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ORIGINAL ARTICLE
Year : 2022  |  Volume : 21  |  Issue : 4  |  Page : 366-370  

Risk factors and occurrence of chronic kidney disease following acute kidney injury in Children


Department of Pediatrics and Pediatric Nephrology, Government Medical College, Srinagar, Jammu and Kashmir, India

Date of Submission21-May-2021
Date of Acceptance16-Sep-2021
Date of Web Publication16-Nov-2022

Correspondence Address:
Mohd Ashraf
Assistant Professor Pediatric Nephrology, Govt Medical College, Srinagar - 190 018, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aam.aam_103_21

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   Abstract 


Background: Chronic kidney disease (CKD) is an irreversible progressive condition with diverse etiologies among which acute kidney injury (AKI) is increasingly being recognized as an important one. Methods: This was a prospective observational study of pediatric intensive care unit (PICU) patients admitted with different etiologies, at a tertiary care hospital for children in Kashmir India, between October 2018 and September 2020. AKI was defined as an increase in absolute serum creatinine (SCr) ≥0.3 mg/dL or by a percentage increase in SCr 50% and/or by a decrease in urine output to <0.5 mL/kg/h for >6 hours (h). Besides analysis of AKI and associated PICU mortality, post-AKI patients after discharge were kept on follow-up for complete 1 year. Results: From 119 enrolled patients with AKI with no preexisting risk factors, 5.6% (n = 8/119) developed CKD. The AKI-associated mortality rate after 48 h of PICU stay was 13.4% (n = 16/119). At time of discharge from hospital, elevated blood pressure (BP) (n = 5/8) and subnephrotic proteinuria (n = 3/8) were the statistically significant sequels of AKI (P value <0.001) for progression to CKD. After 3 months of follow–up, elevated BP (n = 7/8) and subnephrotic proteinuria (n = 3/8) were significantly associated with progression to CKD at 1 year (P < 0.005). Conclusions: Occurrence of CKD after an attack of AKI was not uncommon and the risk of long-term consequences in the form of hypertension, proteinuria, and CKD is significant, which may be much higher than observed. It is prudent that all post-AKI PICU discharged patients must be monitored for the long-term consequences of AKI.

   Abstract in French 

Résumé
Contexte: La maladie rénale chronique (CKD) est une condition progressive irréversible avec diverses étiologies parmi lesquelles une lésion rénale aiguë (AKI) est de plus en plus reconnue comme importante. Méthodes: Il s'agissait d'une étude observationnelle prospective des patients de l'unité de soins intensifs pédiatriques (USIC) admis avec différentes étiologies, dans un hôpital de soins tertiaires pour les enfants du Cachemire, entre octobre 2018 et septembre 2020. L'AKI a été défini comme une augmentation de la créatinine sérique absolue (SCR) ≥ 0,3 mg / dL ou par un pourcentage d'augmentation du SCR 50% et / ou par une diminution de la production d'urine à <0,5 ml / kg / h pendant> 6 heures (H). Outre l'analyse de l'AKI et de la mortalité par USIC associée, les patients post-AKI après libération ont été maintenus sur le suivi pendant 1 an. Résultats: De 119 patients inscrits atteints d'AKI sans facteurs de risque préexistants, 5,6% (n = 8/119) ont développé une CKD. Le taux de mortalité associé à l'AKI après 48 h de séjour PICU était de 13,4% (n = 16/119). Au moment de la sortie de l'hôpital, une pression artérielle élevée (BP) (n = 5/8) et une protéinurie subnéphrotique (n = 3/8) étaient les suites statistiquement significatives de AKI (valeur p <0,001) pour la progression vers CKD. Après 3 mois de suivi - UP, une BP élevée (n = 7/8) et une protéinurie subnéphrotique (n = 3/8) ont été significativement associées à la progression vers la CKD à 1 an (p <0,005). Conclusions: La présence de CKD après une attaque d'AKI n'était pas rare et le risque de conséquences à long terme sous forme d'hypertension, de protéinurie et de CKD est significatif, ce qui peut être beaucoup plus élevé que celle observée. Il est prudent que tous les patients inscrits post-AKI PUCU doivent être surveillés pour les conséquences à long terme de l'AKI.

