Published online August 7, 2006
PEDIATRICS Vol. 118 No. 3 September 2006, pp. e786-e791 (doi:10.1542/10.1542/peds.2006-0557)
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ARTICLE

Childhood Acute Renal Failure: 22-Year Experience in a University Hospital in Southern Thailand

Prayong Vachvanichsanong, MDa, Pornsak Dissaneewate, MDa, Apiradee Lim, MScb and Edward McNeil, MSb

a Department of Pediatrics
b Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. The objectives of this study were to review the prevalence, cause, and morbidity and mortality rates of acute renal failure in a large tertiary care institution in southern Thailand, to examine any differences in acute renal failure cases diagnosed during a 22-year period, and to determine the risk factors indicating death.

METHODS. The case records for children 1 month to 17 years of age who were diagnosed as having acute renal failure between February 1982 and December 2004, in the Department of Pediatrics, Songklanagarind Hospital, in southern Thailand, were reviewed.

RESULTS. A total of 311 children with 318 episodes of acute renal failure were included, that is, 177 boys (55.7%) and 141 girls (44.3%), 1 month to 16.7 years of age (mean age: 7.6 ± 5.1 years; median age: 7.8 years). The causes of acute renal failure in each age group were significantly different. Overall, sepsis was the major cause of acute renal failure, accounting for 68 episodes (21.4%), followed by hypovolemia, poststreptococcal glomerulonephritis, systemic lupus erythematosus, and infectious diseases. Renal replacement therapy was performed in 55 cases (17.3%). The overall mortality rate was 41.5%. Logistic regression analysis showed that disease groups and creatinine levels were significant independent predictors of outcomes.

CONCLUSIONS. The incidence of acute renal failure in Songklanagarind Hospital was 0.5 to 9.9 cases per 1000 pediatric patients, with a mortality rate of 41.5%. Sepsis was a major cause of acute renal failure and death. Causes of acute renal failure and serum creatinine levels were significant independent predictors of death.

Key Words: acute renal failure • renal replacement therapy • peritoneal dialysis

Abbreviations: ARF—acute renal failure • PSAGN—poststreptococcal glomerulonephritis • SLE—systemic lupus erythematosus • RRT—renal replacement therapy • CGN—chronic glomerulonephritis

Acute renal failure (ARF), the sudden deterioration of renal function, is not common in general clinical practice but is not uncommon at tertiary referral centers.1 There are a variety of causes and treatment options, and outcomes vary from country to country and from hospital to hospital. ARF is a life-threatening condition, especially in children, with significantly increased morbidity and mortality rates. Early detection and appropriate treatment can provide complete recovery, a major goal of ARF therapy. ARF, particularly the nonoliguric form, is often missed when only clinical symptoms are considered or is found by chance through abnormal biochemical test results. The objectives of this study were to review the prevalence, causes, and morbidity and mortality rates of ARF in a major tertiary care center in southern Thailand, to examine any differences in ARF cases diagnosed in different periods during the preceding 22 years, and to determine the mortality risk factors.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
The case records of children, 1 month to 17 years of age, who were diagnosed as having ARF between February 1982 and December 2004 in the Department of Pediatrics, Songklanagarind Hospital, in southern Thailand were reviewed. To have comparable numbers of cases, we divided the patients into 3 eras, namely, 1982 to 1994, 1995 to 1999, and 2000 to 2004. ARF was defined on the basis of a sudden increase in serum creatinine concentration of >177 µmol/L (2.00 mg/dL), a serum creatinine concentration that was >2 times previous or subsequent values and that was also higher than the upper limit of normal values for the patient's age,2 or, for patients with preexisting chronic renal impairment, an increase in serum creatinine concentration of >2.00 mg/dL, with the serum creatinine concentration later returning to the initial level. Patients with acute deterioration of chronic renal failure were excluded. The cause of ARF was considered to be the major problem leading to ARF.

The cases were classified according to different common renal problems known to be found in the following 5 age groups: infants (1 month to 1 year), toddlers (>1 year to 5 years), younger children (>5 years to 10 years), older children (>10 years to 13 years), and teenagers (>13 years). Fisher's exact tests and {chi}2 tests were used to compare differences among categorical variables. Logistic regression analysis was used to evaluate multiple risk factors. P values of <.05 were considered significant. R software, version 2.2.0, was used for all statistical analyses.3


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
A total of 311 children with 318 episodes of ARF satisfied the inclusion criteria and had admission forms available for review (1 patient had 3 episodes of ARF and 5 patients had 2 episodes). There were 177 boys (55.7%) and 141 girls (44.3%) (age range: 1 month to 16.7 years; mean age: 7.6 ± 5.1 years; median age: 7.8 years).

