COMMENTARY

Acute Kidney Injury: Increasing Recognition Merits MoreAction

Arvind Bagga & Aditi Sinha

Received: 4 February 2013 /Accepted: 4 February 2013 /Published online: 20 February 2013# Dr. K C Chaudhuri Foundation 2013

Acute kidney injury (AKI), characterized by an abrupt de-cline in kidney function, may have manifestations rangingfrom minimal elevation of serum creatinine to oligoanuricrenal failure. There is recognition that even minor short-termchanges in serum creatinine concentrations are associatedwith increased lengths of hospital stay and mortality inadmitted adult and pediatric patients [1], underscoring theneed for early diagnosis of the disorder. On the long term,the risk of occurrence of chronic kidney disease (CKD) is asignificant concern. While the prevalence of AKI variesaccording to the definition used, the condition is commonin developing as well as developed countries. While mostreports on the incidence of AKI in children are limited todeveloped countries; prospective information on the occur-rence and outcomes of AKI in children from developingregions are lacking.

A major limitation in assessing the impact of this mor-bidity is the lack of common standards to define and rate itsseverity. Two classifications that have been validated for thediagnosis and prognosis of AKI in critically ill adults are theRisk, Injury, Failure, Loss and End stage (RIFLE) system[2] and the one proposed by the Acute Kidney InjuryNetwork (AKIN) [3]. These criteria use serial changes inserum creatinine or estimated glomerular filtration rate(eGFR) and/or the urine output to define the presence andstage of injury. Both definitions, including a pediatric modifi-cation (pRIFLE), have been subsequently used to report theincidence and severity of AKI in hospitalized children. Mostrecently, the Kidney Disease Improving Global Outcome(KDIGO) Clinical Practice Guideline reiterates the AKINdefinition to define AKI as any of the following: (i) increase

in serum creatinine by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 h,(ii) increase in serum creatinine to ≥1.5 times baseline, whichis known or presumed to have occurred within the prior 7 d, or(iii) urine volume ≥0.5 ml/kg/h for 6 h [4].

Due to disparities in definition used, the incidence ofAKI in hospitalized children has varied from 10% to 58%[1, 5, 6]. Most AKI is developed nations is observed in thecontext of a pre-renal insult such as hypotension, post-operative hypovolemia, septicemia or nephrotoxic drugs,contributing to incident AKI in hospitalized patients. Serialmeasurement of the levels of urinary and plasma neutrophilgelatinase-associated lipocalin, urinary IL-18, kidney injurymolecule-1 and cystatin-C are being explored as biomarkersto enable early identification of AKI, and to identify those atrisk of progression to severe stages. In contrast, a majorityof AKI in patients in developing regions is community-acquired, occurring after infectious illnesses (malaria, lep-tospira, dengue), diarrheal dehydration, glomerulonephritisor hemolytic uremic syndrome. Most of these conditions arepreventable and/or benefit from specific management.Importantly, such AKI is already present at admission tothe hospital.

Studies in adults suggest that patients with AKI are at riskof chronic kidney disease (CKD) during follow up. Studiesthat evaluate the progression of AKI to CKD in children arelimited, and this assessment should occur simultaneous to anevaluation of potential biomarkers for disease progression.The recent KDIGO guidelines for AKI propose a newclassification for alterations in kidney function and struc-ture, termed acute kidney damage (AKD), to bridge theexisting definitions of AKI and CKD. However, it remainsto be determined whether early recognition and manage-ment of AKD can improve long-term outcomes.

