TY  - JOUR
AB  - INTRODUCTION: SGLT2 inhibitors are used to reduce the risk of progression of chronic kidney disease (CKD). In patients with type 2 diabetes, they have been found to reduce extracellular volume. Given the high prevalence of extracellular volume expansion and overhydration (OH) in CKD, we investigated whether SGLT2 inhibitors might correct these disturbances in CKD patients. METHODS: CKD patients who started treatment with an SGLT2 inhibitor were investigated in this prospective observational study for 6 months. Body composition and fluid status were measured by bioimpedance spectroscopy. In addition, spot urine samples were analyzed for albuminuria, glucosuria, and urinary aprotinin-sensitive serine protease activity. RESULTS: Forty-two patients (29% with diabetic/hypertensive CKD, 31% with IgA nephropathy; 88% dapagliflozin 10 mg, 10% dapagliflozin 5 mg, 2% empagliflozin 20 mg; median eGFR 46 mL/min/1.73 m2 and albuminuria 1,911 mg/g creatinine) participated in the study. Median glucosuria increased to 14 (10-19) g/g creatinine. At baseline, patients displayed OH with +0.4 (-0.2 to 2.2) L/1.73 m2, which decreased by 0.5 (0.1-1.2) L/1.73 m2 after 6 months. Decrease of OH correlated with higher OH at BL, decrease of albuminuria, glucosuria, and urinary aprotinin-sensitive protease activity. Adipose tissue mass was not significantly reduced after 6 months. CONCLUSION: SGLT2 inhibitors reduce OH in patients with CKD, which is pronounced in the presence of high albuminuria, glucosuria, and urinary aprotinin-sensitive protease activity.
AU  - Schork, A.
AU  - Eberbach, M.L.*
AU  - Bohnert, B.N.
AU  - Wörn, M.
AU  - Heister, D.J.
AU  - Eisinger, F.
AU  - Vogel, E.
AU  - Heyne, N.
AU  - Birkenfeld, A.L.
AU  - Artunc, F.
C1  - 70604
C2  - 55594
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 124-134
TI  - SGLT2 inhibitors decrease overhydration and proteasuria in patients with chronic kidney disease: A longitudinal observational study.
JO  - Kidney Blood Press. Res.
VL  - 49
IS  - 1
PB  - Karger
PY  - 2024
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - BACKGROUND: Overhydration (OH) is common in chronic kidney disease (CKD) and might be related to the excretion of urinary serine proteases. Progression of CKD is associated with proteinuria; however, the interrelations of urinary serine proteases, OH, and progression of CKD remain unclear. METHODS: In n = 179 patients with stable nondialysis-dependent CKD of all stages, OH was measured using bioimpedance spectroscopy (Body Composition Monitor; Fresenius), and urinary serine protease activity was determined using the peptide substrate S-2302. After a median follow-up of 5.9 (IQR: 3.9-6.5) years, progression to end-stage renal disease (ESRD) was analyzed retrospectively. RESULTS: OH correlated with baseline MDRD-eGFR, urinary albumin creatinine ratio (ACR), and urinary aprotinin-sensitive serine protease activity. Progression to ESRD occurred in n = 33 patients (19%) and correlated with OH and urinary serine protease activity as well as MDRD-eGFR and ACR. Patients were divided into 2 groups determined by cutoff values from receiver operating characteristics for MDRD-eGFR (32 mL/min/1.73 m2), ACR (43 mg/g creatinine), urinary serine protease activity (0.9 RU/g creatinine), and OH (1 L/1.73 m2). Across these cutoff values, Kaplan-Meier curves for renal survival showed significant separations of the groups. In Cox regression adjusted for MDRD-eGFR, ACR, P-NT-pro-BNP, systolic blood pressure, and diabetes mellitus, patients with OH >1 L/1.73 m2 had a 3.32 (95% CI: 1.26-8.76)-fold higher risk for progression to ESRD. CONCLUSIONS: Our results corroborate that OH detected by bioimpedance spectroscopy in CKD patients is an independent risk factor for progression to ESRD in addition to GFR and albuminuria. Urinary serine protease activity is associated with OH and progression of CKD and provides a possible underlying mechanism.
AU  - Schork, A.
AU  - Bohnert, B.N.
AU  - Heyne, N.
AU  - Birkenfeld, A.L.
AU  - Artunc, F.
C1  - 60781
C2  - 49525
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 955-968
TI  - Overhydration measured by bioimpedance spectroscopy and urinary serine protease activity are risk factors for progression of chronic kidney disease.
