Epub: 14-08-24

Corrigendum to 'Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial' [American Journal of Transplantation 22 (2022)2880-2891].

• Cite: Kurnikowski A, Nordheim E, Schwaiger E, Krenn S, Harreiter J, Kautzky-Willer A, Leutner M, Werzowa J, Tura A, Budde K, Eller K, Pascual J, Krebs M, Jenssen TG, Hecking M
• PMID: 39160118

Epub: 22-07-24

Continuous glucose monitoring for the prediction of posttransplant diabetes mellitus and impaired glucose tolerance on day 90 after kidney transplantation-A prospective proof-of-concept study.

• Cite: Eleftheriadis G, Naik MG, Osmanodja B, Liefeldt L, Choi M, Halleck F, Schrezenmeier E, Eckardt KU, Pigorsch M, Tura A, Kurnikowski A, Hecking M, Budde K
• PMID: 39047976

Posttransplant diabetes mellitus (PTDM) and prediabetes represent serious complications after kidney transplantation and are associated with increased cardiovascular morbidity and mortality. We assessed the predictive performance of continuous glucose monitoring (CGM) compared with plasma glucose and hemoglobin A1c in 46 kidney transplant recipients (KTRs) without known preexisting diabetes mellitus. CGM (14-day recording duration) was performed on days 8, 30, 45, 60, 90, and 180 posttransplant. Eight patients (17%) developed PTDM and nine (20%) impaired glucose tolerance (IGT), as diagnosed by oral glucose tolerance test (oGTT)-derived 2-hour plasma glucose (2hPG) or glucose-lowering therapy on day 90. CGM-readouts percent of time >140 mg/dL (%TAR (140 mg/dL)) and percent of time >180 mg/dL (%TAR (180 mg/dL)) showed excellent in-sample test characteristics regarding PTDM from day 8 onward (days 8-90 receiver operating characteristic area under the curve: 0.88-0.99) and regarding PTDM/IGT with the commencement of maintenance immunosuppression from day 30 onward (days 30-90 receiver operating characteristic area under the curve: 0.88-0.91). Exploratory CGM-%TAR (140 mg/dL)-screening thresholds of 31.8% on day 8 and 13.2% on day 30 yielded sensitivities/specificities of 88%/83% for PTDM and 94%/78% for PTDM/IGT on day 90, respectively. Although our findings need to be replicated in studies with larger sample sizes, CGM bears promising potential to facilitate clinical practice and research regarding PTDM.

Epub: 21-06-24

Continuous Insulin Therapy to Prevent Post-Transplant Diabetes Mellitus: A Randomized Controlled Trial.

• Cite: Kurnikowski A, Werzowa J, Hödlmoser S, Krenn S, Paschen C, Mussnig S, Tura A, Harreiter J, Krebs M, Song PXK, Eller K, Pascual J, Budde K, Hecking M, Schwaiger E
• PMID: 39157193

Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia.

Epub: 06-06-24

Dialysate Sodium and Mortality: 140 mmol/L at Hemodialysis Initiation by Default?

• Cite: Hecking M, Karaboyas A, Krenn S, Mussnig S, Beige J, Chazot C, Pecoits-Filho R, Rayner H, Port FK
• PMID: 38949884

Epub: 16-05-24

Volume and Body Composition in Hemodialysis Patients: A Bioimpedance Study Assessing Differences by Sex.

• Cite: Mussnig S, Niknam J, Matthias C, Widmer S, Gülmez D, Krenn S, Lorenz M, Chazot C, Wabel P, Schneditz D, Hecking M
• PMID: 38957221

Epub: 01-05-24

Immunosuppressive drug combinations after kidney transplantation and post-transplant diabetes: A systematic review and meta-analysis.

• Cite: Oliveras L, Coloma A, Lloberas N, Lino L, Favà A, Manonelles A, Codina S, Couceiro C, Melilli E, Sharif A, Hecking M, Guthoff M, Cruzado JM, Pascual J, Montero N
• PMID: 38723582

Post-transplant diabetes mellitus (PTDM) is a frequent complication after kidney transplantation (KT). This systematic review investigated the effect of different immunosuppressive regimens on the risk of PTDM. We performed a systematic literature search in MEDLINE and CENTRAL for randomized controlled trials (RCTs) that included KT recipients with any immunosuppression and reported PTDM outcomes up to 1 October 2023. The analysis included 125 RCTs. We found no differences in PTDM risk within induction therapies. In de novo KT, there was an increased risk of developing PTDM with tacrolimus versus cyclosporin (RR 1.71, 95%CI [1.38-2.11]). No differences were observed between tacrolimus+mammalian target of rapamycin inhibitor (mTORi) and tacrolimus+MMF/MPA, but there was a tendency towards a higher risk of PTDM in the cyclosporin+mTORi group (RR 1.42, 95%CI [0.99-2.04]). Conversion from cyclosporin to an mTORi increased PTDM risk (RR 1.89, 95%CI [1.18-3.03]). De novo belatacept compared with a calcineurin inhibitor resulted in 50% lower risk of PTDM (RR 0.50, 95%CI [0.32-0.79]). Steroid avoidance resulted in 31% lower PTDM risk (RR 0.69, 95%CI [0.57-0.83]), whereas steroid withdrawal resulted in no differences. Immunosuppression should be decided on an individual basis, carefully weighing the risk of future PTDM and rejection.

Epub: 30-01-24

Glucometabolism in Kidney Transplant Recipients with and without Posttransplant Diabetes: Focus on Beta-Cell Function.

• Cite: Kurnikowski A, Salvatori B, Krebs M, Budde K, Eller K, Pascual J, Morettini M, Göbl C, Hecking M, Tura A
• PMID: 38397919

Posttransplant diabetes mellitus (PTDM) is a common complication after kidney transplantation. Pathophysiologically, whether beta-cell dysfunction rather than insulin resistance may be the predominant defect in PTDM has been a matter of debate. The aim of the present analysis was to compare glucometabolism in kidney transplant recipients with and without PTDM. To this aim, we included 191 patients from a randomized controlled trial who underwent oral glucose tolerance tests (OGTTs) 6 months after transplantation. We derived several basic indices of beta-cell function and insulin resistance as well as variables from mathematical modeling for a more robust beta-cell function assessment. Mean ± standard deviation of the insulin sensitivity parameter PREDIM was 3.65 ± 1.68 in PTDM versus 5.46 ± 2.57 in NON-PTDM. Model-based glucose sensitivity (indicator of beta-cell function) was 68.44 ± 57.82 pmol∙min∙m∙mM in PTDM versus 143.73 ± 112.91 pmol∙min∙m∙mM in NON-PTDM, respectively. Both basic indices and model-based parameters of beta-cell function were more than 50% lower in patients with PTDM, indicating severe beta-cell impairment. Nonetheless, some defects in insulin sensitivity were also present, although less marked. We conclude that in PTDM, the prominent defect appears to be beta-cell dysfunction. From a pathophysiological point of view, patients at high risk for developing PTDM may benefit from intensive treatment of hyperglycemia over the insulin secretion axis.

Epub: 24-01-24

Mechanistic Basis for Intradialytic Hypertension with Hemodialysis.

• Cite: Hecking M, Mussnig S, Chazot C
• PMID: 38265791

Epub: 18-01-24

Assessment of bioimpedance spectroscopy devices: a comparative study and error analysis of gold-plated copper electrodes.

