Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 1380 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
Table of Contents   
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 421-439
Acute kidney injury in children: A study of etiology, clinical profile, and short-term outcomes at the University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria


Department of Pediatrics, Nephrology Unit, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria

Click here for correspondence address and email

Date of Submission06-Mar-2018
Date of Decision05-Apr-2018
Date of Acceptance07-Apr-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


A major hindrance in programs designed to reduce deaths from acute kidney injury (AKI) is that the extent and nature of AKI are often unknown. This article reports the etiology, clinical profile, and short-term outcomes of children managed for AKI at the University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria. Children aged one month to 15 years managed for AKI (identified by pediatric RIFLE criteria) from January 2017 to December 2017 were followed up for a short period of four weeks following the AKI. Multivariate Cox regression model was used to analyze the predictors of mortality. An annual prevalence of 26 AKI cases per 1000 children was recorded with 43 AKI cases from 1634 children seen during the 12-month period. The median age was 48 months. Twenty-two were males (51.2%). Sepsis (20, 46.6%), acute glomerulonephritis (5, 11.6%), diarrheal dehydration (5, 11.6%), severe falciparum malaria (4, 9.3%), and hemolyticuremic syndrome (4, 9.3%) were the major causes of the AKI. Fourteen children were managed conservatively, while 29 children that required dialysis had access to it. Thirteen children died (percentage mortality of 30.2%). The hazard of dying was eight times more in male gender [95% confidence interval (CI); 1.03–72.9, P = 0.017] and was lower in children without pulmonary edema by 0.14 (95% CI; 0.03–0.63, P = 0.01). In our setting, mortality from AKI is still high, and male children and those with pulmonary edema should be closely managed for AKI to reduce this high mortality.

How to cite this article:
Anigilaje EA, Adebayo AI, Ocheni SA. Acute kidney injury in children: A study of etiology, clinical profile, and short-term outcomes at the University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria. Saudi J Kidney Dis Transpl 2019;30:421-39

How to cite this URL:
Anigilaje EA, Adebayo AI, Ocheni SA. Acute kidney injury in children: A study of etiology, clinical profile, and short-term outcomes at the University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 May 24];30:421-39. Available from: http://www.sjkdt.org/text.asp?2019/30/2/421/256849



   Introduction Top


Acute kidney injury (AKI) is an abrupt decline in renal excretory function characterized by a reversible increase in the blood concentration of creatinine and nitrogenous waste products, often with a decrease in urine output and by the inability of the kidney to regulate fluid and electrolyte homeostasis.[1] AKI is also a major cause of morbidity and mortality in children.[2],[3]

AKI can be community acquired, resulting from an injury or infection before admission to hospital, or can be hospital acquired, arising as a complication of hospital admission.[3] Communityacquired AKI tends to occur in low-resource countries (LRCs)[4],[5],[6],[7],[8],[9],[10],[11] and in young people with considerable comorbidities and multiorgan failures.[12] The major causes of AKI in LRCs are of single disease entities including diarrheal diseases, malaria, hemolytic-uremic syndrome (HUS), and acute glomerulonephritis (AGN).[4],[5],[6],[7],[8],[9],[10],[11] Hospital-acquired AKI occurs more in high-income settings, and in older people (45–80 years), often with several comorbidities and multiorgan failures.[12] Thus, while it is expected that morbidity and mortality from AKI should be lower in LRCs, unfortunately, this is not the case. Reasons adduced for the high AKI morbidity and mortality in LRCs include late presentation to the hospitals, delays in the recognition and treatment of AKI, and the poor access to health care and dialysis.[3],[13] Often, poor access to dialysis results from lack of available equipment and commodities, lack of human capacity to do dialysis, and lack of funding necessary to support dialysis therapy.[3],[13]

The International Society of Nephrology recently set a goal of eliminating preventable deaths from AKI by 2025 – the “0X25” initiative, especially in LRCs.[12],[13] The cornerstones of the “0X25” initiative include identifying the causes of AKI, understanding what resources are available to treat patients at risk for AKI, developing education programs to increase the awareness of the importance of early diagnosis and treatment of AKI, and developing appropriate treatment strategies.[12],[13] However, a major hindrance in the design to effectively implement programs to treat and prevent deaths from AKI in LRCs. is that the extent and nature of AKI are often unknown.[13]

For “0X25” initiative to be successful, more LRCs need to report studies on AKI.

In line with the strategies of the “0X25” initiative, the pediatric nephrology unit of the University of Abuja Teaching Hospital (UATH), Gwagwalada, Abuja, Nigeria, adopted the 2013 National Institute for Health and Care Excellence AKI guideline[14] by December 2106. This guideline emphasizes the importance of risk assessment and prevention of AKI among children seen at the emergency pediatric unit (EPU) and the pediatric medical ward (PMW) of the UATH. This guideline also underscores early recognition and treatment of AKI. The UATH also adopted the definition of AKI based on the modified pediatric RIFLE criteria (pRIFLE- “R” for risk, “I” for injury, “F” for failure, “L” for loss of kidney function, and “E” for end-stage kidney disease)[15] to describe the severity of AKI and also to determine the outcomes (“L” and “E”) of children managed for AKI in our nephrology unit.

This article reports a retrospective analysis of data that were collected prospectively to determine the prevalence, the causes, and the shortterm mortality and morbidity (over the first 4 weeks following treatment of AKI) of AKI in children seen over 12 months (January 2017 to December 2017) at the UATH, Abuja, North Central Nigeria.


   Materials and Methods Top


Study area and setting

The study was carried out at the UATH, Gwagwalada, Abuja, the Federal Capital Territory (FCT) of Nigeria. UATH is a 350-bed hospital. Although a tertiary health center, it also offers primary and secondary health services to its teeming clienteles. It serves as a referral center for other hospitals within the FCT and the surrounding States of Benue, Kogi, Kaduna Nasarawa and Niger States. Gwagwalada is a cosmopolitan town, with a heterogeneous population of many tribes including Gbagyi, Bassa, Hausa, Fulani, Koro, Yoruba, and Igbo, to mention just a few. All acutely ill children are first seen at the EPU, where they are stabilized, and before being transferred to the PMW.