JO  - Kidney Blood Press. Res.
VL  - 45
IS  - 6
PB  - Karger
PY  - 2020
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - Background: Unplanned start of renal replacement therapy is common in patients with end-stage renal disease and often accomplished by hemodialysis (HD) using a central venous catheter (CVC). Urgent start using peritoneal dialysis (PD) could be an alternative for some of the patients; however, this requires a hospital-based PD center that offers a structured urgent start PD (usPD) program. Methods: In this prospective study, we describe the implementation of an usPD program at our university hospital by structuring the process from presentation to PD catheter implantation and start of PD within a few days. For clinical validation, we compared the patient flow before (2013-2015) and after (2016-2018) availability of usPD. Results: In the 3 years before the availability of usPD, 14% (n = 12) of incident PD patients (n = 87) presented in an unplanned situation and were initially treated with HD using a CVC. In the 3 years after implementation of the usPD program, 18% (n = 18) of all incident PD patients (n = 103) presented in an unplanned situation of whom n = 12 (12%) were treated with usPD and n = 6 (6%) with initial HD. usPD significantly reduced the use of HD by 57% (p = 0.0005). Hospital stay was similar in patients treated with usPD (median 9 days) compared to those with elective PD (8 days), and significantly lower than in patients with initial HD (26 days, p = 0.0056). Conclusions: Implementation of an usPD program reduces HD catheter use and hospital stay in the unplanned situation.
AU  - Artunc, F.
AU  - Rueb, S.
AU  - Thiel, K.*
AU  - Thiel, C.*
AU  - Linder, K.
AU  - Baumann, D.
AU  - Bunz, H.
AU  - Muehlbacher, T.
AU  - Mahling, M.
AU  - Sayer, M.*
AU  - Petsch, M.*
AU  - Guthoff, M.
AU  - Heyne, N.
C1  - 57128
C2  - 47570
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 1383-1391
TI  - Implementation of urgent start peritoneal dialysis reduces hemodialysis catheter use and hospital stay in patients with unplanned dialysis start.
JO  - Kidney Blood Press. Res.
VL  - 44
IS  - 6
PB  - Karger
PY  - 2019
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - Background: In patients with renal failure, gadolinium-based contrast agents (GBCA) can be removed by intermittent hemodialysis (iHD) to prevent possible toxic effects. There is no data on the efficacy of GBCA removal via sustained low efficiency daily dialysis (SLEDD) which is mainly used in intensive care unit (ICU) patients. Methods: We compared the elimination of the GBCA gadobutrol in 6 ICU patients treated with SLEDD (6-12 h, 90 L dialysate) with 7 normal ward inpatients treated with iHD (4 h, dialysate flow 500 mL/min). Both groups received 3 dialysis sessions on 3 consecutive days starting after the application of gadobutrol. Blood samples were drawn before and after each session and total dialysate, as well as urine was collected. Gadolinium (Gd) concentrations were measured using mass spectrometry and eliminated Gd was calculated from dialysate and urine. Results: The initial mean plasma Gd concentration was 385 +/- 183 mu M for the iHD and 270 +/- 97 mu M for the SLEDD group, respectively (p > 0.05). The Gd-reduction rate after the first dialysis session was 83 +/- 9 and 67 +/- 9% for the iHD and the SLEDD groups, respectively (p = 0.0083). The Gd-reduction rate after the second and third dialysis was 94-98 and 89-96% for the iHD and the SLEDD groups (p > 0.05). The total eliminated Gd was 89 +/- 14 and 91 +/- 4% of the dose in the iHD and the SLEDD groups, respectively (p > 0.05). Gd dialyzer clearance was 95 +/- 22 mL/min and 79 +/- 19 mL/min for iHD and SLEDD, respectively (p > 0.05). Conclusions: Gd-elimination with SLEDD is equally effective as iHD and can be safely used to remove GBCA in ICU patients.
AU  - Bunz, H.
AU  - Tschritter, O.*
AU  - Haap, M.*
AU  - Riessen, R.*
AU  - Heyne, N.
AU  - Artunc, F.
C1  - 57389
C2  - 47729
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 1363-1371
TI  - Elimination of contrast agent gadobutrol with sustained low efficiency daily dialysis compared to intermittent hemodialysis.
JO  - Kidney Blood Press. Res.