• Cite: Mussnig S, Krenn S, Hecking M, Wabel P
• PMID: 38237199

Bioimpedance spectroscopy (BIS) is a non-invasive diagnostic tool to derive fluid volume compartments from frequency dependent voltage drops in alternating currents by extrapolating to the extracellular resistance (R0) and intracellular resistance (Ri). Here we tested whether a novel BIS device with reusable and adhesive single-use electrodes produces results which are (in various body positions) equivalent to an established system employing only single-use adhesive electrodes.&#xD;Approach: Two BIS devices ("Cella" and the "Body Composition Monitor" [BCM]) were compared using four dedicated resistance testboxes and by measuring 40 healthy volunteers. In-vivo comparisons included supine wrist-to-ankle (WA) reference measurements and wrist-to-wrist (WW) measurements with pre-gelled silver/silver-chloride (Ag/AgCl) electrodes and WW measurements with reusable gold-plated copper electrodes. &#xD;Main Results: Coefficient of variation were < 1 % for all testbox measurements with both BIS devices. Accuracy was within ±1 % of true resistance variability, a threshold which was only exceeded by the Cella device for all resistances in a testbox designed with a low R0/Ri ratio. In-vivo, WA-BIS differed significantly between BIS devices (p < 0.001). Reusable WW electrodes exhibited larger resistances than WW-BIS with Ag/AgCl electrodes (R0: 738.36 and 628.69 Ω; Ri: 1508.18 and 1390 Ω) and the relative error varied from 7.6 to 31.1 % (R0) and -15.6 to 37.3 % (Ri). &#xD;Significance: Both BIS devices produced equivalent resistances measurements but different estimates of body composition both in-vitro and in WA setups in-vivo, suggesting that the devices should not be used interchangeably. Employing WW reusable electrodes as opposed to WA and WW measurement setups with pre-gelled Ag/AgCl electrodes seems to be associated with measurement variations that are too large for safe clinical use. We recommend further investigations of measurement errors originating from electrode material and current path.&#xD.

Epub: 13-11-23

Day-to-day variability in euvolemic body mass.

• Cite: Schneditz D, Hofmann P, Krenn S, Waller M, Mussnig S, Hecking M
• PMID: 37955103

Short-term variability in body mass is a common, everyday phenomenon; however, data on body mass variability are scarce. While the physiological variability of body mass is negligible in healthy individuals, it could have implications for therapy in patients with impaired volume homeostasis, for example, patients with kidney failure undergoing kidney replacement therapy. We analyzed a long-term dataset comprising 9521 days of standardized body mass measurements from one healthy male individual and assessed the variability in body mass as a positive or negative relative difference in body mass measured on subsequent days. The average and median relative differences were zero, with a standard deviation (SD) of 0.53% for the one-day interval, increasing to 0.69% for the 7-day interval, and this variability was constant throughout the observation period. A body mass variability of approximately 0.6% (±450 mL in a 75-kg patient) should be taken into consideration when weight-dependent treatment prescriptions, e.g. the ultrafiltration rates in patients on hemodialysis, are being set. Consequently, a "soft target weight", considering the longitudinal variation of volume markers, such as body mass, might improve treatment quality.

Epub: 14-09-23

Bioimpedance-derived euvolemic weight varies in hemodialysis patients - challenging the fixed target weight concept.

• Cite: Waller M, Krenn S, Mussnig S, Schmiedecker M, Niknam-Saeidi J, Mayer CC, Wabel P, Schneditz D, Chazot C, Hecking M
• PMID: 37708039

Epub: 20-07-23

Perspectives of Nephrologists on Gender Disparities in Access to Kidney Transplantation.

• Cite: Natale P, Hecking M, Kurnikowski A, Scholes-Robertson N, Carrero JJ, Wong G, Strippoli G, Jaure A
• PMID: 37471097

Gender disparities in access to kidney transplantation are apparent with women being up to 20% less likely to receive kidney transplant compared to men across different settings and socioeconomic backgrounds. We aimed to describe nephrologists' perspectives on gender disparities in access to kidney transplantation.

Epub: 14-06-23

Differences in bioimpedance-derived fluid status between two versions of the Body Composition Monitor.

• Cite: Mussnig S, Schmiedecker M, Waller M, Niknam J, Paschen C, Schneditz D, Hecking M, Krenn S
• PMID: 37467529

The Body Composition Monitor (BCM) (Fresenius Medical Care) measures body impedances in alternating currents to subsequently calculate fat and lean tissue mass, fluid compartments, and overhydration (OH). The aim of this study was to investigate differences between two versions of the BCM (an older version, 3.2.5, and a newer version, 3.3.3).

Epub: 26-01-23

Ultrafiltration-induced decrease in relative blood volume is larger in hemodialysis patients with low specific blood volume: Results from a dialysate bolus administration study.

• Cite: Schmiedecker M, Krenn S, Waller M, Paschen C, Mussnig S, Niknam J, Wabel P, Mayer CC, Hecking M, Schneditz D
• PMID: 36703281

Prescribing the ultrafiltration in hemodialysis patients remains challenging and might benefit from the information on absolute blood volume, estimated by intradialytic dialysate bolus administration. Here, we aimed at determining the relationship between absolute blood volume, normalized for body mass (specific blood volume, Vs), and ultrafiltration-induced decrease in relative blood volume (∆RBV) as well as clinical parameters including body mass index (BMI).

Epub: 01-01-23

Fluid volume management in hemodialysis: never give up!

• Cite: Hecking M, Madero M, Port FK, Schneditz D, Wabel P, Chazot C
• PMID: 36603969

Every hemodialysis session starts with the question of how much fluid should be removed, which can currently not be answered precisely. Herein, we first revisit the "probing-dry-weight" concept, using the historical example of Tassin/France (practicing also "long, slow dialysis"): Mortality outcomes were, in the 1980s, better than registry data, but are nowadays similar to European average. In view of the negative primary end point in a recent trial on dry weight assessment, based on lung ultrasound-guided evaluation of fluid excess in the lungs, and a meta-analysis of prospective studies failing to show that bioimpedance-based interventions for correction of volume overload had a direct effect on all-cause mortality, we ask how to ever move forward. Clinical reasoning demands that as much information as possible should be gathered on the fluid status of patients undergoing dialysis. Besides body weight and blood pressure, measurements of bioimpedance and dialysate bolus-derived absolute blood volume can in principle be automatized, whereas lung ultrasound can be obtained routinely. In the era of machine learning, fluid management could consist of flexible target weight prescriptions, adjusted on a daily basis and accounting even for fluctuations in fluid-free body mass. In view of all the negative prospective results surrounding fluid management in hemodialysis, we propose this as a "never-give-up" approach.

Epub: 22-12-22

Revisiting the concept of constant tissue conductivities for volume estimation in dialysis patients using bioimpedance spectroscopy.

• Cite: Schneditz D, Mussnig S, Krenn S, Hecking M
• PMID: 36550616

Current estimation of body fluid volumes in hemodialysis patients using bioimpedance analysis assumes constant specific electrical characteristics of biological tissues despite a large variation in plasma Na concentrations [Na], ranging from 130 to 150 mmol/L. Here, we examined the potential effect of variable [Na] on bioimpedance-derived volume overload.

Epub: 01-12-22

Active fluid management in Tassin/France of the 21 century and outcomes.

• Cite: Hecking M, Schmiedecker M, Waller M, Gil SL, Bieber B, Jean G, Chazot C
• PMID: 36411021

Epub: 22-11-22

The systemic renin-angiotensin system in COVID-19.