Ethical consideration

The Research and Ethics Committee of the UATH provided a permission to use the data of this cohort of children.

Study design and population

By December 2016, the pediatric nephrology unit of the UATH had developed an electronic data capturing system (on Microsoft Excel Worksheet) for collecting information on children managed for AKI. This information include but not limited to age, gender, birth order, anthropometry, socioeconomic conditions of family/caregivers, level of education of the caregivers, religion, ethnicity, family history of renal disease, presenting symptoms and signs, etiology of AKI at diagnosis, the peak/ severity of AKI, hospital-acquired AKI or community-acquired AKI, admission date and duration, daily records of urine output, relevant laboratory investigations including serum creatinine both at baseline and at follow-up, and the final outcomes of AKI in the first three-month of its diagnosis including the outcomes during the follow-up period at the outpatient nephrology clinic.

For hospital-acquired AKI, surveillance[16] (measurement of serum creatinine and comparison with baseline, observation for the development of oliguria/anuria are undertaken on all children on admission) for AKI was actively sought for among children being managed for other illnesses, but who are at a risk of AKI.[16] These at-risk children include those with chronic kidney disease; hypovolemia/dehydration/ diarrhea disease; sepsis; malaria; cardiac failure; liver disease; children <5 years of age; neurological or cognitive impairment or disability; on drugs with nephrotoxic potential (such as nonsteroidal anti-inflammatory drugs, aminoglycosides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics) especially if hypovolemic; hematological malignancies; and those with symptoms or history of urological obstruction, or conditions that may lead to obstruction.[16]

Definitions of terms

AKI in a child was defined, and its severity and outcomes are also described by pRIFLE criteria using the elevated serum creatinine estimation measured by Jaffe’s method.[17] Although AKI was staged at the time of diagnosis, the maximum serum creatinine level reached in each patient was used for the final AKI severity as per injury or failure. Estimation of glomerular filtration rate (eGFR) was by the Schwartz’s formula,[18] and adequacy of urinary output was based on the body weight.

AKI/risk is defined as a decrease of at least 25% in eGFR and a urine output of <0.5 mL/kg/h for >8 h.[15] Injury is a decrease of at least 50% in eGFR and a urine output of <0.5 mL/kg/h for 16 h.[15] Failure is a decrease of at least 75% in eGFR or eGFR <35 mL/min/ 1.73 m2 or urine output <0.3 mL/Kg/h for 24 h or if the child is anuric for 12 h.[15] eGFR <35 mL/min/1.73 m2 only applies to children older than three years of age. When baseline serum creatinine is unknown, a baseline eGFR of 100 mL/min/1.73 m2 was assumed.[15]

Hospital-acquired AKI: AKI that developed in any child (while on admission at the EPU and/or at the PMW) without clinical evidence of AKI at admission (i.e., baseline ≥100 mL/ min/1.73 m2 eGFR) but following either therapeutic intervention, surgery, nosocomial infection, or any other severe clinical conditions listed previously.[16],[19]

Community-acquired AKI: AKI that developed in any child before admission to UATH and/or AKI that had developed in any child before reaching the referral hospital (if it is a case of referral to UATH) in which the child is having an abnormally elevated baseline serum creatinine or eGFR and/or diminished urine output or no urine production at admission.[12],[19]

Late diagnosis of AKI: This is assumed when the presenting complaint(s) (signs and/or symptoms) associated with AKI diagnosis is more than 72 h in duration. Early diagnosis of AKI: This is assumed when the presenting complaint(s) (signs and/or symptoms) associated with AKI diagnosis is equal to or <72 h in duration.

Sepsis in children conformed with its description including the presence of two or more of the following: abnormal temperature (<36.0°C or >38.3°C) or age-specific tachycardia (>140 beat/min for 0–2 years, >120 for 2–6 years, and >110 for >6 years) or acute altered mental status; with a clinical suspicion of new infection including cough/chest pain and or abdominal pain/distension/diarrhea and/or dysuria and or headache with neck stiffness and/or presence of cellulitis/wound infection/joint infection.[20] Blood from all cases of sepsis was also sent for culture and sensitivity tests.

Malaria diagnosis was confirmed by the presence of asexual forms of Plasmodium falciparum on peripheral blood film. Diarrhea was defined as the passage of three or more loose stools per day. HUS is confirmed by the presence of schistocytes on blood film, thrombocytopenia, and elevated serum creatinine with normal clotting profile.[21]

Nephrotic syndrome (NS) was diagnosed in the presence of edema, massive proteinuria of urine protein creatinine ratio of ≥2000 mg/g (≥200 mg/mmol), or ≥300 mg/d L, or 3+ protein on urine dipstick, and hypoalbuminemia ≤2.5 g/dL, (≤25 g/L).[21],[22] AGN was diagnosed in children manifesting with sudden onset of features of glomerular injury, which include hematuria, mild to moderate proteinuria, hypertension, edema, oliguria, and varying degrees of renal insufficiency.[1]

Hypertension was defined as systolic and/or diastolic blood pressure greater than the 95th centile for age, gender, and length using normogram published in the fourth report of the National High Blood Pressure Education Group.[23]

Urinary tract infection (UTI): It is defined as a positive test result for pyuria by either microscopy (10 white blood cells per microliter or ≥5 white blood cells/high power field in uncentrifuged urine specimen) or dipstick test (positive leukocyte esterase test) and a positive growth on culture of at least 50,000 colony-forming unit (CFU)/mL of a single uropathogen in urine specimen obtained by catheterization or >100,000 CFU/mL of a single uropathogen in clean-catch urine specimen or any uropathogen growth in urine obtained suprapubically.[24]

Dialysis indication rate: The proportion of children with AKI who eventually required dialysis for survival. Dialysis access rate: Access to dialysis was defined as the proportion of patients with AKI who received dialysis when indicated.

