delaunay C, Kolenda C, Pepin J, Schwartz BC. Interdisciplinary systems-based intervention to improve IV hydration during parenteral administration of acyclovir. Can J Hosp Pharm. 2016;69(1):7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7515510","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":533922346,"identity":"59ed23e5-6b9e-4e69-8e22-969eab2e86f5","order_by":0,"name":"Marwah Almuzaini","email":"","orcid":"","institution":"King Salman bin Abdulaziz Medical City, Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Marwah","middleName":"","lastName":"Almuzaini","suffix":""},{"id":533922347,"identity":"849f3db5-ce28-40d0-b196-38224bc61390","order_by":1,"name":"Rania Aljehani","email":"","orcid":"","institution":"King Abdulaziz Medical 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16:09:52","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":71315,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7515510/v1/a93f291813ef3b766b6fc28a.html"},{"id":94480137,"identity":"825e0474-8a0d-4a76-b1aa-682eb3426228","added_by":"auto","created_at":"2025-10-27 16:09:55","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":264627,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEnrollment and screening flow diagram\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7515510/v1/9d25f999c078b26b81d556fd.jpeg"},{"id":94480447,"identity":"f8ccc6ce-517d-4be4-a815-bad38b5e8122","added_by":"auto","created_at":"2025-10-27 16:11:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":12244,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC curve for the logistic regression model regression model\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7515510/v1/0d46aca91eb3eda9dd1ef9bd.png"},{"id":102853613,"identity":"5132ba56-0933-495f-b8e1-121ed8acff39","added_by":"auto","created_at":"2026-02-17 14:42:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1589280,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7515510/v1/6ff3f39c-6249-4b87-829f-59f649dcf2c8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of the impact of Hydration on the Incidence of Acute Kidney Injury (AKI) with Intravenous Acyclovir: A retrospective observation study","fulltext":[{"header":"Background","content":"\u003cp\u003eAcyclovir is widely used to treat different viral infections, including herpes simplex and herpes booster infections (Tyring, S. K et al., 2000, Beutner KR, et al., 1995). Despite its efficacy, there are several adverse effects associated with the use of intravenous (IV) acyclovir, including but not limited to nausea, vomiting, headache, increased blood urea nitrogen (BUN) and serum creatinine (SCr) levels and acute kidney injury (AKI) (Beutner KR, et al., 1995; Bean B, et al., 1985). IV acyclovir can cause AKI within 1\u0026ndash;4 days after starting IV acyclovir via precipitation of the drug particles in renal tubules because acyclovir is poorly soluble in urine; thus, renal tubular obstruction can occur (Lee, Eun Ju, et al., 2015, Perazella, et al., 2005, Sawyer, M. H., et al, 1988). There are several risk factors associated with renal impairment, including the presence of other comorbidities, such as diabetes mellitus or underlying renal impairment; a high dose of acyclovir; a rapid rate of infusion;\u003c/p\u003e\u003cp\u003esevere volume depletion; and the use of other nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), vancomycin, and B-lactam antibiotics (Perazella, et al., 2005; Schetz, M., et al., 2005, Lee Eun Ju, et al., 2018).\u003c/p\u003e\u003cp\u003eThere are general strategies used to prevent drug-induced nephrotoxicity, including identifying all risk factors before initiating therapy, minimizing the use of other nephrotoxic medications, and ensuring adequate hydration by using isotonic fluids to increase the urine flow rate to prevent precipitation of the crystals and prevent the obstruction of tubules (Guo, X., et al., 2002, Lee, Eun Ju, et al., 2018).\u003c/p\u003e\u003cp\u003eOne retrospective observational study compared changes in BUN, SCr and estimated glomerular filtration rates as parameters of kidney function in patients who received IV acyclovir and reported that kidney parameters changed in patients who did not receive IV hydration or who were hydrated less than 2 liters (Kim, S., et al., 2015). To our knowledge, no study has compared the incidence of AKI among patients receiving IV acyclovir with proper hydration. Therefore, we aimed to compare the incidence of AKI in patients who received IV acyclovir with or without hydration. Additionally, we will assess the impact of adequate and inadequate hydration on SCr, BUN and urine output.