• Cite: Reindl-Schwaighofer R, Hödlmoser S, Domenig O, Krenn K, Eskandary F, Krenn S, Schörgenhofer C, Rumpf B, Karolyi M, Traugott MT, Abrahamowicz A, Tinhof V, Mayfurth H, Rathkolb V, Mußnig S, Schmölz L, Ullrich R, Heinzel A, König F, Binder C, Bonderman D, St
• PMID: 36418458

SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the "alternative" (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1-7. Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I-II) and alt-RAS (angiotensins 1-7 and 1-5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7. Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (angiotensin I: 86 versus 30 pmol/L, p < 0.01; angiotensin II: 114 versus 58 pmol/L, p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor (angiotensin I: 40 versus 31 pmol/L, p = 0.251; angiotensin II: 76 versus 99 pmol/L, p = 0.833). ALT-S in severe COVID-19 increased with time (days 1-6: 0.12; days 11-16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (1.6 versus 2.6; p < 0.001), but ACE concentrations were similar between groups and correlated weakly with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors. In conclusion, angiotensin II was elevated in severe COVID-19 but was markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.

Epub: 11-10-22

Experiences and challenges faced by patients with COVID-19 who were hospitalised and participated in a randomised controlled trial: a qualitative study.

• Cite: Hofstetter L, Tinhof V, Mayfurth H, Kurnikowski A, Rathkolb V, Reindl-Schwaighofer R, Traugott M, Omid S, Zoufaly A, Tong A, Kropiunigg U, Hecking M
• PMID: 36220325

As part of a randomised controlled trial, this qualitative study aimed to identify experiences and challenges of hospitalised patients with COVID-19 during illness and treatment (objective 1: COVID-19-related perspectives; objective 2: trial participation-related perspectives).

Epub: 01-09-22

Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial.

• Cite: Kurnikowski A, Nordheim E, Schwaiger E, Krenn S, Harreiter J, Kautzky-Willer A, Leutner M, Werzowa J, Tura A, Budde K, Eller K, Pascual J, Krebs M, Jenssen TG, Hecking M
• PMID: 36047565

Posttransplant diabetes mellitus (PTDM) and prediabetes (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) are associated with cardiovascular events. We assessed the diagnostic performance of fasting plasma glucose (FPG) and HbA as alternatives to oral glucose tolerance test (OGTT)-derived 2-hour plasma glucose (2hPG) using sensitivity and specificity in 263 kidney transplant recipients (KTRs) from a clinical trial. Between visits at 6, 12, and 24 months after transplantation, 28%-31% of patients switched glycemic category (normal glucose tolerance [NGT], IGT/IFG, PTDM). Correlations of FPG and HbA against 2hPG were lower at 6 months (r = 0.59 [FPG against 2hPG]; r = 0.45 [HbA against 2hPG]) vs. 24 months (r = 0.73 [FPG against 2hPG]; r = 0.74 [HbA against 2hPG]). Up to 69% of 2hPG-defined PTDM cases were missed by conventional HbA and FPG thresholds. For prediabetes, concordance of FPG and HbA with 2hPG ranged from 6%-9%. In conclusion, in our well-defined randomized trial cohort, one-third of KTRs switched glycemic category over 2 years and although the correlations of FPG and HbA with 2hPG improved with time, their diagnostic concordance was poor for PTDM and, especially, prediabetes. Considering posttransplant metabolic instability, FPG's and HbA 's diagnostic performance, the OGTT remains indispensable to diagnose PTDM and prediabetes after kidney transplantation.

Epub: 31-08-22

Chronic kidney disease is more prevalent among women but more men than women are under nephrological care : Analysis from six outpatient clinics in Austria 2019.

• Cite: Lewandowski MJ, Krenn S, Kurnikowski A, Bretschneider P, Sattler M, Schwaiger E, Antlanger M, Gauckler P, Pirklbauer M, Brunner M, Horn S, Zitt E, Kirsch B, Windpessl M, Wallner M, Aringer I, Wiesholzer M, Hecking M, Hödlmoser S
• PMID: 36044092

A discrepancy between sex-specific treatment of kidney failure by dialysis (higher in men) and the prevalence of chronic kidney disease in the general population (higher in women) has been reported internationally, but the prevalence by sex has not been described for Austria. Sex disparity among nephrology outpatients has not been studied.

Epub: 31-08-22

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study.

• Cite: Staessen JA, Wendt R, Yu YL, Kalbitz S, Thijs L, Siwy J, Raad J, Metzger J, Neuhaus B, Papkalla A, von der Leyen H, Mebazaa A, Dudoignon E, Spasovski G, Milenkova M, Canevska-Taneska A, Salgueira Lazo M, Psichogiou M, Rajzer MW, Fuławka Ł, Dzitkowska-Zabi
• PMID: 36057526

The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker.

Epub: 29-07-22

Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort Study.

• Cite: Swartling O, Yang Y, Clase CM, Fu EL, Hecking M, Hödlmoser S, Trolle-Lagerros Y, Evans M, Carrero JJ
• PMID: 35906075

Reported sex differences in the etiology, population prevalence, progression rates, and health outcomes of people with CKD may be explained by differences in health care.

Epub: 22-07-22

Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19-Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT).

• Cite: Karolyi M, Pawelka E, Omid S, Koenig F, Kauer V, Rumpf B, Hoepler W, Kuran A, Laferl H, Seitz T, Traugott M, Rathkolb V, Mueller M, Abrahamowicz A, Schoergenhofer C, Hecking M, Assinger A, Wenisch C, Zeitlinger M, Jilma B, Zoufaly A
• PMID: 35935856

To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), = 0.036] and a shorter LOS (12 vs. 14 days, = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), = 0.089] was observed. In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials. : [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].

Epub: 02-03-22

Corticosteroid Treatment Prevents Lipopolysaccharide-Induced Increase of ACE2 and Reduces Fibrin Degradation Products in Bronchoalveolar Lavage Fluid.

• Cite: Reindl-Schwaighofer R, Eskandary F, Bartko J, Heinzel A, Jilma B, Hecking M, Schoergenhofer C
• PMID: 35308535

The assessment of systemic corticosteroid effects on intrapulmonary disease biomarkers is challenging. This retrospective evaluation of a human endotoxemia model quantified ACE2 and fibrin degradation product (FDP) concentrations in bronchoalveolar lavage fluid (BALF) samples from a randomized, double-blind, placebo-controlled study (NCT01714427). Twenty-four healthy volunteers received either 2 × 40 mg intravenous dexamethasone or placebo. These doses were administered 12 h apart prior to bronchoscopy-guided intrabronchial lipopolysaccharide (LPS) stimulation (control: saline into the contralateral lung segment). We quantified ACE2 concentration, the Angiotensin-II-to-Angiotensin-1-7 conversion rate as well as FDP in BALF 6 h after LPS instillation. In placebo-treated subjects, LPS instillation increased ACE2 concentrations compared to unstimulated lung segments [1,481 (IQR: 736-1,965) vs. 546 (413-988) pg/mL; = 0.016]. Dexamethasone abolished the increase in ACE2 concentrations (p=0.13). Accordingly, LPS instillation increased the Angiotensin-II-to-Angiotensin-1-7 conversion capacity significantly in the placebo cohort, indicating increased enzymatic activity ( = 0.012). FDP increased following LPS-instillation [8.9 (2.7-12.2) vs. 6.6 (0.9-9.6) ng/mL, = 0.025] in the placebo group, while dexamethasone caused a shut-down of fibrinolysis in both lung segments. LPS instillation increased ACE2 concentration, its enzymatic activity and FDP, which was mitigated by systemic dexamethasone treatment. Our results strengthen previously published findings regarding the efficiency of corticosteroids for the treatment of COVID-19-induced acute lung injury.

