TY  - JOUR
AB  - BACKGROUND AND HYPOTHESIS: The endogenous opioid proenkephalin (PENK) has been identified as an independent risk marker for acute cardiovascular diseases and acute kidney injury (AKI). However, its regulation, its association with other cardiometabolic markers, and its prognostic role in patients with chronic kidney disease (CKD) have not been thoroughly investigated. METHODS: PENK serum levels were cross-sectionally related to renal and cardiometabolic markers across three large cohorts (total N = 4 722), including the Leipzig-CKD cohort (N = 581), as well as the population-based LIFE-Adult (N = 3 093) and Sorbs (N = 1 048) cohort. Furthermore, a longitudinal analysis was performed in the Leipzig-CKD cohort to assess the association between circulating PENK levels at baseline and a composite 4-point major adverse renal events (4P-MARE)-endpoint comprising incident or worsening kidney disease, development of kidney failure (KF) requiring kidney replacement therapy or kidney transplantation, and renal deaths. RESULTS: In the entire cross-sectional cohort (N = 4 722), PENK levels were strongly and inversely correlated with markers of renal function, i.e. estimated glomerular filtration rate (eGFR), creatinine, and urinary albumin creatinine ratio (uACR). In multivariable analysis, eGFR was the strongest, independent, and inverse predictor of circulating PENK levels after adjustment for age, sex, as well as markers of obesity, glucose intolerance, dyslipidemia, and inflammation.Multivariable Cox regression analysis revealed that baseline circulating PENK levels were strongly associated with an increased risk of the 4P-MARE over a median follow-up of 8.7 years. Each doubling of PENK levels was associated with a more than two-fold increase in the risk of developing 4P-MARE, even after adjusting for various clinical and metabolic variables. PENK provided added value for predicting adverse renal outcomes. CONCLUSIONS: PENK levels are strongly, independently, and inversely associated with renal function in cross-sectional analysis. Furthermore, baseline circulating PENK levels are predictive of a 4P-MARE in patients and added independent, prognostic value for identification of patients at risk for adverse renal outcomes.
AU  - Würfel, M.*
AU  - Pirlich, L.*
AU  - Baratashvili, E.*
AU  - Dahlström, E.H.*
AU  - Baalmann, F.*
AU  - Bachmann, A.*
AU  - Breitfeld, J.*
AU  - Wendt, R.*
AU  - Baber, R.*
AU  - Haussmann, M.*
AU  - Bast, I.*
AU  - Beige, J.*
AU  - Isermann, B.*
AU  - Kovacs, P.*
AU  - Blüher, M.
AU  - Stumvoll, M.*
AU  - Schürfeld, R.*
AU  - Tönjes, A.*
AU  - Ebert, T.*
C1  - 75806
C2  - 58105
TI  - Proenkephalin predicts kidney function and major adverse kidney events in CKD.
JO  - Nephrol. Dial. Transplant.
PY  - 2025
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - Ferroptosis is a regulated cell death modality triggered by iron-dependent lipid peroxidation. Ferroptosis plays a causal role in the pathophysiology of various diseases, making it a promising therapeutic target. Unlike all other cell death modalities dependent on distinct signaling cues, ferroptosis occurs when cellular antioxidative defense mechanisms fail to suppress the oxidative destruction of cellular membranes, eventually leading to cell membrane rupture. Physiologically, only two such surveillance systems are known to efficiently prevent the lipid peroxidation chain reaction by reducing (phospho)lipid hydroperoxides to their corresponding alcohols or by reducing radicals in phospholipid bilayers, thus maintaining the integrity of lipid membranes. Mechanistically, these two systems are linked to the reducing capacity of glutathione peroxidase 4 (GPX4) by consuming glutathione (GSH) on the one and ferroptosis suppressor protein 1 (FSP1, formerly AIFM2) on the other hand. Notably, the importance of ferroptosis suppression in physiological contexts has been linked to a particular vulnerability of renal tissue. In fact, early work has shown that mice genetically lacking Gpx4 rapidly succumb to acute renal failure with pathohistological features of acute tubular necrosis. Promising research attempting to implicate ferroptosis in various renal disease entities, particularly those with proximal tubular involvement, has generated a wealth of knowledge with widespread potential for clinical translation. Here, we provide a brief overview of the involvement of ferroptosis in nephrology. Our goal is to introduce this expanding field for clinically versed nephrologists in the hope of spurring future efforts to prevent ferroptosis in the pathophysiological processes of the kidney.
