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Q J Med 1992; 83: 461-471
© 1992 Association of Physicians

research-article

The Immunogenetics of Early Nephropathy in Insulin-dependent Diabetes Mellitus: Association Between the HLA-A2 Antigen and Albuminuria

GF WATTS, N TAUB, V GANT, I WILSON* and KM SHAW{dagger}

Departments of Endocrinology and Chemical Pathology, Public Health Medicine and Microbiology, St. Thomas's Hospital Medical School UMDS, London SE1 7EH *Tissue Typing Laboratory, Wessex Regional Transfusion Centre Coxford Road, Southampton SO9 5UP {dagger}Department of Medicine, Queen Alexandra Hospital Cosham, Portsmouth PO6 3LY

Accepted for publication 23 April 1992.

One-hundred and seventy-two normotensive, insulin-dependent diabetic patients without clinical proteinuria (Albostix negative) were typed for the major histocompatibility complex class 1 (HLA-A, -B) and class II (HLA-DR)antigens. Urinary albumin excretion was measured as the albumin: creatinine ratio (UA/UC, mg/mmol) in an early morning sample. Patients expressing the HLA-A2 antigen had significantly higher UA/UC values than those not expressing the antigen. The observed ratio of geometric means was 1.77 (95 per cent confidence interval (CI) 1.18–2.67; p<0.01); the relative risk of microalbuminuria (UA/UC>3.0 mg/mmol) associated with expression of H LA-A2 was 2.52 (95 per cent CI 1.11–5.73; p<0.05). There was no significant association between UA/UC and HLA-B8, -B15, -DR3, -DR4 or other antigens. Patients were re-studied after a mean period of 5.3 years: multiple linear regression analysis showed that the UA/UC at this time was positively related to the initial glycosylated haemoglobin level (p<0.01) and expression of the HLA-A2 antigen (p<0.05), but not to blood pressure or creatinine clearance. Fifteen patients developed macroalbuminuria at follow-up (UA/UC>45.5 mg/mmol). Compared with a group matched for age, sex, duration of diabetes, and glycosylated haemoglobin who did not develop macroaminuria, macroalbuminuric patients had a higher frequency of HLA-A2 (p<0.01). The odds ratio of progressing to macroalbuminuria associated with HLA-A2 had a 95 per cent CI of 1.71 to infinity. We conclude that an immunogenetic factor may play a role in the development of early diabetic nephropathy and that the risk associated with expression of the HLA-A2 antigen is independent of metabolic control and blood pressure.


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