Higher soluble ICAM-1 levels may predict progressive nephropathy

In type 1 diabetes, higher soluble intercellular adhesion molecule 1 levels were associated with an increased risk for progressive nephropathy, according to study findings.

Researchers measured levels of high-sensitivity C-reactive protein, soluble ICAM-1, soluble vascular cell adhesion molecule 1 and soluble tumor necrosis factor alpha receptor 1 in stored blood samples from participants (n=1,441) of the Diabetes Control and Complications Trial.

They determined the average annual change in urinary albumin excretion rate by tertiles of each biomarker and estimated the RR for incident-sustained microalbuminuria according to levels of each biomarker.

After adjustment, there was an increase in albumin excretion rate of 5.9 mcg/minute^–1/year^–1 for participants in the highest tertile compared with participants in the lowest tertile of baseline soluble ICAM-1 (P=.04).

Participants in the highest tertile of soluble ICAM-1 had an adjusted RR of 1.67 (95% CI, 0.96-2.92) for developing incident-sustained microalbuminuria, according to the researchers.

“Higher baseline plasma ICAM-1 was independently associated with increasing albumin excretion rate over time as well as with incident-sustained microalbuminuria in type 1 diabetes,” the researchers wrote.

“These findings suggest that inflammation and endothelial dysfunction play important roles in progressive nephropathy in type 1 diabetes and that soluble ICAM-1 may be a potential early biomarker that would allow for risk stratification of patients,” they wrote. – by Christen Haigh

Diabetes Care. 2008;31:2338-2343.

Lin et al reported baseline HbA1c was significantly associated with high-sensitivity CRP and soluble ICAM-1. Diabetes duration was associated with high-sensitivity CRP, soluble tumor necrosis factor alpha receptor 1 and soluble ICAM-1. There was also an association between baseline albumin excretion rate and soluble ICAM-1 tertiles. Change in albumin excretion rate was not associated with CRP but was associated with soluble ICAM-1, and this was still a factor when baseline albumin excretion rate was taken into account and when the treatment group (intensive vs. control) was taken into account. However, the researchers did not mention whether on-trial HbA1c removed the significance of the soluble ICAM-1 effect, and it well might. Nevertheless, this is a somewhat interesting hypothesis-generating paper that suggests a relationship between a marker of vascular inflammation and albuminuria. That is certainly something we expect to be the case, particularly as (to some extent, and at least in some patient groups) albuminuria is a marker of generalized endothelial dysfunction rather than just of renal glomerular disease.

– Zachary T. Bloomgarden, MD

Endocrine Today Editorial Board member