AU  - Seibt, T.
AU  - Wahida, A.
AU  - Hoeft, K.*
AU  - Kemmner, S.*
AU  - Linkermann, A.*
AU  - Mishima, E.
AU  - Conrad, M.
C1  - 70635
C2  - 55902
SP  - 1754-1761
TI  - The biology of ferroptosis in kidney disease.
JO  - Nephrol. Dial. Transplant.
VL  - 39
IS  - 11
PY  - 2024
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - BACKGROUND AND HYPOTHESIS: Organ transplantation reverses cognitive impairment in chronic kidney disease (CKD), indicating that cognitive impairment driven by CKD is therapeutically amendable. We recently demonstrated that impaired cognition in CKD is linked to IL-1β-release from microglia and IL-1R1-signaling in neuronal cells, thereby identifying a signaling pathway that can be exploited therapeutically. However, the mechanism of IL-1β-maturation in microglia in CKD remains unknown. We hypothesized that microglia cells require caspase-1 for CKD-driven cognitive impairment. METHODS: We used a combination of single cell analyses, in situ analyses, genetically modified mouse models (including newly generated Cre-LoxP mouse models) and in vitro models. The current study builds on a recently identified intercellular crosstalk between microglia and neurons that impairs cognition in chronic kidney disease (CKD). RESULTS: Here, we show that despite NLRP3 inflammasome activation in the brain and protection of mice with constitutive NLRP3 deficiency from CKD-induced cognitive impairment, (i) caspase-1 is not required for IL-1β maturation in microglia and (ii) targeted caspase-1 deficiency in microglia does not improve cognition in CKD mice. These data indicate that IL-1β maturation in microglia is independent of the NLRP3-caspase-1 interaction in CKD. Indeed, microglia activation in CKD induces noncanonical, cathepsin C-caspase-8 mediated IL-1β maturation. Depletion of cathepsin C or caspase-8 blocks IL-1β maturation in microglia. Preliminary analyses suggest that noncanonical microglia IL-1β maturation occurs also in diabetes mellitus. CONCLUSION: These results identify a noncanonical IL-1β-maturation pathway as a potential therapeutic target to combat microglia-induced neuronal dysfunction in CKD and possible other peripheral diseases.
AU  - Zimmermann, S.*
AU  - Mathew, A.*
AU  - Bondareva, O.
AU  - Elwakiel, A.*
AU  - Jiang, S.*
AU  - Rana, R.*
AU  - Bechmann, I.*
AU  - Goldschmidt, J.*
AU  - Klöting, N.
AU  - Sheikh, B.
AU  - Isermann, B.*
C1  - 72234
C2  - 56510
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 929-942
TI  - Noncanonical microglial IL-1β maturation in chronic kidney disease.
JO  - Nephrol. Dial. Transplant.
VL  - 40
IS  - 5
PB  - Oxford Univ Press
PY  - 2024
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - BACKGROUND: We aimed to evaluate the relationship of fatty liver, estimated by fatty liver index (FLI), with kidney function and chronic kidney disease (CKD) in a German cohort study, given the lack of prospective evidence in Europeans. METHODS: We included 2920 participants (51.6% women, mean age 56.1 years) from the KORA study, of which 1991 were followed up for an average of 6.4 (± 0.3) years. Kidney function was assessed using the glomerular filtration rate estimated by creatinine (eGFR-cr) or cystatin C (eGFR-cc). We used multiple logistic or linear regressions to evaluate the associations between FLI, kidney function and CKD (eGFR < 60 ml/min per 1.73 m2), and mediation analysis to explore the mediation effects of metabolic factors. RESULTS: The prevalence of FLI ≥ 60 and CKD were 40.4% and 5.6% at baseline, and 182 participants developed CKD during the follow-up. Cross-sectionally, FLI was significantly inversely associated with eGFR-cc [β, 95%CI: -1.14 (-1.81, -0.47)] and prevalent CKD based on eGFR-cc [OR, 95%CI: 1.28 (1.01, 1.61)], but not with other markers. After adjusting for lifestyle factors, we found a positive association between FLI and incident CKD defined by eGFR-cc or/eGFR-cr, which was attenuated after controlling for metabolic risk factors. Mediation analysis showed that the association was completely mediated by inflammation, diabetes and hypertension jointly. CONCLUSIONS: The positive association between FLI and CKD incidence was fully mediated by the joint effect of metabolic risk factors. Future longitudinal studies need to explore the chronological interplay between fatty liver, cardiometabolic risk factors and kidney function with repeated measurements.