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003esetting:\u003c/strong\u003e This was a retrospective, observational single-center study conducted at King Abdulaziz Medical City (KAMC) in Jeddah. Data were collected from December 2019 to February 2022. Data were retrieved from an in-house built Hospital Information System (BESTCare2.0A). The system is a fully integrated healthcare electronic system that executes multiple functions like Electronic Health Record (EHR), Computerized Physician\u0026apos;s Order Entry (CPOE), pharmacy, laboratory and radiology services, \u0026hellip;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population:\u003c/strong\u003e Adult patients (aged \u0026ge; 18 years) who required hospital admission and received IV acyclovir for at least 2 doses. Patients who had received dialysis in the prior 120 days and patients in the intensive care unit (ICU) were excluded. Only patients with complete details on dosing and kidney function will be included. Different qualitative and quantitative data for the study population were collected from the Electronic Health Records (EHR): demographic data, laboratory tests (SCr \u0026amp; BUN), urine output, acyclovir dose, hydration status, type of hydration, volume of hydration, and other nephrotoxic medications (NSAIDs, ACEIs/ARBs, vancomycin, B-lactam antibiotics, and aminoglycosides)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received approval from the institutional review board of the King Abdullah International Medical Research Center (KAIMRC), Saudi Arabia, IRB approval number (IRB/1117/22), approved study number (NRJ22J/065/04) in June 2022. The study adhered to the principles outlined in the Declaration of Helsinki as well as both national and institutional standards. In consideration of the study\u0026apos;s retrospective observation design that didn\u0026rsquo;t interfere with patient care at any level, and in accordance with institutional/national guidelines, written informed consent was not required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAKI\u003c/strong\u003e was determined on the basis of the Kidney Disease Improving Global Outcomes (KDIGO 2012) criteria: an increase in serum creatinine of \u0026ge; 0.3 mg/dL (\u0026ge; 26.5 mmol/L) within 48 hours. The increase in serum creatinine to \u0026ge; 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days. The urine volume was \u0026lt; 0.5 mL/kg/hour for 6 hours. \u003cstrong\u003eAdequate hydration\u003c/strong\u003e is defined as receiving continuous hydration daily during the whole course of acyclovir, including any type of intravenous fluid with at least 1500 mL. A volume of less than 1500 mL may be acceptable if the patient\u0026rsquo;s medical condition requires fluid restriction, for example, for patients who have heart failure and edema.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA list of patients who received IV acyclovir generated in an Excel sheet. Patient demographic data and laboratory test data were extracted from the patients\u0026rsquo; electronic medical records. The laboratory tests included the collection of SCr and BUN and reported their baseline and peak values during the administration of IV acyclovir. Descriptive statistical analysis is presented, depicting categorical outcomes through frequencies and percentages, whereas continuous outcomes are represented as the means with standard deviations (SDs). Univariate descriptive analysis, the chi-square test and Fisher\u0026apos;s exact test were used for categorical variables, whereas the t test was used for normally distributed numeric variables. To assess potential differences in acute kidney status between patients with and without hydration, a multiple binary logistic regression model was applied. To improve the regression model, a forward stepwise selection model technique has been used to select significant predictors (McCarthy RV, et al., 2022). Only significant predictors with specified significant level remain in the final model. For further model selection step, we also used the area under the curve to assure the specificity and sensitivity of our selected model. The threshold for statistical significance was set at P\u0026lt;0.05 (two-sided). All analyses were executed via SAS 9.4(McCarthy RV, et al., 2022).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the 281 screened patients, 201 were included; of those patients, 33 had repeated courses, so 266 courses were assessed for primary and secondary outcomes. The reasons for excluding the remaining 80 participants are shown in Figure 1.\u003c/p\u003e\n\u003cp\u003eTwo hundred fifty patients received hydration, while 16 patients did not receive hydration. Table 1 summarizes the demographic data and baseline characteristics of the participants. The baseline characteristics of the two groups were similar. The mean age of the patients in the hydrated group was 47 years, whereas that in the nonhydrated group was 52 years. In total, 152 (60.8%) out of 250 patients in the hydrated group had underlying diseases (i.e., diabetes, hypertension, diarrhea, heart failure, and chronic kidney disease), and 13 (81.25%) out of 16 patients in the nonhydrated group had other comorbidities. Eighty-eight percent of the hydrated patients received other nephrotoxic medications (i.e., nonsteroidal anti-inflammatory drugs, vancomycin, aminoglycoside, beta-lactam, amphotericin, trimethoprim sulfamethoxazole, colistin, and radiocontrast dye), whereas 94% of the nonhydrated patients did. Most of the patients in both groups received the appropriate dose of IV acyclovir\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(68%), with 171 patients in the hydrated group and 11 patients in the nonhydrated group. Patients who received hydration had a mean duration of 8.9 days of acyclovir treatment, whereas nonhydrated patients had a mean duration of 5.8 days of acyclovir treatment. The mean baseline BUN and SCr levels were relatively similar in both groups.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eBaseline characteristics of patients administered\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eacyclovir\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;with and without hydration (univariate analysis).