Short time mortality: The number of children with AKI that died while on admission and within the first four weeks of follow-up.

Renal recovery: This is defined as the number of children who survived AKI and became independent from dialysis, with progressive improvement in eGFR to values ≥100 mL/min/ 1.73 m2. Children with eGFR <100 mL/min/ 1.73 m2 who did not require dialysis were closely monitored for evidence of kidney damage (e.g., albumin excretion rate ≥30 mg/24 h) and were managed as per the stage of the chronic kidney disease (GFR in mL/min/1.73 m2 G1; ≥90, G2; 60–89, G3a; 45–59, G3b; 30–44, G4; 15–29 and G5 ≤15).[25]

Management of acute kidney injury at the University of Abuja Teaching Hospital, Gwagwalada, Abuja

Management of AKI involved requesting for the following etiological-directed investigations as appropriate including a complete blood count; blood culture; serial serum glucose levels; serum sodium, potassium, chloride, urea nitrogen, creatinine, calcium, and phosphorus; total protein and albumin; urine for urinary sediment microscopy; urine osmolality and urinary concentrations of sodium and creatinine before a diuretic agent was administered; urine dipstick testing and further testing as appropriate (nitrites or leukocytes → microscopy, culture and sensitivities, blood ≥+ → nephritis screen, protein ≥+ → early morning urine albumin:creatinine ratio); serum antistreptolysin O titers and C3 and C4 when nephritis was suspected; renal ultrasound scan to rule out urinary tract obstruction in all patients with unexplained AKI; chest radiograph and electro-cardiography in volume overloaded (respiratory or cardiac signs) and hyperkalemic patients; blood film, platelet counts, and coagulation screen if HUS was suspected; and C3, C4, antinuclear antibody, and antineutrophil cytoplasmic antibodies for rapidly progressive AKI.[16],[26] Indications for renal biopsy were deteriorating renal functions with an unclear etiology (could be rapidly progressive crescentic glomerulonephritis) and patients with the nephritic/nephrotic presentation.[26]

Treatment focused on initial fluid management, ongoing fluid management and management for specific clinical complications such as energy and protein catabolism, hyponatremia, hyperkalemia, hypocalcemia, metabolic acidosis, convulsion, and hypertension.[16],[26]

While vigorous fluid resuscitation was avoided in malarial-induced AKI, the following initial fluid management was applied. This initial fluid management depends on the status of intravascular volume as per if the child was hypovolemic, euvolemic, or hypovolemic. For the hypovolemic patient, a fluid bolus of 0.9% saline at 10 mL/Kg of body weight was given over 30 min after which the child will be assessed for urine output and repeat if necessary. If the urine output increases (5–10 mL/kg of urine, over 1–3 h) and renal function improves, then prerenal azotemia was likely. For the euvolemic child, fluid management includes giving ongoing fluid losses plus insensible fluid (400 mL/m2/day) plus fluid volume that equals the previous urine output volume and then assessed for urine production and improvement in renal function. For the hypervolemic child, IV fluid was restricted, and the child was given intravenous frusemide (2–4 mg/kg IV; maximum 5 mg/kg/day). Dialysis was indicated for the hypervolemic child with pulmonary edema and those with no response to the diuretic challenge.

The ongoing fluid management for the hypovolemic and euvolemic child (in stage “R” of pRIFLE) responding well to initial fluid management involves the continuation of body weight-dependent maintenance fluid (with correction for the fluid deficit for the hypovolemic child).

Children with stage “I” and “F” of pRIFLE and those in stage “R” not responding to the initial fluid management will continue fluid limitation given as insensible losses (400 mL/m2/day) plus mL for mL replacement of urine output plus replacement of any significant ongoing losses. All fluids given orally, intravenously, and as medication were also strictly accounted for. The review of fluid balance takes place every 4–6 h. If at review it was clear that AKI and fluid and electrolyte status was improving, the fluid regimen was stepped down to a simpler fluid regimen. Generally, 0.9% saline with 5% dextrose was used, but this depends on the diagnosis and the serum sodium and fluid status.[26]

Specific management was also provided for hyponatremia, hyperkalemia, hypocalcemia, metabolic acidosis, convulsion, and hypertension. To minimize catabolism of body protein which tends to exacerbate azotemia of AKI, energy intake of 70–100 kcal/kg body weight/day was usually provided in combination with a protein intake of 0.7–1 g/kg of body weight/day. Dietary sodium, potassium, and phosphate are usually restricted during AKI treatment.

Hypertension due to fluid overload was treated with IV frusemide, after ensuring that the hypertension was not due to intense compensatory vasoconstriction from hypovolemia. Children with severe hypertension and encephalopathy were treated aggressively with IV hydralazine (0.2 mg/kg loading dose, 5–20 mg every 4 h) or IV labetalol 0.2–1 mg/kg, maintenance 0.4–3 mg/kg. Less severe hypertension was treated with nifedipine 0.25–0.5 mg/kg up to 10 mg per dose. Dialysis was indicated in hypervolemic and hypertensive patients with congestive heart failure and pulmonary edema failing to respond to treatment. Before dialysis was commenced, children with pulmonary edema receive the following: no intravenous fluid, nursed prop up on bed, received 100% oxygen at 3–4 L/min to keep oxygenation persistently above 92%, received high doses of IV frusemide at 5 mg/kg, received low-dose dopamine at of 0.5–5 μg/kg/min, and IV morphine at 0.1 mg/kg. Intubation and mechanical ventilation were also offered for children with pulmonary edema having persistent hypoxemia, acidosis, and impaired consciousness. Other clinical indications for dialysis include AKI with multisystem failure, patients with uremic symptoms (encephalopathy, pericarditis, intractable vomiting, and hemorrhage), symptomatic severe anemia, and anuria of more than 24 h.