AU  - Cai, X.
AU  - Thorand, B.
AU  - Hohenester, S.*
AU  - Koenig, W.*
AU  - Rathmann, W.*
AU  - Peters, A.
AU  - Nano, J.
C1  - 66385
C2  - 53162
SP  - 1240-1248
TI  - Association between the fatty liver index and chronic kidney disease: The population-based KORA study.
JO  - Nephrol. Dial. Transplant.
VL  - 38
IS  - 5
PY  - 2022
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - BACKGROUND: Inflammatory processes have been implicated in the development of chronic kidney disease (CKD). We investigated the association of a large panel of inflammatory biomarkers reflecting aspects of immunity with kidney function and CKD incidence. METHODS: We used data from two independent population-based studies, KORA F4 (discovery, n = 1,110, mean age 70.3 years, 48.7% male) and ESTHER (replication, n = 1,672, mean age 61.9 years, 43.6% male). Serum levels of biomarkers were measured using proximity extension assay technology. The association of biomarkers with estimated glomerular filtration rate (eGFR) at baseline and with incident CKD was investigated using linear and logistic regression models adjusted for cardiorenal risk factors. Independent results from prospective analyses of both studies were pooled. The significance level was corrected for multiple testing by false-discovery rate (PFDR < 0.05.). RESULTS: In the KORA F4 discovery study, 52 out of 71 inflammatory biomarkers were inversely associated with eGFR estimated based on serum creatinine. Top biomarkers included CD40, TNFRSF9 and IL10RB. Forty-two of these 52 biomarkers were replicated in the ESTHER study. Nine of the 42 biomarkers were associated with incident CKD independently of cardiorenal risk factors in the meta-analysis of the KORA (n = 142, mean follow-up of 6.5 years) and ESTHER (n = 103, mean follow-up of 8 years) studies. Pathway analysis revealed the involvement of inflammatory and immunomodulatory processes reflecting cross-communication of innate and adaptive immune cells. CONCLUSIONS: Novel and known biomarkers of inflammation were reproducibly associated with kidney function. Future studies should investigate their clinical utility and underlying molecular mechanisms in independent cohorts.
AU  - Nano, J.
AU  - Schöttker, B.*
AU  - Lin, J.
AU  - Huth, C.
AU  - Ghanbari, M.*
AU  - Matias-Garcia, P.R.
AU  - Maalmi, H.*
AU  - Karrasch, S.
AU  - Koenig, W.*
AU  - Rothenbacher, D.*
AU  - Roden, M.*
AU  - Meisinger, C.
AU  - Peters, A.
AU  - Brenner, H.*
AU  - Herder, C.*
AU  - Thorand, B.
C1  - 63299
C2  - 51460
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 1916-1926
TI  - Novel biomarkers of inflammation, kidney function and chronic kidney disease in the general population.
JO  - Nephrol. Dial. Transplant.
