NCT04521049

Tubular Markers in Response to Saxagliptin Therapy

A New Clinical Utility for Tubular Markers to Identify Kidney Responders to Saxagliptin Treatment in Patients With Diabetic Nephropathy

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: Beni-Suef University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Diabetes Mellitus, Type 2

Interventions

Type	Name	Description
DRUG	Saxagliptin 5mg	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

Timeline

• Start date: 2019-03-01
• Primary completion: 2020-03-01
• Completion: 2020-04-01
• First posted: 2020-08-20
• Last updated: 2020-08-20

Locations

1 site across 1 country: Egypt