6533b85afe1ef96bd12b8d66

RESEARCH PRODUCT

The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy: u-NGAL, u-KIM1 and u-LFABP.

Georg HessDietmar ZdunekStine Elkjaer NielsenHans-henrik ParvingPeter RossingKasper RossingBerit R. Jensen

subject

Malemedicine.medical_specialtyUrinary systemClinical BiochemistryUrologyRenal functionEnzyme-Linked Immunosorbent AssayType 2 diabetesurologic and male genital diseasesFatty Acid-Binding ProteinsDiabetic nephropathyRenin-Angiotensin SystemIrbesartanLipocalin-2Internal medicineDiabetes mellitusProto-Oncogene ProteinsmedicineHumansDiabetic NephropathiesHepatitis A Virus Cellular Receptor 1AgedMembrane Glycoproteinsurogenital systembusiness.industryGeneral MedicineMiddle Agedmedicine.diseaseLipocalinsEndocrinologyKidney TubulesAlbuminuriaReceptors VirusMicroalbuminuriaFemalemedicine.symptombusinessmedicine.drugAcute-Phase Proteins

description

Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding protein (LFABP).A substudy of a double-masked, randomized, cross-over study including 52 patients with type 2 diabetes, hypertension and microalbuminuria. After 2 months washout of all antihypertensive medication except bendroflumethiazid, patients were treated in random order with irbesartan 300, 600 and 900 mg for 2 months.Urinary tubular markers at baseline and after each treatment period (ELISA), 24-h blood pressure, glomerular filtration rate (GFR, (51)CrEDTA) and 24-h urine albumin excretion (UAER).Fifty-two patients completed the study (41 male). Age (mean (SD)): 58(10) years and diabetes duration 13(8) years. Baseline GFR was 101(24) and UAER (geometric mean [95%CI]) 133 (103-172) mg/24 h. With increasing doses of irbesartan (300, 600, 900 mg) u-KIM1 was reduced with 15%, 10% and 15% (p = 0.07 between 300 mg vs. baseline and no difference between doses). Patients with high u-KIM1 at baseline (above median) had a 32% reduction in u-KIM1 during treatment (p = 0.01). No significant decline in U-NGAL compared to baseline. U-LFABP increased during treatment (p0.01).Irbesartan treatment reduced levels of the tubular marker u-KIM1 in patients with type 2 diabetes and microalbuminuria. u-NGAL changed insignificantly and u-LFABP increased. More studies with longer follow up are needed to determine the role of tubular markers in monitoring treatment effect and prediction of prognosis in diabetic nephropathy.

10.3109/00365513.2011.645055https://pubmed.ncbi.nlm.nih.gov/22268365