Background: Diabetes is a growing public health problem. Diabetic kidney disease (DKD) is the most prevalent chronic renal disease and the major cause of end-stage renal failure worldwide, predominantly due to the increase of Type 2 diabetes associated with obesity. The intimate mechanisms leading to the development and progression of renal injury in DKD are not well understood, but current knowledge indicates that its pathogenesis is multifactorial, where the immune response and inflammation appear to be relevant factors. Summary: This review summarizes the role of relevant inflammatory molecules and pathways that participate in the development of DKD. Likewise, we focused on the new therapeutic approaches based on anti-inflammatory effects of different drugs. Key Messages: This new pathogenic perspective of DKD as an inflammatory condition leads to novel horizons, such as the potential role of inflammatory signaling pathways and their downstream products as emerging biomarkers and promising therapeutic targets.

1.
Martínez-Castelao A, Navarro-González J, Górriz JL, de Alvaro F: The concept and the epidemiology of diabetic nephropathy have changed in recent years. J Clin Med 2015; 4: 1207–1216.
2.
García-García PM, Getino-Melián MA, Dominguez-Pimentel V, Navarro-González JF: Inflammation in diabetic kidney disease. Worl J Diabetes 2014; 5: 431–443.
3.
Donate-Correa J, Martín-Nuñez E, Muros-de-Fuentes M, Mora-Fernández C, Navarro-González JF: Inflammatory cytokines in diabetic nephropathy. J Diabetes Res 2015; 2015: 948417.
4.
Alicic RZ, Johnson EJ, Tuttle KR: Inflammatory mechanisms as new biomarkers and therapeutic targets for diabetic kidney disease. Adv Chronic Kidney Dis 2018; 25: 181–191.
5.
Navarro-González J, Mora-Fernández C: The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 2008; 19: 433–442.
6.
Navarro-González J, Mora-Fernández C, Muros de Fuentes M, García-Pérez J: Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol 2011; 7: 327–340.
7.
Hojs R, Ekart R, Bevc S, Hojs N: Markers of inflammation and oxidative stress in the development and progression of renal disease in diabetic patients. Nephron 2016; 133: 159–162.
8.
Ruster C, Wolf G: The role of chemokines and chemokine receptors in diabetic nephropathy. Front Biosci 2008; 13: 944–955.
9.
Avci E, Uzeli S: The role of adhesion molecules and cytokines in patients with diabetic nephropathy. Biomed Res 2016:S343–S348.
10.
Marrero MB, Banes-Berceli AK, Stern DM, Eaton DC: Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am J Physiol Renal Physiol 2006; 290: 762–768.
11.
Ortiz-Muñoz G, Lopez-Parra V, Lopez-Franco O, Fernandez-Vizarra P, Mallavia B, Flores C, et al: Suppressors of cytokine signaling abrogate diabetic nephropathy. J Am Soc Nephrol 2010; 21: 763–772.
12.
Jha JC, Banal C, Chow BS, Cooper ME, Jandeleit-Dahm K: Diabetes and kidney disease: role of oxidative stress. Antioxid Redox Signal 2016; 25: 657–684.
13.
Pérez-Gomez MV, Sanchez-Niño MD, Sanz AB, Zheng B, Martín-Cleary C, Ruiz-Ortega M, et al: Targeting inflammation in diabetic kidney disease: early clinical trials. Expert Opin Investig Drugs 2016; 25: 1045–1058.
14.
McCormick B, Sydor A, Akbari A, Fergusson D, Doucette S, Knoll G: The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. Am J Kidney Dis 2008; 52: 454–463.
15.
Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, Chahin J, Méndez ML, Gallego E, et al: Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. J Am Soc Nephrol 2015; 26: 220–229.
16.
Navarro-González JF, Sánchez-Niño MD, Donate-Correa J, Martín-Núñez E, Ferri C, Pérez-Delgado N, et al: Effects of pentoxifylline on soluble Klotho concentrations and renal tubular cell expression in diabetic kidney disease. Diabetes Care 2018; 41: 1817–1820.
17.
Menne J, Eulberg D, Beyer D, Baumann M, Saudek F, Valkusz Z, et al: C-C motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria. Nephrol Dial Transplant 2017; 32: 307–315.
18.
de Zeeuw D, Bekker P, Henkel E, Hasslacher C, Gouni-Berthold I, Mehling H, et al: The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial. Lancet Diabetes Endocrinol 2015; 3: 687–696.
19.
Tuttle KR, Brosius FC 3rd, Adler SG, Kretzler M, Mehta RL, Tumlin JA, et al: JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a phase 2 randomized controlled clinical trial. Nephrol Dial Transplant 2018, Epub ahead of print.
20.
Liu Q, Xing L, Wang L, Yao F, Liu S, Hao J, et al: Therapeutic effects of suppressors of cytokine signaling in diabetic nephropathy. J Histochem Cytochem 2014; 62: 119–128.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.