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http://dx.doi.org/10.4062/biomolther.2020.204

Diabetic Nephropathy - a Review of Risk Factors, Progression, Mechanism, and Dietary Management  

Natesan, Vijayakumar (Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University)
Kim, Sung-Jin (Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.29, no.4, 2021 , pp. 365-372 More about this Journal
Abstract
Type 2 diabetes mellitus (T2DM) leads to many health problems like diabetic nephropathy (DN). One of the key factors for chronic kidney disease and end-stage renal disease (ESRD) is T2DM. Extensive work is being done to delineate the pathogenesis of DN and to extend possible remedies. This review is intended to understand the nature of DN risk factors, progression, effects of glycemic levels, and stages of DN. We also explored the novel diagnostic and therapeutic approaches for DN such as gene therapy and stem cell treatments.
Keywords
Diabetic nephropathy; Kidney disease; Hyperglycemia; Novel drugs;
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1 Fu, H., Liu, S., Bastacky, S. I., Wang, X., Tian, X. J. and Zhou, D. (2019) Diabetic kidney diseases revisited: a new perspective for a new era. Mol. Metab. 30, 250-263.   DOI
2 Kim, H. Y. (2014) Nutritional intervention for a patient with diabetic nephropathy. Clin. Nutr. Res. 3, 64-68.   DOI
3 Kim, S. S., Song, S. H., Kim, I. J., Jeon, Y. K., Kim, B. H., Kwak, I. S., Lee, E. K. and Kim, Y. K. (2013) Urinary cystatin C and tubular proteinuria predict progression of diabetic nephropathy. Diabetes Care 36, 656-661.   DOI
4 Kopel, J., Pena-Hernandez, C. and Nugent, K. (2019) Evolving spectrum of diabetic nephropathy. World J. Diabetes 10, 269-279.   DOI
5 Krock, B. L., Skuli, N. and Simon, M. C. (2011) Hypoxia-induced angiogenesis: good and evil. Genes Cancer 2, 1117-1133.   DOI
6 Lerner, S. M. (2008) Kidney and pancreas transplantation in type 1 diabetes mellitus. Mt. Sinai J. Med. 75, 372-384.   DOI
7 Niewczas, M. A., Gohda, T., Skupien, J., Smiles, A. M., Walker, W. H., Rosetti, F., Cullere, X., Eckfeldt, J. H., Doria, A., Mayadas, T. N., Warram, J. H. and Krolewski, A. S. (2012) Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. J. Am. Soc. Nephrol. 23, 507-515.   DOI
8 Oates, P. J. (2010) Aldose reductase inhibitors and diabetic kidney disease. Curr. Opin. Investig. Drugs 11, 402-417.
9 Perry, R. J. and Shulman, G. I. (2020) Sodium-glucose cotransporter-2 inhibitors: understanding the mechanisms for therapeutic promise and persisting risks. J. Biol. Chem. 295, 14379-14390.   DOI
10 Panduru, N. M., Forsblom, C., Saraheimo, M., Thorn, L., Bierhaus, A., Humpert, P. M. and Groop, P. H.; FinnDiane Study Group (2013) Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care 36, 2077-2083.   DOI
11 Satko, S. G., Langefeld, C. D., Daeihagh, P., Bowden, D. W., Rich, S. S. and Freedman, B. I. (2002) Nephropathy in siblings of African Americans with overt type 2 diabetic nephropathy. Am. J. Kidney Dis. 40, 489-494.   DOI
12 Scott, L. J., Warram, J. H., Hanna, L. S., Laffel, L. M., Ryan, L. and Krolewski, A. S. (2001) A nonlinear effect of hyperglycemia and current cigarette smoking are major determinants of the onset of microalbuminuria in type 1 diabetes. Diabetes 50, 2842-2849.   DOI
13 Papadopoulou-Marketou, N., Kanaka-Gantenbein, C., Marketos, N., Chrousos, G. P. and Papassotiriou, I. (2017) Biomarkers of diabetic nephropathy: a 2017 update. Crit. Rev. Clin. Lab. Sci. 54, 326-342.   DOI
14 Li, J. Y., Chen, X. X., Lu, X. H., Zhang, C. B., Shi, Q. P. and Feng, L. (2018) Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes. Biosci. Rep. 38, BSR20181100.   DOI
15 Liu, D., Cheng, F., Pan, S. and Liu, Z. (2020) Stem cells: a potential treatment option for kidney diseases. Stem Cell Res. Ther. 11, 249.   DOI
16 Navarro, J. F., Milena, F. J., Mora, C., Leon, C., Claverie, F., Flores, C. and Garcia, J. (2005) Tumor necrosis factor-alpha gene expression in diabetic nephropathy: relationship with urinary albumin excretion and effect of angiotensin-converting enzyme inhibition. Kidney Int. Suppl. (99), S98-S102.