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"704\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHydration group,\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;N(%)\u003csup\u003e1,\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e250 (93.98)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Hydration\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;N(%), 16 (6.02)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003csup\u003e4\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (year)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean/median/standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47/ 45/18.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52/ 51/17.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e121 (48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e10 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBody Mass Index (BMI) (kg/m\u003csup\u003e2)\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean/median/Standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25.74/ 25.26/6.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28.25/ 27.71 /6.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities \u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e152 (60.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e13 (81.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNephrotoxic Medications \u003csup\u003e3\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e220 (88.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e15 (93.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum creatinine level (baseline)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean/median/standard deviation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72.98/60 /50.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e84.68/69 /34.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood urea nitrogen (baseline)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean/median/standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.29/4 /4.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.98/4.3 /2.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAppropriate dose\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e171 (68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e11 (68.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of Acyclovir (days)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean/median/standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8.91/7 /7.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.81/4 /5.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.7557%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of acyclovir courses/patient\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean/median/standard deviation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.1591%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.05/1 /1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.3182%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.25/1 /0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.767%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1 N (%) frequency and percentage\u003c/p\u003e\n \u003cp\u003e2 Diabetes, hypertension, diarrhea, heart failure, and chronic kidney disease, allergies\u003c/p\u003e\n \u003cp\u003e3 Nonsteroidal anti-inflammatory drug, Vancomycin, Aminoglycoside, Beta-lactam, Amphotericin, trimethoprim sulfamethoxazole, Colistin, radiocontrast dye\u003c/p\u003e\n \u003cp\u003e4\u0026nbsp;chi-square test, fisher exact test, and t-test when appropriate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eMultiple logistic regression model to examine differences between patients with and\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ewithout adequate hydration\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 51.6975%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdequate hydration (no vs yes)\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003csup\u003e1\u003c/sup\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds ratio (OR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConfidence interval (CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.98, 1,09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.4, 1.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eFemale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBody Mass Index (BMI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.96, 1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.17, 1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedication given\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.47, 2.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnuria\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e3.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(1.02, 13.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAppropriate does\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.59, 2.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcute Kindy disease\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.31, 2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003eReference group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003eReference group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum creatine level (day peak) \u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(1.001, 1.