The traditional chronic kidney disease (CKD) biomarkers (eGFR based on serum creatinine, sex and age and albuminuria) cannot predict a patient’s individual risk for developing progressive CKD. For this reason, it is necessary to identify novel CKD biomarkers that will be able to predict which patients are prone to develop progressive disease and discriminate between disease processes in different parts of the nephron (glomeruli or tubules). A good biomarker should change before or simultaneously with lesion development and its changes should correlate strongly with lesion development. Also, there should be a close relationship between severity of injury and amount of detectable biomarker and its levels should decrease with diminishing injury. Among the large number of molecules under investigation, we have reviewed the most promising ones: NGAL and KIM-1, MCP-1, MMP-9, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1 and suPAR. All these, have been studied as biomarkers for prediction of CKD progression in cohorts of patients with chronic kidney disease of different stages and various aetiologies (proteinuric and non-proteinuric, glomerulonephritides, diabetic, hypertensive and polycystic kidney disease). There is evidence that these molecules could be useful as biomarkers for progressive chronic kidney disease, however, the available data are not enough to draw final conclusions. Further studies with large cohorts and long follow-up are required to identify appropriate biomarkers, that will be able to accurately and reliably define the risk for progressive chronic kidney disease.

Chronic Kidney Disease (CKD) is considered as a major public health problem as it can lead to end-stage kidney failure, which requires replacement therapy. A prompt and accurate diagnosis, along with the appropriate treatment, can delay CKD’s progression, significantly. Herein, we sought to determine whether CKD etiology can be reflected in urine metabolomics during its early stage. This is achieved through the analysis of the urine metabolic fingerprint from 108 CKD patients by means of Nuclear Magnetic Resonance (NMR) spectroscopy metabolomic analysis. We report the first NMR—metabolomics data regarding the three most common etiologies of CKD: Chronic Glomerulonephritis (IgA and Membranous Nephropathy), Diabetic Nephropathy (DN) and Hypertensive Nephrosclerosis (HN). Analysis aided a moderate glomerulonephritis clustering, providing characterization of the metabolic fluctuations between the CKD subtypes and control disease. The urine metabolome of IgA Nephropathy reveals a specific metabolism, reflecting its different etiology or origin and is useful for determining the origin of the disease. In contrast, urine metabolomes from DN and HN patients did not reveal any indicative metabolic pattern, which is consistent with their fused clinical phenotype. These findings may contribute to improving diagnostics and prognostic approaches for CKD, as well as improving our understanding of its pathology.

Background: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. Methods: Thirty-three patients with stage I–IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. Results: Patients with stage I–IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. Conclusion: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.