17 Oltean, S., Coward, R., Collino, M. and Baelde, H. (2017) Diabetic nephropathy: novel molecular mechanisms and therapeutic avenues. Biomed. Res. Int. 2017, 3146524.
18 Otoda, T., Kanasaki, K. and Koya, D. (2014) Low-protein diet for diabetic nephropathy. Curr. Diab. Rep. 14, 523.   DOI
19 Petrie Aronin, C. E. and Tuan, R. S. (2010) Therapeutic potential of the immunomodulatory activities of adult mesenchymal stem cells. Birth Defects Res. C Embryo Today 90, 67-74.   DOI
20 Pugliese, G., Penno, G., Natali, A., Barutta, F., Di Paolo, S., Reboldi, G., Gesualdo, L. and De Nicola, L.; Italian Diabetes Society and the Italian Society of Nephrology (2020) Diabetic kidney disease: new clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function". J. Nephrol. 33, 9-35.   DOI
21 Kowluru, R. A. (2010) Role of Matrix metalloproteinase-9 in the development of diabetic retinopathy and its regulation by H-ras. Invest. Ophthalmol. Vis. Sci. 51, 4320-4326.   DOI
22 Retnakaran, R., Cull, C. A., Thorne, K. I., Adler, A. I. and Holman, R. R.; UKPDS Study Group (2006) Risk factors for renal dysfunction in type 2 diabetes: U.K. prospective diabetes study 74. Diabetes 55, 1832-1839.   DOI
23 Gheith, O., Farouk, N., Nampoory, N., Halim, M. A. and Al-Otaibi, T. (2016) Diabetic kidney disease: world wide difference of prevalence and risk factors. J. Nephropharmacol. 5, 49-56.
24 Kitada, M., Ogura, Y., Monno, I. and Koya, D. (2018) A low-protein diet for diabetic kidney disease: its effect and molecular mechanism, an approach from animal studies. Nutrients 10, 544.   DOI
25 Lacquaniti, A., Donato, V., Pintaudi, B., Di Vieste, G., Chirico, V., Buemi, A., Di Benedetto, A., Arena, A. and Buemi, M. (2013) "Normoalbuminuric" diabetic nephropathy: tubular damage and NGAL. Acta Diabetol. 50, 935-942.   DOI
26 Anders, H. J., Davis, J. M. and Thurau, K. (2016) Nephron protection in diabetic kidney disease. N. Engl. J. Med. 375, 2096-2098.   DOI
27 Bohman, S. O., Tyden, G., Wilczek, H., Lundgren, G., Jaremko, G., Gunnarsson, R., Ostman, J. and Groth, C. G. (1985) Prevention of kidney graft diabetic nephropathy by pancreas transplantation in man. Diabetes 34, 306-308.   DOI
28 Chatzikyrkou, C., Menne, J., Izzo, J., Viberti, G., Rabelink, T., Ruilope, L. M., Rump, C., Mertens, P. R. and Haller, H. (2017) Predictors for the development of microalbuminuria and interaction with renal function. J. Hypertens 35, 2501-2509.   DOI
29 Nielsen, S. E., Andersen, S., Zdunek, D., Hess, G., Parving, H. H. and Rossing, P. (2011) Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy. Kidney Int. 79, 1113-1118.   DOI
30 Amalan, V. and Vijayakumar, N. (2015) Antihyperglycemic effect of p-coumaric acid on streptozotocin induced diabetic rats. Indian J. Appl. Res. 5, 2249-2255.
