Urinary excretion rate of NC1 and Tamm-Horsfall protein in the microalbuminuric type I diabetic patient

Abstract

Fifty-six type I diabetic patients with microalbuminuria (albumin excretion rate 20–200 μg/min) were characterized as to sex, age, duration of diabetes, smoking habits, blood pressure, glomerular filtration rate, urinary NC1 (the carboxy-terminal domain of collagen IV), and Tamm-Horsfall protein excretion rate. Albumin excretion rate was considered a sign of glomerular damage, NC1 excretion rate a measure of renal basement membrane turnover, and Tamm-Horsfall protein excretion rate a marker for distal tubular function. There were no differences between males and females and between smokers and nonsmokers with respect to blood pressure, body-mass index, albumin excretion rate, glomerular filtration rate, excretion rate of NC1, and Tamm-Horsfall protein. As a group, the patients with microalbuminuria had normal glomerular filtration rate, excretion rate of NC1, and Tamm-Horsfall protein. The latter was influenced by glycosylated hemoglobin (HbA 1c) levels, especially so in patients with an albumin excretion rate less than the median value of 53.0 μg/min ( r = −0.61, p < 0.01). Furthermore, both excretion rate of NC1 and Tamm-Horsfall protein were increased in patients with high glomerular filtration rate ≥130 mL min −1 1.73 m −2). There was no association between glomerular filtration rate and HbA 1c levels. As glomerular filtration rate is related to kidney size, these observations suggest that patients with a high glomerular filtration rate have an increased mass and turnover of tubular basement membrane. Because high glomerular filtration rate has been suggested to be a predictor for the development of clinical nephropathy it may be suggested that changes in excretion rate of NC1 and/or Tamm-Horsfall protein may reflect important pathogenic mechanisms for the development of nephropathy. Furthermore, a low Tamm-Horsfall protein excretion rate in patients with poor metabolic control and with an albumin excretion rate in the lower range of microalbuminuria may indicate an early and potentially reversible tubular dysfunction.