Risk of chronic kidney disease in children who developed acute kidney injury secondary to nephrotoxic medication exposure in infancy

Figures & data

Figure 1. shows the flow chart of the study population recruitment. Of 466 eligible participants, 18 cases and 30 controls were enrolled for the study.

Table 1. Demographic characteristics by AKI status.

	AKI (N = 18)	Non-AKI (N = 30)	p value
Gestation age (weeks), median (IQR)	25 (24–30)	29 (24–36)	0.39
Birth weight (grams), median (IQR)	695 (595–1657)	1040 (628–2342)	0.32
Post-conception age of first NTM exposure (weeks), median (IQR)	32 (26–38)	35 (30–42)	0.10
NTM exposure days, median (IQR)	14 (7–26)	7 (5–14)	<0.05
NTM category, n (%)			0.60
Vancomycin (V)	2 (11.1%)	4 (13.3%)
Aminoglycoside (A)	6 (33.3%)	15 (50%)
Vancomycin + Aminoglycoside (VA)	8 (44.4%)	8 (26.6%)
Vancomycin + Aminoglycoside + other NTM meds (VA + 1)	2 (11.1%)	3 (10%)
Age at follow up (years), median (IQR)	5 (3.7–5)	5 (4–6)	0.35
Height (cm) at follow up, median (IQR)	110.5 (100–115)	105.5 (98–111)	0.23
Sex			0.33
Female, n (%)	7 (39%)	16 (53.3%)
Male, n (%)	11 (61%)	14 (46.7%)
Race			0.55
Black, n (%)	11 (61%)	15 (50%)
White, n (%)	7 (39%)	15 (50%)
Apgar score at 5 minutes, median (IQR)	6 (6-9)	7 (5–8)	0.90
Surgical NEC, n (%)	7 (38.8%)	5 (16.6%)	0.10
Small for gestation age, n (%)	2 (11.1%)	4 (13.3%)	1.0
PDA needing intervention, n (%)	1 (5.5%)	6 (20%)	0.23
CLD (oxygen dependence at the time of follow up), n (%)	0	6 (20%)	0.07
Maternal hypertension, n (%)	4 (22.2%)	10 (33.3%)	0.52
Maternal Diabetes, n (%)	0	4 (13.3%)	0.28

Continuous values are reported as median with interquartile range and categorical values are reported as proportion/percentage (%).

NTM: nephrotoxic medication; AKI: acute kidney injury; NEC: necrotizing enterocolitis, PDA: patent ductus arteriosus, CLD (chronic lung disease); V: Vancomycin with or without other NTM, other than Aminoglycoside; A: Aminoglycoside with or without other NTM, other than Vancomycin; VA: Vancomycin and Aminoglycoside exposure; VA + 1: Other NTM medication exposure in addition to Vancomycin and Aminoglycoside.

Table 2. Clinical outcome by AKI status.

Primary Outcome n (%)	AKI (N = 18)	Non- AKI (N = 30)	p value
Composite CKD Outcome	11 (61.1%)	14 (46.6%)	0.33
eGFR <90 ml/min/1.73 m^2	4 (22.2%)	5 (16.6%)	0.63
Random UPCR >0.2 (mg/mg)	8 (44.4%)	9 (31%) *	0.31
SBP and or DBP >95^th	1 (5.5%)	0
SBP			0.14
SBP < 90^th	16 (89%)	30
SBP between 90^th–95th	1 (5.5%)	0
SBP >95^th	1 (5.5%)	0
DBP			0.24
DBP <90^th	15 (83.3%)	28 (96.5%)
DBP between 90^th–95^th	2 (11.1%)	1 (3.4%)
DBP >95^th	1(5.5%)	0
Continuous Outcome
Median (IQR)
eGFR (ml/min/1.73 m^2)	98.1 (89.7–104.4)	101.4 (92.7–113.2)	0.25
UPCR (mg/mg)	0.17 (0.12–0.3)	0.15 (0.110.23)	0.30
Average SBP (mm Hg)	91 (82-96)	91 (83-97)	0.95
Average DBP (mm Hg)	57 (53–59)	54 (51–59)	0.21
Urine KIM^-1(ng/dl)	13.4 (3–25.7)	27.6 (5.9–39.7)	0.057
UKC (ng/mg)	0.197 (0.110–0.474)	0.366 (0.226–0.59)	0.12

Primary outcome is reported as proportion/percentage (%) and the continuous outcome is reported as median with an interquartile range.