VL  - 44
IS  - 6
PB  - Karger
PY  - 2019
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - Background: Sodium-glucose cotransporter 2 (SGLT2) inhibition has been shown to reduce cardiovascular mortality and preserve kidney function in patients with type 2 diabetes. Kidney transplant recipients with diabetes demonstrate increased risk and accelerated progression of micro- and macrovascular complications and may specifically benefit from SGLT2 inhibition. However, potential concerns of SGLT2 inhibition include volume depletion and urinary tract infections. Objectives: We report data on the use of SGLT2 inhibitors in a case series of ten patients with diabetes after kidney transplantation in order to analyze efficacy, safety, and the effect on renal function. Methods: Patients with a stable allograft function and no history of recurrent urinary tract infections were eligible. The SGLT2 inhibitor empagliflozin was given as add-on to preexisting antidiabetic treatment with initial dose reduction of the latter. Results: Median estimated glomerular filtration rate at baseline was 57 mL/min/1.73 m(2) and remained stable throughout the follow-up of 12.0 (5.3-12.0) months. Median HbA(1c) decreased from 7.3 to 7.1%. The rate of urinary tract infections and other side effects was low. Conclusions: SGLT2 inhibition is feasible and well tolerated in selected kidney transplant recipients with diabetes. Whether SGLT2 inhibition is able to reduce cardiovascular mortality and improve allograft survival in these patients has to be addressed in further studies.
AU  - Mahling, M.
AU  - Schork, A.
AU  - Nadalin, S.*
AU  - Fritsche, A.
AU  - Heyne, N.
AU  - Guthoff, M.
C1  - 56798
C2  - 47363
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 984-992
TI  - Sodium-glucose cotransporter 2 (SGLT2) inhibition in kidney transplant recipients with diabetes mellitus.
JO  - Kidney Blood Press. Res.
VL  - 44
IS  - 5
PB  - Karger
PY  - 2019
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - Background/Aims: Posttransplantation diabetes mellitus (PTDM) impacts patient and allograft survival after kidney transplantation. Prediabetes, which is an independent risk factor for PTDM, is modifiable also in a post-transplant setting. Understanding the risks and dynamics of impaired glucose metabolism after transplantation is a key component for targeted intervention. Methods: A retrospective chart analysis of all adult non-diabetic renal allograft recipients (n=251, 2007-2014) was performed. Longitudinal follow-up included fasting plasma glucose and HbA1c, as well as data on allograft function and immunosuppression at consecutive time points (months 3-6 to >5 years post transplantation). Results: Throughout follow-up, median prevalence of prediabetes and PTDM was 53.3 [52.4-55.7]% and 15.4 [15.0-16.5]%, respectively. Continuously high fluxes between states of glucose metabolism, with individual patients' state deteriorating or improving over time, resulted in a high number of incident patients even long after transplantation. The greatest number of patients shifted between normal glucose tolerance and prediabetes, followed by those between prediabetes and PTDM. Conclusion: Prediabetes and PTDM are highly prevalent after kidney transplantation and incidences remain relevant throughout follow-up. Patient fluxes into and out of the prediabetic state show that glucose metabolism is highly dynamic after transplantation. This provides a continuous opportunity for intervention in an aim to reduce diabetes-associated complications.
AU  - Guthoff, M.
AU  - Wagner, R.
AU  - Weichbrodt, K.*
AU  - Nadalin, S.*
AU  - Koenigsrainer, A.*
AU  - Häring, H.-U.
AU  - Fritsche, A.
AU  - Heyne, N.
C1  - 52394
C2  - 43935
CY  - Basel
SP  - 598-607
TI  - Dynamics of glucose metabolism after Kkdney transplantation.
JO  - Kidney Blood Press. Res.