Biochemical indications for dialysis include hyperkalemia >6.5 mmol/L and increasing serum creatinine levels despite conservative management, severe hyponatremia (Na <118 mmol/L with oliguria), severe hypernatremia (Na >160 mmol/L with oliguria), severe hypocalcemia [total Ca (corrected) <1.75 mmol/L, ionized Ca <0.8 mmol/L] not responding to therapy, severe hyperphosphatemia (PO4 >1.7 mmol/L), hyperuricemia (serum uric acid >15 mg/dL), and severe intractable acidosis (plasma bicarbonate <10 mmol/L).[26] The choice of dialysis was either peritoneal dialysis (PD) or hemodialysis (HD). During the period of this study, all children with viral infections [hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)] needing HD were referred to another hospital where there was a designated HD machine for this group of children. There was no capacity for continuous renal replacement therapy. PD was opted for small-sized patients (weight <25 kg), when vascular access cannot be secured in a bigger child, in uremic diathesis, and when there was cardiovascular instability. The details of the dialysis therapy will be published in another article.

For AKI survivors, the follow-up at the nephrology clinic was planned for the following investigations including eGFR, urinalysis, renal ultrasound at one month, three months, six months, 12 months, and at five years following AKI. Closer attention was given to children with residual hypertension, those with persistent proteinuria (≥2+ on dipstick urinalysis on two occasions, 4 weeks apart), or with albumin excretion rate of >30 mg/24 h, and those with reduced eGFR of <100 mL/min/1.73 m2.


   Statistical Analysis Top


Analysis of the data was performed using Statistical Package for the Social Sciences version 15.0 (SPSS Inc., Chicago, IL, USA). Continuous data were summarized as medians and interquartile range, while categorical data were presented as counts and percentages. Age in months was grouped into three categories (<12, 12–60, >60) to take cognizance of infant and under-five mortality as it relates to AKI.

The annual prevalence of AKI was calculated as the number of AKI cases from the total number of children (aged one month to 15 years) seen over the one-year period of data collection and expressed as per 1000 children. The main outcome of the study was mortality among AKI patients from the point of diagnosis to the end of short-term follow-up at four weeks. Cox regression hazard models were used to determine baseline characteristics (clinicodemography and laboratory) associated with mortality. Factors found to be significant predictors of mortality in bivariate Cox regression hazard model (P <0.05) were entered into multivariate Cox regression model. Kaplan–Meier survival analysis was also done for factors that remained significant at multivariate Cox regression and expressed as log-rank tests. Censoring occurred for children that died and those that were followed up to the end of the study (December 2017). For all analyses, confidence intervals (CIs) were set at 95% level, and P <0.05 was considered as statistically significant.


   Results Top


A total of 43 cases of AKI were managed among 1634 children seen at the EPU and the PMW of the UATH between January 2017 and December 2017. Thus, an annual prevalence rate of AKI was 26 AKI cases per 1000 children. All the 43 cases have been followed up to a minimum of four weeks following discharge from the UATH. No child was lost to follow-up as the three children with viral hepatitis B, hepatitis C (two had coinfections with hepatitis B and C), and HIV who were referred for HD also came back for follow-up at the nephrology clinic of the UATH. Renal recovery (i.e., eGFR >100 mL/min/1.73 m2) among the 30 survivors at six weeks of follow-up was excellent, and only one child had a lower value (eGFR <100 mL/min/1.73 m2). [Figure 1] is the diagrammatic sketch of the follow-up of the 43 children with AKI.
Figure 1: A diagrammatic sketch of the follow-up of the 43 children with acute kidney injury.
EPU: Emergency Pediatric Unit, PMW: Pediatric Medical Ward, UATH: University of Abuja Teaching Hospital, AKI: Acute kidney injury, eGFR: Estimated glomerular filtration rate.


Click here to view


[Table 1] shows that out of the 43 cases, 22 were males and 21 females, giving a male:female ratio of 1:0.95. The median age of the AKI cases was 48 months, with a range of 1 month to 15 years. Most (17, 39.6%) of these children were between the ages of 12 months and 60 months. Community-acquired AKI was diagnosed in 27 (62.8%) children, and hospital-acquired AKI in 16 (37.2%) children, the majority of whom had (13/16, 81.3%) sepsis. A case of pelvic-ureteric junction obstruction, a case of poorly rehydrated diarrheal disease, and a case of gentamicin nephritis accounted for the remaining three cases of the hospital-acquired AKI. All the 29 patients requiring dialysis (i.e., dialysis indication rate of 67.4%) for management had access to it (i.e., dialysis access rate of 100%), with most (19, 65.5%) children having acute PD and the remaining 10 children having HD. At the peak of elevated serum creatinine, 31 (72.1%) children had injury and 12 (27.9%) had failure. The other common clinical and laboratory characteristics of the patients are shown in [Table 1].
Table 1: Pattern of some clinical and laboratory characteristics of the children with acute kidney injury.

Click here to view


[Table 2] reveals that sepsis (20, 46.6%), AGN (5, 11.6%), diarrheal dehydration (5, 11.6%), severe falciparum malaria (4, 9.3%), and hemolytic-uremic syndrome (4, 9.3%) were the major causes of the AKI. All the four cases of severe falciparum malaria had intravascular hemolysis evident by anemia and hemoglobinuria on dipstick urinalyses.
Table 2: Etiological classification of acute kidney injury among the children.

Click here to view


[Table 3] depicts some of the comorbidities seen with the three common causes of AKI. For the 20 children with sepsis, one child was found to be HIV infected and most (8, 40%) also had anemic heart failure and acute bacterial meningitis (7, 35%). Among the five children who had poststreptococcal glomerulonephritis, two (40%) of them also had sickle cell anemia, UTIs, and viral hepatitis B and C.
Table 3: Pattern of the comorbidities associated with the etiology of acute kidney injury.

Click here to view


[Table 4] reveals the clinical and laboratory indications for dialysis among the children. Most (21, 72.4%) of the children who had multiple complications of congestive heart failure, severe uncontrolled hypertension, pulmonary edema, and multiple seizures ended with dialysis. Six children with anuria of more than 24 h were also dialyzed. Increasing serum creatinine levels among all the 29 children was the most common laboratory indication in this cohort. The other common indications for dialysis dialysis are shown in [Table 4].
Table 4: Indications for dialysis among the children with acute kidney injury.