31 Berhane, A. M., Weil, E. J., Knowler, W. C., Nelson, R. G. and Hanson, R. L. (2011) Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death. Clin. J. Am. Soc. Nephrol. 6, 2444-2451.   DOI
32 Caramori, M. L., Fioretto, P. and Mauer, M. (2000) The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 49, 1399-1408.   DOI
33 Oh, S. W., Kim, S., Na, K. Y., Chae, D. W., Kim, S., Jin, D. C. and Chin, H. J. (2012) Clinical implications of pathologic diagnosis and classification for diabetic nephropathy. Diabetes Res. Clin. Pract. 97, 418-424.   DOI
34 Hill, N. R., Fatoba, S. T., Oke, J. L., Hirst, J. A., O'Callaghan, C. A., Lasserson, D. S. and Hobbs, F. D. R. (2016) Global prevalence of chronic kidney disease - a systematic review and meta-analysis. PLoS ONE 11, e0158765.   DOI
35 Kanauchi, N., Ookawara, S., Ito, K., Mogi, S., Yoshida, I., Kakei, M., Ishikawa, S. E., Morishita, Y. and Tabei, K. (2015) Factors affecting the progression of renal dysfunction and the importance of salt restriction in patients with type 2 diabetic kidney disease. Clin. Exp. Nephrol. 19, 1120-1126.   DOI
36 Rojas, M. A., Zhang, W., Xu, Z., Nguyen, D. T., Caldwell, R. W. and Caldwell, R. B. (2011) Interleukin 6 has a critical role in diabetesinduced retinal vascular inflammation and permeability. Invest. Ophthalmol. Vis. Sci. 52, 1003.   DOI
37 Conway, B. R., Manoharan, D., Manoharan, D, Jenks, S., Dear, J. W., McLachlan, S., Strachan, M. W. and Price, J. F. (2012) Measuring urinary tubular biomarkers in type 2 diabetes does not add prognostic value beyond established risk factors. Kidney Int. 82, 812-818.   DOI
38 Gonzalez, D. E., Foresto, R. D. and Ribeiro, A. B. (2020) SGLT-2 inhibitors in diabetes: a focus on renoprotection. Rev. Assoc. Med. Bras. 66, s17-s24.   DOI
39 Pettitt, D. J., Saad, M. F., Bennett, P. H., Nelson, R. G. and Knowler, W. C. (1990) Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 33, 438-443.   DOI
40 Schrijvers, B. F., De Vriese, A. S. and Flyvbjerg, A. (2004) From hyperglycemia to diabetic kidney disease: the role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines. Endocr. Rev. 25, 971-1010.   DOI
41 Skupien, J., Warram, J. H., Smiles, A., Galecki, A., Stanton, R. C. and Krolewski, A. S. (2014) Improved glycemic control and risk of ESRD in patients with type 1 diabetes and proteinuria. J. Am. Soc. Nephrol. 25, 2916-2925.   DOI
42 Taylor, R. W. and Turnbull, D. M. (2005) Mitochondrial DNA mutations in human disease. Nat. Rev. Genet. 6, 389-402.   DOI
43 Bornhorst, C., Russo, P., Veidebaum, T., Tornaritis, M., Molnar, D., Lissner, L., Marild, S., De Henauw, S., Moreno, L. A., Floegel, A., Ahrens, W. and Wolters, M. (2020) The role of lifestyle and non-modifiable risk factors in the development of metabolic disturbances from childhood to adolescence. Int. J. Obes. (Lond.) 44, 2236-2245.   DOI
44 Shahbazian, H. and Rezaii, I. (2013) Diabetic kidney disease; review of the current knowledge. J. Renal Inj. Prev. 2, 73-80.