VL  - 37
IS  - 10
PB  - Oxford Univ Press
PY  - 2022
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - Background. Chronic kidney disease (CKD) is a recognized global health problem. While some CKD patients remain stable after initial diagnosis, others can rapidly progress towards end-stage renal disease (ESRD). This makes biomarkers capable of detecting progressive forms of CKD extremely valuable, especially in non-invasive biofluids such as urine. Screening for metabolite markers using non-targeted metabolomic techniques like nuclear magnetic resonance spectroscopy is increasingly applied to CKD research.Methods. A cohort of CKD patients (n = 227) with estimated glomerular filtration rates (eGFRs) ranging from 9.4-130 mL/min/1.73 m(2) was Devaluated and urine metabolite profiles were characterized in relation to declining eGFR. Nested in this cohort, a retrospective subset (n = 57) was investigated for prognostic metabolite markers of CKD progression, independent of baseline eGFR. A transcriptomic analysis of murine models of renal failure was performed to validate selected metabolomic findings.Results. General linear modeling revealed 11 urinary metabolites with significant associations to reduced eGFR. Linear modelling specifically showed that increased urine concentrations of betaine (P < 0.05) and myo-inositol (P < 0.05) are significant prognostic markers of CKD progression.Conclusions. Renal organic osmolytes, betaine and myoinositol play a critical role in protecting renal cells from hyperosmotic stress. Kidney tissue transcriptomics of murine preclinical experimentation identified decreased expression of Slc6a12 and Slc5a11 mRNA in renal tissue consistent with defective tubular transport of these osmolytes. Imbalances in renal osmolyte regulation lead to increased renal cell damage and thus more progressive forms of CKD. Increases in renal osmolytes in urine could provide clinical diagnostic and prognostic information on CKD outcomes.
AU  - Gil, R.B.
AU  - Ortiz, A.P.*
AU  - Sanchez-Niño, M.D.*
AU  - Markoska, K.*
AU  - Schepers, E.*
AU  - Vanholder, R.*
AU  - Glorieux, G.*
AU  - Schmitt-Kopplin, P.
AU  - Heinzmann, S.S.
C1  - 53278
C2  - 44514
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 2156-2164
TI  - Increased urinary osmolyte excretion indicates chronic kidney disease severity and progression rate.
JO  - Nephrol. Dial. Transplant.
VL  - 33
IS  - 12
PB  - Oxford Univ Press
PY  - 2018
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - Background. Although haemodialysis (HD) leads to alterations of systemic haemodynamics that can be monitored using dilution methods, there is a lack of data on the diagnostic and prognostic significance of haemodynamic monitoring during routine HD. Methods. In this multicentre study, we measured cardiac index (CI), access flow (AF) and central blood volume index (CBVI) during a single HD session in stable HD patients (n ¼ 215) using the Transonic HD03 monitor (Transonic, Ithaca, NY, USA). Systemic CI (SCI) was defined as CI corrected for AF. In a subset of patients (n ¼ 82), total end-diastolic volume index (TEDVI) and total ejection fraction (TEF) were derived from dilution curves. Data were correlated with clinical parameters, cardiac biomarkers and bioimpedance measurements (body composition monitor; Fresenius Medical Care, Homburg, Germany). Mortality was assessed prospectively after a median follow-up of 2.6 years. Results. Median CI, CBVI and AF were 2.8 L/min/m2 (interquartile range 2.4–3.4), 15 mL/kg (14.5–15.7) and 980 mL/min (740–1415), respectively, at the beginning of HD. At the end of HD, CI, CBVI and AF significantly fell by 10% (22 to 3, P < 0.0001), 9% (23 to 3, P < 0.0001) and 4% (13 to 5, P ¼ 0.0004), respectively. Peripheral resistance (PR) increased slightly (P ¼ 0.01) and blood pressure fell by 6/3 mmHg to 128/63 mmHg (P < 0.0001). Independent predictors of DCI were age and ultrafiltration rate, whereas AF, overhydration and PR were protective. TEF was strongly associated with mortality [area under the dilution curve 0.77, P < 0.0001], followed by TEDVI (0.72, P ¼ 0.0002) and SCI (0.60, P ¼ 0.02). Conclusions. HD leads to a reduction of CI due to ultrafiltration. Haemodynamic monitoring identifies a significant number of HD patients with cardiac impairment that are at risk for increased mortality.
AU  - Haag, S.*
AU  - Friedrich, B.*
AU  - Peter, A.
AU  - Häring, H.-U.
AU  - Heyne, N.
AU  - Artunc, F.
C1  - 54151
C2  - 45324
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 1419-1427
TI  - Systemic haemodynamics in haemodialysis: Intradialytic changes and prognostic significance.
JO  - Nephrol. Dial. Transplant.
