Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease-The Promised Land?

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, and it leads to end-stage renal disease (ESRD). The clinical manifestations of ADPKD are variable, with extreme differences observable in its progression, even among members of the same family with the same genetic mutation. In an age of new therapeutic options, it is important to identify patients with rapidly progressive evolution and the risk factors involved in the disease's poor prognosis. As the pathophysiological mechanisms of the formation and growth of renal cysts have been clarified, new treatment options have been proposed to slow the progression to end-stage renal disease. Furthermore, in addition to the conventional factors (PKD1 mutation, hypertension, proteinuria, total kidney volume), increasing numbers of studies have recently identified new serum and urinary biomarkers of the disease's progression, which are cheaper and more easily to dosing from the early stages of the disease. The present review discusses the utility of new biomarkers in the monitoring of the progress of ADPKD and their roles in new therapeutic approaches.

Hypoxia-Inducible Factors and Diabetic Kidney Disease-How Deep Can We Go?

Diabetes is one of the leading causes of chronic kidney disease (CKD), and multiple underlying mechanisms involved in pathogenesis of diabetic nephropathy (DN) have been described. Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden, considering that about 40% of type 2 diabetes patients will develop nephropathy. In the past years, some research found that hypoxia response and hypoxia-inducible factors (HIFs) play critical roles in the pathogenesis of DN. Hypoxia-inducible factors (HIFs) HIF-1, HIF-2, and HIF-3 are the main mediators of metabolic responses to the state of hypoxia, which seems to be the one of the earliest events in the occurrence and progression of diabetic kidney disease (DKD). The abnormal activity of HIFs seems to be of crucial importance in the pathogenesis of diseases, including nephropathies. Studies using transcriptome analysis confirmed by metabolome analysis revealed that HIF stabilizers (HIF-prolyl hydroxylase inhibitors) are novel therapeutic agents used to treat anemia in CKD patients that not only increase endogenous erythropoietin production, but also could act by counteracting the metabolic alterations in incipient diabetic kidney disease and relieve oxidative stress in the renal tissue. In this review, we present the newest data regarding hypoxia response and HIF involvement in the pathogenesis of diabetic nephropathy and new therapeutic insights, starting from improving kidney oxygen homeostasis.