45 Smith, A. and Harris, C. (2018) Type 1 diabetes: management strategies. Am. Fam. Physician 98, 154-162.
46 Nielsen, H. B., Almeida, M., Juncker, A. S., Rasmussen, S., Li, J., Sunagawa, S., Plichta, D. R., Gautier, L., Pedersen, A. G., Le Chatelier, E., Pelletier, E., Bonde, I., Nielsen, T., Manichanh, C., Arumugam, M., Batto, J. M., Quintanilha Dos Santos, M. B., Blom, N., Borruel, N., Burgdorf, K. S., Boumezbeur, F., Casellas, F., Dore, J., Dworzynski, P., Guarner, F., Hansen, T., Hildebrand, F., Kaas, R. S., Kennedy, S., Kristiansen, K., Kultima, J. R., Leonard, P., Levenez, F., Lund, O., Moumen, B., Le Paslier, D., Pons, N., Pedersen, O., Prifti, E., Qin, J., Raes, J., Sorensen, S., Tap, J., Tims, S., Ussery, D. W., Yamada, T.; MetaHIT Consortium, Renault, P., Sicheritz-Ponten, T., Bork, P., Wang, J., Brunak, S., Ehrlich, S. D. (2014) Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat. Biotechnol. 32, 822-828.   DOI
47 Rota, C., Morigi, M. and Imberti, B. (2019) Stem cell therapies in kidney diseases: progress and challenges. Int. J. Mol. Sci. 20, 2790.   DOI
48 Ahmad, T., Ulhaq, I., Mawani, M. and Islam, N. (2017) Microalbuminuria in type-2 diabetes mellitus; the tip of iceberg of diabetic complications. Pak. J. Med. Sci. 33, 519-523.
49 Ahola, K. A. J., Forsblom, C. and Groop, P. H. (2018) Adherence to special diets and its association with meeting the nutrient recommendations in individuals with type 1 diabetes. Acta Diabetol. 55, 843-851.   DOI
50 Bonora, E., Evangelisti, C., Bonichon, F., Tallini, G. and Romeo, G. (2006) Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas. Br. J. Cancer 95, 1529-1536.   DOI
51 Vallon, V. (2015) The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu. Rev. Med. 66, 255-270.   DOI
52 Sulaiman, M. K. (2019) Diabetic nephropathy: recent advances in pathophysiology and challenges in dietary management. Diabetol. Metab. Syndr. 11, 7.   DOI
53 Tervaert, T. W., Mooyaart, A. L., Amann, K., Cohen, A. H., Cook, H. T., Drachenberg, C. B., Ferrario, F., Fogo, A. B., Haas, M., de Heer, E., Joh, K., Noel, L. H., Radhakrishnan, J., Seshan, S. V., Bajema, I. M. and Bruijn, J. A.; Renal Pathology Society (2010) Pathologic classification of diabetic nephropathy. J. Am. Soc. Nephrol. 21, 556-563.   DOI
54 Tonneijck, L., Muskiet, M. H. A., Smits, M. M., van Bommel, E. J., Heerspink, H. J. L., van Raalte, D. H. and Joles, J. A. (2017) Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J. Am. Soc. Nephrol. 28, 1023-1039.   DOI
55 Wada, J., Makino, H. and Kanwar, Y. S. (2002) Gene expression and identification of gene therapy targets in diabetic nephropathy. Kidney Int. 61, S73-S78.