Epub: 01-03-22

The Other Way Around: Living With Chronic Kidney Disease From the Perspective of Men

• Cite: Hecking M, Hödlmoser S, Ahmed S, Carrero J
• PMID: 35718360

A wealth of evidence has suggested sex (biological) and gender (sociocultural) differences in the prevalence, progression, and outcomes of persons with chronic kidney disease. Much of this evidence tends to emphasize differences in which women are disadvantaged, and less attention is paid to findings in which women are better off or similar to men. However, gender medicine recognizes that men and women have different disease determinants, presentation, and attitudes, and it pertains to both sexes. In this review, we revisit chronic kidney disease through the perspective of men, and illustrate a population segment at need of stringent preventative and management strategies.

Epub: 10-02-22

Feasibility of Dialysate Bolus-Based Absolute Blood Volume Estimation in Maintenance Hemodialysis Patients.

• Cite: Krenn S, Schmiedecker M, Schneditz D, Hödlmoser S, Mayer CC, Wassertheurer S, Omic H, Schernhammer E, Wabel P, Hecking M
• PMID: 35223900

Absolute blood volume (ABV) is a critical component of fluid status, which may inform target weight prescriptions and hemodynamic vulnerability of dialysis patients. Here, we utilized the changes in relative blood volume (RBV), monitored by ultrasound (BVM) upon intradialytic 240 mL dialysate fluid bolus-infusion 1 h after hemodialysis start, to calculate the session-specific ABV. With the main goal of assessing clinical feasibility, our sub-aims were to (i) standardize the BVM-data read-out; (ii) determine optimal time-points for ABV-calculation, "before-" and "after-bolus"; (iii) assess ABV-variation.

Epub: 24-01-22

Sex Differences in Kidney Transplantation: Austria and the United States, 1978-2018.

• Cite: Hödlmoser S, Gehrig T, Antlanger M, Kurnikowski A, Lewandowski M, Krenn S, Zee J, Pecoits-Filho R, Kramar R, Carrero JJ, Jager KJ, Tong A, Port FK, Posch M, Winkelmayer WC, Schernhammer E, Hecking M, Ristl R
• PMID: 35141249

Systematic analyses about sex differences in wait-listing and kidney transplantation after dialysis initiation are scarce. We aimed at identifying sex-specific disparities along the path of kidney disease treatment, comparing two countries with distinctive health care systems, the US and Austria, over time.

Epub: 08-01-22

Effect of liver resection-induced increases in hepatic venous pressure gradient on development of postoperative acute kidney injury.

• Cite: Reiterer C, Taschner A, Luf F, Hecking M, Tamandl D, Zotti O, Reiberger T, Starlinger P, Mandorfer M, Fleischmann E
• PMID: 34996372

The impact of changes in portal pressure before and after liver resection (defined as ΔHVPG) on postoperative kidney function remains unknown. Therefore, we investigated the effect of ΔHVPG on (i) the incidence of postoperative AKI and (ii) the renin-angiotensin system (RAAS) and sympathetic nervous system (SNS) activity.

Epub: 04-01-22

Combined sodium glucose co-transporter-2 inhibitor and angiotensin-converting enzyme inhibition upregulates the renin-angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double-blind, placebo-controlled exploratory

• Cite: Antlanger M, Domenig O, Kaltenecker CC, Kovarik JJ, Rathkolb V, Müller MM, Schwaiger E, Hecking M, Poglitsch M, Säemann MD, Kopecky C
• PMID: 34984822

Sodium glucose co-transporter-2 inhibitors (SGLT-2i) improve cardiorenal outcomes in patients with chronic kidney disease (CKD), with and without type 2 diabetes. The molecular mechanisms underlying these pleiotropic effects remain unclear, yet it is speculated that SGLT-2i elicit a neurohormonal modulation resulting in renin-angiotensin system (RAS) activation. We hypothesized that combined SGLT-2 and angiotensin-converting enzyme inhibition (ACEi) favours RAS regulation towards the beneficial angiotensin-(1-7)-driven axis.

Epub: 27-12-21

Kidney Function, Kidney Replacement Therapy, and Mortality in Men and Women.

• Cite: Hödlmoser S, Carrero JJ, Kurnikowski A, Fu EL, Swartling O, Winkelmayer WC, Schernhammer ES, Hecking M
• PMID: 35257057

Women are more likely to have chronic kidney disease (CKD), compared with men, yet they are less likely to receive dialysis. Whether this sex disparity, which has predominantly been observed in nephrology-referred or CKD-specific cohorts so far, has a biological root cause remains unclear.

Epub: 27-12-21

Kidney Function, Kidney Replacement Therapy, and Mortality in Men and Women

• Cite: Hödlmoser S, Carrero J, Kurnikowski A, Fu E, Swartling O, Winkelmayer W, Schellhammer E, Hecking M
• PMID: 35257057

Women are more likely to have chronic kidney disease (CKD), compared with men, yet they are less likely to receive dialysis. Whether this sex disparity, which has predominantly been observed in nephrology-referred or CKD-specific cohorts so far, has a biological root cause remains unclear.

Epub: 01-12-21

Sex-Specific Differences in Mortality and Incident Dialysis in the Chronic Kidney Disease Outcomes and Practice Patterns Study.

• Cite: Hecking M, Tu C, Zee J, Bieber B, Hödlmoser S, Reichel H, Sesso R, Port FK, Robinson BM, Carrero JJ, Tong A, Combe C, Stengel B, Pecoits-Filho R
• PMID: 35257054

More men than women start kidney replacement therapy (KRT) although the prevalence of chronic kidney disease (CKD) is higher in women than men. We therefore aimed at analyzing sex-specific differences in clinical outcomes among 8237 individuals with CKD in stages 3 to 5 from Brazil, France, Germany, and the United States participating in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps).

Epub: 01-12-21

Sex-Specific Differences in Mortality and Incident Dialysis in the Chronic Kidney Disease Outcomes and Practice Patterns Study

• Cite: Hecking M, Tu C, Zee J, Bieber B, Hödlmöser S, Reichel H, Sesso R, Port F, Robinson B, Carrero J, Tong A, Combe C, Stengel B, Picots-Filho R
• PMID: 35257054

More men than women start kidney replacement therapy (KRT) although the prevalence of chronic kidney disease (CKD) is higher in women than men. We therefore aimed at analyzing sex-specific differences in clinical outcomes among 8237 individuals with CKD in stages 3 to 5 from Brazil, France, Germany, and the United States participating in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps).

Epub: 09-11-21

Nephrologists' Perspectives on Gender Disparities in CKD and Dialysis.

• Cite: Tong A, Evangelidis N, Kurnikowski A, Lewandowski M, Bretschneider P, Oberbauer R, Baumgart A, Scholes-Robertson N, Stamm T, Carrero JJ, Pecoits-Filho R, Hecking M
• PMID: 35257055

Globally, there are more women with chronic kidney disease (CKD), yet they comprise only 40% of patients receiving kidney replacement therapy by dialysis. We aimed to describe the perspectives of nephrologists on gender disparities in access to care and outcomes in CKD and dialysis.

Epub: 09-11-21

Nephrologists' Perspectives on Gender Disparities in CKD and Dialysis

• Cite: Tong A, Evangelidis N, Kurnikowski A, Lewandowski M, Bretschneider P, Oberbauer R, Baumgart A, Scholes-Robertson N, Stamm T, Carrero J, Pecoits-Filho R, Hecking M
• PMID: 35257055

Globally, there are more women with chronic kidney disease (CKD), yet they comprise only 40% of patients receiving kidney replacement therapy by dialysis. We aimed to describe the perspectives of nephrologists on gender disparities in access to care and outcomes in CKD and dialysis.