Mots-clés: Blessures rénales aiguës, enfants, soins intensifs, mortalité, résultats

Keywords: Acute kidney injury, children, critical care, mortality, outcomes


How to cite this article:
Jan M, Ashraf M, Baba RA, Bhat SA. Risk factors and occurrence of chronic kidney disease following acute kidney injury in Children. Ann Afr Med 2022;21:366-70

How to cite this URL:
Jan M, Ashraf M, Baba RA, Bhat SA. Risk factors and occurrence of chronic kidney disease following acute kidney injury in Children. Ann Afr Med [serial online] 2022 [cited 2022 Nov 29];21:366-70. Available from: https://www.annalsafrmed.org/text.asp?2022/21/4/366/361246




   Introduction Top


Acute kidney injury (AKI) is a heterogeneous clinical syndrome characterized by an abrupt decline in renal functions that has multiple etiologies, variable pathogenesis, and diverse outcome.[1] Besides bearing a daunting incidence of 26.9% among critically ill children and young adults, AKI is also associated with poor long-term outcomes, including increased mortality.[2] In adults, a modest 0.3 mg/dl rise of creatinine level is associated with a fourfold increase in mortality,[3] while seriously ill pediatric AKI patients requiring dialysis experience mortality rates of 20%–79% depending on the AKI definition used.[4] Animal studies hypothesize that an episode of AKI can cause permanent long-term kidney damage due to irreversible reduction in peritubular capillaries,[5] molecular pathways disruption, cellular inflammation even after serum creatinine (SCr) returns to baseline,[6] a mechanism that could be operating in humans as well.[7] In one of the landmark retrospective studies by Hessey et al., while analyzing the medical records of 2041 post-AKI pediatric intensive care unit (PICU) transfer out children, observed that, only 66% had a renal function assessment obtained between ICU transfer and hospital discharge,[8] while a similar study by Greenberg et al. observed that <5% postcardiac surgery AKI children had pediatric nephrology consult after discharge.[9] About 60% of children who survive an AKI attack are likely to experience residual renal abnormalities such as proteinuria, hypertension, and reduced glomerular filtration rates (GFRs).[10],[11]

In absence of standard guidelines, the frequency of follow-up in AKI patients is dictated by GFR, albuminuria, underlying comorbid conditions, disease state, and risk of progression. Unlike adults who have coexisting hypertension, diabetes, and/or cirrhosis that commonly confound the process of progression of AKI to CKD, pediatric AKI patients in general do not have such chronic coexisting conditions, and provide a unique opportunity to show a direct role of AKI progression to CKD, its stigmata, and an increased risk of death. The present prospective hospital-based study was conducted with a minimum follow-up of 1 year to have first-hand knowledge in our setting, as the data regarding the long-term sequel among the survivors of pediatric AKI are very scarce in the Kashmir Valley of India.


   Methods Top


The study was conducted from October 2018 to September 2020, in the PICU of the Department of Pediatrics G. B. Pant Hospital, an associated hospital of Government Medical College Srinagar, Jammu and Kashmir, India. The study group included all PICU patients between the ages of 1 month to 18 years who developed AKI and were on follow-up for a period of at least 1 year from the date of discharge from the hospital. However, patients (a) with previous history of AKI, (b) having AKI from primary kidney disease (e.g., acute glomerulonephritis or obstructive uropathy), and (c) with preexisting CKD, were excluded from the study. Written informed consent was obtained from parents, and the study protocol was approved by the Ethics Committee of Government Medical College Srinagar, J&K, India (Ref. No. 140/ETH/GMC; Date: 22/10/2018).

Patients were enrolled through PICU admission register and were kept under surveillance for the development of AKI during the PICU stay. Except for patients who became dialysis dependent after AKI, all other AKI patients who first developed and then recovered/improved from AKI, indicated by return of SCr to baseline values and/or improvement in urine output to normal (>1 ml/kg/h), were followed up over a period of 1 year. Patients who survived to hospital discharge were on weekly follow-up during 1st month, fortnightly follow-up for next 2 months, then 3 monthly follow-up till completion of at least 1 year.

