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

Objective. 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? Material and methods. 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. Results. 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. Conclusion. 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.

• Albuminuria
• diabetic nephropathy
• death
• cardiovascular death
• tubular dysfunction
• Tamm–Horsfall protein
• uraemia