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Urinary apolipoprotein AI in children with kidney disease
Amanda J Clark1, Kathy Jabs2, Tracy E Hunley2
1Department of Pediatrics, Monroe Carrell Children's Hospital at Vanderbilt, Nashville, TN, USA.
Insights
Urinary apolipoprotein AI (apoAI), a high-density lipoprotein (HDL) component, is elevated in children with kidney disease, particularly in conditions affecting proximal tubules like focal segmental glomerulosclerosis (FSGS). Abnormal apoAI isoforms are also observed in these patients.
Area of Science:
- Nephrology
- Cardiovascular Research
- Biochemistry
Background:
- High-density lipoprotein (HDL) plays roles in various cell types within the cardiovascular system.
- The function and presence of HDL, specifically apolipoprotein AI (apoAI), in the kidney remain largely uncharacterized.
Purpose of the Study:
- To investigate the urinary excretion of apolipoprotein AI (apoAI) in children with kidney disorders.
- To determine if urinary apoAI levels correlate with specific kidney diseases and identify associated apoAI isoforms.
Main Methods:
- Collected urine samples from 228 children with kidney diseases and 40 controls.
- Measured urinary apoAI and albumin using ELISA.
- Analyzed apoAI isoforms via Western blot and examined renal biopsies for apoAI distribution.
Main Results:
- Children with kidney disease exhibited significantly higher urinary apoAI levels compared to controls (p < 0.001).
- Elevated apoAI was most pronounced in tubulopathies, renal dysplasia, glomerulonephritis, and nephrotic syndrome (NS) in relapse.
- Focal segmental glomerulosclerosis (FSGS) was associated with increased high molecular weight (HMW) apoAI isoforms and specific apoAI staining patterns in renal biopsies.
Conclusions:
- Urinary apoAI excretion varies in pediatric kidney diseases, with notable elevations in conditions impacting proximal tubules.
- The presence of abnormal HMW apoAI isoforms, particularly in FSGS, suggests a potential role in renal pathology.
- Further research is needed to ascertain whether altered urinary apoAI serves as a marker or contributes to kidney disease progression.
Background:
Although high-density lipoprotein (HDL) modulates many cell types in the cardiovascular system, little is known about HDL in the kidney. We assessed urinary excretion of apolipoprotein AI (apoAI), the main protein in HDL.
Methods:
We enrolled 228 children with various kidney disorders and 40 controls. Urinary apoAI, albumin, and other markers of kidney damage were measured using ELISA, apoAI isoforms with Western blot, and renal biopsies stained for apoAI.
Results:
Patients followed in nephrology clinic had elevated urinary apoAI vs. controls (median 0.074 μg/mg; interquartile range (IQR) 0.0160-0.560, vs. 0.019 μg/mg; IQR 0.004-0.118, p < 0.001). Patients with tubulopathies, renal dysplasia/congenital anomalies of the kidney and urogenital tract, glomerulonephritis, and nephrotic syndrome (NS) in relapse had the greatest elevations (p ≤ 0.01). Patients with NS in remission, nephrolithiasis, polycystic kidney disease, transplant, or hypertension were not different from controls. Although all NS in relapse had higher apoAI excretion than in remission (0.159 vs. 0.0355 μg/mg, p = 0.01), this was largely driven by patients with focal segmental glomerulosclerosis (FSGS). Many patients, especially with FSGS, had increased urinary apoAI isoforms. Biopsies from FSGS patients showed increased apoAI staining at proximal tubule brush border, compared to diffuse cytoplasmic distribution in minimal change disease.
Conclusions:
Children with kidney disease have variably increased urinary apoAI depending on underlying disease. Urine apoAI is particularly elevated in diseases affecting proximal tubules. Kidney disease is also associated with high molecular weight (HMW) apoAI isoforms in urine, especially FSGS. Whether abnormal urinary apoAI is a marker or contributor to renal disease awaits further study.
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