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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2009  |  Volume : 20  |  Issue : 1  |  Page : 69-76
Acute renal failure in pediatric patients: Etiology and predictors of outcome


Department of Nephrology, Mubarak Al-Kabeer Hospital, Kuwait

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   Abstract 

Acute renal failure (ARF) is the acute loss of kidney function over hours or days, the etiology of which varies in different countries. The data on the etiology and outcome of ARF in Arab children is limited. Our objective was to define the causes and predictors of outcome of ARF in Kuwaiti children, and the variables determining their fitness for dialysis. A total of 32 children with ARF were evaluated regarding their demographic and clinical data, the cause of ARF and the co-morbidities. Data were analyzed to find the independent variables determining fitness for dia­lysis and outcome. Males comprised 62.5% of the study children; 46.9% of ARF cases were due to sepsis and 56.2% underwent renal replacement therapy (RRT). Univariate analysis showed that age, hemodynamic instability, use of vasopressors, multi-organ failure (MOF), and mechanical venti­lation contributed to fitness for dialysis. However, MOF was the only independent variable affecting fitness for dialysis. The overall mortality was 43.8%. Univariate analysis showed that age below 24-months, hemodynamic instability, use of vasopressors, fluid overload, need for mecha­nical ventilation, MOF and late referral to the nephrologist were associated with poor outcome. However, multivariate analysis documented MOF, and the time of nephrologists' intervention as independent prognostic indicators. Our study suggests that sepsis was the major cause of pediatric ARF. RRT is the optimal treatment, and the only factor determining child's fitness for dialysis is MOF.

Keywords: Multi-organ failure, Dialysis, Unstable hemodynamics, Vasopressors, Mechanical ventilation

How to cite this article:
Ghani AA, Al Helal B, Hussain N. Acute renal failure in pediatric patients: Etiology and predictors of outcome. Saudi J Kidney Dis Transpl 2009;20:69-76

How to cite this URL:
Ghani AA, Al Helal B, Hussain N. Acute renal failure in pediatric patients: Etiology and predictors of outcome. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2019 Nov 17];20:69-76. Available from: http://www.sjkdt.org/text.asp?2009/20/1/69/44709

   Introduction Top


Acute renal failure (ARF) is a life threatening condition especially in children, with signifi­cant increased morbidity and mortality. [1] It is defined as the sudden loss of the ability of the kidney to excrete water, regulate electrolytes and acid-base status and eliminate waste pro­ducts. [2],[3] It is a relatively uncommon condition in pediatric practice. [4],[5] The etiology of ARF can be pre-renal, renal and post-renal with pre-renal.ARF being the most common form in children. [6]

The mortality rates among children with ARF differ in the various studies reported and de­pend on the nature of the underlying disease, with the highest mortality rates reported in children with multi-organ failure (MOF). [7],[8],[9] Continuous renal replacement therapy (CRRT) has become an important supportive therapy for critically ill children with ARF, oliguria, and fluid overload, allowing for slower fluid remo­val rates than with hemodialysis. Thus, CRRT is a therapy better suited for fluid removal in children with hemodynamic instability. [10]

Limited data are available on the etiology and outcome of ARF in Arab children. This pros­pective study was carried out in Kuwait to investigate the causes and outcome of ARF, as well as factors determining fitness for dialysis in children with ARF.


   Material and Methods Top


A prospective, descriptive, epidemiologic study was conducted over a four-year period from January 2003 to December 2006. All admi­ssions to pediatric intensive care unit (PICU) with ARF were included in the study. Baseline data including age, gender, weight, height, baseline serum creatinine as well as creatinine level at time of evaluation by the attending nephrologist, diagnosis on admission to pedia­tric ICU, the direct cause of ARF and time of involving the nephrologist after the onset of ARF were noted. ARF was defined as doubling of baseline serum creatinine as recorded on admission to PICU. In patients with history of chronic renal insufficiency defined as GFR 10­60 mL/min/1.73m 2 , ARF was defined as an in­crease of serum creatinine by a minimum of 25% from the baseline level. To be considered acute, renal failure had to develop over less than 72 hours. Hypotension was defined as sys­tolic blood pressure less than 70 mm Hg + 2 × age in years. Hyperkalemia was defined as se­rum potassium of more than 6.5 meq/L. Multi­organ failure was defined as dysfunction of more than two vital organs.