VL  - 33
IS  - 8
PB  - Oxford Univ Press
PY  - 2018
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - Background. Renal function is known to affect glucose metabolism. The aim of this study was to assess glucose metabolism in end-stage renal disease (ESRD) patients and in matched controls with normal renal function and to delineate its underlying pathophysiology. Methods. ESRD patients without diabetes mellitus on the active kidney transplant waiting list of a large European university hospital were metabolically phenotyped by an oral glucose tolerance test (OGTT) and by calculating insulin sensitivity and secretion indices. Matched controls with normal renal function were derived from the TUEF (Tuebingen Family) study cohort, which includes healthy non-diabetic individuals with an increased risk of developing type 2 diabetes. Matches were made for (i) gender, age and body mass index (BMI) (cohort 1) and for (ii) gender, age, BMI, fasting plasma glucose (FPG) and 2-h glucose in OGTT (cohort 2). Results. A total of 107 patients ( 90 on haemodialysis and 17 on peritoneal dialysis) and two cohorts, each comprising 107 matched controls, were investigated. ESRD patients had significantly lower FPG. Additional matching for OGTT glucose concentrations revealed significantly lower insulin sensitivity in ESRD patients than in controls. This finding was abrogated after adjustment for triglyceride levels. Insulin secretion, however, was significantly higher in ESRD patients. Insulin kinetics during OGTT as well as C-peptide levels demonstrate higher insulin secretion to be a compensation for lower insulin sensitivity and not to result from impaired insulin clearance. Conclusion. Our study is the first to provide metabolic phenotyping in patients with ESRD and to compare them with matched controls with normal renal function. Glucose metabolism differs substantially between cohorts, with insulin resistance and a compensatory increase in insulin secretion in ESRD patients.
AU  - Guthoff, M.
AU  - Wagner, R.
AU  - Vosseler, D.*
AU  - Peter, A.
AU  - Nadalin, S.*
AU  - Häring, H.-U.
AU  - Fritsche, A.
AU  - Heyne, N.
C1  - 51220
C2  - 42924
CY  - Oxford
SP  - 670-676
TI  - Impact of end-stage renal disease on glucose metabolism-a matched cohort analysis.
JO  - Nephrol. Dial. Transplant.
VL  - 32
IS  - 4
PB  - Oxford Univ Press
PY  - 2017
SN  - 0931-0509
ER  - 

TY  - JOUR
AU  - Gil, R.B.
AU  - Heinzmann, S.S.*
AU  - Wörmann, K.
AU  - Pontillo, C.*
AU  - Vanholder, R.*
AU  - Schmitt-Kopplin, P.
AU  - Mischak, H.*
C1  - 47085
C2  - 39212
TI  - Non-targeted metabolomics approaches for elucidation of novel diagnostic markers in chronic kidney disease.
JO  - Nephrol. Dial. Transplant.
VL  - 30
PY  - 2015
SN  - 0931-0509
ER  - 

TY  - JOUR
AU  - Le, M.*
AU  - Rathkolb, B.*
AU  - Aigner, B.*
AU  - Hrabě de Angelis, M.
AU  - Wolf, E.*
AU  - Wanke, R.*
AU  - Kemter, E.*
C1  - 47083
C2  - 39214
TI  - Detailed morphological analyses of a novel mouse model of site-specific glomerular thrombotic microangiopathy.
JO  - Nephrol. Dial. Transplant.
VL  - 30
PY  - 2015
SN  - 0931-0509
ER  - 

TY  - JOUR
AU  - Zawada, A.M.*
AU  - Fell, L.H.*
AU  - Untersteller, K.*
AU  - Seiler, S.*
AU  - Rogacev, K.S.*
AU  - Fliser, D.*
AU  - Ziegler-Heitbrock, L.
AU  - Heine, G.H.*
C1  - 47084
C2  - 39213
TI  - Gating strategy for the identification of intermediate monocytes in patients with chronic kidney disease.
JO  - Nephrol. Dial. Transplant.
VL  - 30
PY  - 2015
SN  - 0931-0509
ER  - 

TY  - JOUR
AU  - Dumann, K.*
AU  - Hörrmann, B.*
AU  - Lammert, A.*
AU  - Rheinberger, M.*
AU  - Gorski, M.*
AU  - Krämer, B.K.*
AU  - Heid, I.M.
