Biomarkers for predicting outcomes in chronic kidney disease.

PURPOSE OF REVIEW: Current biomarkers for chronic kidney disease (CKD) are limited by lack of sensitivity and inability to prognosticate CKD progression. Significant recent research has better characterized novel biomarker candidates that are associated with CKD progression and cardiovascular mortality in CKD. This review discusses the most significant advances within the past year. RECENT FINDINGS: We discuss biomarkers for outcomes in CKD under two categories: emerging (defined as having been validated in an independent cohort), which include serum cystatin C, serum ß-trace protein, ß2-microglobulin, soluble urokinase-type plasminogen activator receptor, soluble tumor necrosis factor receptors 1/2, urinary monocyte chemotactic protein-1, neutrophil gelatin-associated lipocalin, kidney injury molecule-1, and fibroblast growth factor-23; and novel (which have shown associations in smaller observational studies but have not been validated yet), which include indoxyl sulfate, p-cresyl sulfate, trimethylamine-N-oxide, IL-18, Klotho, markers of endothelial dysfunction, vimentin, and procollagen type III N-terminal propeptide. Further, we also discuss future directions for biomarker research including unbiased -omics approaches. SUMMARY: There are a number of promising biomarkers that can better prognosticate outcomes in and progression of CKD. Further research is warranted to examine whether these biomarkers validate independently as well, and if their incorporation improves clinical practice or trial enrollment.

Mouse fetal liver cells in artificial capillary beds in three-dimensional four-compartment bioreactors.

Bioreactors containing porcine or adult human hepatocytes have been used to sustain acute liver failure patients until liver transplantation. However, prolonged function of adult hepatocytes has not been achieved due to compromised proliferation and viability of adult cells in vitro. We investigated the use of fetal hepatocytes as an alternative cell source in bioreactors. Mouse fetal liver cells from gestational day 17 possessed intermediate differentiation and function based on their molecular profile. When cultured in a three-dimensional four-compartment hollow fiber-based bioreactor for 3 to 5 weeks these cells formed neo-tissues that were characterized comprehensively. Albumin liberation, testosterone metabolism, and P450 induction were demonstrated. Histology showed predominant ribbon-like three-dimensional structures composed of hepatocytes between hollow fibers. High positivity for proliferating cell nuclear antigen and Ki-67 and low positivity for terminal dUTP nick-end labeling indicated robust cell proliferation and survival. Most cells within these ribbon arrangements were albumin-positive. In addition, cells in peripheral zones were simultaneously positive for alpha-fetoprotein, cytokeratin-19, and c-kit, indicating their progenitor phenotype. Mesenchymal components including endothelial, stellate, and smooth muscle cells were also observed. Thus, fetal liver cells can survive, proliferate, differentiate, and function in a three-dimensional perfusion culture system while maintaining a progenitor pool, reflecting an important advance in hepatic tissue engineering.