Continuous venovenous hemofiltration (CVVHF) was performed using Prisma continuous fluid management system (by Gambro Lakewood Co.) using M 60 or M100 dialyzer sets (AN69 membrane), with surface area of 0.42 and 0.90 m 2 respectively, with bicarbonate buffered solu­tion for CRRT from Hospal with the following solute composition in mmol/L: calcium (Ca 2+ ), 1.75; magnesium (mg 2+ ), 0.5; sodium (Na + ), 140; chloride (Cl - ), 109.5; lactate - , 3; and bicar­bonate (HCO3 - ), 32. Blood flow rate was set at 80-100 mL/min, and the substitution fluid rate was 40 mL/kg body weight/hour. Ultrafiltration rate was set according to the desired fluid removal rate. Anticoagulation was achieved by adjusting a constant heparin infusion to main­tain activated partial thromboplastin time bet­ween 130-150 seconds. Heparin was withheld in patients with bleeding disorders. The fre­quency and duration of dialysis therapy was determined based upon the requirements of the child. Vascular access was obtained by the attending nephrologist using 8-12 french dual lumen catheters (Quinton, Bothell, WA). Cycler assisted peritoneal dialysis (CAPD) was used in one patient using Stay Safe fluid from Baxter using an exchange volume of 20 mL/kg body weight.


   Statistical Methods Top


Data were analyzed using SPSS for windows version 12 (SPSS, Inc, Chicago, IL). Numerical variables were expressed as mean ± SD, where­as categorical variables were expressed as fre­quencies and percentages. Fisher exact test was used for univariate analysis using risk ratio and 95% confidence interval (CI). Logistic regre­ssion analysis was used for multivariate ana­lysis for statistically significant variables in the univariate analysis. Results were considered statistically significant if the P value was < 0.05.


   Results Top


A total of 32 patients were identified as having ARF. Their age ranged between 14 days and 175 months with a mean of 86.92 ± 59.44 and a median of 72 months. Their body weight ranged between 2.5 and 65 kg with a mean of 28.60 ± 19.32 and a median of 37 kg. Their mean height was 80.50 ± 32.15 cm, with a range of 45-120 cm. There were 20 males (62.5%) and 12 fe­males (37.5%) in the study. Their mean base­line serum creatinine was 65.34 ± 43.45 µmol/L, and the mean serum creatinine at presentation was 380.56 ± 174.75 µmol/L. Patient's demo­graphic data as well as the clinical charac­teristics at presentation with ARF are shown in [Table 1].

Sepsis was the major cause of ARF accounting for 46.9% of cases followed by hematological malignancies complicated by tumor lysis syn­drome accounting for 12.5%. The underlying causes of ARF as well as the co-morbidities are shown in [Table 1].

At evaluation, 17 patients (53.1%) were hemo­dynamically unstable, 19 patients (59.4%) re­quired vasopressor support at sometime during the disease course, 21 patients (65.6%) required mechanical ventilation, 15 children (46.9%) were euvolemic, 12 (37.7%) were volume overloaded, and five (15.6%) were volume depleted; 12 pa­tients (37.5%) had MOF.

Dialysis was required in 23 children (71.9%) either due to persistent hyperkalemia, severe metabolic acidosis not responding to conserva­tive measures, fluid overload refractory to diu­retic therapy, or uremic symptoms. Seven pa­tients (30.4%) were found unfit for dialysis. Univariate analysis showed that factors affec­ting children's fitness for dialysis included; pa­tient's age (p= 0.02), hemodynamic status (p= 0.01), use of vasopressors (p= 0.003), presence of MOF (p< 0.001) and use of mechanical ventilator (p= 0.01). On the other hand, gender, volume status, underlying cause of renal failure and associated co-morbidities had no significant effect on the patient's fitness for dialysis (p= 0.61, 0.46, 0.81, 0.61 respectively) [Table 2]. Logistic regression analysis showed that the only independent variable affecting children's fitness for dialysis was the presence of MOF (p= 0.04, odds ratio = 0.064, CI 0.005-0.89). Renal replacement therapy was attempted in 18 patients (56.3%). Of them, CVVHF was per­formed in 17 (53.2%), and CAPD was performed in one patient (3.1%). Nine patients (28.1%) responded positively to conservative measures.