Data regarding detailed history, physical examination including weight, height, body mass index, and vital signs were recorded in predesigned Proforma. Blood pressure (BP) for each participant was measured using an oscillometric device and higher values were confirmed by an auscultatory sphygmomanometer device. Mid-stream clean catch or catheterized urine sample was collected from each enrolled patient to determine the presence of albuminuria (defined as albumin–creatinine ratio (ACR) 30 mg/g or overt proteinuria as ACR (300 mg/g).[12] Persistent albuminuria or proteinuria was defined as two positive samples at least 1 month apart during a 3–6 month period.[13]

Definition of acute kidney injury

AKI was defined as an abrupt (within 48 h) decrease in kidney function with an absolute increase in SCr ≥0.3 mg/dL (26.4 mmol/L), a percentage increase in SCr level more than 50% (1.5-fold from baseline), or a decrease in urine output (<0.5 ml/kg/h for 6 h).[14] The degree of AKI severity was based on estimation of either SCr or urine output, by AKIN severity classification (Stages 1–3) during PICU stay. Individuals who received renal replacement therapy (RRT) were classified as AKI Stage 3 irrespective of SCr or urine output stage at the time of RRT.[15] Only those with a urinary catheter in situ were defined by urine output criteria. Baseline SCr level was defined as the lowest level at admission or preadmission SCr value within a period of 3 months. The estimated GFR (eGFR) was calculated by original Schwartz formula.[15] We labeled severe AKI as Stage 2/3 AKI as these Stage 2/3 AKIs have been associated with increased mortality in studies involving children.[16]

All the study participant patients underwent peripheral blood sampling for SCr. SCr levels were measured by a kinetic method using Siemen's Analyzer and monitored daily during PICU stay and then on follow-up. Twenty-four-hour urine protein was analyzed using catheterized samples in the ICU patients, and serial samples were analyzed during in follow-up visits and were subjected to calorimetric quantitative analysis using Siemen's CLINITEK Advantus® Urine Chemistry Analyzer.

Statistical analysis

We analyzed our data by using the Microsoft Excel Spreadsheet and the Statistical Package for Social Sciences Program (SPSS) for Windows version 20.0 (IBM Corp, Armonk, NY, USA). Normal distribution was represented by mean and standard deviation, whereas skewed distribution was expressed by median. Categorical variables in proportions were analyzed using Chi-square test or Fisher's exact test or Student's t-test. P < 0.05 was considered as being statistically significant. All P values were two tailed.

Data generation

Upon follow-up, we assessed each patient for the presence or absence of CKD, defined as either kidney damage or abnormal kidney function based on the NKF-KDOQI. Kidney damage denotes any pathologic abnormalities or markers of damage, including persistent proteinuria or microalbuminuria or rise of SCr. We defined those at risk of CKD as having a mildly decreased GFR of 60–90 ml/min/1.73 m2, persistent hypertension, and/or proteinuria/albuminuria.


   Results Top


Out of 119 patients enrolled [Figure 1] without any primary renal disease/preexisting risk factors, 17.4% (21) of patients reached Stage 1 AKI, 8.4% (10) of patients reached Stage 2, and 6.7% (8) of patients reached Stage 3 AKI on 5th day of PICU stay, and increased correspondingly to 20%, 26.4%, and 14.4%, respectively, on 10th day of PICU stay, implying an AKI incidence of 5.6%. Similarly, BP and subnephrotic proteinuria did show an increased trend at the time of discharge from the hospital, as is shown in [Table 1]. At 3 months post discharge, 88 patients were on regular follow-up, where 37.5% (33) patients had a risk factor for CKD, 5.7% (5) and 3.4% (3) of patients already reached CKD Stages 3 and 4, respectively, while 53.4% (47) patients had no features of CKD. The presence of elevated BP and subnephrotic proteinuria at the time of discharge and at 3 months was significantly associated with the occurrence of CKD at 1 year (P value <0.05). Similarly, 1 year post AKI, 19.3% (17) of patients had at least one risk factor of CKD, while 5.7% (5) and 3.4% (3) of patients had confirmed CKD Stages 3 and 4, respectively, provided a CKD occurrence rate of 9.09%.
Figure 1: Flow diagram of studied patients. AKI: Acute kidney injury, CKD: Chronic kidney disease

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Table 1: Relationship of elevated blood pressure and 24 h urine protein with occurence of chronic kidney disease at 1 year

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   Discussion Top


CKD and end-stage kidney disease are increasingly being considered as one of the sequels of AKI, which carry high economic, and family burden.[17],[18] We found that 5.6% (119/2125) of PICU patients, without any preexisting risk factor, developed AKI. During the PICU stay, 16 (13.4%) patients died, pointing to a high mortality rate among AKI patients despite no risk factors prior to PICU admission. The highest mortality was observed among AKI Stage 3 AKI patients (75%, n = 12/16), which is in conformity with the uniformly observed phenomenon from earlier studies.[2],[19]

Etiologically sepsis followed by gastroenteritis was the most common, nonrenal cause of AKI, which is contrary to the finding of Kari et al.[20] and Mammen et al.,[10] where the most common cause of AKI among the PICU patients was postcardiac surgery. This contradiction can be explained by the fact that our hospital does not have surgical wings of corresponding subspecialities, and all postsurgical patients stand excluded.

