TY - JOUR AB - Type 2 diabetes mellitus (T2D) has become a global epidemic affecting the health of millions of people. T2D is a complex and multifactorial metabolic disease, largely characterized by a combination of impaired insulin secretion from β cells residing within the islets of the pancreas and peripheral insulin resistance. In this article, we discuss the current state and risk factors for T2D, conventional treatment options, and upcoming strategies, including progress in the areas of allogeneic and xenogeneic islet transplantation, with a major focus on stem cell-derived β cells and associated technologies. AU - Ashe, S.* AU - Hebrok, M. C1 - 68732 C2 - 54941 CY - 1600 John F Kennedy Boulevard, Ste 1800, Philadelphia, Pa 19103-2899 Usa TI - Role of cell-based therapies in T2D. JO - Semin. Nephrol. VL - 43 IS - 3 PB - W B Saunders Co-elsevier Inc PY - 2023 SN - 0270-9295 ER - TY - JOUR AB - Metabolites are small molecules that are intermediates or products of metabolism, many of which are freely filtered by the kidneys. In addition, the kidneys have a central role in metabolite anabolism and catabolism, as well as in active metabolite reabsorption and/or secretion during tubular passage. This review article illustrates how the coupling of genomics and metabolomics in genome-wide association analyses of metabolites can be used to illuminate mechanisms underlying human metabolism, with a special focus on insights relevant to nephrology. First, genetic susceptibility loci for reduced kidney function and chronic kidney disease (CKD) were reviewed systematically for their associations with metabolite concentrations in metabolomics studies of blood and urine. Second, kidney function and CKD-associated metabolites reported from observational studies were interrogated for metabolite-associated genetic variants to generate and discuss complementary insights. Finally, insights originating from the simultaneous study of both blood and urine or by modeling intermetabolite relationships are summarized. We also discuss methodologic questions related to the study of metabolite concentrations in urine as well as among CKD patients. In summary, genome-wide association analyses of metabolites using metabolite concentrations quantified from blood and/or urine are a promising avenue of research to illuminate physiological and pathophysiological functions of the kidney. AU - Köttgen, A.* AU - Raffler, J. AU - Sekula, P.* AU - Kastenmüller, G. C1 - 53214 C2 - 44650 SP - 151-174 TI - Genome-wide association studies of metabolite concentrations (mGWAS): Relevance for nephrology. JO - Semin. Nephrol. VL - 38 IS - 2 PY - 2018 SN - 0270-9295 ER - TY - JOUR AB - Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI. The detection of AKI in hospitalized patients implies the need for early, accurate, robust, and easily accessible biomarkers of AKI evolution and outcome prediction because only a narrow window exists to implement the earlier-described measures. Even more challenging is the multifactorial origin of AKI and the fact that the changes of molecular expression induced by AKI are difficult to distinguish from those of the diseases associated or causing AKI as shock or sepsis. During the past decade, a considerable number of protein biomarkers for AKI have been described and we expect from recent advances in the field of omics technologies that this number will increase further in the future and be extended to other sorts of biomolecules, such as RNAs, lipids, and metabolites. However, most of these biomarkers are poorly defined by their AKI-associated molecular context. In this review, we describe the state-of-the-art tissue and biofluid proteomic and metabolomic technologies and new bioinformatics approaches for proteomic and metabolomic pathway and molecular interaction analysis. In the second part of the review, we focus on AKI-associated proteomic and metabolomic biomarkers and briefly outline their pathophysiological context in AKI. AU - Marx, D.* AU - Metzger, J.* AU - Pejchinovski, M.* AU - Gil, R.B. AU - Frantzi, M.* AU - Latosinska, A.* AU - Belczacka, I.* AU - Heinzmann, S.S. AU - Husi, H.* AU - Zoidakis, J.* AU - Klingele, M.* AU - Herget-Rosenthal, S.* C1 - 52172 C2 - 44199 CY - Philadelphia SP - 63-87 TI - Proteomics and metabolomics for AKI diagnosis. JO - Semin. Nephrol. VL - 38 IS - 1 PB - W B Saunders Co-elsevier Inc PY - 2018 SN - 0270-9295 ER - TY - JOUR AB - The development of proteomic and metabolomic technologies holds the promise to significantly impact patient management by improving diagnosis, unraveling more appropriate therapeutic targets, and enabling more precise prognosis of disease development. Proteomics and metabolomics have been applied with the aim of improving dialysis, defining uremic toxins, and unraveling their origin. Ideally, these technologies should inform us which proteomic or metabolomic compounds are subject to significant alterations of concentration or structure as a result of failing kidney function, and thus can be considered as potential uremic toxins. After a few years of applying these technologies in the area of uremic toxicity studies we are now in a position where we can estimate how and what they can contribute to the field. In this review we critically examine the current literature on the application of proteomics and metabolomics in the context of dialysis and uremic toxins. We highlight the most promising findings, indicate where we see the current need, and which future developments consequently are to be expected, given the technological constraints that undoubtedly exist. AU - Mullen, W.* AU - Saigusa, D.* AU - Abe, T.* AU - Adamski, J. AU - Mischak, H.* C1 - 31184 C2 - 34313 CY - Philadelphia SP - 180-190 TI - Proteomics and metabolomics as tools to unravel novel culprits and mechanisms of uremic toxicity: Instrument or hype? JO - Semin. Nephrol. VL - 34 IS - 2 PB - W B Saunders Co-elsevier Inc PY - 2014 SN - 0270-9295 ER -