Tubular injury: the first symptom of hypertensive kidney involvement?

Tubular injury is an important component of hypertensive nephropathy, but its pathogenesis is not completely clear. We attempted to determine whether tubular injury precedes glomerular involvement, and to evaluate the role of vascular damage and metabolic disturbances in this process.

25 patients with newly diagnosed primary non-treated hypertension without microalbuminuria were studied. 15 healthy volunteers served as controls. We measured total urine activity of N-acetyl-beta-D-glucosaminidase (NAG) as a marker of tubular injury, albumin excretion, serum concentrations of insulin, uric acid and lipids. Intravenous glucose tolerance tests and oral fructose loading tests were performed to assess carbohydrate and purine metabolism. The plasma glucose area (PGA) under the curve of glucose levels obtained from the former test was calculated, as well as the plasma uric acid area (PUAA) under the curve of uric acid levels from the latter. Hypertensive vascular injury was investigated by direct ophthalmoscopy.

Significantly higher NAG activity was found in hypertensives in comparison with healthy controls. NAG activity was not influenced by the extent of ophthalmoscopically detectable vascular injury. We found positive correlation between urine NAG activity and PGA. A borderline significant association was also found between NAG activity and PUAA in hypertensive patients.

Our results suggest that tubular injury is present in the early stages of hypertensive nephropathy and may precede glomerular damage. Ischemia due to changes in small vessels may not be the only factor responsible for this injury. Metabolic disturbances, especially carbohydrate abnormalities, may also play a role.