*n = 29 in non-AKI group.

AKI: Acute kidney injury; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate is defined by CKiD-U25 equation based on serum creatinine and cystatin C, SBP: systolic blood pressure; DBP: diastolic blood pressure; UPCR: urine Protein Creatinine ratio; UKC: urine kidney injury molecule-1 creatinine ratio.

Table 3. Baseline characteristics by composite primary outcome (CKD).

	CKD (N = 25)	No CKD (N = 23)	p value
History of NTM-AKI, n (%)	11 (44%)	7 (30%)	0.33
Gestation age (weeks), median (IQR)	29 (24–37)	27 (24–31)	0.72
Birth weight (grams), median (IQR)	840 (617–2630)	950 (595–1560)	0.45
Post-conception age of first exposure (weeks), median (IQR)	37 (28–43)	33 (29–38)	0.62
NTM exposure days, median (IQR)	7 (4–23)	12 (6–17)	0.74
NTM category, n (%)			0.32
Vancomycin (V)	5 (20%)	1 (4.3%)
Aminoglycoside (A)	9 (36%)	12 (52%)
VA	8 (32%)	8 (34%)
VA + 1	3 (12%)	2 (8.6%)
Age at the time of follow-up (Years), median (IQR)	5 (3–5)	4 (4–5)	0.41
Sex			0.55
Female, n (%)	13 (52%)	10 (43.5%)
Male, n (%)	12 (48%)	13 (56.5%)
Race			0.36
Black, n (%)	12 (48%)	15 (65%)
White, n (%)	13 (52 %)	8 (35%)
Height (cm) at follow-up, median (IQR)	105 (94–112)	108 (103.5–116)	0.06
AKI events, median (IQR)	0 (0–1)	0 (0–1)	0.45
AKI days, median (IQR)	0 (0–2.5)	0 (0–1)	0.30
Apgar score at 5 minutes, median (IQR)	8 (6–8)	7 (5–8)	0.44
NEC with surgical intervention, n (%)	6 (24%)	6 (26%)	0.86
PDA receiving intervention, n (%)	7 (100%)	0	0.006
Small for gestation age, n (%)	2 (8%)	4 (17%)	0.32
CLD (oxygen dependence at the time of follow up), n (%)	4 (16%)	2 (8.6%)	0.44
Maternal hypertension, n (%)	5 (20%)	9 (39%)	0.25
Maternal Diabetes, n (%)	2 (4%)	2 (8.6%)	0.93

Continuous values are reported as median with interquartile range, and categorical values are reported as proportion/percentage.

CKD- chronic kidney disease, NTM- nephrotoxic medication, PDA- patent ductus arteriosus, NEC- necrotizing enterocolitis, CLD- chronic lung disease.

Table 4. Comparison of studies looking at CKD risk in children with a history of AKI during infancy.

Study	Type of AKI	Median age of follow up (years)	Number of AKI patients	CKD in AKI group	eGFR less than 90 ml/min per 1.73 m^2	Proteinuria/ microalbuminuria	Hypertension	Median urinary KIM-1/Creatinine ratio (ng/mg)
Ameta et al.	AKI after NTM exposure	5	18	61%	22%	44%	5.5% (>95^th percentile)	0.197 (0.110–0.474)
Harer et al. (2017)	AKI in VLBW infants	5	20	65%	20%	20%	10% (>95^th percentile)	NA
Cooper et al. (2016)	AKI after cardiopulmonary bypass surgery	7.9	33	NA*	14.3% (n = 21)	3.9% (n = 26) (microalbuminuria)	14% (n = 28) (>90^th percentile)	0.619 (0.437–0.728) (n = 30)
Abitbol et al. (2003)	AKI in ELBW infants	6.6	20	85%	45%	93.5% (n = 16)	10%	NA

NA*- Information not available in the publication.

NA: Not applicable.