Epub: 20-10-21

Country-specific sex disparities in living kidney donation.

• Cite: Kurnikowski A, Krenn S, Lewandowski MJ, Schwaiger E, Tong A, Jager KJ, Carrero JJ, Hecking M, Hödlmoser S
• PMID: 34669961

Epub: 13-10-21

Statin initiation in dialysis patients: The hardship of non-prescription.

• Cite: Hecking M, Karaboyas A, Schernthaner GH, Wanner C
• PMID: 34663493

Epub: 05-09-21

Anticoagulation use and the risk of stroke and major bleeding in patients on hemodialysis: From the VIVALDI, a population-based prospective cohort study.

• Cite: Königsbrügge O, Meisel H, Beyer A, Schmaldienst S, Klauser-Braun R, Lorenz M, Auinger M, Kletzmayr J, Hecking M, Winkelmayer WC, Lang I, Pabinger I, Säemann M, Ay C
• PMID: 34418291

Evidence supporting the use of anticoagulation for the prevention of stroke and thromboembolism in patients with kidney failure on hemodialysis (HD) and atrial fibrillation (AF) is limited. We prospectively assessed the incidences of stroke and major bleeding, as well as anticoagulation strategies in patients on HD with AF.

Epub: 22-08-21

Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial.

• Cite: Schwaiger E, Krenn S, Kurnikowski A, Bergfeld L, Pérez-Sáez MJ, Frey A, Topitz D, Bergmann M, Hödlmoser S, Bachmann F, Halleck F, Kron S, Hafner-Giessauf H, Eller K, Rosenkranz AR, Crespo M, Faura A, Tura A, Song PXK, Port FK, Pascual J, Budde K, Ristl R,
• PMID: 34330770

Post-transplantation diabetes mellitus (PTDM) might be preventable.

Epub: 01-05-21

ACE2 Elevation in Severe COVID-19.

• Cite: Reindl-Schwaighofer R, Hödlmoser S, Eskandary F, Poglitsch M, Bonderman D, Strassl R, Aberle JH, Oberbauer R, Zoufaly A, Hecking M
• PMID: 33600742

Epub: 27-02-21

Parathyroid Hormone Concentrations in Maintenance Hemodialysis: Longitudinal Evaluation of Intact and Biointact Assays.

• Cite: Berner C, Marculescu R, Frommlet F, Kurnikowski A, Schairer B, Aigner C, Bieglmayer C, Hecking M
• PMID: 34136780

Management of chronic kidney disease mineral and bone disorder requires parathyroid hormone (PTH) concentrations. "Biointact" PTH immunoassays detect "whole" PTH (wPTH), whereas "intact" immunoassays measure PTH plus PTH fragments (iPTH). We aimed to determine whether longitudinal changes in PTH concentrations can be evaluated using biointact and intact immunoassays alike.

Epub: 27-01-21

Patient experiences of sleep in dialysis: systematic review of qualitative studies.

• Cite: Cheng E, Evangelidis N, Guha C, Hanson CS, Unruh M, Wilkie M, Schell J, Hecking M, Gonzalez AM, Ju A, Eckert DJ, Craig JC, Tong A
• PMID: 33571871

Sleep problems affect more than half of patients receiving dialysis and are associated with increased risk of mortality, cardiovascular events, depression and impaired functioning and quality of life. Symptoms such as fatigue and exhaustion may be attributed to sleep problems or sleep disorders, as well as the burden of kidney disease and treatment. This study aims to describe the patient perspectives on the reasons, impact and management of sleep problems in dialysis.

Epub: 18-12-20

Sex differences in chronic kidney disease awareness among US adults, 1999 to 2018.

• Cite: Hödlmoser S, Winkelmayer WC, Zee J, Pecoits-Filho R, Pisoni RL, Port FK, Robinson BM, Ristl R, Krenn S, Kurnikowski A, Lewandowski M, Ton A, Carrero JJ, Schernhammer ES, Hecking M
• PMID: 33338051

Chronic kidney disease (CKD) is less prevalent among men than women, but more men than women initiate kidney replacement therapy. Differences in CKD awareness may contribute to this gender gap, which may further vary by race/ethnicity. We aimed to investigate trends in CKD awareness and the association between individual characteristics and CKD awareness among US men versus women.

Epub: 28-11-20

Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics.

• Cite: Hecking M, Sharif A, Eller K, Jenssen T
• PMID: 33135259

Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium-glucose-linked transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1-RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1-RAs that have not brought forth major concerns, likely indicating that GLP1-RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.

Epub: 09-09-20

Interdialytic Weight Gain and Hemoglobin Concentrations in the Japanese Dialysis Outcomes and Practice Patterns Study: Further Considerations.

• Cite: Hecking M, Wabel P
• PMID: 33104081

Epub: 06-09-20

Glucose Metabolism After Kidney Transplantation: Insulin Release and Sensitivity With Tacrolimus- Versus Belatacept-Based Immunosuppression.

• Cite: Müller MM, Schwaiger E, Kurnikowski A, Haidinger M, Ristl R, Tura A, Pacini G, Werzowa J, Hecking M
• PMID: 32905816

Epub: 01-09-20

Patients' perspectives of pain in dialysis: systematic review and thematic synthesis of qualitative studies.

• Cite: Zhang K, Hannan E, Scholes-Robertson N, Baumgart A, Guha C, Kerklaan J, Hanson CS, Craig JC, Davison SN, Hecking M, Tong A
• PMID: 32453133

Pain is a severe and common symptom in patients receiving dialysis but remains inadequately managed in clinical practice. Understanding patient experiences of pain can inform strategies to address this patient-important symptom. We aimed to describe patients' perspectives on causes, experiences, and impacts of dialysis-associated pain. MEDLINE, Embase, PsycINFO, and CINAHL were searched to August 2019 for all qualitative studies that described the perspectives of pain in adults aged 18 years or older receiving dialysis. Findings from the primary studies were analyzed using thematic synthesis. We included 60 studies across 14 countries involving 1343 participants (1215 receiving hemodialysis and 128 receiving peritoneal dialysis), and identified 6 themes: gripped by an all-consuming agony (draining cognitive capacity, exacerbating other symptoms); suffering in silence (surrendering to the inevitable, ignored or dismissed, hiding symptoms to protect others); provoking fear of treatment (resistance to cannulation, avoiding dialysis, anxious from witnessing other patients in pain); preventing life participation (preventing fulfilment of valued roles, depleting the will to live); coping aided by connection with others (shared understanding among patients, comforted and supported by others); and developing awareness, assertiveness, and self-reliance (procedural vigilance, finding strategies to minimize pain, bodily understanding and knowing thresholds, positive thinking). Struggling with pain in dialysis involved a progression of agony, fear, avoidance, and despair. However, support from others and self-management strategies were used to cope with pain. Strategies to empower patients to report and minimize pain and its consequences in dialysis are needed.

Epub: 02-06-20

Hyperkalemia: A persisting risk. A case report and update on current management.

• Cite: Schnaubelt S, Niederdoeckl J, Schoergenhofer C, Cacioppo F, Schuetz N, Spiel AO, Hecking M, Domanovits H
• PMID: 32983489

We report a case of hemodynamic instability due to bradycardia on the basis of severe hyperkalemia. Diabetic ketoacidosis and acute kidney injury together with polypharmacy triggered the acute onset. Potentially life-threatening hyperkalemia is often induced by drug interactions. ECG features may be crucial for diagnosis, and treatment depends on setting and resources.

