The role of urinary TGF-β₁, TNF-α, IL-6 and microalbuminuria for monitoring therapy in posterior urethral valves

Pediatr Nephrol. 2013 Oct;28(10):1991-2001. doi: 10.1007/s00467-013-2506-8. Epub 2013 Jun 8.

Abstract

Background: Long-term renal deterioration is common in patients with posterior urethral valves (PUV), and early identification of detrimental factors can help in counselling patients as well as in guiding future therapy. The aim of our study was (1) to evaluate urinary transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels and microalbuminuria before and after ablation of PUV and (2) to examine the effect of early induction of angiotensin-converting enzyme inhibitors (ACE-I) on renal recovery.

Methods: The study included 30 patients with diagnosed PUV. Urinary cytokines were measured pre-operatively and post-operatively for 1 year. The study group was subdivided into two subgroups at 6 months after surgery. Group 1 included 16 patients whose urinary TGF-β1 level showed a declining trend. Group 2 included 14 patients whose urinary TGF-β1 showed a rising trend or plateaued; these patients were started on ACE-I therapy, which they received for at least 6 months.

Results: Urinary TGF-β1, TNF-α and microalbumin levels were high in patients with PUV. In Group 1 patients, urinary TGF-β1, TNF-α and microalbumin levels fell significantly following valve ablation and continued to decline for 12 months. In Group 2 patients, after an initial fall following valve ablation, urinary TGF-β1, TNF-α and microalbumin showed a continued rise until 6 months post-surgery. After ACE-I therapy, there was 53.43 % fall in urinary TGF-β1, 43.15 % fall in microalbuminuria, 28.57 % improvement in split renal function and 35.80 % improvement in GFR.

Conclusions: Based on our results, urinary TGF-β1, urinary TNF-α and microalbuminuria can be used as biomarkers for the early recognition of ongoing renal damage in patients with PUV. ACE-I plays a role in retarding renal damage in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / diagnosis
  • Albuminuria / etiology
  • Albuminuria / therapy
  • Albuminuria / urine*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Biomarkers / urine
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukin-6 / urine*
  • Prospective Studies
  • Time Factors
  • Transforming Growth Factor beta1 / urine*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / urine*
  • Urethra / abnormalities*
  • Urethra / drug effects
  • Urethra / surgery
  • Urethral Stricture / diagnosis
  • Urethral Stricture / etiology
  • Urethral Stricture / therapy
  • Urethral Stricture / urine*
  • Urologic Surgical Procedures

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha