Kidney disease represents a serious global health problem. One of the main concerns is its late diagnosis, only feasible in a progressed disease state. The lack of a clinical manifestation in the early stages and the fact that the commonly measured parameters of renal function are markedly reduced only during advanced stages of the disease are the main cause. Changes at the molecular level of the kidney tissue occur even before nitrogenous substances, such as creatinine and urea, start to accumulate in the blood. Renal proximal tubules contain a large number of mitochondria and are critical for the energy-demanding process of reabsorption of water and solutes. Mitochondria are the largest producers of oxygen radicals, which, in turn, increase the susceptibility of kidneys to oxidative stress-induced damage. Free radicals and prooxidants produced during acute or chronic kidney injury may further aggravate the course of the disease and play a role in the pathogenesis of subsequent complications. Prevention might be the solution in CKD, but patients are often reluctant to undergo preventive examinations. Noninvasive markers and the possibility to obtain samples at home might help to increase compliance. This review will provide an overview of the possible uses of markers of oxidative status in noninvasive biofluids in patients with renal disease.

Progressive kidney diseases and renal fibrosis are associated with endothelial injury and capillary rarefaction. However, our understanding of these processes has been hampered by the lack of tools enabling the quantitative and noninvasive monitoring of vessel functionality. Here, we used micro-computed tomography (µCT) for anatomical and functional imaging of vascular alterations in three murine models with distinct mechanisms of progressive kidney injury: ischemia-reperfusion (I/R, days 1–56), unilateral ureteral obstruction (UUO, days 1–10), and Alport mice (6–8 weeks old). Contrast-enhanced in vivoµCT enabled robust, noninvasive, and longitudinal monitoring of vessel functionality and revealed a progressive decline of the renal relative blood volume in all models. This reduction ranged from −20% in early disease stages to −61% in late disease stages and preceded fibrosis. Upon Microfil perfusion, high-resolution ex vivoµCT allowed quantitative analyses of three-dimensional vascular networks in all three models. These analyses revealed significant and previously unrecognized alterations of preglomerular arteries: a reduction in vessel diameter, a prominent reduction in vessel branching, and increased vessel tortuosity. In summary, using µCT methodology, we revealed insights into macro-to-microvascular alterations in progressive renal disease and provide a platform that may serve as the basis to evaluate vascular therapeutics in renal disease.

Cell-free DNA (cfDNA) is present in various body fluids and originates mostly from blood cells. In specific conditions, circulating cfDNA might be derived from tumours, donor organs after transplantation or from the foetus during pregnancy. The analysis of cfDNA is mainly used for genetic analyses of the source tissue —tumour, foetus or for the early detection of graft rejection. It might serve also as a nonspecific biomarker of tissue damage in critical care medicine. In kidney diseases, cfDNA increases during haemodialysis and indicates cell damage. In patients with renal cell carcinoma, cfDNA in plasma and its integrity is studied for monitoring of tumour growth, the effects of chemotherapy and for prognosis. Urinary cfDNA is highly fragmented, but the technical hurdles can now be overcome and urinary cfDNA is being evaluated as a potential biomarker of renal injury and urinary tract tumours. Beyond its diagnostic application, cfDNA might also be involved in the pathogenesis of diseases affecting the kidneys as shown for systemic lupus, sepsis and some pregnancy-related pathologies. Recent data suggest that increased cfDNA is associated with acute kidney injury. In this review, we discuss the biological characteristics, sources of cfDNA, its potential use as a biomarker as well as its role in the pathogenesis of renal and urinary diseases.