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Background Augmented renal clearance (ARC) refers to a condition where there is an increased elimination of renal solutes, presenting notable challenges in the Pediatric Intensive Care Unit (PICU). This phenomenon can have a significant impact on various aspects of patient care, such as medication dosing, treatment effectiveness, and overall clinical outcomes. In clinical practice, managing ARC necessitates close monitoring and individualized approaches tailored to each patient's unique renal status. ARC is associated with suboptimal exposure to critical medications, particularly hydrophilic antibiotics including ß-lactams, Vancomycin, Aminoglycosides leading to treatment failure and development of resistance. Mechanisms for ARC in critically ill patients are incompletely defined. Aggressive fluid resuscitation, presence of SIRS, capillary leak, use of vasopressors and inotropes, neuro hormonal changes, activation of renal functional reserve in young individuals lead to increase in renal perfusion and increase in GFR. Objectives of the Study was to Assess magnitude and associated clinical and demographic factors of augmented renal clearance in PICUs of TASH and ALERT Hospitals in Addis Ababa, and to assess practice of antimicrobial prescription in patients with augmented renal clearance
We conducted a prospective Follow up cross sectional study on patients admitted to PICUs of two tertiary hospitals in Addis Ababa from July 2024 - December 2024. ARC was assessed by measuring serum creatinine levels and calculating estimated glomerular filtration rate (eGFR) using the modified Schwartz formula during the first three days of PICU admission. Correlation analysis was done to assess conditions associated with ARC. Mann witney U test, independent samples t-test and one way ANOVA tests were done to compare different variables in relation to ARC. Logistic regression analysis was used to determine risk factors for ARC and death at day7 of PICU admission.
This study examined the incidence and associated factors of augmented renal clearance (ARC) among 170 pediatric patients admitted to the Pediatric Intensive Care Units (PICUs) of two hospitals: TASH and ALERT. The cohort comprised 105 males and 65 females, with 108 patients admitted to TASH and 62 to ALERT. During the first three days of PICU admission, 66 patients (38.8%) experienced at least one documented episode of ARC. Of 438 serum creatinine measurements, 112 were indicative of ARC. Patients experiencing ARC exhibited a median estimated glomerular filtration rate (eGFR) that increased over the first three days of PICU admission: 108.59 mL/min/1.73m² on day one, 115.8 mL/min/1.73m² on day two, and 185.9 mL/min/1.73m² on day three. A statistically significant positive correlation was observed between eGFR and total fluid input on day one. Furthermore, specific diagnoses including febrile neutropenia, brain tumors, and admissions for surgical interventions were significantly associated with the occurrence of ARC. A Mann-Whitney U test revealed that patients without any record of ARC within the initial three days demonstrated significantly lower values for age, weight, height, and body surface area (BSA) compared to those with ARC. Older age, greater BSA, and the presence of febrile neutropenia, hematologic malignancies, brain tumors, and admission for surgical reasons were each independently associated with an elevated risk of ARC. Furthermore, higher PHOENIX scores, vasopressor use, hypotension and febrile neutropenia were associated with increased mortality by day seven of PICU admission.
Table 1 Patient characteristics
ARC
No ARC
P-value
Age, years; medianQ1-Q3(0.5-5)
2.58(0.915-7.5)
1(0.33-4)
0.003
Gender
Female
19
45
0.076
Male
46
60
Weight(kg),median(Q1-Q3)
12(8.4-17)
8(5-14)
0.001
Height(cm), median(Q1-Q3)
90(71-112.5)
74(56-99.5)
Body Surface area, median(Q1-Q3)
m2
0.54(0.395-0.74)
0.41(0.285-0.61)
Admission Category
Medical
37
74
Surgical
28
26
0.023
Trauma
0
5
Phoenix score, median(Q1-Q3)
3(2-4.5)
2.86(1-4)
0.827
Length of PICU stay(day), median(Q1-Q3)
6(3-7)
4(2-6.71)
0.032
Number of death(%)
19(42)
26(57.8)
<0.001
Total input(mL), median(Q1-Q3)
2872(1818-4340))
2465(1624-3753))
Antibiotic therapy
65(38.9)
102(61.1)
Duration of Antimicrobial therapy(days), median(Q1-Q3)
10(6-14)
10(6.75-14)
Mechanical ventilation
30(42.2)
41(57.8)
eGFR, Median(Q1-Q3)
Day1
108.59(80.035-133.6)
70.04(50-83.82)
Day2
115.8(90.517-171.175)
69.1(51.80-88.75)
Day3
185.90(122.46-272.58)
74.78(54.5-88.93)
Patients treated with meropenem(%)
29(41.4)
41(58.6)
Patients treated with Vancomycin(%)
36(40.9)
52(59.1)
The magnitude of ARC in our setting is high. Early recognition and dosing adjustments can improve outcomes in critically ill pediatric patients. Factors like age and laboratory markers influence ARC development, emphasizing the need for routine monitoring in high-risk groups. Personalized medicine is crucial in PICU care, with potential for future studies on dosing algorithms and risk factors. Clinical guidelines based on these findings can enhance care for vulnerable patients.
