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      Effects of aminophylline therapy on urine output and kidney function in children with acute kidney injury

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          Abstract

          Background

          Acute kidney injury (AKI) is a frequent complication of children admitted to the paediatric intensive care unit. One key management modality of AKI is the use of diuretics to reduce fluid overload. Aminophylline, a drug that is well known for its use in the treatment of bronchial asthma, is also purported to have diuretic effects on the kidneys. This retrospective cohort study assesses the effect of aminophylline in critically ill children with AKI.

          Methods

          A retrospective chart review of children admitted to the paediatric intensive care unit of the Red Cross War Memorial Children’s Hospital (RCWMCH) with AKI who received aminophylline (from 2012 to June 2018) was carried out. Data captured and analyzed included demographics, underlying disease conditions, medications, urine output, fluid balance, and kidney function.

          Results

          Data from thirty-four children were analyzed. Urine output increased from a median of 0.4 mls/kg/hr [IQR: 0.1, 1.1] at six hours prior to aminophylline administration to 0.6 mls/kg/hr [IQR: 0.2, 1.9] at six hours and 1.6 mls/kg/hr [IQR:0.2, 4.2] at twenty-four hours post aminophylline therapy. The median urine output significantly varied across the age groups over the 24-h time period post-aminophylline, with the most response in the neonates. There was no significant change in serum creatinine levels six hours post-aminophylline administration [109(IQR: 77, 227)—125.5(IQR: 82, 200) micromole/l] P-value = 0.135. However, there were significant age-related changes in creatinine levels at six hours post-aminophylline therapy.

          Conclusions

          Aminophylline increases urine output in critically ill children with AKI.

          Graphical abstract

          A higher resolution version of the Graphical abstract is available as Supplementary information

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00467-023-06065-y.

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          Most cited references37

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          Acute kidney injury in the intensive care unit according to RIFLE.

          To apply the RIFLE criteria "risk," "injury," and "failure" for severity of acute kidney injury to patients admitted to the intensive care unit and to evaluate the significance of other prognostic factors. Retrospective analysis of the Riyadh Intensive Care Program database. Riyadh Intensive Care Unit Program database of 41,972 patients admitted to 22 intensive care units in the United Kingdom and Germany between 1989 and 1999. Acute kidney injury as defined by the RIFLE classification occurred in 15,019 (35.8%) patients; 7,207 (17.2%) patients were at risk, 4,613 (11%) had injury, and 3,199 (7.6%) had failure. It was found that 797 (2.3%) patients had end-stage dialysis-dependent renal failure when admitted to an intensive care unit. None. : Patients with risk, injury, and failure classifications had hospital mortality rates of 20.9%, 45.6%, and 56.8%, respectively, compared with 8.4% among patients without acute kidney injury. Independent risk factors for hospital mortality were age (odds ratio 1.02); Acute Physiology and Chronic Health Evaluation II score on admission to intensive care unit (odds ratio 1.10); presence of preexisting end-stage disease (odds ratio 1.17); mechanical ventilation (odds ratio 1.52); RIFLE categories risk (odds ratio 1.40), injury (odds ratio 1.96), and failure (odds ratio 1.59); maximum number of failed organs (odds ratio 2.13); admission after emergency surgery (odds ratio 3.08); and nonsurgical admission (odds ratio 3.92). Renal replacement therapy for acute kidney injury was not an independent risk factor for hospital mortality. The RIFLE classification was suitable for the definition of acute kidney injury in intensive care units. There was an association between acute kidney injury and hospital outcome, but associated organ failure, nonsurgical admission, and admission after emergency surgery had a greater impact on prognosis than severity of acute kidney injury.
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            Acute kidney injury associates with increased long-term mortality.