56 Saran, R., Robinson, B., Abbott, K. C., Agodoa, L. Y., Albertus, P., Ayanian, J., Balkrishnan, R., Bragg-Gresham, J., Cao, J., Chen, J. L., Cope, E., Dharmarajan, S., Dietrich, X., Eckard, A., Eggers, P. W., Gaber, C., Gillen, D., Gipson, D., Gu, H., Hailpern, S. M., Hall, Y. N., Han, Y., He, K., Hebert, H., Helmuth, M., Herman, W., Heung, M., Hutton, D., Jacobsen, S. J., Ji, N., Jin, Y., Kalantar-Zadeh, K., Kapke, A., Katz, R., Kovesdy, C. P., Kurtz, V., Lavalee, D., Li, Y., Lu, Y., McCullough, K., Molnar, M. Z., Montez-Rath, M., Morgenstern, H., Mu, Q., Mukhopadhyay, P., Nallamothu, B., Nguyen, D. V., Norris, K. C., O'Hare, A. M., Obi, Y., Pearson, J., Pisoni, R., Plattner, B., Port, F. K., Potukuchi, P., Rao, P., Ratkowiak, K., Ravel, V., Ray, D., Rhee, C. M., Schaubel, D. E., Selewski, D. T., Shaw, S., Shi, J., Shieu, M., Sim, J. J., Song, P., Soohoo, M., Steffick, D., Streja, E., Tamura, M. K., Tentori, F., Tilea, A., Tong, L., Turf, M., Wang, D., Wang, M., Woodside, K., Wyncott, A., Xin, X., Zang, W., Zepel, L., Zhang, S., Zho, H., Hirth, R. A. and Shahinian, V. (2017) US Renal Data System 2016 Annual Data Report: epidemiology of kidney disease in the United States. Am. J. Kidney Dis. 69, A7-A8.   DOI
57 Sabbisetti, V. S., Waikar, S. S., Antoine, D. J., Smiles, A., Wang, C., Ravisankar, A., Ito, K., Sharma, S., Ramadesikan, S., Lee, M., Briskin, R., De Jager, P. L., Ngo, T. T., Radlinski, M., Dear, J. W., Park, K. B., Betensky, R., Krolewski, A. S. and Bonventre, J. V. (2014) Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J. Am. Soc. Nephrol. 25, 2177-2186.   DOI
58 Chou, K. M., Lee, C. C., Chen, C. H. and Sun, C. Y. (2013) Clinical value of NGAL, L-FABP and albuminuria in predicting GFR decline in type 2 diabetes mellitus patients. PLoS ONE 8, e54863.   DOI
59 De Sanctis, V., Incorvaia, C., Soliman, A. T., Candini, G., Pepe, A., Kattamis, C., Soliman, N. A., Elsedfy, H. and Kholy, M. E. (2015) Does insulin like growth factor-1 (IGF-1) deficiency have a "protective" role in the development of diabetic retinopathy in thalassamia major patients? Mediterr. J. Hematol. Infect. Dis. 7, e2015038.   DOI
60 Gall, M. A., Hougaard, P., Borch-Johnsen, K. and Parving, H. H. (1997) Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study. BMJ 314, 783-788.   DOI
61 Mohammad, G. and Siddiquei, M. M. (2012) Role of matrix metalloproteinase-2 and -9 in the development of diabetic retinopathy. J. Ocul. Biol. Dis. Infor. 5, 1-8.   DOI
62 Dande, R. R., Peev, V., Altintas, M. M. and Reiser, J. (2017) Soluble urokinase receptor and the kidney response in diabetes mellitus. J. Diabetes Res. 2017, 3232848.
63 Dellamea, B. S., Pinto, L. C., Leitao, C. B., Santos, K. G. and Canani, L. H. (2014) Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and meta-analysis. BMC Med. Genet. 15, 9.
64 Amalan, V., Vijayakumar, N. and Ramakrishnan, A. (2015) p-Coumaric acid regulates blood glucose and antioxidant levels in streptozotocin induced diabetic rats. J. Chem. Pharm. Res. 7, 831-839.
65 Trimeche, A., Selmi, Y., Ben Slama. F., Ben Amara, H., Hazar, I., Ben Mami, F. and Achour, A. (2013) Effect of protein restriction on renal function and nutritional status of type 1 diabetes at the stage of renal impairment. Tunis. Med. 91, 117-122.
