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      Nephrotoxicity as a cause of acute kidney injury in children

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      Publication date (Electronic):
      Journal: Pediatric Nephrology (Berlin, Germany)
      Publisher: Springer Berlin Heidelberg
      Keywords: Renal side effects

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          Abstract

          Many different drugs and agents may cause nephrotoxic acute kidney injury (AKI) in children. Predisposing factors such as age, pharmacogenetics, underlying disease, the dosage of the toxin, and concomitant medication determine and influence the severity of nephrotoxic insult. In childhood AKI, incidence, prevalence, and etiology are not well defined. Pediatric retrospective studies have reported incidences of AKI in pediatric intensive care units (PICU) of between 8% and 30%. It is widely recognized that neonates have higher rates of AKI, especially following cardiac surgery, severe asphyxia, or premature birth. The only two prospective studies in children found incidence rates of 4.5% and 2.5% of AKI in children admitted to PICU, respectively. Nephrotoxic drugs account for about 16% of all AKIs most commonly associated with AKI in older children and adolescents. Nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, amphotericin B, antiviral agents, angiotensin-converting enzyme (ACE) inhibitors, calcineurin inhibitors, radiocontrast media, and cytostatics are the most important drugs to indicate AKI as significant risk factor in children. Direct pathophysiological mechanisms of nephrotoxicity include constriction of intrarenal vessels, acute tubular necrosis, acute interstitial nephritis, and—more infrequently—tubular obstruction. Furthermore, AKI may also be caused indirectly by rhabdomyolysis. Frequent therapeutic measures consist of avoiding dehydration and concomitant nephrotoxic medication, especially in children with preexisting impaired renal function.

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          Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score.

          A. de Mendonca, J-L Vincent, P Suter … (2000)
          To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. Prospective, multicenter, observational cohort analysis. Forty ICUs in 16 countries. All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. Of the patients, 348 (24.7%) developed ARF, as diagnosed by a serum creatinine of 300 micromol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p < 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8% vs 14.0%, p < 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95%: 1.23-2.06], p < 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.
          Article 0 comments Cited 144 times – based on 0 reviews     Review now
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            Hospital-acquired renal insufficiency: a prospective study.

            S Hou, D Bushinsky, J B Wish … (1983)
            Twenty-two hundred sixty-two consecutive medical and surgical admissions were evaluated prospectively to determine the contribution of iatrogenic factors to the development of renal insufficiency in hospital. Of 2,216 patients at risk, some degree of renal insufficiency developed in 4.9 percent. Decreased renal perfusion, postoperative renal insufficiency, radiographic contrast media, and aminoglycosides accounted for 79 percent of the episodes. Iatrogenic factors, broadly defined, accounted for 55 percent of all episodes. Poor prognostic indicators included oliguria, urine sediment abnormalities and, most importantly, severity of renal insufficiency; with an increase in serum creatinine of 3 mg/dl or greater, the mortality rate was 64 percent. Age, admission serum creatinine levels, and the number of episodes of renal insufficiency did not significantly affect outcome. We conclude that there is a substantial risk of the development of renal failure in hospital and that the mortality rate due to hospital-acquired renal insufficiency remains high.
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              Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group.

              F Liaño, J Pascual (1996)
              There are very limited data on overall epidemiology of ARF. It is crucial to know the incidence, etiology and clinical feature of ARF to promote prevention strategies and to implement adequate resources for the management of this entity. During a nine month period, a collaborative prospective protocol with 98 variables was developed to assess all ARF episodes encountered in the 13 tertiary-care hospitals in Madrid, Spain (covering 4.2 million people of over 14 years of age). ARF was considered when a sudden rise in serum creatinine concentration (SCr) to more than 177 mumol/liter was found in patients with normal renal function, or when the sudden rise (50% or more) was observed in patients with previous mild-to-moderate chronic renal failure (SCr < 264 mumol/liter). Of the 748 cases of ARF studied, 665 episodes presented in inhabitants from the Madrid area. This gives an overall incidence of ARF of 209 cases per million population (p.m.p.; 95% CJ 195 to 223). The incidence of acute tubular necrosis (ATN) was 88 cases p.m.p. (95% CI 79 to 97), prerenal ARF 46 p.m.p (95% CI 40 to 52), acute-onset chronic ARF 29 p.m.p. (95% CI 24 to 34), and obstructive ARF 23 p.m.p. (95% CI 19 to 27). The mean age was 63 +/- 17 years. The most frequent causes of ARF were ATN (45%), prerenal (21%), acute-onset chronic renal failure (12.7%) and obstructive ARF (10%). Renal function was normal at admission in 48% of patients who later developed ARF. Mortality (45%) was much higher than that of the other patients admitted (5.4%, P < 0.001). This real outcome correlated extremely well with the expected outcome calculated through out the severity index of ARF (SI) 0.433 +/- 0.246 (mean +/- SD). In 187 cases, mortality was attributed to underlying disease, thus corrected mortality due to ARF was 26.7%. Dialysis was required in 36% of patients, and was associated with a significantly higher SI of ARF (0.57 +/- 0.23 vs. 0.35 +/- 0.19, P < 0.001) and mortality (65.9 vs. 33.2%, P < 0.001). Mortality in patients hemodialyzed with biocompatible synthetic membranes (N = 50) was similar to that observed with cellulosic ones (N = 84; 66% vs. 59.5%, NS). Mortality was higher in patients with coma, assisted respiration, hypotension, jaundice (all P < 0.001) and oliguria (P < 0.02). This study gives, for the first time, the incidence of all forms of ARF in a developed country. ARF is iatrogenically induced at a high rate by modern medicine. Prevention strategies, particularly in the perioperative period, are needed to decrease its impact.
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                Author and article information

                Contributors
                Ludwig Patzer: l.patzer@krankenhaus-halle-saale.de
                Journal
                Journal ID (nlm-ta): Pediatr Nephrol
                Journal ID (iso-abbrev): Pediatr. Nephrol
                Title: Pediatric Nephrology (Berlin, Germany)
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0931-041X
                ISSN (Electronic): 1432-198X
                Publication date (Electronic): 1 December 2008
                Publication date PMC-release: 1 December 2008
                Publication date (Print): 2008
                Volume: 23
                Issue: 12
                Pages: 2159-2173
                Affiliations
                Children’s Hospital St. Elisabeth and St. Barbara, Mauerstrasse 5, 06110 Halle/S., Germany
                Article
                Publisher ID: 721
                DOI: 10.1007/s00467-007-0721-x
                PMC ID: 6904399
                PubMed ID: 18228043
                SO-VID: a3f87aba-b3c8-4f65-86cd-a527ae90b59d
                Copyright © © IPNA 2007
                License:

                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
                Date received : 15 August 2007
                Date revision received : 2 October 2007
                Date accepted : 4 October 2007
                Categories
                Subject: Educational Feature
                Custom metadata
                issue-copyright-statement © IPNA 2008

                ScienceOpen disciplines: Nephrology
                Keywords: renal side effects
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: renal side effects

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