VL  - 42
IS  - 3
PB  - Karger
PY  - 2017
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - End stage renal disease (ESRD) invariably leads to anemia which has been mainly attributed to compromised release of erythropoietin from the defective kidneys with subsequent impairment of erythropoiesis. However, erythropoietin replacement only partially reverses anemia pointing to the involvement of additional mechanisms. As shown more recently, anemia of ESRD is indeed in large part a result of accelerated erythrocyte loss due to suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the cell surface. Phosphatidylserine exposing erythrocytes are bound to and engulfed by macrophages and are thus rapidly cleared from circulating blood. If the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis, stimulation of eryptosis leads to anemia. Eryptotic erythrocytes may further adhere to the vascular wall and thus impair microcirculation. Stimulators of eryptosis include complement, hyperosmotic shock, energy depletion, oxidative stress, and a wide variety of xenobiotics. Signaling involved in the stimulation of eryptosis includes increase of cytosolic Ca2+ activity, ceramide, caspases, calpain, p38 kinase, protein kinase C, Janus-activated kinase 3, casein kinase 1 alpha, and cyclin-dependent kinase 4. Eryptosis is inhibited by AMP-activated kinase, p21-activated kinase 2, cGMP-dependent protein kinase, mitogen-and stress-activated kinase MSK1/2, and some illdefined tyrosine kinases. In ESRD eryptosis is stimulated at least in part by a plasma component, as it is triggered by exposure of erythrocytes from healthy individuals to plasma from ESRD patients. Several eryptosis-stimulating uremic toxins have been identified, such as vanadate, acrolein, methylglyoxal, indoxyl sulfate, indole-3-acetic acid and phosphate. Attempts to fully reverse anemia in ESRD with excessive stimulation of erythropoiesis enhances the number of circulating suicidal erythrocytes and bears the risk of interference with micocirculation, At least in theory, anemia in ESRD could preferably be treated with replacement of erythropoietin and additional inhibition of eryptosis thus avoiding eryptosis-induced impairment of microcirculation. A variety of eryptosis inhibitors have been identified, their efficacy in ESRD remains, however, to be shown.
AU  - Lang, F.*
AU  - Bissinger, R.*
AU  - Abed, M.*
AU  - Artunc, F.
C1  - 52672
C2  - 44216
CY  - Basel
SP  - 749-760
TI  - Eryptosis - the neglected cause of anemia in end stage renal disease.
JO  - Kidney Blood Press. Res.
VL  - 42
IS  - 4
PB  - Karger
PY  - 2017
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - Background: Adequate removal of sodium (Na) and phosphorus (P) is of paramount importance for patients with dialysis-dependent kidney disease can easily quantified in peritoneal dialysis (PD) patients. Some studies suggest that automated PD (APD) results in lower Na and P removal. Methods. In this study we retrospectively analysed our data on Na and P removal in PD patients after implementation of a routine monitoring in 2011. Patients were stratified in those treated with continuous ambulatory PD (CAPD, n=24), automated PD (APD, n=23) and APD with one bag change (CAPD+APD, n=10). Until 2015 we collected time-varying data on Na and P removal from each patient (median 5 [interquartile range 4-8] values). Results: Peritoneal Na and P removal (mmol per 24h +/- standard deviation) was 102 +/- 48 and 8 +/- 2 in the CAPD, 90 +/- 46 and 9 +/- 3 in the APD and 126 +/- 39 and 13 +/- 2 in the CAPD+APD group (ANOVA P=0.141 and <0.001). Taking renal excretion into account total Na and P removal (mmol per 24h) was 221 +/- 65 and 16 +/- 5 in the CARD, 189 +/- 58 and 17 +/- 6 in the APD and 183 +/- 38 and 16 +/- 6 in the CAPD+APD group (P=0.107 and 0.764). Over time, peritoneal removal of Na but not that of P increased in all groups. In patients with modifications of PD treatment, Na but not P removal was significantly increased over-time. Conclusions: Overall Na and P removal were similar with different PD modalities. Individualized adjustments of PD prescription including icodextrin use or higher glucose concentration can improve Na removal while P removal is mainly determined by the dialysate volume.
AU  - Moor, V.*
AU  - Wagner, R.
AU  - Sayer, M.*
AU  - Petsch, M.*
AU  - Rueb, S.
AU  - Häring, H.-U.
AU  - Heyne, N.
AU  - Artunc, F.
C1  - 51519
C2  - 43168
CY  - Basel
SP  - 257-266
TI  - Routine monitoring of sodium and phosphorus removal in peritoneal dialysis (PD) patients treated with continuous ambulatory PD (CAPD), automated PD (APD) or combined CAPD plus APD.
JO  - Kidney Blood Press. Res.
VL  - 42
IS  - 2
PB  - Karger
PY  - 2017
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - BACKGROUND/AIMS: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. METHODS: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. RESULTS: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. CONCLUSIONS: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age.
AU  - Li, J.*
AU  - Lu, Y.P.*
AU  - Reichetzeder, C.*
AU  - Kalk, P.*
AU  - Kleuser, B.*
AU  - Adamski, J.
AU  - Hocher, B.*
C1  - 48520
C2  - 41117
CY  - Basel
SP  - 250-257
TI  - Maternal PCaaC38:6 is associated with preterm birth - a risk factor for early and late adverse outcome of the offspring.