66 Wallner, E. I., Wada, J., Lin, S., Pan, X., Reddy, J. K., Chugh, S. S. and Kanwar, Y. S. (2002) Renal gene expression in embryonic and newborn diabetic mice. Exp. Nephrol. 10, 130-138.   DOI
67 Liu, A. G., Ford, N. A., Hu, F. B., Zelman, K. M., Mozaffarian, D. and Kris-Etherton, P. M. (2017) A healthy approach to dietary fats: understanding the science and taking action to reduce consumer confusion. Nutr. J. 16, 53.   DOI
68 Lu, B., Wen, J., Song, X. Y., Dong, X. H., Yang, Y. H., Zhang, Z. Y., Zhao, N. Q., Ye, H. Y., Mou, B., Chen, F. L., Liu, Y., Shen, Y., Wang, X. C., Zhou, L. N., Li, Y. M., Zhu, X. X. and Hu, R. M. (2017) High prevalence of albuminuria in population-based patients diagnosed with type 2 diabetes in the Shanghai downtown. Diabetes Res. Clin. Pract. 75, 184-192.   DOI
69 Narres, M., Claessen, H., Droste, S., Kvitkina, T., Koch, M., Kuss, O. and Icks, A. (2016) The incidence of end-stage renal disease in the diabetic (compared to the non-diabetic) population: a systematic review. PLoS ONE 11, e0147329.   DOI
70 Werner, N., Nickenig, G. and Sinning, J. M. (2018) Complex PCI procedures: challenges for the interventional cardiologist. Clin. Res. Cardiol. 107, 64-73.   DOI
71 Young, B. A., Maynard, C. and Boyko, E. J. (2003) Racial differences in diabetic nephropathy, cardiovascular disease, and mortality in a national population of veterans. Diabetes Care 26, 2392-2399.   DOI
72 Zeni, L., Norden, A. G. W., Cancarini, G. and Unwin, R. J. (2017) A more tubulocentric view of diabetic kidney disease. J. Nephrol. 30, 701-717.   DOI
73 Zha, Y. and Qian, Q. (2017) Protein nutrition and malnutrition in CKD and ESRD. Nutrients 9, 208.   DOI
74 Azizi, M., Menard, J., Bissery, A., Guyene, T. T. and Bura-Riviere, A. (2007) Hormonal and hemodynamic effects of aliskiren and valsartan and their combination in sodium-replete normotensive individuals. Clin. J. Am. Soc. 2, 947-955.
75 Motawi, T. K., Shehata, N. I., ElNokeety, M. M. and El-Emady, Y. F. (2018) Potential serum biomarkers for early detection of diabetic nephropathy. Diabetes Res. Clin. Pract. 136, 150-158.   DOI
76 Zakrzewski, W., Dobrzynski, M., Szymonowicz, M. and Rybak, Z. (2019) Stem cells: past, present, and future. Stem Cell Res. Ther. 10, 68.   DOI
77 Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M. and Matthews, D. R.; CANVAS Program Collaborative Group (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N. Engl. J. Med. 377, 644-657.   DOI
78 Fioretto, P., Steffes, M. W., Sutherland, D. E., Goetz, F. C. and Mauer, M. (1998) Reversal of lesions of diabetic nephropathy after pancreas transplantation. N. Engl. J. Med. 339, 69-75.   DOI
79 Mussbacher, M., Salzmann, M., Brostjan, C., Hoesel, B., Schoergenhofer, C., Datler, H., Hohensinner, P., Basilio, J., Petzelbauer, P., Assinger, A. and Schmid, J. A. (2019) Cell type-specific roles of NF-κB linking inflammation and thrombosis. Front. Immunol. 10, 85.   DOI
80 Wanner, C., Inzucchi, S. E., Lachin, J. M., Fitchett, D., von Eynatten, M., Mattheus, M., Johansen, O. E., Woerle, H. J., Broedl, U. C. and Zinman, B.; EMPA-REG OUTCOME Investigators (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N. Engl. J. Med. 375, 323-334.   DOI
81 Gentile, G., Mastroluca, D., Ruggenenti, P. and Remuzzi, G. (2014) Novel effective drugs for diabetic kidney disease? or not? Expert Opin. Emerg. Drugs 19, 571-601.   DOI
82 Eberhard, J., Drosos, Z., Tiemann, M., Jepsen, S. and Schroder, J. M. (2006) Immunolocalization of lactoferrin in healthy and inflamed gingival tissues. J. Periodontol. 77, 472-478.   DOI
83 Fioretto, P., Sutherland, D. E., Najafian, B. and Mauer, M. (2006) Remodeling of renal interstitial and tubular lesions in pancreas transplant recipients. Kidney Int. 69, 907-912.   DOI