The incidence of ARF through the years is shown in Fig 1, which shows a dramatic increase in 1995, compared with previous years. Although there was a significant hospital expansion at that time, including pediatric case admissions, the ARF/total pediatric case ratio increased from 0.5 to 3.3 cases per 1000 cases before 1995 to 4.6 to 9.9 cases per 1000 cases after 1995.


Figure 1
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  		FIGURE 1 Comparison of the incidences of general pediatric admissions and ARF cases according to year.

 
Causes of ARF according to age group, renal replacement therapy (RRT), and mortality rates are shown in Table 1. The causes of ARF were classified into 11 groups (8 children had unknown causes). The causes of ARF in each age group were significantly different (P < .001). Overall, sepsis was the major cause of ARF, accounting for 68 episodes (21.4%), followed by hypovolemia, poststreptococcal glomerulonephritis (PSAGN), systemic lupus erythematosus (SLE), and infectious diseases. Of the 30 infectious disease cases, 11 involved leptospirosis and 19 dengue hemorrhagic shock syndrome.


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  		TABLE 1 Distributions of Age Groups and Causes of ARF, Showing Maximal Creatinine Levels of >2 mg/dL, RRT, and Mortality Rates

 
RRT was performed for 55 patients (17.3% overall; intermittent peritoneal dialysis, continuous peritoneal dialysis, and continuous arteriovenous hemofiltration in 12, 40, and 3 cases, respectively). Of those, 35 patients (63.6%) died.

Continuous arteriovenous hemofiltration was performed for 2 patients with dengue hemorrhagic shock syndrome who had unstable hemodynamic features and 1 patient who had multiple injuries, without evidence of hypovolemia, for whom the definitive cause of ARF was not determined. These 3 patients died as a result of multiorgan failure.

Examination of the association between dialysis and disease showed that patients with SLE, chronic glomerulonephritis (CGN), infectious diseases, and miscellaneous and unknown causes of renal failure tended to require dialysis more than patients with other diseases. Figure 2 shows that these patients had very high creatinine levels. In our institution, it is standard procedure to perform RRT for children who develop symptoms of volume overload and/or metabolic disturbances as well as increasing creatinine levels. Therefore, children with creatinine levels of >5 mg/dL normally receive RRT.


Figure 2
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  		FIGURE 2 Comparison of serum creatinine levels according to disease cause. KUB indicates kidney, ureter, and bladder.

 
A total of 174 children recovered completely, 116 died, 6 refused treatment, and 22 developed chronic renal failure, of whom 16 died, 4 are alive currently, and 2 were lost to follow-up monitoring. The overall mortality rate was 41.5%, with an immediate mortality rate of 36.5%. Male and female patients had similar mortality rates (39.5% and 40.0%, respectively). The mortality rates for infants, toddlers, young children, older children, and teenagers were 53.8%, 30.8%, 38.2%, 46.3%, and 41.4%, respectively (P = .12), but rates were significantly different between diseases (P < .0001).

In a comparison of the 3 eras (1982–1994, 1995–1999, and 2000–2004), no statistically significant differences were demonstrated regarding gender and age group (P = .8 and P = .5, respectively); however, the causes of ARF were significantly different (P = .006). RRT rates were not significantly different (P = .3). The mortality rates declined from 47% to 43% to 35% in the 3 periods, respectively, but these rates were not significantly different (P = .18) (Table 2).


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  		TABLE 2 Distributions of Causes, RRT, and Mortality Rates of ARF According to Year of Admission

 
Logistic regression analysis showed that disease groups and creatinine levels were significant independent predictors of outcome (death) (Table 3). We chose hypovolemia as the reference disease group because PSAGN and kidney, ureter, and bladder anomalies did not cause any deaths and hypovolemic ARF had the lowest mortality rate. Children with sepsis, malignancy, or CGN were >10 times more likely to die as a result of ARF, children with malignancy or unknown or miscellaneous diseases were 6 to 9 times more likely to die, and children with toxins or infectious diseases were 3 to 4 times more likely to die than were children with hypovolemia. Children who presented with serum creatinine concentrations of >2 mg/dL were twice as likely to die as a result of ARF than were children who presented with serum creatinine concentrations of ≤2 mg/dL (P = .009), although there was no additional correlation between creatinine levels of >2 mg/dL and increased risk of death.


