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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.

High--resolution two--dimension electrophoresis technique for protein with silver staining was used to characterise urinary high density lipoprotein (HDL)--apolipoproteins. Sequential ultracentrufugation method was used to isolate urinary lipoprotein particles of the same density as serum HDL. Immunostaining of electroblotted proteins further confirmed the presence of HDL--Apos in urine. HDL--Apolipoprotein A--1, A--11 and C were identified in urine of normal subjects, diabetic patients and patients with biopsy proven glomerular proteinuria. An in-house ELISA method was used to quantify urinary HDL--Apo A--1. Selectivity indices were also determined. A high degree of association was found between selectivity index and urinary HDL--Apo A--1 (r = 0.87) and also between HFL--APO A--1 loss/24 h and total protein loss/24 h (r = 0.91). This appear to indicate that HDL loss in urine was a function of glomerular selectivity. Urinary HDL--Apo A--1 levels were significantly raised in the patients with glomerular proteinuria (p less than 0.01). HDL--Apo A--1 levels appear to be a marker for glomerular proteinuria. Consistent with glomerular proteinuria serum lipids and protein loss were significantly higher in patients with glomerular proteinuria (p less than 0.001) but HDL--Cholesterol was lower (p less than 0.001).