TY  - JOUR
AB  - Chronic kidney disease (CKD) has a high prevalence in the general population and is associated with high mortality; a need therefore exists for better biomarkers for diagnosis, monitoring of disease progression and therapy stratification. Moreover, very sensitive biomarkers are needed in drug development and clinical research to increase understanding of the efficacy and safety of potential and existing therapies. Metabolomics analyses can identify and quantify all metabolites present in a given sample, covering hundreds to thousands of metabolites. Sample preparation for metabolomics requires a very fast arrest of biochemical processes. Present key technologies for metabolomics are mass spectrometry and proton nuclear magnetic resonance spectroscopy, which require sophisticated biostatistic and bioinformatic data analyses. The use of metabolomics has been instrumental in identifying new biomarkers of CKD such as acylcarnitines, glycerolipids, dimethylarginines and metabolites of tryptophan, the citric acid cycle and the urea cycle. Biomarkers such as c-mannosyl tryptophan and pseudouridine have better performance in CKD stratification than does creatinine. Future challenges in metabolomics analyses are prospective studies and deconvolution of CKD biomarkers from those of other diseases such as metabolic syndrome, diabetes mellitus, inflammatory conditions, stress and cancer.
AU  - Hocher, B.*
AU  - Adamski, J.
C1  - 50615
C2  - 42454
CY  - New York
SP  - 269-284
TI  - Metabolomics for clinical use and research in chronic kidney disease.
JO  - Nat. Rev. Nephrol.
VL  - 13
IS  - 5
PB  - Nature Publishing Group
PY  - 2017
SN  - 1759-5061
ER  - 

TY  - JOUR
AB  - Insulin resistance is a systemic disorder that affects many organs and insulin-regulated pathways. The disorder is characterized by a reduced action of insulin despite increased insulin concentrations (hyperinsulinaemia). The effects of insulin on the kidney and vasculature differ in part from the effects on classical insulin target organs. Insulin causes vasodilation by enhancing endothelial nitric oxide production through activation of the phosphatidylinositol 3-kinase pathway. In insulin-resistant states, this pathway is impaired and the mitogen-activated protein kinase pathway stimulates vasoconstriction. The action of insulin on perivascular fat tissue and the subsequent effects on the vascular wall are not fully understood, but the hepatokine fetuin-A, which is released by fatty liver, might promote the proinflammatory effects of perivascular fat. The strong association of salt-sensitive arterial hypertension with insulin resistance indicates an involvement of the kidney in the insulin resistance syndrome. The insulin receptor is expressed on renal tubular cells and podocytes and insulin signalling has important roles in podocyte viability and tubular function. Renal sodium transport is preserved in insulin resistance and contributes to the salt-sensitivity of blood pressure in hyperinsulinaemia. Therapeutically, renal and vascular insulin resistance can be improved by an integrated holistic approach aimed at restoring overall insulin sensitivity and improving insulin signalling.
AU  - Artunc, F.
AU  - Schleicher, E.
AU  - Weigert, C.
AU  - Fritsche, A.
AU  - Stefan, N.
AU  - Häring, H.-U.
C1  - 50085
C2  - 42011
CY  - New York
SP  - 721-737
TI  - The impact of insulin resistance on the kidney and vasculature.
JO  - Nat. Rev. Nephrol.
VL  - 12
IS  - 12
PB  - Nature Publishing Group
PY  - 2016
SN  - 1759-5061
ER  - 

TY  - JOUR
AB  - New data suggest that treatment with patiromer or sodium zirconium cyclosilicate for up to 8 weeks reduces plasma potassium levels in hyperkalaemic patients. If proven safe and effective for long-term use, these therapies might be administered together with intensive renin-angiotensin-aldosterone blockade to reduce adverse effects and renal and cardiovascular risk.
AU  - Roscioni, S.
AU  - Heerspink, H.J.*
C1  - 44463
C2  - 36967
CY  - New York
SP  - 205-206
TI  - New nonabsorbable potassium-exchange resins in hyperkalaemia.
JO  - Nat. Rev. Nephrol.
VL  - 11
IS  - 4
PB  - Nature Publishing Group
PY  - 2015
SN  - 1759-5061
ER  -