Epub: 08-03-20

Blood pressure and volume management in dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

• Cite: Flythe JE, Chang TI, Gallagher MP, Lindley E, Madero M, Sarafidis PA, Unruh ML, Wang AY, Weiner DE, Cheung M, Jadoul M, Winkelmayer WC, Polkinghorne KR,
• PMID: 32278617

Blood pressure (BP) and volume control are critical components of dialysis care and have substantial impacts on patient symptoms, quality of life, and cardiovascular complications. Yet, developing consensus best practices for BP and volume control have been challenging, given the absence of objective measures of extracellular volume status and the lack of high-quality evidence for many therapeutic interventions. In February of 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference titled Blood Pressure and Volume Management in Dialysis to assess the current state of knowledge related to BP and volume management and identify opportunities to improve clinical and patient-reported outcomes among individuals receiving maintenance dialysis. Four major topics were addressed: BP measurement, BP targets, and pharmacologic management of suboptimal BP; dialysis prescriptions as they relate to BP and volume; extracellular volume assessment and management with a focus on technology-based solutions; and volume-related patient symptoms and experiences. The overarching theme resulting from presentations and discussions was that managing BP and volume in dialysis involves weighing multiple clinical factors and risk considerations as well as patient lifestyle and preferences, all within a narrow therapeutic window for avoiding acute or chronic volume-related complications. Striking this challenging balance requires individualizing the dialysis prescription by incorporating comorbid health conditions, treatment hemodynamic patterns, clinical judgment, and patient preferences into decision-making, all within local resource constraints.

Epub: 01-03-20

Cardiovascular events associate with diabetes status rather than with early basal insulin treatment for the prevention of post-transplantation diabetes mellitus.

• Cite: Topitz D, Schwaiger E, Frommlet F, Werzowa J, Hecking M
• PMID: 31803915

Epub: 18-02-20

Bioimpedance spectroscopy for fluid status assessment in patients with decompensated liver cirrhosis: Implications for peritoneal dialysis.

• Cite: Schwaiger E, Simon A, Wabel P, Schairer B, Berner C, Signorini L, Ernstbrunner M, Evstatiev R, Schwabl P, Hinterholzer G, Frommlet F, Vychytil A, Müller CJ, Hecking M
• PMID: 32071351

Bioimpedance spectroscopy (BIS) is routinely used in peritoneal dialysis patients and might aid fluid status assessment in patients with liver cirrhosis, but the effect of ascites volume removal on BIS-readings is unknown. Here we determined changes in BIS-derived parameters and clinical signs of fluid overload from before to after abdominal paracentesis. Per our pre-specified sample size calculation, we studied 31 cirrhotic patients, analyzing demographics, labs and clinical parameters along with BIS results. Mean volume of the abdominal paracentesis was 7.8 ± 2.6 L. From pre-to post-paracentesis, extracellular volume (ECV) decreased (20.2 ± 5.2 L to 19.0 ± 4.8 L), total body volume decreased (39.8 ± 9.8 L to 37.8 ± 8.5 L) and adipose tissue mass decreased (38.4 ± 16.0 kg to 29.9 ± 12.9 kg; all p < 0.002). Correlation of BIS-derived parameters from pre to post-paracentesis ranged from R² = 0.26 for body cell mass to R² = 0.99 for ECV. Edema did not correlate with BIS-derived fluid overload (FO ≥ 15% ECV), which occurred in 16 patients (51.6%). In conclusion, BIS-derived information on fluid status did not coincide with clinical judgement. The changes in adipose tissue mass support the BIS-model assumption that fluid in the peritoneal cavity is not detectable, suggesting that ascites (or peritoneal dialysis fluid) mass should be subtracted from adipose tissue if BIS is used in patients with a full peritoneal cavity.

Epub: 16-02-20

Antithrombotic agents for primary and secondary prevention of cardiovascular events in patients with end-stage renal disease on chronic hemodialysis.

• Cite: Königsbrügge O, Schmaldienst S, Auinger M, Klauser-Braun R, Lorenz M, Tabernig S, Kletzmayr J, Enzenberger B, Eigner M, Hecking M, Siller-Matula JM, Pabinger I, Säemann M, Ay C
• PMID: 32126388

Cardiovascular disease (CVD) is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). However, antithrombotic therapy to prevent CVD increases the risk of bleeding. We aimed to investigate the prevalence of CVD and the practice patterns of antithrombotic agents in patients with ESRD on HD.

Epub: 03-02-20

Determinants of the intercept and slope of glomerular filtration rate in recipients of a live donor kidney transplant.

• Cite: Hamböck M, Staudenherz A, Kainz A, Geist B, Hecking M, Doberer K, Hacker M, Böhmig GA
• PMID: 32016508

Donor kidney function is considered a critical determinant of allograft survival after live donor (LD) kidney transplantation, but its independent impact on the evolution of graft function is less well defined. The objective of this study was to dissect the relative contribution of LD kidney function to baseline estimated glomerular filtration rate (eGFR) of recipients and its decline.

Epub: 24-10-19

Sex Differences in Kidney Replacement Therapy Initiation and Maintenance.

• Cite: Antlanger M, Noordzij M, van de Luijtgaarden M, Carrero JJ, Palsson R, Finne P, Hemmelder MH, Aresté-Fosalba N, Reisæter AV, Cases A, Traynor JP, Kramar R, Massy Z, Jager KJ, Hecking M,
• PMID: 31649071

More men than women undergo kidney replacement therapy (KRT) despite a larger number of women being affected by CKD. The aim of this multinational European study was to explore whether there might be historic and geographic trends in sex-specific incidence and prevalence of various KRT modalities.

Epub: 23-09-19

Considerations for SGLT2 inhibitor use in post-transplantation diabetes.

• Cite: Hecking M, Jenssen T
• PMID: 31235880

Epub: 01-06-19

Sex-specific analysis of haemodialysis prevalence, practices and mortality over time: the Austrian Dialysis Registry from 1965 to 2014.

• Cite: Kainz A, Berner C, Ristl R, Simon A, Stamm T, Zitt E, Kramar R, Antlanger M, Kautzky-Willer A, Schmaldienst S, Schernhammer E, Port FK, Carrero JJ, Jager KJ, Hecking M
• PMID: 30476247

Despite a higher prevalence of chronic kidney disease among women, more men than women start renal replacement therapy (RRT). We hypothesized that gender differences in health care access exist and therefore aimed at determining whether characteristics and outcomes of haemodialysis patients over time differ by sex.

Epub: 18-04-19

Self-reported Urine Volume in Hemodialysis Patients: Predictors and Mortality Outcomes in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).

• Cite: Hecking M, McCullough KP, Port FK, Bieber B, Morgenstern H, Yamamoto H, Suri RS, Jadoul M, Gesualdo L, Perl J, Robinson BM
• PMID: 31005373

Epub: 13-04-19

Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

• Cite: Chan CT, Blankestijn PJ, Dember LM, Gallieni M, Harris DCH, Lok CE, Mehrotra R, Stevens PE, Wang AY, Cheung M, Wheeler DC, Winkelmayer WC, Pollock CA,
• PMID: 30987837

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions.

Epub: 27-03-19

The Renaissance of Cholemic Nephropathy: A Likely Underestimated Cause of Renal Dysfunction in Liver Disease.

• Cite: Mandorfer M, Hecking M
• PMID: 30746731

Epub: 05-02-19

Associations between Hemodialysis Facility Practices to Manage Fluid Volume and Intradialytic Hypotension and Patient Outcomes.

• Cite: Dasgupta I, Thomas GN, Clarke J, Sitch A, Martin J, Bieber B, Hecking M, Karaboyas A, Pisoni R, Port F, Robinson B, Rayner H
• PMID: 30723164

Fluid overload and intradialytic hypotension are associated with cardiovascular events and mortality in patients on hemodialysis. We investigated associations between hemodialysis facility practices related to fluid volume and intradialytic hypotension and patient outcomes.