Click here to view


[Table 5] depicts the Cox regression analyses for some predictors of mortality among the children managed for AKI. At bivariate analyses, gender, sepsis, convulsion, pulmonary edema, urinary proteinuria, and hypernatremia were significantly associated with mortality. However, in multivariate analyses, only gender and pulmonary edema were still predictive of mortality. The trend was such that the hazard of dying was eight times more in male gender (95% CI; 1.03–72.9, P = 0.017), and the hazard of dying was reduced in children without pulmonary edema by 0.14 (95% CI; 0.03–0.63, P = 0.01). When tested by Chi-square analyses, the predictiveness of the male gender was not significantly associated with age groups (P = 0.420), neither was it to early or late presentation (P = 0.488) as defined previously. However, statistical significance was found when gender was tested against having septic AKI and mortality (P = 0.0001).
Table 5: Cox regression analysis of predictors of mortality among the children with acute kidney injury.

Click here to view


The other characteristics in [Table 5] were not significantly associated with mortality in this cohort. Mortality among who had dialysis was 43.5% (10/29), and it was 21.4% (3/14) among those managed conservatively.

Furthermore, the log-rank survival analyses of mortality were found to be statistically significant by gender (P = 0.001) and by pulmonary edema (P = 0. 001) [Figure 2] and [Figure 3].
Figure 2: Kaplan–Meier survival analysis by gender.
Test of equality of survival distributions for the different levels of gender (M: Male, F: Female, df: Degree of freedom).


Click here to view
Figure 3: Kaplan–Meier survival analysis by pulmonary edema.
Test of equality of survival distributions for the different levels of pulmonary edema (df: Degree of freedom).


Click here to view



   Discussion Top


Our findings indicate that with the 43 cases of AKI over one year, the annual prevalence of AKI among children seen at our EPU and the PMW was 26 AKI cases per 1000 children. While most cases of AKI are acquired in the community (62.8%), preventable causes such as sepsis, AGN, diarrheal dehydration, severe falciparum malaria, and HUS still predominate. Thirteen children with AKI died, with a mortality rate of 30.2%. We also found that the hazard of dying was eight times more in the male gender and was reduced in children without pulmonary edema.

With 43 cases of AKI over one year, our finding was higher than the annual cases of 35 cases per year reported by Esezobor et al in Lagos Nigeria[11] and the respective 123 cases and the 211 cases over nine and 18 years periods by Anochie and Eke in Port-Harcourt, Nigeria[9] and Olowu and Adelusola in Ile-Ife, Nigeria.[10] Elsewhere in Africa, the annual 43 cases of AKI in our study was higher than the 105 AKI cases over six years in Congo-Brazzaville[5] and the 87 cases over nine years in Cameroon.[27] However, the 43 cases seen in our study was lower than the average of 68 annual cases reported by Antwi et al in Ghana.[28] Nevertheless, our data still support the fact that the prevalence of AKI may be increasing in developing countries of the world.[29]

We attribute the high cases of AKI detected in our cohort to close surveillance, as we actively searched for hospital-acquired AKI among children hitherto admitted for other illnesses. This is reflected in hospital-acquired AKI being responsible for 16 (37.2%) of the 43 cases, especially seen among our patients with sepsis. In addition, the sensitivity of the pRIFLE criteria in early recognition of AKI (most were injury, 72.1%) cases is another reason for a large number of AKI in this series.

While variations exist for the causes of pediatric AKI within countries and across continents, the finding of sepsis (46.6%), acute glomerulonephritis (11.6%), diarrheal dehydration (11.6%), severe falciparum malaria (9.3%), and hemolytic-uremic syndrome (9.3%) as the major causes of AKI in our study, is not greatly different from what have been reported earlier in other LRCs.[5],[9],[10],[11],[27],[28]

In Congo-Brazzaville, gastroenteritis (25.7%), NS (14.7%), sepsis (15.23%), malaria (12.38%), and AGN were reported to be the main causes of AKI.[15] Anochie and Eke reported gastroenteritis (28.9%) and malaria (13.7%) as the major causes of AKI in Port-Harcourt, Nigeria.[9] In Ile-Ife, Nigeria, malaria (42.53%), renal Burkitt’s lymphoma (29%), sepsis (28.73%), AGN (27.8%), NS (16.7%), and HUS (5.5%) accounted for the majority of AKI in that series.[10] Esezobor et al in Lagos, Nigeria, revealed that primary kidney disease (AGN, NS, HUS, and pyelonephritis) caused 38.6% of AKI, while sepsis (25.7%) and malaria (11.4%) explained the main others.[11] Halle et al in Cameroon reported sepsis (57.5%), severe malaria (21.8%), hypovolemia (16.1%), and the use of herbal concoctions (6.9%) to be the main causes in their cohorts.[27] Antwi et al in Ghana also reported hemoglobinuria, obstructive uropathy, tumor infiltration, gastroenteritis, and glomerulonephritis.[28]

In general, given that most of the causes of AKI in our series and those of others[5],[9],[10],[11],[27],[28] appear to be of preventable causes, this note-worthiness must not be lost on nephrologist working in LRCs. While the gains seen in the control of gastroenteritis and the prevention of dehydration/hypovolemia from gastroenteritis over the last decades should be sustained,[29] efforts at controlling and detecting sepsis cases for antimicrobial therapy cannot be overlooked.

Although rapid diagnostic test (RDT) for malaria diagnosis is nowadays straightforward, unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of nonmalarial febrile illnesses in the tropics.[30] While cultures for sepsis screen are being awaited, there is also an urgent need to foster the development of sufficiently sensitive antigen-based RDTs for the diagnosis of common bacterial causes of sepsis in our setting.

