High levels of immunoglobulin M (IgM) in the urine of diabetic patients may predict development of end-stage renal disease (ESRD) and death from cardiovascular disease (CVD), independent of albuminuria, a small study suggests.

Omran Bakoush MD, PhD, of the University Hospital of Lund in Sweden, and colleagues studied 139 patients with type 1 diabetes who regularly visited the Lund University Hospital’s diabetes outpatient clinic between 1984 and 2003. The patients’ average age at enrollment was 35 years. The investigators followed patients until October 2007 or death, whichever came first. During follow-up, ESRD developed in 20 patients, 32 died from a cardiovascular event, and six died from other causes.

The investigators divided the patients into those with low IgM (mean urine IgM level of 0.0055 mg/mmol) and those with high IgM (mean urine IgM level of 0.258 mg/mmol).

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The risk of developing ESRD was 2.2% per patient-year in individuals with high IgM levels compared with 0.35% among those with low IgM levels, which corresponds to a 6.4 times increased risk of developing ESRD associated with high IgM levels.

The risk of dying from a cardiovascular event was 2.1% per patient-year among individuals with microalbuminuria and high IgM excretion levels compared with 0.46% among those with microalbuminuria and low IgM levels, according to a report in BMC Medicine (2009;7:39). This translates into a 4.6 times higher risk of a cardiovascular death among subjects with high IgM levels.

In addition, patients with macroalbuminuria and high urine IgM excretion had a higher risk for cardiovascular mortality (4.8%  per patient-year) than those with low IgM excretion (1.7%  per patient-year).

Dr. Bakoush’s previous research on other kidney diseases supports these findings. The severe glomerular damage due atherosclerosis causes increased escape of large proteins such as IgM into the urine. That is why increased urine IgM excretion associated with severe diabetic complication and increased cardiovascular mortality.