This issue of the Journal features a prospective study onthe incidence of AKI in hospitalized children in South India[7]. Over a period of 10 mo, Krishnamurthy et al. screened

A. Bagga (*) :A. SinhaDivision of Nephrology, Department of Pediatrics,All India Institute of Medical Sciences, Ansari Nagar,New Delhi 110029, Indiae-mail: arvindbagga@hotmail.com

Indian J Pediatr (March 2013) 80(3):247–248DOI 10.1007/s12098-013-0989-8

2,477 children aged 1 mo to 13 y, and found AKI, as definedby the AKI network [3], in 5.2% patients in the wards and25.1% in the intensive care unit, with an overall rate of 7%.These rates compare well with those reported elsewhere,including in a prospective study from north India [8].Patients had AKI at or within 48 h of admission; the meancreatinine at admission was 1.1 (0.9–1.6) mg/dl. Etiologieswere largely pre-renal, but a fair proportion of patients hadestablished AKI at admission due to glomerulonephritis,tropical infections or hemolytic uremic syndrome. Sincethe AKIN definition has been validated chiefly for incidentAKI, it would be worthwhile to also examine the occur-rence, risk factors and outcomes after excluding patientsadmitted with AKI. Progression of AKI was noted in asignificant proportion; almost similar proportions ofpatients had AKI stage 1, 2 and 3 as the maximal stage.The authors did not find that AKI was a predictor ofmortality, suggesting that the underlying medical condi-tions were perhaps more important in determining out-comes. Similarly, AKI did not result in any significantchange in length of hospital stay. Among survivors, theshort-term outcome was satisfactory, with some persistentrenal injury in one-sixth of the patients.

Despite strong associations with length of hospital stay,healthcare costs and mortality in other reports, the currentemphasis on AKI is clearly inadequate, and requires publicawareness, clinical education and training and basic and clin-ical research. There is considerable potential of interventionsto reduce the risk of AKI, hasten its diagnosis and improveacute and long-term outcomes. Studies similar to that dis-cussed above are required to generate accurate data aboutthe true incidence and clinical impact of pediatric AKI, par-ticularly in developing countries. Additional studies arenecessary to address gaps in knowledge regarding specificstrategies for early diagnosis, reverse renal injury and preventprogression to chronic kidney disease. Individual centersshould focus on developing protocols to manage prerenal

causes of AKI, including specific infections, and increaseawareness about the importance of serial monitoring of bloodlevels of creatinine and urine output in high-risk and criticallyill patients.

The motto of the Eighth World Kidney Day, on 14 March2013, is to enhance awareness that AKI is common, harm-ful, preventable and treatable [www.worldkidneyday.org]. Itis hoped that the occasion shall enhance opportunities foreducation and clinical research in AKI and initiate policydevelopment targeting the prevention and treatment of thismajor morbidity across the world.

References

1. Schneider J, Khemani R, Grushkin C, Bart R. Serum creatinine asstratified in the RIFLE score for acute kidney injury is associatedwith mortality and length of stay for children in the pediatricintensive care unit. Crit Care Med. 2010;38:933–9.

2. The ADQI Workgroup, Bellomo R, Ronco C, Kellum JA, Mehta RL,Palevsky P. Acute renal failure: definition, outcome measures, animalmodels, fluid therapy and information technology needs: the secondinternational consensus conference of the acute dialysis quality initia-tive (ADQI) group. Crit Care. 2004;8:R204–12.

3. Mehta RL, Kellum JA, Shah SV, et al. Acute kidney injury network:Report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007;11:R31.

4. KDIGO. Clinical practice guideline for acute kidney injury. KidneyInt. 2012;2:S1–138.

5. Palmieri T, Lavrentieva A, Greenhalgh D. An assessment of acutekidney injury with modified RIFLE criteria in pediatric patients withsevere burns. Intensive Care Med. 2009;35:2125–9.

6. Zappitelli M, Moffett BS, Hyder A, Goldstein SL. Acute kidneyinjury in non-critically ill children treated with aminoglycosideantibiotics in a tertiary healthcare centre: a retrospective cohortstudy. Nephrol Dial Transplant. 2011;26:144–50.

7. Krishnamurthy S, Mondal N, Narayanan P, Biswal N, Srinivasan S,Soundravally R. Incidence and etiology of acute kidney injury insouthern India. Indian J Pediatr. 2012; doi:10.1007/s12098-012-0791-2.

8. Mehta P, Sinha A, Sami A, et al. Incidence of acute kidney injury inhospitalized children. Indian Pediatr. 2012;49:537–42.

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