Epub: 25-01-19

Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety.

• Cite: Schwaiger E, Burghart L, Signorini L, Ristl R, Kopecky C, Tura A, Pacini G, Wrba T, Antlanger M, Schmaldienst S, Werzowa J, Säemann MD, Hecking M
• PMID: 30585690

The safety and efficacy of sodium-glucose cotransporter 2 inhibitors in posttransplantation diabetes mellitus is unknown. We converted stable kidney transplant patients to 10 mg empagliflozin, aiming at replacing their insulin therapy (<40 IU/d). N = 14 participants (the required sample size) completed the study visits through 4 weeks and N = 8 through 12 months. Oral glucose tolerance test (OGTT)-derived 2-hour glucose (primary end point) increased from 232 ± 82 mg/dL (baseline) to 273 ± 116 mg/dL (4 weeks, P = .06) and to 251 ± 71 mg/dL (12 months, P = .41). Self-monitored blood glucose and hemoglobin A1c were also clinically inferior with empagliflozin monotherapy, such that insulin was reinstituted in 3 of 8 remaining participants. Five participants (2 of them dropouts) vs nine of 24 matched reference patients developed bacterial urinary tract infections (P = .81). In empagliflozin-treated participants, oral glucose insulin sensitivity decreased and beta-cell glucose sensitivity increased at the 4-week and 12-month OGTTs. Estimated glomerular filtration rate and bioimpedance spectroscopy-derived extracellular and total body fluid volumes decreased by 4 weeks, but recovered. All participants lost body weight. No participant developed ketoacidosis; 1 patient developed balanitis. In conclusion, although limited by sample size and therefore preliminary, these results suggest that empagliflozin can safely be used as add-on therapy, if posttransplant diabetes patients are monitored closely (NCT03113110).

Epub: 01-10-18

Greater fluid overload and lower interdialytic weight gain are independently associated with mortality in a large international hemodialysis population.

• Cite: Hecking M, Moissl U, Genser B, Rayner H, Dasgupta I, Stuard S, Stopper A, Chazot C, Maddux FW, Canaud B, Port FK, Zoccali C, Wabel P
• PMID: 29688512

Fluid overload and interdialytic weight gain (IDWG) are discrete components of the dynamic fluid balance in haemodialysis patients. We aimed to disentangle their relationship, and the prognostic importance of two clinically distinct, bioimpedance spectroscopy (BIS)-derived measures, pre-dialysis and post-dialysis fluid overload (FOpre and FOpost) versus IDWG.

Epub: 08-03-18

A randomized controlled trial-based algorithm for insulin-pump therapy in hyperglycemic patients early after kidney transplantation.

• Cite: Werzowa JM, Säemann MD, Mohl A, Bergmann M, Kaltenecker CC, Brozek W, Thomas A, Haidinger M, Antlanger M, Kovarik JJ, Kopecky C, Song PXK, Budde K, Pascual J, Hecking M
• PMID: 29518094

Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment. CSII was initiated in 24 patients aged 55±12 years, without diabetes history, receiving tacrolimus. The mean daily insulin lispro dose was 9.2±5.2 IU. 2.3±1.1% of the total insulin dose were administered between 00:00 and 6:00, 19.5±11.6% between 6:00 and 12:00, 62.3±15.6% between 12:00 and 18:00 and 15.9±9.1% between 18:00 and 24:00. Additional bolus injections were necessary in five patients. Mild hypoglycemia (52-60 mg/dL) occurred in two patients. During the first post-operative week glucose control in CSII patients was overall superior compared to standard-of-care as well as once-daily insulin isophane for fasting and post-supper glucose. We present an algorithm for CSII treatment in kidney transplant recipients, demonstrating similar safety and superior short-term efficacy compared to standard-of-care and once-daily insulin isophane.

Epub: 21-02-18

Correspondence regarding the impact of kidney transplantation on insulin sensitivity.

• Cite: Bergfeld L, Werzowa J, Säemann M, Hecking M
• PMID: 29377325

Epub: 22-01-18

Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease.

• Cite: Carrero JJ, Hecking M, Chesnaye NC, Jager KJ
• PMID: 29355169

Improved understanding of sex and gender-specific differences in the aetiology, mechanisms and epidemiology of chronic kidney disease (CKD) could help nephrologists better address the needs of their patients. Population-based studies indicate that CKD epidemiology differs by sex, affecting more women than men, especially with regard to stage G3 CKD. The effects of longer life expectancy on the natural decline of glomerular filtration rate (GFR) with age, as well as potential overdiagnosis of CKD through the inappropriate use of GFR equations, might be in part responsible for the greater prevalence of CKD in women. Somewhat paradoxically, there seems to be a preponderance of men among patients starting renal replacement therapy (RRT); the protective effects of oestrogens in women and/or the damaging effects of testosterone, together with unhealthier lifestyles, might cause kidney function to decline faster in men than in women. Additionally, elderly women seem to be more inclined to choose conservative care instead of RRT. Dissimilarities between the sexes are also apparent in the outcomes of CKD. In patients with predialysis CKD, mortality is higher in men than women; however, this difference disappears for patients on RRT. Although access to living donor kidneys among men and women seems equal, women have reduced access to deceased donor transplantation. Lastly, health-related quality of life while on RRT is poorer in women than men, and women report a higher burden of symptoms. These findings provide insights into differences in the underlying pathophysiology of disease as well as societal factors that can be addressed to reduce disparities in access to care and outcomes for patients with CKD.

Epub: 16-11-17

The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck® parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment.

• Cite: Knafl D, Müller M, Pajenda S, Genc Z, Hecking M, Wagner L
• PMID: 29145491

Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), depends on the expression of these proteins in cells of the urinary sediment.

Epub: 10-10-17

Feedback Control in Hemodialysis-Much Ado about Nothing?

• Cite: Hecking M, Schneditz D
• PMID: 29018099

Epub: 29-08-17

Intravenous Fluid Challenge Decreases Intracellular Volume: A Bioimpedance Spectroscopy-Based Crossover Study in Healthy Volunteers.

• Cite: Ernstbrunner M, Kabon B, Zotti O, Zeitlinger M, Berner C, Hinterholzer G, Säemann M, Frommlet F, Fleischmann E, Hecking M
• PMID: 28851933

The effects of intravenous fluid therapy on fluid compartments and hemodynamics of the human body remain enigmatic. We therefore tested the efficacy of bioimpedance spectroscopy in a crossover study, where 15 males received 0.5 ml/kg/min ELO-MEL-isoton (osmolarity = 302 mosmol/l) during 60 minutes, or nothing at all. In group "Fluid", fluid load increased from -0.2 ± 1.0 l extracellular volume at baseline to its maximum of 1.0 ± 0.9 l in minute 70, and remained continuously elevated throughout minute 300. In group "Zero", fluid load decreased from 0.5 ± 1.1 l at baseline to its minimum of -1.1 ± 1.1 l in minute 300. In group "Fluid", intracellular volume decreased from 26.8 ± 3.9 l at baseline to its minimum of 26.0 ± 3.9 l in minute 70, and remained continuously decreased throughout minute 300. In group "Zero", intracellular volume increased from 26.5 ± 3.8 l at baseline to its maximum of 27.1 ± 3.9 l in minute 120, and decreased thereafter. In group "Fluid" compared to "Zero", systolic blood pressure was significantly higher, from minute 50-90. In conclusion, intravenous fluid therapy caused a clinically meaningful, sustained increase in fluid load, and a decrease in intracellular volume. These data raise interest in studying fluid administration by the gastrointestinal route, perhaps even when managing critical illness.