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  		TABLE 3 Logistic Regression Analyses Showing Disease Groups and Serum Creatinine Levels of >2 mg/dL Predicting Mortality Rates

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Because our institution is the major tertiary care center for 14 provinces in southern Thailand, all severe or complicated cases from the region are referred to us. There was a sudden increase in the number of ARF cases beginning in 1995 (Fig 1). We presume that this was attributable to the arrival of a pediatric nephrologist in the hospital in 1993, with a subsequent increase in referrals that took ~2 years to eventuate. For the ARF cases, we found sepsis to be a major cause, although there are many other causes. For example, hemolytic uremic syndrome was reported as a major cause of ARF in some studies,1,4–8 whereas hemolytic uremic syndrome was found in only 7 cases in our study (2% of all cases, classified as miscellaneous in our study).

Other studies indicated that sepsis is a major cause of death in ARF.9–11 In centers where cardiac surgery is available, surgery for treatment of congenital heart disease has been a major cause of death, because of hypoxia and poor perfusion leading to multiorgan failure.8 One tertiary care center in the United Kingdom reported that cardiac surgery was a major cause of ARF in a group of neonates.8 Our study did not include neonates. In our institution, however, cardiac surgery has been performed only since 2000 and, during the study period, was still limited in the neonatal group, although, as shown in Table 2, the proportion of congestive heart failure-attributable ARF increased from 4% in the first 2 eras to 16% in the most recent era (since 2000).

Hypovolemia was the second most common cause of ARF in our study. The causes of hypovolemia included gastroenteritis and inadequate fluid therapy for patients who presented with other problems, such as trauma and injury. Fortunately, early detection and proper management in our institution produced favorable outcomes in such cases. Of the 39 hypovolemic ARF cases, only one 8-month-old child, who had diarrhea with an elevated serum creatinine level of 9.6 mg/dL, required intermittent peritoneal dialysis for 2 days and then recovered completely.

The prevalence of PSAGN-attributable ARF seems quite high in this study, because simple PSAGN is not commonly found in our institution. However, because of our role as a referral destination, cases of PSAGN with renal failure need to be referred to us for confirmation of diagnosis and treatment.

SLE is one of the most common causes of severe glomerulonephritis in children and young adults. Aggressive chemotherapy is required to rescue renal function, and sometimes RRT is essential before renal function can recover. Of the 32 patients with SLE, 12 recovered completely, 13 died in the hospital, and 7 developed chronic renal failure and died. SLE cases were classified differently from other CGN cases, because such cases have more-severe glomerulonephritis and disease progression is rapid. In this study, however, we found that SLE cases had similar outcomes, compared with other causes of CGN (classified here as CGN).

Malignancies, such as leukemia, lymphoma involving the kidneys, neuroblastoma, and Wilms' tumors, and nephrotoxic chemotherapy were less common than sepsis. However, children with malignancies tend to develop sepsis, particularly during chemotherapy. If such malignancies that cause mass effects resulting in kidney, ureter, and bladder obstruction are corrected in a timely way, such as through surgical intervention or percutaneous nephrostomy, then favorable outcomes can be expected. In this study, there were 2 episodes of tumor lysis syndrome and 3 cases of obstructive uropathy, of which all had favorable outcomes (the obstructive nephropathy cases were classified in the miscellaneous group).

Nephrotoxic ARF commonly is associated with aminoglycoside.12 In our study, aminoglycoside-related ARF was not found. However, because methods to differentiate between aminoglycoside-related ARF and sepsis are not available in general practice, sepsis is normally given as the cause of ARF; therefore, this failure to note any such cases is to be expected and cannot be interpreted to mean that the condition was not present. In fact, ARF may result from a combination of factors with additive effects that lead to renal injury, such as sepsis with aminoglycoside, congestive heart failure with enalapril, or SLE with sepsis.