AU  - Böger, C.A.*
C1  - 31456
C2  - 34504
SP  - iii419
TI  - Association of cutaneous Advanced Glycation End Products (AGES) with Chronic Kidney Disease (CKD) in Diabetes Mellitus type 2 (DM2): A subgroup analysis of the diacore study baseline visit.
JO  - Nephrol. Dial. Transplant.
VL  - 29
PY  - 2014
SN  - 0931-0509
ER  - 

TY  - JOUR
AU  - Fischereder, M.*
AU  - Michalke, B.
AU  - Schmoeckel, E.*
AU  - Habicht, A.*
AU  - Szabados, B.*
AU  - Nelson, P.J.*
AU  - Stangl, M.*
C1  - 31868
C2  - 34823
CY  - Oxford
SP  - 14
TI  - Tissue sodium content varies interindividually and correlates with glycosaminoglycan expression.
JO  - Nephrol. Dial. Transplant.
VL  - 29
PB  - Oxford Univ Press
PY  - 2014
SN  - 0931-0509
ER  - 

TY  - JOUR
AU  - Rheinberger, M.*
AU  - Hörmann, B.*
AU  - Lammert, A.*
AU  - Dumann, K.*
AU  - Gorski, M.*
AU  - Heid, I.M.
AU  - Krämer, B.K.*
AU  - Böger, C.A.*
C1  - 31477
C2  - 34503
SP  - 424
TI  - Chronic Kidney Disease (CKD) and obesity in Diabetes Mellitus type 2 (DM2): Baseline characteristics of the Diabetes Cohorte study (DIACORE).
JO  - Nephrol. Dial. Transplant.
VL  - 29
PY  - 2014
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - The prevalence of obesity is increasing worldwide and contributes to many health problems, including kidney disease. Unexpectedly, 10-30% of obese individuals are apparently not at increased risk of metabolic diseases, e.g. type 2 diabetes, cardiovascular disease and risk of renal disease. Their phenotype is labeled 'metabolically healthy obesity'. In the search for mechanisms explaining this unexpected condition, a favourable type of body fat distribution with low insulin resistance and with low subclinical inflammation has been identified. Furthermore, signalling pathways have been found that distinguish between metabolically benign and malignant obesity. In addition, the important roles of fatty acids, adipokines and hepatokines were identified. These factors regulate insulin resistance and subclinical inflammation. Onset and evolution of chronic kidney disease (CKD) are affected by obesity. CKD also increases the risk of insulin resistance and subclinical inflammation, two pathways that play an important role in the pathogenesis of renal malfunction. This brief review summarizes novel insights, specifically how distinct body fat compartments (including perivascular and even renal sinus fat) may have an impact on progression of CKD.
AU  - Stefan, N.
AU  - Artunc, F.*
AU  - Heyne, N.*
AU  - Machann, J.
AU  - Schleicher, E.D.*
AU  - Häring, H.-U.
C1  - 47504
C2  - 39338
TI  - Obesity and renal disease: Not all fat is created equal and not all obesity is harmful to the kidneys.
JO  - Nephrol. Dial. Transplant.
PY  - 2014
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - BACKGROUND: Serum metabolites are associated cross-sectionally with kidney function in population-based studies. METHODS: Using flow injection and liquid chromatography tandem mass spectrometry methods, we examined longitudinal associations of baseline concentrations of 140 metabolites and their 19 460 ratios with kidney function decline and chronic kidney disease (CKD) incidence over 7 years in 1104 participants of the Cooperative Health Research in the Region of Augsburg S4/F4 study. RESULTS: Corrected for multiple testing, a significant association with annual change in the estimated glomerular filtration rate was observed for spermidine (P = 5.8 × 10-7) and two metabolite ratios, the phosphatidylcholine diacyl C42:5-to-phosphatidylcholine acyl-alkyl C36:0 ratio (P = 1.5 × 10-6) and the kynurenine-to-tryptophan ratio (P = 1.9 × 10-6). The kynurenine-to-tryptophan ratio was also associated with significantly higher incidence of CKD at the follow-up visit with an odds ratio of 1.36 per standard deviation increase; 95% confidence interval 1.11-1.66, P = 2.7 × 10-3). In separate analyses, the predictive ability of the metabolites was assessed: both the three significantly associated metabolite (ratios) as well as a panel of 35 metabolites selected from all metabolites in an unbiased fashion provided as much but not significantly more prognostic information than selected clinical predictors as judged by the area under the curve. CONCLUSIONS: Baseline serum concentrations of spermidine and two metabolite ratios were associated with kidney function change over subsequent years in the general population. In separate analyses, baseline serum metabolites were able to predict incident CKD to a similar but not better extent than selected clinical parameters. Our longitudinal findings provide a basis for targeted studies of certain metabolic pathways, e.g. tryptophan metabolism, and their relation to kidney function decline. KEYWORDS: GFR, incident chronic kidney disease, kidney function loss, metabolites, prediction  
AU  - Goek, O.-N.*
AU  - Prehn, C.