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood urea nitrogen (baseline)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.94, 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.8148%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum creatine level (after 48 hours)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25%;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.6975%;\"\u003e\n \u003cp\u003e(0.24, 1.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.48765%;\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1 adjusted binary logistic regression model with including significant predictors for hydration.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 \u0026ldquo;adequate hydration\u0026rdquo; is the reference group in the model.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e AKI: Acute Kidney Injury; BUN: blood urea nitrogen, CI: Confidence interval; SCr: serum creatinine (SCr), IV: intravenous, OR: Odds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe estimated incidence of AKI was 11.6% in the hydrated group versus 18.8% in the nonhydrated group, with no statistically significant difference between the two groups (P=0.39). See table 2. According to the multiple logistic regression model, there was a 19% lower odds of AKI in patients who received adequate hydration than in those who received inadequate hydration, but this difference was not statistically significant (OR= 0.81, 95% CI (0.31\u0026ndash;2.17)). The model performance is shown in figure 2. We assessed the impact inadequate hydration on SCr, BUN and urine output compared to patients who received adequate hydration. A statistically significant increase in the odds of anuria (OR= 3.64, 95% CI (1.02 - 13.01)) and the serum creatinine level (OR= 1.06, 95% CI (1.001, 1.12)) was reported as summarized in table 3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePrimary outcome.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"662\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.30816%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.565%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eNo Hydration, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e16 (6.02)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.6586%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eHydration group, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e250 (93.98)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.4683%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.30816%;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.565%;\"\u003e\n \u003cp dir=\"LTR\"\u003e3 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.6586%;\"\u003e\n \u003cp dir=\"LTR\"\u003e29 (11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45.4683%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eIncidence of AKI in patients who received IV Acyclovir with hydration versus no hydration, N (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRoc curve or also called the area under the curve is a metrics to evaluate the model\u0026rsquo;s performance, the closer to 1 the better is the model. The more that the ROC curve hugs the top left corner of the plot, the better the model does at classifying the data into categories. Roc curve is also a plot that displays the sensitivity and specificity of a logistic regression model.\u003c/p\u003e\n\u003cp\u003eIn our analysis, we compared different logistic regression models, and the existed one is the best fit with AUC of 0.76.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective observational study, the incidence of acute kidney injury was greater among patients who received IV acyclovir and who were nonhydrated or did not receive adequate hydration; however, the differences were not statistically significant. Anuria and elevated serum creatinine were significantly greater among patients who received inadequate hydration.\u003c/p\u003e\n\u003cp\u003eAcyclovir-induced acute kidney injury has been well documented and is most likely due to crystal precipitation.\u003c/p\u003e\n\u003cp\u003eIn our cohort, the dose was considered appropriate if it was dosed maximally at 10 mg/kg on the basis of actual body weight (ABW) (BMI \u0026lt; 30 kg/m2) or if (ABW \u0026lt; IBD) and adjusted body weight (AdjBW) for obese patients (BMI \u0026gt; 30 kg/m2), with adjustment of the frequency on the basis of creatinine clearance.\u003c/p\u003e\n\u003cp\u003eIn the present study, the failure to detect differences in AKI between the two groups could be attributed to the small number of patients who did not receive hydration and the low incidence of AKI in our sample. Moreover, the relatively small incidence of AKI could be related to the preparation of IV acyclovir at our institution. Most treatment doses of acyclovir are prepared in at least 250 mL of suitable fluid. Although one retrospective study revealed that the preparation of acyclovir at 250 mL was not associated with a significant decrease in the incidence of AKI, it was associated with a significant decrease in the doubling of serum creatinine. (Dubrofsky, L., et al. 2016)\u003c/p\u003e\n\u003cp\u003eOur findings highlight the importance of maintaining daily continuous hydration in patients who receive IV acyclovir to prevent acyclovir-associated kidney injury. Our results are in line with those of published studies (Guo, X., et al., 2002; Lee, Eun Ju, et al., 2018; Kim, S., et al., 2015). However, the present study has several limitations. First, this was a single-center retrospective study, and we did not have the opportunity to standardize the amount of IV fluid used. Second, the number of patients who were compared in the study was relatively small. Third, there is no established literature definition for adequate hydration, so we set our specific definition by considering the hydration status of those patients.