Tubular and glomerular injury in diabetes and the impact of ACE inhibition

  1. Stine E. Nielsen, MD (Sene{at},
  2. Takeshi Sugaya, MD, PhD2,
  3. Lise Tarnow, MD, DMSc1,
  4. Maria Lajer, Cand.Sci1,
  5. Katrine J Schjoedt, MD1,
  6. Anne Sofie Astrup, MD1,
  7. Tsuneharu Baba, MD, PhD3,
  8. Hans-Henrik Parving, MD, DMSc4,5 and
  9. Peter Rossing, MD, DMSc1
  1. 1Steno Diabetes Center, Copenhagen, Denmark
  2. 2Research Unit for Organ Regeneration Riken Kobe Institute Hyogo Japan
  3. 3Düsseldorf Germany
  4. 4Faculty of Health Sciences, University of Aarhus
  5. 5Dep. of Medical Endocrinology, Rigshospitalet, University Hospital, Copenhagen, Denmark


    Objective: We studied tubular and glomerular damage in type 1 diabetic patients by measuring u-LFABP (urinary liver-type fatty acid-binding protein) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on u-LFABP in patients with diabetic nephropathy.

    Research Design and Methods: Caucasians with type 1 diabetes (T1D): 58 with normoalbuminuria (u-albumin<30mg/24h), 45 with persistent microalbuminuria (30-300 mg/24h) and 45 with persistent macroalbuminuria (≥300 mg/24h). A control group consisted of 57 healthy individuals. The groups were matched by gender and duration of diabetes. In addition U-LFABP were measured in 48 T1D patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with lisinopril 20, 40, and 60 mg once daily in random order.

    Results: In the cross sectional study, the median levels (IQR) of u-LFABP (μg/g creatinine) were significantly higher in normoalbuminuric vs. control group (2.6 (1.3-4.1) vs. 1.9 (0.8-3.0), p=0.02) and increased with increasing levels of albuminuria, microalbuminuric 4.2 (1.8-8.3), nephropathy group 71.2 (8.1-123.4), p<0.05 for all comparisons. U-LFABP correlates with urinary albumin/creatinine ratio (UACR) (R2=0.54, p <0.001).

    Results: In the intervention study, all doses of lisinopril significantly reduced urinary albumine excretion rate (UAER) and u-LFABP from baseline. The reductions (95%CI) in u-LFABP were 43%, 46%, and 40% with increasing doses of lisinopril (NS).

    Conclusion: Early and progressive rise in tubulointerstitial damage as reflected by increased u-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular and glomerular damage and dysfunction.


      • Received March 5, 2009.
      • Accepted May 25, 2009.