Tubular Markers in Response to Saxagliptin Therapy
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      the study aims to investigate whether treatment with saxagliptin would induce beneficial
      changes in renal NGAL and L-FABP biomarkers and if they would be used as a tool to identify
      patients' categories with a particular renal response to DPP-4inhibition. Secondly, to find
      an association between NGAL and L-FABP, and the relevant renal parameters for both baseline
      values and rate of changes across defined time points.
    

Detailed description: 
      Diabetic kidney disease (DKD) is considered a substantial cause of end-stage kidney disease
      (ESKD) worldwide. Incorporation of renoprotective options during interventions to prevent the
      development of DKD and attenuation of its progression; is of the utmost importance.
      Incretin-based therapies, specifically dipeptidyl peptidase 4 (DPP-4) inhibitors exhibited
      albuminuria lowering potential beyond their antihyperglycemic effects. Saxagliptin, a potent
      selective DPP-4 inhibitor which has been used as monotherapy or in combination with
      antidiabetics, has demonstrated great renal efficiency on both experimental and clinical
      scale .

      Although albumin excretion rate (AER) is a powerful predictor of kidney function
      deterioration and progressive renal dysfunction, it is primarily a marker of glomerular
      damage and it has some drawbacks. For example; some patients may follow a non-albuminuric
      pathway to kidney impairment, others do not progress to macroalbuminuria but remain at
      microalbuminuria or even regress to normoalbuminuria. Thus, more sensitive and specific renal
      biomarkers than AER will be valuable in predicting early kidney injury and the progression of
      diabetic renal damage.

      Besides glomerular damage, tubulointerstitial dysfunction largely contributes to the
      pathology of diabetic nephropathy. Neutrophil gelatinase-associated lipocalin (NGAL) and
      liver type fatty acid binding protein (L-FABP) are apparent as excellent biomarkers of
      tubular damage and are earlier predictors of acute kidney injury relative to
      microalbuminuria. NGAL is produced by neutrophils, highly expressed in tubular epithelium and
      released from tubular cells following damage . L-FABP is expressed in the proximal tubules
      and secreted into urine upon tubulointerstitial damage. Clinical significance of these
      biomarkers lies in their emergence in normoalbuminuric patients and their association with
      increased albuminuria and progression to ESRD with sustained high urinary markers' levels.
    

Intervention name(s): Saxagliptin 5mg
Intervention type(s): Drug
Intervention description(s): Patients would be assigned to saxagliptin (Onglyza® AstraZeneca Pharmaceuticals LP, Indiana, USA), either received a dose of 5 mg or 2.5 mg daily if patients had eGFR <50 mL/min/1.73 m2
Other intervention name(s): Onglyza
Intervention MeSH terms: Saxagliptin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: saxagliptin; uNGAL; u L-FABP; DKD