RRT was administered to patients with severe ARF who were unable to maintain fluid and electrolyte balance. We did not compare mortality rates between patients with and without RRT, because there was concern about selection bias. Normally, dialysis is the last modality of treatment for ARF with volume load or metabolic disturbances. Therefore, patients who received dialysis were likely to have severe ARF, and the mortality rate would be expected to be higher in this group. This means not that RRT is a poor procedure but that RRT is a rescue procedure when renal failure occurs; RRT is the most important procedure for bridging the time needed for recovery. In this study, peritoneal dialysis saved more than one third of the patients who required it (20 of 52 patients, 38%).

We again emphasize that our institution is a tertiary referral center, where most patients who are referred have severe medical or surgical conditions. The overall mortality rate in our series was 41.5%, which is comparable to results from studies in both developing and developed countries.13–21 Williams et al4 reported that a large number of nonsurviving ARF cases were found in the postcardiac surgery groups in the 2 decades they surveyed (1979–1988 and 1989–1998). They found that younger patients had poorer prognoses but sepsis-attributable ARF was significantly less prevalent in the second decade (3%, compared with 23%; P < .001). The data from our study are not directly comparable to the data from the study by Williams et al,4 because we are not a well-established cardiac center. Sepsis was a major cause of ARF in each era, with the sepsis mortality rates not improving, although antibiotics certainly advanced during this time. However, mortality rates for ARF do not always directly reflect the quality of treatment, because disease cause seems to be the most important risk factor.

The cause of ARF changed during the 22-year period of our study (Table 2) and the mortality rate generally improved, although not significantly. In our hospital, the RRT rate has not increased, which suggests that RRT does not have any effect on the mortality rate. RRT is not a treatment of choice, because it is known that RRT is not essential in all ARF cases. Supportive treatment usually plays the most important role.

In Thailand, the past decade has seen much improvement in transportation; however, there are various factors to consider and we could not determine whether this improvement would have a positive or negative effect on our findings. Better transportation would increase the number of cardiac cases referred to institutions where the patients would have a better chance of survival, but the ability of patients, particularly severely debilitated children, to travel long distances also might affect mortality rates in our institution. Mortality rates could increase because of the increasing number of cardiac surgical procedures performed or could decrease because of improved treatment.

At least 2 studies reported that patients <1 year of age had higher mortality rates,22,23 but this was not seen in our study. The reasons for this difference likely involved the different causes of ARF and probably also the severity of the condition; one half of the patients in our group had serum creatinine concentrations of 1 to 2 mg/dL, which indicates that overall our patients' ARF was less severe.

Usually ARF is a secondary problem following the failure of other organs, rather than resulting from original renal disease. Usually, when the primary problem is treatable, the ARF also has an excellent outcome with appropriate care, with or without RRT.8 For patients with multiorgan failure, mortality rates are very high, even with RRT,1,4,10,24,25 being >50% for patients with failure of 3 organs in at least 1 study.25

ARF itself is not a fatal condition, because RRT is advanced in this era,26 but timing is a major consideration. The best way to avoid the condition is prevention, followed by early detection, then conservative treatment, and finally referral to an institution where RRT is available. However, problems with other vital organs (ie, brain, heart, lung, or liver) also influence the outcome if these problems are not correctable.18 It is anticipated that RRT and ICU care will continue to advance, which should improve the outcomes of ARF cases, but we must consider the fact that congenital heart disease surgery and oncologic treatments are also advancing, which will increase the number of cases and complications. ARF related to other systemic diseases occurs more frequently than ARF attributable to primary renal disease; therefore, advances in treating the condition, with reductions in mortality rates, may well be offset by an increased number of cases resulting from secondary causes. In this study, the cause of ARF was significantly associated with age and with the resultant mortality rate5,21,25 but the mortality rate itself was not related directly to age,4,11,16 that is, there was a strong association between cause and age group and also mortality rates; however, age was not an independent predictor of mortality rates.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
The incidence of ARF in Songklanagarind Hospital was found to be 0.5 to 9.9 cases per 1000 pediatric patients, with a mortality rate of 41.5%. Sepsis was a major cause of ARF and death. Causes of ARF and serum creatinine levels were significant independent predictors of mortality rates. The rate of ARF has increased over the years, although the mortality rate has not improved significantly; this is a problem we should be addressing.


   FOOTNOTES
 
Accepted Apr 10, 2006.

Address correspondence to Prayong Vachvanichsanong, MD, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, Thailand. E-mail: vprayong{at}msn.com

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics

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