6533b827fe1ef96bd1285c86

RESEARCH PRODUCT

Effects of Pentoxifylline on Soluble Klotho Concentrations and Renal Tubular Cell Expression in Diabetic Kidney Disease

José Luis GórrizMaria Dolores Sanchez-niñoJuan F. Navarro-gonzálezErnesto Martín-núñezAlberto Martínez-castelaoAlberto OrtizCarmen Mora-fernándezJavier Donate-correaCarla FerriNayra Pérez-delgado

subject

AdultMalemedicine.medical_specialtyEndocrinology Diabetes and MetabolismUrinary system030232 urology & nephrologyRenal function030204 cardiovascular system & hematologyKidneyurologic and male genital diseasesPentoxifyllineDiabetic nephropathyMice03 medical and health sciences0302 clinical medicineInternal medicineInternal MedicineAlbuminuriaAnimalsHumansMedicineDiabetic NephropathiesPentoxifyllineRenal Insufficiency ChronicKlotho ProteinsKlothoCells CulturedAgedGlucuronidaseAdvanced and Specialized NursingTumor Necrosis Factor-alphabusiness.industryKidney metabolismMiddle Agedmedicine.diseasefemale genital diseases and pregnancy complicationsKidney TubulesEndocrinologyDiabetes Mellitus Type 2AlbuminuriaFemalemedicine.symptombusinessFollow-Up StudiesGlomerular Filtration RateKidney diseasemedicine.drug

description

OBJECTIVE The effect of pentoxifylline on Klotho levels in patients with type 2 diabetes mellitus with chronic kidney disease (CKD) was assessed in a post hoc analysis of the Pentoxifylline for Renoprotection in Diabetic Nephropathy (PREDIAN) trial. RESEARCH DESIGN AND METHODS Circulating and urinary tumor necrosis factor-α (TNF-α) and Klotho were measured before and after 1 year of pentoxifylline. The effect on Klotho expression was assessed in cultured renal tubular cells. RESULTS Pentoxifylline administration resulted in decreased serum and urinary TNF-α, whereas serum and urinary Klotho increased significantly. Changes in urinary Klotho, urinary TNF-α, and phosphorus were associated with changes in serum Klotho; changes in estimated glomerular filtration rate, urinary TNF-α, and albuminuria were related to urinary Klotho variation. In renal tubular cells, pentoxifylline prevented the decrease in Klotho expression induced by inflammatory cytokines or albumin. CONCLUSIONS Pentoxifylline increased Klotho levels in patients with diabetes with stage 3–4 CKD and prevented reduced Klotho expression in vitro. This beneficial effect may be related to anti-inflammatory and antialbuminuric activity.

yearjournalcountryeditionlanguage
2018-06-04Diabetes Care
https://doi.org/10.2337/dc18-0078