15 E.V. Lerma and V. Batuman (eds.), Diabetes and Kidney Disease, DOI 10.1007/978-1-4939-0793-9_3, © Springer Science+Business Media New York 2014 Introduction Diabetic kidney disease (DKD) has historically been called diabetic nephropathy if there is macroalbuminuria or pro- teinuria [1, 2]. DKD is a progressive kidney disease as a complication of prolonged hyperglycemia that occurs in both type 1 (T1) and type 2 (T2) diabetes mellitus (DM). Some of the secondary causes of DM include medications, pancreatic disorder, and excess of hormones such as cortisol, catecholamine, or growth hormone, and genetic predisposi- tion [3]. According to national diabetes fact sheet of 2011, DM is the most common cause of renal failure in 2008 in the United States (USA), making about 44 % of all new cases [4]. Another survey among US adults collected by National Health and Nutrition Examination Survey (NHANES) in 2010 showed that prevalence of end stage renal disease (ESRD) due to diabetes increased 1.8 % to 656 million per population [5]. The incidence of ESRD secondary to diabe- tes is the most common accounting for 152 per million popu- lation in 2010 [5]. T2DM accounts for about 90 % of diabetes; thus it is a more common cause of DKD including ESRD [5]. ESRD secondary to T2DM varies among coun- tries and racial group from 43 % in Europe to 61 % in Australia [6]. Similarly among patients with T1DM, ESRD from initial diagnosis has occurred 2.2 % at 20 years and 7.8 % at 30 years in Finland [7] and 4 % at 10 years and 7 % at 20 years after development of persistent microalbuminuria in Diabetes Control and Complication Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) Study [8]. The use of terminology for DKD has been introduced for consistent classification of chronic kidney disease (CKD) by Diabetes and CKD guidelines and its use has been endorsed by Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines and Clinical Practice Recommendations (CPGCPR) for Diabetes and CKD [9]. It has been suggested to use the term DKD as “presumptive diagnosis of kidney disease caused by diabetes” in place of diabetic nephropathy [9]. KDOQI CPGCPR recommends using the term diabetic glo- merulopathy for kidney disease due to diabetes diagnosed by kidney biopsy [9]. Natural History of DKD in T1DM Studies in the 1960s to 1980s have recognized that at diagno- sis of T1DM changes occur in kidneys’ function, structure and biochemical parameters and have laid the groundwork to characterization of the natural course of DKD, which occurs in series of five stages [10–15]. As the clinical onset of T1DM is well known compared to T2DM, where diagnosis may have been delayed, much of our understanding of DKD has been delineated mainly from experimental animal mod- els and partly from patients with T1DM. However, not all animal models resemble the actual human disease process and thus the knowledge of the course of kidney disease comes with limitations. Approximately 25–40 % of patients with T1DM and 5–40 % with T2DM develop diabetic nephropathy [10]. Numerous factors have been associated with the development of DKD such as hypertension, cardio- vascular disease (CVD), hyperlipidemia, and obesity (BMI ≥ 30) [9]. This chapter will discuss the current under- standing of the etiology, disease course, different stages of and modification related to DKD. Natural Course (Stages/Evidence-Based Discussion) Aileen K. Wang and Tina K. Thethi 3 A.K. Wang, M.D. (*) Department of Medicine, Section of Endocrinology, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL-53, 1601 Perdido Street, New Orleans, LA 70112, USA e-mail: awang7@tulane.edu T.K. Thethi, M.D., M.P.H. Department of Medicine, Section of Endocrinology, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL-53, 1601 Perdido Street, New Orleans, LA 70112, USA Southeast Louisiana Veterans Health Care, New Orleans, LA, USA