Decreased urinary concentration of Tamm–Horsfall protein is associated with development of renal failure and cardiovascular death within 20 years in type 1 but not in type 2 diabetic patients

Abstract

The first changes in the diabetic kidney are glycogen deposits in the epithelial cells of the thick ascending limb of Henle. These cells produce Tamm-Horsfall protein (THP). Is low excretion of THP associated with the development of renal insufficiency or cardiovascular disease? Urine samples were collected at baseline in patients with type 1 (n = 131) and type 2 (n = 108) diabetes who were followed for a mean of 14 years (range 1-20 years) and 4.5 years (range 1-15 years), respectively. Twenty percent of type 1 and 54% of type 2 diabetic patients died and 24% and 29%, respectively developed uraemia. A decreased urinary concentration of THP (u-THP) was associated with an eight-fold increased risk of renal failure and cardiovascular death in type 1 but not in type 2 diabetic patients, irrespective of the degree of albuminuria and glycosylated haemoglobin and blood pressure levels. There were no differences in the degrees of albuminuria, serum creatinine or u-THP between the two types of diabetic patients at baseline. Low u-THP occurred in 8% and 9% of normoalbuminuric type 1 and type 2 diabetic patients, respectively. A decreased u-THP was associated with an eight-fold increased risk of cardiovascular death and uraemia in type 1 but not in type 2 diabetic patients.