Of the patients who underwent renal replace­ment therapy, 94.4% were above two years of age (p= 0.004). Heparin-free dialysis was per­formed in 47.1% of cases. Vascular access was obtained by the attending nephrologists without any complications. Ten patients (31.3%) had right internal jugular vein catheterization, six patients (16.8%) had right subclavian vein catheterization, one patient (3.1%) had right femoral vein cathe­terization, and one patient had surgical placement of Tenckoff peritoneal dialysis catheter for CAPD. The mean duration of the dialysis therapy was 86.44 ± 40.79 hours. A total of 17 patients (53.1%) recovered completely, 11 (34.4%) died before improvement of kidney function, three (9.4%) died after improvement of their renal functions, and one patient (3.1%) ended up on regular hemodialysis.

The overall mortality was 43.8% (14 patients). Univariate analysis showed that mortality ten­ded to be higher in children below 24-months of age (p = 0.04), hemodynamically unstable patients (p= 0.01), children requiring vaso­pressor support (p= 0.01), fluid overloaded chi­dren (p= 0.04), those on mechanical ventilator (p= 0.03), children with MOF (p< 0.001) and in cases of late referral to the nephrologist (p= 0.002). Associated co-morbidities had an effect on mortality with patients having hematological malignancies, those after cardiac surgery and patients with burns having a higher mortality rate compared to patients who presented with infections (p= 0.03, 0.01, and 0.01 respectively). Gender, the necessity for dialysis, the nature of dialysis procedure and the underlying cause of renal failure had no significant effect on mor­tality (p= 0.2, 0.46, 0.18, 0.84) [Table 3]. Multi­variate binary logistic regression models re­vealed that among the factors that showed a significant difference between survivors and non-survivors, only the presence of MOF (p= 0.04), and the time of referral to the nephro­logist (p= 0.02) could be regarded as indepen­dent determinants of the prognosis of ARF in children.


   Discussion Top


Acute renal failure is a serious condition in critically ill children. [11] The available literature suggests that not only the severity of ARF (needing dialysis), but also the mild forms of ARF may have an impact on morbidity and mortality of affected patients. [12],[13] Furthermore, identifying patients in the early stage of ARF and identifying the risk factors associated with those early stages, may help in preventing fur­ther worsening of renal function if timely inter­vention is undertaken. [13]

The etiology of ARF seems to differ in diffe­rent countries. [14] In the present study, sepsis was found to be the most common cause of ARF accounting for 46.9% of cases followed by hematological malignancies complicated with the tumor-lysis syndrome. Our result is in con­cordance with Flynn et al. who reported post operative sepsis as a prominent cause of ARF in the pediatric population. [15] Several other studies also have reported sepsis as the major cause of ARF in children. [1],[16],[17] However, in studies from high income countries, cardiovascular surgeries and the hemolytic uremic syndrome (HUS) are the most important risk factors associated with ARF in the pediatric population. [18],[19] Bailey et al reported that more than 50% of ARF cases were due to HUS, hematological malignancies or car­diac surgeries. [11] On the other hand, Vachva­vichsanong et al reported that hematological malignancies involving the kidneys and neph­rotoxic chemotherapy were less common cau­ses. However, children with malignances tend to develop sepsis particularly during chemo­therapy. [1]

Mortality rates in children with ARF tend to be high. In the present study, 43.8% of the studied population died. Mortality rates of 25­50% have been reported in other studies depen­ ding on the underlying disorder. [7],[14],[20],[21],[22],[23]

Our study showed that the mortality rate is higher in younger children. The same was re­ported by Vachvanichsanong et al. [1] Several studies have reported that the cause of ARF was significantly associated with age and with the resultant mortality rates but, age by itself was not an independent predictor of mortality. [1],[17],[22],[24] In the present study, children with MOF were found to have a higher mortality (88.3%). Pre­vious studies have documented that when the kidneys are involved in MOF, the prognosis is very poor with a mortality rate of 45-75%. In contrast, the prognosis is better when primary renal disorder is the cause of ARF, wherein the mortality rate is 9 to 12.5%. [7],[8],[14],[20],[25],[26],[27]

The outcome of renal replacement therapy (RRT) in children varies throughout the world. [14] The present study did not find significant difference in mortality rates in patients treated with or without RRT. Otukesh et al. showed a higher mortality rate in patients treated with hemo­dialysis than those treated with peritoneal dialysis and attributed this to the recurrent hypotensive episodes that occur during hemo­dialysis. [14]

