One of the most frequent complications in patients with diabetes mellitus is diabetic nephropathy (DN). At present, it constitutes the first cause of end stage renal disease, and the main cause of cardiovascular morbidity and mortality in these patients. Therefore, it is clear that new strategies are required to delay the development and the progression of this pathology. This new approach should look beyond the control of traditional risk factors such as hyperglycemia and hypertension. Currently, inflammation has been recognized as one of the underlying processes involved in the development and progression of kidney disease in the diabetic population. Understanding the cascade of signals and mechanisms that trigger this maladaptive immune response, which eventually leads to the development of DN, is crucial. This knowledge will allow the identification of new targets and facilitate the design of innovative therapeutic strategies. In this review, we focus on the pathogenesis of proinflammatory molecules and mechanisms related to the development and progression of DN, and discuss the potential utility of new strategies based on agents that target inflammation.

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.

Diabetic kidney disease is one of the most relevant complications in diabetes mellitus patients, which constitutes the main cause of end-stage renal disease in the western world. Delaying the progression of this pathology requires new strategies that, in addition to the control of traditional risk factors (glycemia and blood pressure), specifically target the primary pathogenic mechanisms. Nowadays, inflammation is recognized as a critical novel pathogenic factor in the development and progression of renal injury in diabetes mellitus. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with rheologic properties clinically used for more than 30 years in the treatment of peripheral vascular disease. In addition, this compound also exerts anti-inflammatory actions. In the context of diabetic kidney disease, pentoxifylline has shown significant antiproteinuric effects and a delay in the loss of estimated glomerular filtration rate, although at the present time there is no definitive evidence regarding renal outcomes. Moreover, recent studies have reported that this drug can be associated with a positive impact on new factors related to kidney health, such as Klotho. The use of pentoxifylline as renoprotective therapy for patients with diabetic kidney disease represents a new example of drug repositioning.

Objective: To confirm the accuracy of serum proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and Prostate Health Index (PHI) and to test the value of prostate dimension-adjusted related index p2PSA density (p2PSAD), %p2PSA density (%p2PSAD) and PHI density (PHID) in discriminating between patients with and without prostate cancer (PCa). Patients and Methods: This is a prospective cohort study of 275 patients with a total PSA (tPSA) of 2-10 ng/ml who underwent initial prostate biopsy. Multivariate logistic regression models were complemented by predictive accuracy analysis. Results: PCa was diagnosed in 31.2% of subjects. Median tPSA did not differ between groups, while PSA density (PSAD), percent free PSA (%fPSA), p2PSA, %p2PSA, PHI, p2PSAD, %p2PSAD and PHID (all p < 0.05) were different between men with and without PCa. Univariate accuracy analysis showed p2PSAD (area under the receiver-operating characteristic curve [AUC]: 0.71), %p2PSAD (AUC: 0.76) and PHID (AUC: 0.77) to be the most accurate predictors of PCa at biopsy, significantly outperforming tPSA (AUC: 0.54), PSAD (AUC: 0.68) and %fPSA (AUC: 0.59) (p ≤ 0.001). At multivariate logistic regression models, p2PSAD and PHID significantly increased the accuracy of the basal multivariate model (all p < 0.01). At 90% specificity, sensitivity for p2PSAD, %p2PSAD and PHID were 33.7, 43 and 40.7%, respectively. Spearman's rho coefficient analysis demonstrated a significant relationship between Gleason score, %p2PSA (r = 0.216, p = 0.046), PHI (r = 0.223, p = 0.039) and %p2PSAD (r = 0.205, p = 0.05). Conclusions: Considering patients suited for initial prostate biopsy by a tPSA range of 2-10 ng/ml, PSA isoforms were confirmed to be strong predictors of PCa. The prostate dimension-adjusted PSA isoforms have been shown to differentiate between patients with or without PCa, with an AUC of 0.71-0.77, p2PSAD offering a gain in accuracy with respect to tPSA, %fPSA and PSAD.