            Acute kidney injury (AKI) associates with higher in-hospital mortality, but whether it also associates with increased long-term mortality is unknown, particularly after accounting for residual kidney function after hospital discharge. We retrospectively analyzed data from US veteran patients who survived at least 90 d after discharge from a hospitalization. We identified AKI events not requiring dialysis from laboratory data and classified them according to the ratio of the highest creatinine during the hospitalization to the lowest creatinine measured between 90 d before hospitalization and the date of discharge. We estimated mortality risks using multivariable Cox regression models adjusting for demographics, comorbidities, medication use, primary diagnosis of admission, length of stay, mechanical ventilation, and postdischarge estimated GFR (residual kidney function). Among the 864,933 hospitalized patients in the study cohort, we identified 82,711 hospitalizations of patients with AKI. In the study population of patients who survived at least 90 d after discharge, 17.4% died during follow-up (AKI 29.8%, without AKI 16.1%). The adjusted mortality risk associated with AKI was 1.41 (95% confidence interval [CI] 1.39 to 1.43) and increased with increasing AKI stage: 1.36 (95% CI 1.34 to 1.38), 1.46 (95% CI 1.42 to 1.50), and 1.59 (95% CI 1.54 to 1.65; P < 0.001 for trend). In conclusion, AKI that does not require dialysis associates with increased long-term mortality risk, independent of residual kidney function, for patients who survive 90 d after discharge. Long-term mortality risk is highest among the most severe cases of AKI.
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              Modified RIFLE criteria in critically ill children with acute kidney injury.

              A classification system has been proposed to standardize the definition of acute kidney injury in adults. These criteria of risk, injury, failure, loss, and end-stage renal disease were given the acronym of RIFLE. We have modified the criteria based on 150 critically ill pediatric RIFLE (pRIFLE) patients to assess acute kidney injury incidence and course along with renal and/or non-renal comorbidities. Of these children, 11 required dialysis and 24 died. Patients without acute kidney injury in the first week of intensive care admission were less likely to subsequently develop renal Injury or Failure; however, 82% of acute kidney injury occurred in this initial week. Within this group of 123 children, 60 reached pRIFLEmax for Risk, 32 reached Injury, and 31 reached Failure. Acute kidney injury during admission was an independent predictor of intensive care; hospital length of stay and an increased risk of death independent of the Pediatric Risk of Mortality (PRISM II) score (odds ratio 3.0). Our results show that a majority of critically ill children develop acute kidney injury by pRIFLE criteria and do so early in the course of intensive care. Acute kidney injury is associated with mortality and may lead to increased hospital costs. We suggest that the pRIFLE criteria serves to characterize the pattern of acute kidney injury in critically ill children.
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                Author and article information

                Contributors
                rajibinan@yahoo.com
                Journal
                Pediatr Nephrol
                Pediatr Nephrol
                Pediatric Nephrology (Berlin, Germany)
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0931-041X
                1432-198X
                3 August 2023
                3 August 2023
                2024
                : 39
                : 2
                : 559-567
                Affiliations
                [1 ]Department of Paediatrics, University of Ghana Medical Centre, ( https://ror.org/01r22mr83) Legon, Accra, Ghana
                [2 ]Department of Paediatrics and Child Health, University of Cape Town, ( https://ror.org/03p74gp79) Cape Town, South Africa
                [3 ]Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, ( https://ror.org/04d6eav07) Rondebosch, Cape Town, South Africa
                [4 ]Department of Biostatistics, School of Public Health, University of Ghana, ( https://ror.org/01r22mr83) Legon, Accra, Ghana
                Author information
                http://orcid.org/0000-0002-7758-0838
                Article
                6065
                10.1007/s00467-023-06065-y
                10728232
                37532898
                5be2e156-46c3-4619-9859-1f25a487fc5e
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 January 2023
                : 13 June 2023
                : 13 June 2023
                Funding
                Funded by: University of Cape Town
                Categories
                Original Article
                Custom metadata
                © International Pediatric Nephrology Association 2024

                Nephrology
                acute kidney injury,aminophylline,urine output,serum creatinine
                Nephrology
                acute kidney injury, aminophylline, urine output, serum creatinine

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