Tubular Markers in Response to Saxagliptin Therapy

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.

Inclusion criteria

• T2 DM,
• prevalent albuminuria (30-3000mg/g),
• controlled hypertension (defined as blood pressure <140/90 mm Hg) on a selected angiotensin receptor blocker, olmesartan 20mg/day for at least 4 weeks before intervention.

Exclusion criteria

• type 1 diabetes,
• poorly controlled hypertension (140-160/90-100 mm Hg),
• pancreatitis,
• malignancies
• albuminuria more than 3000mg/g.
• cardiovascular diseases (acute myocardial infarction, cerebrovascular disease in the past 6months,
• End Stage Renal Disease (ESRD) on chronic dialysis, renal transplant, a serum creatinine >6.0 mg/dL, or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.