Sepsis was the most common cause of AKI in our cohort, and most of these children acquired the AKI while on admission at our hospital. This finding calls for a more aggressive surveillance of AKI among children being managed for sepsis as an earlier and appropriate antimicrobials use has been associated with lower risk of AKI (for each hour of antimicrobial delay, the risk of AKI increased by approximately 40%) and with a greater likelihood of kidney recovery from sepsis-associated AKI.[31],[32]

Given the insensitivity of serum creatinine and the unreliability of urine production in detecting AKI, biomarkers such as plasma neutrophil gelatinase-associated lipocalin, urine kidney injury molecule–1, plasma tissue inhibitor of metalloproteinases-2, and insulin-like growth factor binding protein-7 have shown promises for early detection of preclinical (detect renal stress or damage before change is evident) and subclinical AKI (detect AKI in the absence of functional change).[31] These biomarkers can also be explored in RLC for the early diagnosis of septic AKI.

The possibility of genetic predisposition to septic AKI among our patients cannot be ignored, and this possibility should be explored in future genetic and translational studies. Recently, genomic-wide association study of septic AKI has found that polymorphisms of the gene controlling transcription factor on chromosome 4 that is involved in innate immunity pathway is associated with greater risk of AKI.[33] Furthermore, the gene involved in the control of transforming growth factor beta on chromosome 22 has been linked with a greater risk of septic AKI.[34] These genes are also worthy of study even among our children with sepsis.

Mortality from septic AKI implies that this peculiar AKI should be managed cautiously.[31] For example, caution must be applied in the fluid management as recent evidence suggests that aggressive fluid therapy is unwarranted and may in actual fact be injurious in septic AKI.[31] However, the use of vasodilators such as nonepinephrine and continuous renal replacement therapy appears to be more suitable in managing septic AKI.[31] Interestingly, whereas septic AKI is associated with a high mortality,[31] septic AKI is also known to be associated with[35] improved renal recovery[35] as also seen in this study.

Our study revealed that HUS (9.3%) may not be an uncommon cause of AKI as was previously assumed. HUS was also reported in the series of Antwi et al (6, 2.9%),[28] Olowu et al (2, 5.5%),[19] and Esezobor et al (4, 14.8%).[11]

While HUS is largely the reported leading cause of AKI in children in South and Eastern Africa[7],[36] and in developed countries and South America,[37],[38],[39] a high index of suspicion may probably reveal more children having HUS as the cause of AKI even in LRCs.

We also found mortality to be 30.2% in this study. While this mortality rate compares better than the 37%,[5] 40.5%,[9] 46.2%,[10] and 50.7%[27] reported from previous studies in sub-Saharan Africa, it was, however, higher than 20.9% and 28.4% reported by Antwi et al in Ghana[28] and Esezobor et al in Lagos, Nigeria,[11] respectively.

Our mortality of 30.2% reveals that even when surveillance for AKI subsists, mortality for AKI in LRCs remains high.

At multivariate analyses, the mortality seen in our study was not associated with age of patients and other indicators of severe AKI (coma, oliguria, anuria, bleeding diathesis, hypertension, hyponatremia, metabolic acidosis, and uremia). The mortality was also unrelated to the types of AKI (either hospital acquired or community acquired). Although the mortality was higher (10/29, 43.5%) among patients who had dialysis compared to those managed conservatively (3/14, 21.4%), this finding was not statistically significant.

It is worthy of note that dialysis access rate in our cohort was 100%, reflecting the fact that when adequate information about the need for dialysis for AKI is provided, the parents/care-givers of our pediatric AKI would strive to make finances available for dialysis. The high dialysis access rate in this study may also reflect the better socioeconomic conditions of these Abuja residents compared to other regions in Nigeria where dialysis accessibility is sub-optimal.[10],[11] Abuja is the cosmopolitan FCT of Nigeria.

Only gender and the presence of pulmonary edema were found to be significantly associated with mortality in multivariate analyses. The trend was such that the hazard of dying was eight times more in the male gender, and male children with sepsis who developed AKI are more likely to die in our cohort. Furthermore, the hazard of dying is reduced in children without pulmonary edema.

The risk of death among the male children with sepsis may be supporting a gender-related susceptibility to severe sepsis,[40],[41] and thus, a possible increased mortality from septic AKI. Otherwise, the higher risk of deaths among our male children may as well reflect the higher infant and under-five mortality that have been noted previously in most parts of the world.[42],[43],[44]

Pulmonary edema results from fluid leaks from the pulmonary capillary network into the lung interstitium and the alveoli as a result of elevated pulmonary capillary pressure and the inability of the lymphatic to filtrate off excess fluid from the alveoli and the interstitium. In the context of AKI, pulmonary edema can result from congestive heart failure (left-sided failure); it can be a form of noncardiogenic pulmonary edema from oliguric AKI; and it can also be an adult-like respiratory distress syndrome complicating sepsis, pneumonia, and hypovolemia. Pulmonary edema, impaired gaseous exchange, and increased work of breathing ultimately lead to respiratory failure and death.

Sadly, most of the children that died in our study also had other comorbidities that can kill them regardless of AKI or its severity. For example, most of the children with septic AKI also have anemic heart failure, meningitis, and pneumonia, which cumulatively may have contributed to the mortality seen in these children. Similar contributions of comorbidities to mortality of AKI have been noted earlier by other researchers.[10],[45],[46] This also strongly suggests that early detection and aggressive management of these comorbidities are important in efforts at reducing AKI mortality.


   Limitations of the Study Top


A major limitation of this study is the small sample size of 43 which may have reduced the power in detecting predictors of mortality at multivariate Cox regression analysis. Thus, other predictors of mortality noted at bivariate analyses should also be considered cautiously in concerted efforts at reducing AKI mortality in our setting.

It also remains valid that some of the patients that died from pulmonary edema would have survived if intubation and mechanical ventilatory supports had been provided. Unfortunately, the available ventilators were being used for other patients when needed for these patients with AKI.

