development and progression of DN. The authors discuss the potential utility of agents that target inflammatory-related factors or pathways, including inflammatory cytokines, oxidative stress or pro-inflammatory pathways, such as Signal transducers and activator of transcription (STAT/JAK) or Nuclear Factor-кB, to be used as new therapeutic targets in this pathology. However, they remarked on the necessity of perform new clinical trials to examine the potential renoprotective efficacy of these approaches in the context of DN. In this sense, Lavoz et al. [2] highlighted the importance of one of these inflammatory processes, the Th17 immune response, in the pathogenesis of diabetic renal injury. In this article, authors reviewed the current information about the involvement of Th17/IL-17A in diabetes J. Clin. Med. 2020, 9, 813; doi:10.3390/jcm9030813 www.mdpi.com/journal/jcm J. Clin. Med. 2020, 9, 813 2 of 4 and diabetes-induced end-organ, with special attention to the kidney. They postulated reasonably the possible use of antibodies against IL-17A as an additional therapy in patients with DN. Other well-defined mechanisms implicated in the progression of diabetic complications are oxidative stress and extracellular matrix (ECM) accumulation. Concerning oxidative stress, Caro-Ordieres et al. [3] explain the antioxidant effects of natural antioxidant compounds, flavonoids, and remark on their anti-inflammatory and anti-diabetic properties. They review the recent pre-clinical and clinical investigations about the use of flavonoids to ameliorate diabetic complications. On the other hand, Garcia-Fernandez et al. [4] focused their review in the importance of the balance between the levels of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in maintaining renal ECM homeostasis, as well as their contribution to ECM accumulation in DN. Although there is already a wide range of articles studying MMPs/TIMPs, the authors highlight the existence of some contradictory results, which manifest the complex regulation of MMPs, TIMPs, proinflammatory and profibrotic factors in this pathology. One important problem is the growing number of DN patients, which highlights the urgent need for novel biomarkers that allow an earlier diagnosis of renal damage, as well as the identification of patients that rapidly progress to ERSD. In this Special Issue, there are four original papers about diagnostic methods in DN. De Bruyne et al.’s [5] study describes a new method to gain insight into biochemical changes occurring in renal cortical tissue before histological damage can be detected by conventional pathology. The method consists of the innovative application of near-infrared spectroscopy to renal biopsies in an objective and nondestructive way that could be used on routine stained tissue sections. However, large-scale prospective follow-up studies will be indispensable to translate their findings into the clinic. They found some spectral changes related to carbamoylation and glycation reactions, showing a biochemical signature associated with DN, and suggest that this method could be a useful tool to complement histopathological analysis, especially in post-transplant surveillance kidney biopsies. Another controversial point in the management of DN is the definition of renal function. In clinical practice, the renal function is calculated using different mathematical algorithms, including several variables, such as serum creatinine or cystatin-C levels, weight, height, and gender, leading to an estimated glomerular filtration rate (GFR). The study developed by Luis-Lima et al. [6] showed the relevance of the correct GFR estimation in diabetic patients. They demonstrated that the estimated GFR shows around a 30% error compared to measured GFR. Moreover, this error is even higher in patients with measured GFR less than 60 mL/min. Moreover, 25% of patients with hyperfiltration have the wrong diagnosis and 30% of DN patients are not located in the correct CKD stage. Authors demonstrate that the actual creatinine and/or cystatin-C based formulas in type 2 diabetes failed to properly reflect the renal function in diabetic patients in a wide range of GFR (from advanced CKD to hyperfiltration). Actually, microalbuminuria is one of the most used non-invasive diagnosis urinary biomarkers in DN to identify renal function decline. However, better urinary biomarkers are needed. In the manuscript of Koziolek et al. [7], a urinary proteomics approach was used to identify small proteins and peptides associated with pathological changes at first stage of the diabetic disease in a big cohort (563 diabetic patients). They identified several differentially expressed proteins between DN and healthy controls, including apolipoprotein A-I, beta-2-microglobulin, epithelial cadherin (E-cadherin) and lithostathine-1-alpha. Among them, they identified E-cadherin as a key protein in diabetes-induced renal damage and showed that its urinary excretion levels had enough sensibility to discriminate between the CKD different stages, suggesting E-cadherin as a potential urinary biomarker for diabetic patients. On the other hand, cardiovascular events are the main cause of death in DN patients; therefore, the definition of biomarkers of cardiovascular risk is very important. Vascular calcification (VC) has been identified as one of the main predictors of