AU  - Sekula, P.*
AU  - Römisch-Margl, W.
AU  - Döring, A.
AU  - Gieger, C.
AU  - Heier, M.
AU  - Koenig, W.*
AU  - Wang-Sattler, R.
AU  - Illig, T.
AU  - Suhre, K.
AU  - Adamski, J.
AU  - Köttgen, A.*
AU  - Meisinger, C.
C1  - 24775
C2  - 31673
SP  - 2131-2138
TI  - Metabolites associate with kidney function decline and incident chronic kidney disease in the general population.
JO  - Nephrol. Dial. Transplant.
VL  - 28
IS  - 8
PB  - Oxford Univ. Press
PY  - 2013
SN  - 0931-0509
ER  - 

TY  - JOUR
AB  - BACKGROUND: Dimethylarginines are inhibitors of NO synthesis and are involved in the pathogenesis of vascular diseases. In this study, we ask the question if asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels change during fatal and reversible acute rejection, and contribute to the pathogenesis of chronic vasculopathy. METHODS: The Dark Agouti to Lewis rat strain combination was used to investigate fatal acute rejection. Fischer 344 kidneys were transplanted to Lewis rats to study reversible acute rejection episode and the process of chronic rejection. Isograft recipients and untreated Lewis rats were used as controls. l-arginine derivatives were determined by HPLC, and ADMA-metabolizing enzymes were studied by quantitative RT-PCR and western blotting. RESULTS: Renal transplantation transiently increased dimethylarginine levels independent of acute rejection. ADMA plasma levels did not importantly differ between recipients undergoing fatal or reversible acute rejection, whereas SDMA was even lower in recipients of Fisher 344 grafts. In comparison to isograft recipients, ADMA and SDMA levels were slightly elevated during reversible, but not during the process of chronic rejection. Increased dimethylarginine levels, however, did not block NO synthesis. Interestingly, protein methylation, but not ADMA degradation, was increased in allografts. CONCLUSIONS: Our data do not support the concept that renal allografts are protected from fatal rejection by dimethylarginines. Dimethylarginines may play a role in triggering chronic rejection, but a contribution to vascular remodelling itself is improbable. In contrast, differential arginine methylation of yet unknown proteins by PRMT1 may be involved in the pathogenesis of acute and chronic rejection.
AU  - Zakrzewicz, D.*
AU  - Zakrzewicz, A.*
AU  - Wilker, S.*
AU  - Boedeker, R.H.*
AU  - Padberg, W.*
AU  - Eickelberg, O.
AU  - Grau, V.*
C1  - 6098
C2  - 28074
SP  - 124-135
TI  - Dimethylarginine metabolism during acute and chronic rejection of rat renal allografts.
JO  - Nephrol. Dial. Transplant.
VL  - 26
IS  - 1
PB  - Oxford Univ. Press
PY  - 2011
SN  - 0931-0509
ER  - 

TY  - JOUR
AU  - Lieb, W.*
AU  - Mayer, B.*
AU  - Stritzke, J.*
AU  - Döring, A.
AU  - Hense, H.-W.*
AU  - Löwel, H.
AU  - Erdmann, J.*
AU  - Schunkert, H.*
C1  - 2313
C2  - 24260
SP  - 2780-2787
TI  - Association of low-grade urinary albumin excretion with left ventricular hypertrophy in the general population: The MONICA/KORA Augsburg echocardiographic substudy.
JO  - Nephrol. Dial. Transplant.
VL  - 21
PY  - 2006
SN  - 0931-0509
ER  -