JO  - Kidney Blood Press. Res.
VL  - 41
IS  - 3
PB  - Karger
PY  - 2016
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - Background/Aims: Due to the increasing prevalence of risk factors for chronic kidney disease (CKD), kidney dysfunction becomes a major public health problem. We investigated the CKD prevalence and determined to what extent the variation of risk factors explains the different CKD prevalence in Germany. Methods: We analyzed data from 6,054 participants, aged 31 to 82 years, from the Study of Health in Pomerania (SHIP-1) in Northeast Germany and the Cooperative Health Research in the Region of Augsburg (KORA F4) Study in Southern Germany. Regional differences in selected percentiles corresponding to the cutpoints for estimated glomerular filtration rate (eGFR, <60 ml/min per 1.73 m2) and albumin-to-creatinine ratio (ACR, ≥30 mg/g) were tested using quantile regression models that adjusted for CKD risk factors. Results: The prevalence of decreased eGFRcreatinine-cystatinC (5.9 vs. 3.1 %, p <0.001) and albuminuria (20.2 vs. 8.8 %, p<0.001) were higher in SHIP-1 than in KORA F4. The differential distribution of risk factors explained 18-21% of the regional differences of decreased eGFRcreatinine-cystatinC and high ACR. Conclusions: The CKD prevalence is higher in Northeast than in Southern Germany. Differences in the prevalence of risk factors partly explain the higher disease burden of CKD in Northeast than in Southern Germany.
AU  - Aumann, N.*
AU  - Baumeister, S.E.*
AU  - Rettig, R.*
AU  - Lieb, W.*
AU  - Werner, A.*
AU  - Döring, A.
AU  - Peters, A.
AU  - Koenig, W.*
AU  - Hannemann, A.*
AU  - Wallaschofski, H.*
AU  - Nauck, M.*
AU  - Stracke, S.*
AU  - Völzke, H.*
AU  - Meisinger, C.
C1  - 44658
C2  - 36968
CY  - Basel
SP  - 231-243
TI  - Regional variation of chronic kidney disease in Germany: Results from two population-based surveys.
JO  - Kidney Blood Press. Res.
VL  - 40
IS  - 3
PB  - Karger
PY  - 2015
SN  - 1420-4096
ER  - 

TY  - JOUR
AB  - Chronic kidney disease (CKD) is common, affecting about 10% of the general population, and causing significant morbidity and mortality. Apart from the risk conferred by traditional cardiovascular risk factors, there is a strong genetic component. The method of a genome-wide association study (GWAS) is a powerful hypothesis-free approach to unravel this component by association analyses of CKD with several million genetic variants distributed across the genome. Since the publication of the first GWAS in 2005, this method has led to the discovery of novel loci for numerous human common diseases and phenotypes. Here, we review the recent successes of meta-analyses of GWAS on renal phenotypes. UMOD, SHROOM3, STC1, LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2/SH2B3, DACH1, UBE2Q2, and SLC7A9 were uncovered as loci associated with estimated glomerular filtration rate (eGFR) and CKD, and CUBN as a locus for albuminuria in cross-sectional data of general population studies. However, less than 1.5% of the total variance of eGFR and albuminuria is explained by the identified variants, and the relative risk for CKD is modified by at most 20% per locus. In African Americans, much of the risk for end-stage nondiabetic kidney disease is explained by common variants in the MYH9/APOL1 locus, and in individuals of European descent, variants in HLA-DQA1 and PLA(2)R1 implicate most of the risk for idiopathic membranous nephropathy. In contrast, genetic findings in the analysis of diabetic nephropathy are inconsistent. Uncovering variants explaining more of the genetically determined variability of kidney function is hampered by the multifactorial nature of CKD and different mechanisms involved in progressive CKD stages, and by the challenges in elucidating the role of low-frequency variants. Meta-analyses with larger sample sizes and analyses of longitudinal renal phenotypes using higher-resolution genotyping data are required to uncover novel loci associated with severe renal phenotypes.
AU  - Böger, C.A.*
AU  - Heid, I.M.
C1  - 6049
C2  - 28761
CY  - Basel, Switzerland
SP  - 225-234
TI  - Chronic kidney disease: Novel insights from genome-wide association studies.
JO  - Kidney Blood Press. Res.
VL  - 34
IS  - 4
PB  - Karger
PY  - 2011
SN  - 1420-4096
ER  -