In addition, the presence of other comorbidities occurring along with sepsis, acute glomerulonephritis, and diarrheal disease suggest that more than one pathophysiologic process may have operated in the causation of AKI in this cohort, and as such, the association of mortality with some specific causes of AKI may have been misplaced in the statistical analyses.

We also do not have data of AKI among the neonates in this cohort as the neonatologists conservatively managed this peculiar group of children in our center.

However, the prospective nature of this study remains a strong strength.


   Conclusion Top


With a prevalence of 43 cases of AKI over 12 month’s period, our study has proven that there is a huge burden of pediatric AKI in our setting. With a predominance of sepsis, acute glomerulonephritis, diarrheal dehydration, severe falciparum malaria, and HUS, our data also suggest that geographical variations exist in the etiology of AKI in Nigeria. Nevertheless, concerted efforts can be put in place to reduce most of these preventable causes of AKI mortality. AKI in male children, especially those with sepsis and children who developed acute pulmonary edema are at greater risks of dying; thus, the cautious management of this group of children cannot be over-underscored. While short-term recovery of renal function is excellent in our cohort, AKI should be prevented as much as possible, as even a single episode of AKI has been noted to be associated with increased subsequent risk of chronic kidney disease.[31] Prevention of AKI is cheaper, and initiatives such as improvement in basic personal and environmental sanitation, control of malaria through the use of insecticide-treated bed nets and environmental control of mosquitoes, and the prompt application of oral and intravenous rehydration for diarrhea only need to be reemphasized.[47] Empirical treatment algorithms based on locally available epidemiological studies on sepsis should be encouraged as a way of reducing septic AKI.[47]


   Acknowledgment Top


We are grateful to parents whose children made the population of this study.

Conflict of interest: None declared.



 
   References Top

1.
Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet 2012;380:756-66.  Back to cited text no. 1
    
2.
Susantitaphong P, Cruz DN, Cerda J, et al. World incidence of AKI: A meta-analysis. Clin J Am Soc Nephrol 2013;8:1482-93.  Back to cited text no. 2
    
3.
Olowu WA, Niang A, Osafo C, et al. Outcomes of acute kidney injury in children and adults in Sub-Saharan Africa: A systematic review. Lancet Glob Health 2016;4:e242-50.  Back to cited text no. 3
    
4.
Bailey D, Phan V, Litalien C, et al. Risk factors of acute renal failure in critically ill children: A prospective descriptive epidemiological study. Pediatr Crit Care Med 2007;8:29-35.  Back to cited text no. 4
    
5.
Assounga AG, Assambo-Kieli C, Mafoua A, Moyen G, Nzingoula S. Etiology and outcome of acute renal failure in children in Congo-Brazzaville. Saudi J Kidney Dis Transpl 2000; 11:40-3.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001. Am J Kidney Dis 2005;45:96-101.  Back to cited text no. 6
    
7.
Van Biljon G. Causes, prognostic factors and treatment results of acute renal failure in children treated in a tertiary hospital in South Africa. J Trop Pediatr 2008;54:233-7.  Back to cited text no. 7
    
8.
Olowu WA. Renal failure in Nigerian children: Factors limiting access to dialysis. Pediatr Nephrol 2003;18:1249-54.  Back to cited text no. 8
    
9.
Anochie IC, Eke FU. Acute renal failure in Nigerian children: Port Harcourt experience. Pediatr Nephrol 2005;20:1610-4.  Back to cited text no. 9
    
10.
Olowu WA, Adelusola KA. Pediatric acute renal failure in Southwestern Nigeria. Kidney Int 2004;66:1541-8.  Back to cited text no. 10
    
11.
Esezobor CI, Ladapo TA, Osinaike B, Lesi FE. Paediatric acute kidney injury in a tertiary hospital in Nigeria: Prevalence, causes and mortality rate. PLoS One 2012;7:e51229.  Back to cited text no. 11
    
12.
Mehta RL, Cerdá J, Burdmann EA, et al. International Society of Nephrology’s 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): A human rights case for nephrology. Lancet 2015;385:2616-43.  Back to cited text no. 12
    
13.
Anand S, Cruz DN, Finkelstein FO. Understanding acute kidney injury in low resource settings: A step forward. BMC Nephrol 2015;16:5.  Back to cited text no. 13
    
14.
Acute Kidney Injury: Prevention, Detection and Management of Acute Kidney Injury. NICE Guideline CG169. August, 2013. Available from: https://www.nice.org.uk/guidance/cg169. Last accessed 10 February 2016.  Back to cited text no. 14
    
15.
Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 2007;71: 1028-35.  Back to cited text no. 15
    
16.
Acute Kidney Injury-Nottingham University Hospitals NHS Trust. Available from: https://www.nuh.nhs.uk/handlers/downloads.as hx?id=61144. Last accessed accessed 15 April, 2016.  Back to cited text no. 16
    
17.
Newman DJ, Prize CP. Renal function. In: Burtis CA, Ashwood ER, editors. Tietz Textbook of Clinical Chemistry. Philadelphia: WB Saunders Company; 1999. p. 1241-6.  Back to cited text no. 17
    
18.
Schwartz GJ, Haycock GB, Edelmann CM Jr., Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58:259-63.  Back to cited text no. 18
    
19.
Olowu WA, Adefehinti O, Bisiriyu AL. Hospital-acquired acute kidney injury in critically ill children and adolescents. Saudi J Kidney Dis Transpl 2012;23:68-77.  Back to cited text no. 19
[PUBMED]  [Full text]  
20.
Daniels R. Surviving the first hours in sepsis: Getting the basics right (an intensivist’s perspective). J Antimicrob Chemother 2011 ;66 Suppl 2:ii11-23.  Back to cited text no. 20
    
21.
Rees L, Brogan PA, Bockenhauer D, Webb NJ. Glomerular diseases In: Paediatric Nephrology. 2nd ed. Oxford, United Kingdom: Oxford University Press; 2012. p. 192-216.  Back to cited text no. 21
    
22.
KDIGO Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2012;2:139-274.  Back to cited text no. 22
    
23.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555-76.  Back to cited text no. 23
    
