Hydronephrosis promotes expression of hypoxia-inducible factor 1 alpha

Obstructive uropathy is argued to involve an ischemia-type tissue injury. Further, hypoxia-inducible factor 1 alpha (HIF-1 alpha) constitutes a nuclear transcription factor normally upregulated under hypoxic conditions. We hypothesized that HIF-1 alpha is expressed in the hydronephrotic renal pelvis, as a result of tissue hypoxia.

Renal pelvis tissue specimens were obtained from 2 patient groups. Group 1 (controls, n = 10) consisted of patients who underwent nephrectomy due to nonobstructive renal malignancy. Group 2 (n = 18) consisted of patients who underwent open procedures due to intractable hydronephrosis, not amenable to conservative measures. HIF-1 alpha detection was conducted via immunohistochemical techniques, while histological alterations in both groups were also recorded.

Smooth muscle hypertrophy and urothelial hyperplasia were major findings in group 2. HIF-1 alpha-positive cells (fibroblasts and occasionally macrophages), mainly localized in the stroma, were also found to a greater extent in group 2 (p = 0.0066).

We conclude that HIF-1 alpha is mainly expressed in stroma fibroblasts of the hydronephrotic renal pelvis, implying the presence of significant tissue hypoxia at the dilated upper urinary tract.