Elevated Urinary ApoAI in Renal Disease

Computer rendering of a glomerulus in the kidney.
Levels are particularly high in proximal tubulopathies.

Children with kidney disease, especially children with diseases affecting proximal tubules, have increased levels of urinary apolipoprotein AI (apoAI), according to results published in Pediatric Nephrology. The study adds to emerging evidence of apoAI’s role in the kidney.

“Urine apoAI is particularly elevated in proximal tubulopathies, dysplasia, and proteinuric glomerular disease, but only modestly parallels the magnitude of albuminuria,” said Valentina Kon, M.D., Margaret T. and H. Laird Smith Chair and professor of pediatrics at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

Nine disease entities were represented in the study, including nephrolithiasis, tubulopathy, polycystic kidney disease (PCKD), congenital anomalies of kidney and urinary tract (CAKUT), glomerulonephritis (GN), transplant, nephrotic syndrome (NS) relapse, NS remission and hypertension.

“Urine apoAI is particularly elevated in proximal tubulopathies, dysplasia, and proteinuric glomerular disease, but only modestly parallels the magnitude of albuminuria.”

ApoAI Elevation

The study enrolled 228 participants between the ages of three and 18 seeking care in the Vanderbilt Pediatric Nephrology Clinic, plus an additional 40 healthy participants from a general pediatric setting.

Levels of urinary apoAI in the clinic patient cohort were elevated compared to the control group (median 0.074 versus 0.019 μg/mg), with levels varying among the different diseases. While urinary apoAI levels were higher in patients with tubulopathies, renal dysplasia/CAKUT, GN and NS in relapse, apoAI levels were consistent with controls in patients with nephrolithiasis, PCKD, transplants, NS in remission, PCKD or hypertension.

Disease Distinctions

Of particular interest to Kon was the difference in urinary apoAI levels between proximal versus distal tubulopathies.

“Within the tubulopathy group, patients with disorders principally affecting proximal tubules, including Fanconi syndrome, Dent disease, Lowe syndrome, and cystinosis, had higher urinary apoAI levels than patients with primarily distal tubule dysfunction including distal renal tubular acidosis, diabetes, insipidus and Bartter syndrome,” she said.

Kon also notes that urinary apoAI levels were elevated for diseases with disruption of the glomerular filtration barrier (i.e. GN and NS), yet apoAI levels did not always correlate with albumineria, a marker of glomerular dysfunction. Within the NS relapse group, although patients with minimal change disease (MCD) and focal and segmental glomerulosclerosis (FSGS) showed a comparable degree of albuminuria, FSGS patients had significantly higher urinary apoAI levels than those with MCD. The findings suggest there may be distinct pathways for tubular uptake of albumin and apoAI.

The study also found irregular, high molecular weight forms of urinary apoAI in patients with certain renal diseases, particularly patients with FSGS in relapse.

A Biomarker of Renal Disease

Previous research has reported an increase in urinary excretion of apoAI as a result of proximal tubular reabsorption failure from Fanconi syndrome. The authors indicate that increased urinary apoAI observed in their latest study may be due to acquired and chronic progressive kidney damage involving disruption in the glomerular filtration barriers and/or the proximal tubules.

The research points to the idea that urinary apoAI may serve as a biomarker. “These findings suggest the potential utility of measuring urinary apoA1 to identify abnormal renal handling of lipoproteins and reflecting renal disease,” Kon said.