In the present study, we found normal preexisting renal functions and BP along with absent proteinuria/albuminuria among all patients who developed AKI during PICU stay. On follow-up, there was a progressive trend of declining eGFR and rise in BP and/or proteinuria among the patients who developed CKD over a period of time [Table 2], a pattern observed in earlier studies.[21],[22]
Table 2: Time-lined, different variables measured among the studied

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Among the 88 post-discharge follow-up patients, 47 (53.4%) were males. The most common age group involved was between 1 and 5 years (70, 79.5%). This observation of predominant involvement of under 5 year age group with insignificant gender bias is in accordance with the published research among the PICU patients.[23] Keenswijk et al. found six episodes of AKI/1000 children, with a median age of children being 6.1 years with a 50.8% male population.[23]

At 3 months of follow-up, 33 patients (37.5%) had elevated BP, 5 (5.7%) patients had subnephrotic proteinuria, and 16 (18.2%) had mildly increased SCr, while as 5 and 3 patients were labeled as CKD 3 and CKD 4, respectively, based on eGFR. At the completion of 3 months, 47 (53.4%) patients had complete recovery with no residual renal impairment. However, at the end of 1-year follow-up of the same number of patients, 11 patients (12.5%) had elevated BP, whereas 6 (6.8%) patients each had Stage 1 hypertension and proteinuria (6.8%), implying a renal recovery rate of approximately 41.50%, an observation similar to the findings of Menon et al.[22] and Hollander et al.[24]

This disease pattern of AKI among the PICU survivors with subsequent CKD occurrence in 8 patients (9%) is similar to findings of Hessey et al.,[25] in which children of ≤18 years from two PICUs were included with the median admission age of 3.7 years, where 21% of patients developed AKI during PICU admission, and at 5 years postdischarge, 2% patients had a CKD diagnosis. It is noteworthy that patients with any stage of AKI had an increased risk of a CKD, which is similar to the adult AKI to CKD trend, implying that even mild forms of AKI are at increased risk for CKD, where this window of opportunity may be utilized to arrest the disease progression.

Limitations

Our study was a single-center study with a smaller sample size, we did not employ ambulatory BP monitoring, that way, we may have missed many cases of masked hypertension, we did not include postsurgical patients which probably will decrease CKD estimation among AKI survivors, and finally, we could not comment on the future outcomes of renal health, as our follow-up was limited to 1 year only.


   Conclusions Top


With an AKI incidence of 5.6%, mortality of 13.4% among in-PICU patients, and 9% occurrence of CKD among the AKI survivors, these limited data emphasize that occurrence of AKI, associated mortality, risk of CKD, and sequels such as HTN and proteinuria over a period of time are significant. This time period serves as a window of opportunity for timely intervention of disease progression, and enhances renal recovery by monitoring of BP, serum creatine, and proteinuria after an attack of AKI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Menon S, Kirkendall ES, Nguyen H, Goldstein SL. Acute kidney injury associated with high nephrotoxic medication exposure leads to chronic kidney disease after 6 months. J Pediatr 2014;165:522-7.e2.  Back to cited text no. 22
    
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Hollander SA, Montez-Rath ME, Axelrod DM, Krawczeski CD, May LJ, Maeda K, et al. Recovery from acute kidney injury and CKD following heart transplantation in children, adolescents, and young adults: A retrospective cohort study. Am J Kidney Dis 2016;68:212-8.  Back to cited text no. 24
    
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Hessey E, Morissette G, Lacroix J, Perreault S, Samuel S, Dorais M, et al. Healthcare utilization after acute kidney injury in the pediatric intensive care unit. Clin J Am Soc Nephrol 2018;13:685-92.  Back to cited text no. 25
    


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