\u003c/p\u003e"},{"header":"Conclusion","content":"The present study highlights that maintaining continuous daily hydration may be essential for preventing acyclovir-induced nephrotoxicity. Although there was no statistically significant difference in the overall incidence of AKI between hydrated and nonhydrated patients, our findings showed that inadequate hydration during IV acyclovir administration led to a statistically significant increase in serum creatinine levels and cases of anuria."},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eABW\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eActual Body Weight\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eACEIs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAngiotensin Converting Enzyme Inhibitors\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAdjBW\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAdjusted Body Weight\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAKI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAcute Kidney Injury\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eARBs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAngiotensin Receptor Blockers\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBody Mass Index\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBUN\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBlood Urea Nitrogen\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eConfidence interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIntravenous\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNSAIDs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNone Steroidal Anti-inflammatory Drugs\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eOdd\u0026rsquo;s Ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSCr\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSerum Creatinine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received approval from the institutional review board of the King Abdullah International Medical Research Center, Saudi Arabia (IRB/1117/22), in June 2022. The study adhered to the principles outlined in the Declaration of Helsinki as well as both national and institutional standards. In consideration of the study\u0026apos;s retrospective design, and no active intervention or interference with regular patient care, informed consent was not obtained from the participants.\u003c/p\u003e\n\u003ch4\u003eConsent for publication: Not applicable\u0026nbsp;\u003c/h4\u003e\n\u003ch4\u003eAvailability of data and materials:\u0026nbsp;\u003c/h4\u003e\n\u003cp\u003eData were retrieved from an in-house built Hospital Information System. The system is a fully integrated healthcare electronic system that executes multiple functions like Electronic Health Record (EHR), Computerized Physician\u0026apos;s Order Entry (CPOE), pharmacy, laboratory and radiology services, \u0026hellip;.\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch4\u003eCompeting interests:\u0026nbsp;The authors declare that they have no competing interests\u003c/h4\u003e\n\u003ch4\u003eFunding:\u0026nbsp;We received no fund for this research paper\u0026nbsp;\u003c/h4\u003e\n\u003ch4\u003eAuthors\u0026apos; contributions\u003c/h4\u003e\n\u003ch4\u003eMA worked on data collection, and started initial manuscript writing\u003c/h4\u003e\n\u003ch4\u003eRA is the idea owner, revised the manuscript\u003c/h4\u003e\n\u003ch4\u003e\u0026nbsp;DA Participated in framing the final idea, revised the manuscript\u003c/h4\u003e\n\u003ch4\u003eAA Participated in data collection and revised the manuscript\u003c/h4\u003e\n\u003ch4\u003eMR did the statistical data analysis, participated in writing the statistical part of the manuscript\u003c/h4\u003e\n\u003ch4\u003eEY Participated in framing the idea, helped in data analysis, did the final manuscript revision\u003c/h4\u003e\n\u003ch4\u003eAcknowledgements: Not applicable\u0026nbsp;\u003c/h4\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBeutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39(7):1546\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000;9(9):863.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBean B, Braun C, Balfour JRH. Acyclovir therapy for acute herpes zoster. Lancet. 1982;320(8290):118\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBean B, Aeppli D. Adverse effects of high-dose intravenous acyclovir in ambulatory patients with acute herpes zoster. J Infect Dis. 1985;151(2):362\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee EJ, Jang HN, Cho HS, Bae E, Lee TW, Chang SH, Park DJ. The incidence, risk factors, and clinical outcomes of acute kidney injury (staged using the RIFLE classification) associated with intravenous acyclovir administration. Ren Fail. 2018;40(1):687\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerazella MA. Drug-induced nephropathy: an update. Exp Opin Drug Saf. 2005;4(4):689\u0026ndash;706.