In the present study, multivariate analysis showed that the independent variables deter­mining outcome of ARF in children were the presence of MOF, as well as the time of referral to the nephrologist. Between them, MOF was the most significant and the best predictor of mortality. Several studies reported MOF as a determining factor for patient outcome with very high mortality rates > 50% even with RRT. [15],[24],[16],[28] Previous studies reported that ARF by itself is not a fatal condition because of the availability of advanced CRRT but, timing of starting appropriate management is a major consideration. [20],[23],[28],[29],[30] Loza et al reported age­ groups and oliguria as independent factors affecting outcome of ARF in children, [17] while Otukesh et al. reported the use of mechanical ventilator, the necessity for dialysis and disse­minated intravascular coagulopathy as inde­pendent determinants of the prognosis of ARF in children. [14] On the contrary, our study did not find the age-group or need for mechanical ven­tilator as independent determinants of mortality in children with ARF.

None of the previous studies tested the varia­bles accounting for children's fitness for dia­lysis. Our study showed that the only indepen­dent factor determining fitness for dialysis is the presence or absence of MOF with 95% of children without MOF being fit for dialysis versus 33.3% of those with MOF. This seems logical as patients with MOF are usually hemo­dynamically unstable, and as such starting them on dialysis becomes technically difficult.


   Conclusion Top


ARF is a serious disease in children with a high mortality. The commonest cause of ARF in pediatric population is found to be acute tubular necrosis secondary to sepsis. Factors determining outcome of ARF in children inclu­ded the presence of MOF and the time of refe­rral to the nephrologist. However, MOF was found to be the most important independent predictor of fitness for dialysis

 
   References Top

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2.Esson ML, Schrier RW. Diagnosis and treat­ment of acute tubular necrosis. Ann Intern Med 2002;137(9):744-52.  Back to cited text no. 2    
3.Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med 1996;334(22):1448-60.  Back to cited text no. 3    
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5.Warady BA, Bunchman T. Dialysis therapy for children with acute renal failure: Survey results. Pediatr Nephrol 2000;15(1-2):11-3.  Back to cited text no. 5    
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10.Goldstein SL, Currier H, Graf JM, et al. Out­come in children receiving continuous veno­venous hemofiltration. Pediatrics 2001;107(6): 1309-12.  Back to cited text no. 10    
11.Bailey D, Phan V, Litalien C, et al. Risk factors of acute renal failure in critically ill children: a retrospective epidemiological study. Pediatr Crit Care Med 2007;8(1):29-35.  Back to cited text no. 11    
12.Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous venovenous hemo­filtration on outcome of acute renal failure: a prospective randomized trial. Lancet 2000; 356 (9223):26-30.  Back to cited text no. 12    
13.Lowrie L. Renal replacement therapies in pedia­tric multiorgan dysfunction syndrome. Pediatr Nephrol 2000;14(1):6-12.  Back to cited text no. 13    
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15.Flynn JT. Causes, management approaches and outcome of acute renal failure in children. Curr Opin Pediatr 1998;10(2):184-9.  Back to cited text no. 15    
16.Smoyer WE, McAdams C, Kaplan BS, Sher­botie JR. Determinants of survival in pediatric continuous hemofiltration. J Am Soc Nephrol 1995;6(5):1401-9.  Back to cited text no. 16    
17.Loza R, Estremadoyro L, Loza C, Cieza J. Factors associated with mortality in acute renal failure in children. Pediatr Nephrol 2006;21(1):106-9.  Back to cited text no. 17    
18.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(2):156-60.  Back to cited text no. 18    
19.Moghal NE, Brocklebank JT, Meadow SR. A review of acute renal failure in children: inci­dence, etiology and outcome. Clin Nephrol 1998;49(2):91-5.  Back to cited text no. 19    
20.Arora P, Kher V, Rai PK, Singhal MK, Gulati S, Gupta A. Prognosis of acute renal failure in children: a multivariate analysis. Pediatr Nephrol 1997;11(2):153-5.  Back to cited text no. 20    
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26.Barretti P, Soares VA. Acute renal failure: Cli­nical outcome and cause of death. Ren Fail 1997;19(2):253-7.  Back to cited text no. 26    
27.Fargason CA, Langman CB. Limitations of pediatric risk of mortality score in assessing children with acute renal failure. Pediatr Nephrol 1993;7(6):703-7.  Back to cited text no. 27    
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Correspondence Address:
Amal Abdel Ghani
Nephrology Unit, Mubarak Al Kabeer Hospital, P.O. Box 43787, code 3205 Hawally
Kuwait
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    Tables

  [Table 1], [Table 2], [Table 3]

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