Proteinuria and Activated T-Lymphocytes in Diabetic Nephropathy

The reasons for the presence of activated T-lymphocytes (ATL) in some long-standing insulin-dependent diabetic (IDDM) patients are unknown. These cells have been implicated in the genesis of proteinuria in some forms of immune-mediated renal disease. We measured ATL in 18 IDDM patients with diabetic nephropathy, 10 with nonnephrotic proteinuria (total urinary protein excretion rate >0.5 and <3.5 g/24 h) and 8 with nephrotic proteinuria (total urinary protein excretion rate > 3.5 g/24 h), and in 17 age-, sex-, and duration-of-diabetes–matched diabetic control subjects without clinical proteinuria (total urinary protein <0.5 g/24 h). T-lymphocytes purified from peripheral blood were stained by direct immunofluorescence with the fluorescein-labeled monoclonal antibody anti-HLA-DR. Absolute number and percent of DR-positive T-lymphocytes were significantly higher in patients with nonnephrotic proteinuria (median and range 162 × 10⁶/ml, 40–320 × 10⁶/ml; 13.9%, 8.1–19.4%) compared with nonproteinuric control subjects (81 × 10⁶/ml, 2–240 × 10⁶/ml, P < .05; 6.2%, 0–13.1%, P < .01). In 8 patients with nephrotic proteinuria, absolute and percent DR-positive T-lymphocytes tended to be lower (36 × 10⁶/ml, 14–56 × 10⁶/ml; 3.4%, 1.1–5.4%) than in nonproteinuric control subjects. An increased number of activated T-lymphocytes may be part of an immune-mediated process associated with the development of proteinuria in diabetic nephropathy. In advanced renal disease with nephrotic proteinuria, this immune process may become exhausted.