24.
Robinson JL, Finlay JC, Lang ME, Bortolussi R; Canadian Paediatric Society, Infectious Diseases and Immunization Committee, Community Paediatrics Committee. Urinary tract infections in infants and children: Diagnosis and management. Paediatr Child Health 2014;19:315-25.  Back to cited text no. 24
    
25.
KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 2013;3:19-62.  Back to cited text no. 25
    
26.
Rees L, Brogan PA, Bockenhauer D, Webb NJ. Acute kidney injury In: Paediatric Nephrology. 2nd ed. Oxford, United Kingdom: Oxford University Press; 2012. p. 377-94.  Back to cited text no. 26
    
27.
Halle MP, Lapsap CT, Barla E, et al. Epidemiology and outcomes of children with renal failure in the pediatric ward of a tertiary hospital in Cameroon. BMC Pediatr 2017;17: 202.  Back to cited text no. 27
    
28.
Antwi S, Sarfo A, Amoah A, Appia AS, Obeng E. Topic: Acute kidney injury in children: 3-year data review from Ghana. Int J Pediatr Res 2015;1:5.  Back to cited text no. 28
    
29.
Word Health Organization. Preventing diarrhoea through better water, sanitation and hygiene. Exposures and Impacts in Low- and Middle-Income Countries. Word Health Organization; 2014. Available from: http://www.apps. who.int/iris/bitstream/10665/150112/1/9789241 564823_eng.pdf. Last accessed 20 May 2016.  Back to cited text no. 29
    
30.
Crump JA, Gove S, Parry CM. Management of adolescents and adults with febrile illness in resource limited areas. BMJ 2011;343:d4847.  Back to cited text no. 30
    
31.
Bellomo R, Kellum JA, Ronco C, et al. Acute kidney injury in sepsis. Intensive Care Med 2017;43: 816-28.  Back to cited text no. 31
    
32.
Bagshaw SM, Lapinsky S, Dial S, et al. Acute kidney injury in septic shock: Clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med 2009;35:871-81.  Back to cited text no. 32
    
33.
Haase-Fielitz A, Haase M, Bellomo R, Dragun D. Genetic polymorphisms in sepsis- and cardiopulmonary bypass-associated acute kidney injury. Contrib Nephrol 2007;156:75-91.  Back to cited text no. 33
    
34.
Zhao B, Lu Q, Cheng Y, et al. A genome-wide association study to identify single-nucleotide polymorphisms for acute kidney injury. Am J Respir Crit Care Med 2017;195:482-90.  Back to cited text no. 34
    
35.
Bagshaw SM, Uchino S, Bellomo R, et al. Septic acute kidney injury in critically ill patients: Clinical characteristics and outcomes. Clin J Am Soc Nephrol 2007;2:431-9.  Back to cited text no. 35
    
36.
Shimelis D, Tadesse Y. Clinical profile of acute renal failure in children admitted to the department of pediatrics, Tikur Anbessa hospital. Ethiop Med J 2004;42:17-22.  Back to cited text no. 36
    
37.
Latta K, Offner G, Brodehl J. Continuous peritoneal dialysis in children. Adv Perit Dial 1992; 8:406-9.  Back to cited text no. 37
    
38.
Yoshiya K, Iijima K, Yoshikawa N. A clinicopathological study of 90 children with acute renal failure. Nihon Jinzo Gakkai Shi 1997;39: 483-9.  Back to cited text no. 38
    
39.
Spizzirri FD, Rahman RC, Bibiloni N, Ruscasso JD, Amoreo OR. Childhood hemolytic uremic syndrome in Argentina: Long-term follow-up and prognostic features. Pediatr Nephrol 1997; 11:156-60.  Back to cited text no. 39
    
40.
García-Gómez E, González-Pedrajo B, Camacho-Arroyo I. Role of sex steroid hormones in bacterial-host interactions. Biomed Res Int 2013;2013:928290.  Back to cited text no. 40
    
41.
Schröder J, Kahlke V, Staubach KH, Zabel P, Stüber F. Gender differences in human sepsis. Arch Surg 1998;133:1200-5.  Back to cited text no. 41
    
42.
Waldron I. Sex differences in infant and early childhood mortality: major causes of death and possible biological causes. In: Too young to die genes or gender? New York: United Nations, Department of Economic and Social Affairs, Population Division; 1998. p. 64-83.  Back to cited text no. 42
    
43.
Sawyer CC. Child mortality estimation: Estimating sex differences in childhood mortality since the 1970s. PLoS Med 2012;9: e1001287.  Back to cited text no. 43
    
44.
Pongou R. Why is infant mortality higher in boys than in girls? A new hypothesis based on preconception environment and evidence from a large sample of twins. Demography 2013;50: 421-44.  Back to cited text no. 44
    
45.
Werner HA, Wensley DF, Lirenman DS, LeBlanc JG. Peritoneal dialysis in children after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1997;113:64-8.  Back to cited text no. 45
    
46.
Gordillo-Paniagua G, Hernandez-Rodriquez O. Physiology, diagnosis and treatment of acute renal insufficiency. Bol Med Hosp Infant Mex 1999;48:656-62.  Back to cited text no. 46
    
47.
Lewington AJ, Cerdá J, Mehta RL. Raising awareness of acute kidney injury: A global perspective of a silent killer. Kidney Int 2013; 84:457-67.  Back to cited text no. 47
    

Top
Correspondence Address:
Emmanuel A Anigilaje
Department of Pediatrics, Nephrology Unit, University of Abuja Teaching Hospital, Gwagwalada, Abuja
Nigeria
Login to access the Email id


DOI: 10.4103/1319-2442.256849

PMID: 31031378

Rights and Permissions


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
    Materials and Me...
   Statistical Analysis
   Results
   Discussion
    Limitations of t...
   Conclusion
   Acknowledgment
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed210    
    Printed1    
    Emailed0    
    PDF Downloaded40    
    Comments [Add]    

Recommend this journal