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim S, Byun Y. Comparison of renal function indicators according to hydration volume in patients receiving intravenous acyclovir with CNS infection. Biol Res Nurs. 2015;17(1):55\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchetz M, Dasta J, Goldstein S, Golper T. Drug-induced acute kidney injury. Curr Opin Crit Care. 2005;11(6):555\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuo X, Nzerue C. How to prevent, recognize, and treat drug-induced nephrotoxicity. Cleve Clin J Med. 2002;69(4):289\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaschilas F, Wolff M, Delatour F, Chaffaut C, De Broucker T, Chevret S, Lebon P, Canton P, Rozenberg F. Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis. 2002;35(3):254\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSawyer MH, Webb DE, Balow JE, Straus SE. Acyclovir-induced renal failure: clinical course and histology. Am J Med. 1988;84(6):1067\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcCarthy RV, McCarthy MM, Ceccucci W, McCarthy RV, McCarthy MM, Ceccucci W. Predictive models using regression. Appl Predictive Analytics: Finding Value Data. 2022:87\u0026ndash;121.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim S, Byun Y. Comparison of renal function indicators according to hydration volume in patients receiving intravenous acyclovir with CNS infection. Biol Res Nurs. 2015;17(1):55\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDubrofsky L, Kerzner RS, Delaunay C, Kolenda C, Pepin J, Schwartz BC. Interdisciplinary systems-based intervention to improve IV hydration during parenteral administration of acyclovir. Can J Hosp Pharm. 2016;69(1):7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acyclovir, intravenous acyclovir, nephrotoxicity/acyclovir, acute kidney injury/acyclovir, intravenous hydration/acyclovir","lastPublishedDoi":"10.21203/rs.3.rs-7515510/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7515510/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eIntravenous (IV) acyclovir use is associated with adverse events, including acute kidney injury (AKI). Hydration to increase the urine flow to prevent crystal precipitation is a strategy to prevent acyclovir-induced nephrotoxicity. To our knowledge, no study has compared the incidence of AKI among patients receiving IV acyclovir with proper hydration. We aimed to compare the incidence of AKI in patients who received IV acyclovir with or without hydration.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis was a retrospective, observational study at King Abdulaziz Medical City, Jeddah. Adult patients who received IV acyclovir from 2019\u0026ndash;2022 were included. We compared the incidence of AKI between hydrated and nonhydrated patients and between patients who received adequate hydration and those who received inadequate hydration. Adequate hydration is defined as at least 1500 mL of IV fluid daily during the whole course of acyclovir. For descriptive univariate analysis, Fisher\u0026rsquo;s exact test and a t test were used. For potential differences in AKI status, we used multiple binary logistic and multiple logistic regression models through SAS 9.4. The two-sided statistical significance level was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA list of 281 patients was generated. Two hundred and one patients were eligible, 33 of whom had repeated courses. Two hundred sixty-six treatment courses were included in the final analysis. The baseline characteristics were similar between the two groups. The estimated incidence of AKI was 11.6% in the hydrated group vs. 18.8% in the nonhydrated group, with no statistically significant difference between the two groups (P\u0026thinsp;=\u0026thinsp;0.39). According to the multiple logistic regression model, there was no statistically significant difference in the odds of AKI between patients who received adequate hydration and those who received inadequate hydration (OR\u0026thinsp;=\u0026thinsp;0.81, 95% CI (0.31\u0026ndash;2.17)). There was a statistically significant increase in the odds of anuria (OR\u0026thinsp;=\u0026thinsp;3.64, 95% CI (1.02\u0026ndash;13.01)) and the serum creatinine level (OR\u0026thinsp;=\u0026thinsp;1.06, 95% CI (1.001, 1.12)).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eFewer AKIs trend among hydrated patients than among nonhydrated patients was detected. Additionally, inadequate hydration with IV acyclovir resulted in an increase in serum creatinine and anuria. Maintaining continuous daily hydration could be the key to preventing acyclovir-induced nephrotoxicity.\u003c/p\u003e","manuscriptTitle":"Assessment of the impact of Hydration on the Incidence of Acute Kidney Injury (AKI) with Intravenous Acyclovir: A retrospective observation study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-27 15:22:17","doi":"10.21203/rs.3.rs-7515510/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3924119e-d638-4ec9-b0ee-b9d3bc1b876f","owner":[],"postedDate":"October 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-17T14:42:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-27 15:22:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7515510","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7515510","identity":"rs-7515510","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}