Epub: 17-07-17

Blood volume-monitored regulation of ultrafiltration to decrease the dry weight in fluid-overloaded hemodialysis patients: a randomized controlled trial.

• Cite: Antlanger M, Josten P, Kammer M, Exner I, Lorenz-Turnheim K, Eigner M, Paul G, Klauser-Braun R, Sunder-Plassmann G, Säemann MD, Hecking M
• PMID: 28716046

Because chronic fluid volume overload is associated with higher mortality, we tested whether blood-volume monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) would facilitate dry weight reduction, in comparison to conventional dialysis (CONV).

Epub: 24-05-17

Regional Differences in the Associations Between Prescribed Dialysate Sodium Concentration and Interdialytic Weight Gain in the Dialysis Outcomes and Practice Patterns Study.

• Cite: Hecking M, Wong MMY, Port FK, Robinson BM, McCullough KP
• PMID: 28549537

Epub: 23-05-17

Chronic Kidney Disease, Gender, and Access to Care: A Global Perspective.

• Cite: Carrero JJ, Hecking M, Ulasi I, Sola L, Thomas B
• PMID: 28532558

Little is known regarding the ways in which chronic kidney disease (CKD) prevalence and progression differ between the sexes. Still less is known regarding how social disparities between men and women may affect access to care for CKD. In this review, we briefly describe biological sex differences, noting how these differences currently do not influence CKD management recommendations. We then describe what is known within the published literature regarding differences in CKD epidemiology between sexes; namely prevalence, progression, and access to treatment throughout the major world regions. We highlight that health care expenditure and social gender disparities ultimately may determine whether women have equitable access to care for CKD and end-stage kidney disease. Among many high- and low-income settings, women more often donate and are less likely to receive kidney transplants when compared with men. Research is needed urgently to elucidate the reasons behind these disparities, as well as to develop CKD treatment strategies tailored to women's unique health care needs.

Epub: 11-04-17

Heart Failure with Preserved and Reduced Ejection Fraction in Hemodialysis Patients: Prevalence, Disease Prediction and Prognosis.

• Cite: Antlanger M, Aschauer S, Kopecky C, Hecking M, Kovarik JJ, Werzowa J, Mascherbauer J, Genser B, Säemann MD, Bonderman D
• PMID: 28395286

Heart failure (HF) is a main cause of mortality of hemodialysis (HD) patients. While HF with reduced ejection fraction (HFrEF) is known to only affect a minority of patients, little is known about the prevalence, associations with clinical characteristics and prognosis of HF with preserved ejection fraction (HFpEF).

Epub: 21-12-16

Fluid status and outcome in patients with heart failure and preserved ejection fraction.

• Cite: Koell B, Zotter-Tufaro C, Duca F, Kammerlander AA, Aschauer S, Dalos D, Antlanger M, Hecking M, Säemann M, Mascherbauer J, Bonderman D
• PMID: 28062131

Most heart failure with preserved ejection fraction (HFpEF) patients, at some point, present to an emergency department with typical symptoms of volume overload. Clinically, most respond well to standard diuretic therapy, sometimes at the cost of renal function. The study sought to define the prognostic significance of fluid status versus renal function in patients with HFpEF.

Epub: 17-11-16

Interdialytic Weight Gain: Trends, Predictors, and Associated Outcomes in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).

• Cite: Wong MM, McCullough KP, Bieber BA, Bommer J, Hecking M, Levin NW, McClellan WM, Pisoni RL, Saran R, Tentori F, Tomo T, Port FK, Robinson BM
• PMID: 27866963

High interdialytic weight gain (IDWG) is associated with adverse outcomes in hemodialysis (HD) patients. We identified temporal and regional trends in IDWG, predictors of IDWG, and associations of IDWG with clinical outcomes.

Epub: 13-09-16

Effects of angiotensin-converting-enzyme inhibitor therapy on the regulation of the plasma and cardiac tissue renin-angiotensin system in heart transplant patients.

• Cite: Kovarik JJ, Kopecky C, Antlanger M, Domenig O, Kaltenecker CC, Werzowa J, Hecking M, Mahr S, Grömmer M, Wallner C, Aumayr K, Kain R, Zuckermann A, Poglitsch M, Säemann MD
• PMID: 27773450

Angiotensin-converting enzyme (ACE) inhibitors (ACEis) are beneficial in patients with heart failure, yet their role after heart transplantation (HTx) remains ambiguous. Particularly, the effects of ACEis on plasma and cardiac metabolites of the "classical" and "alternative" renin-angiotensin system (RAS) in HTx patients are unknown.

Epub: 01-07-16

Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis.

• Cite: Cobo G, Hecking M, Port FK, Exner I, Lindholm B, Stenvinkel P, Carrero JJ
• PMID: 27252402

Sex and gender differences are of fundamental importance in most diseases, including chronic kidney disease (CKD). Men and women with CKD differ with regard to the underlying pathophysiology of the disease and its complications, present different symptoms and signs, respond differently to therapy and tolerate/cope with the disease differently. Yet an approach using gender in the prevention and treatment of CKD, implementation of clinical practice guidelines and in research has been largely neglected. The present review highlights some sex- and gender-specific evidence in the field of CKD, starting with a critical appraisal of the lack of inclusion of women in randomized clinical trials in nephrology, and thereafter revisits sex/gender differences in kidney pathophysiology, kidney disease progression, outcomes and management of haemodialysis care. In each case we critically consider whether apparent discrepancies are likely to be explained by biological or psycho-socioeconomic factors. In some cases (a few), these findings have resulted in the discovery of disease pathways and/or therapeutic opportunities for improvement. In most cases, they have been reported as merely anecdotal findings. The aim of the present review is to expose some of the stimulating hypotheses arising from these observations as a preamble for stricter approaches using gender for the prevention and treatment of CKD and its complications.

Epub: 23-03-16

Molecular regulation of the renin-angiotensin system in haemodialysis patients.

• Cite: Kovarik JJ, Antlanger M, Domenig O, Kaltenecker CC, Hecking M, Haidinger M, Werzowa J, Kopecky C, Säemann MD
• PMID: 27190396

Epub: 25-11-15

Prophylactic CMV therapy does not improve three-yr patient and graft survival compared to preemptive therapy.

• Cite: Werzowa J, Schwaiger B, Hecking M, Strassl R, Schmaldienst S, Böhmig GA, Genser B, Säemann MD
• PMID: 26458731

Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long-term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate-risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV-related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30-0.75; p < 0.001). There was a trend for higher three-yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62-41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32-2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m(2) lower in the prophylactic group (95% CI -11.68 to -1.81; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post-transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed.

Epub: 17-07-15

Comparison of glycemic control and variability in patients with type 2 and posttransplantation diabetes mellitus.

• Cite: Werzowa J, Pacini G, Hecking M, Fidler C, Haidinger M, Brath H, Thomas A, Säemann MD, Tura A
• PMID: 26264400

Posttransplantation diabetes mellitus (PTDM) is a common complication after renal transplantation leading to increased cardiovascular morbidity and mortality. In subjects with type 2 diabetes (T2DM) increased glycemic variability and poor glycemic control have been associated with cardiovascular complications. We therefore aimed at determining glycemic variability and glycemic control in subjects with PTDM in comparison to T2DM subjects.

Epub: 23-05-15

The diagnosis of posttransplantation diabetes mellitus: meeting the challenges.

• Cite: Werzowa J, Hecking M, Haidinger M, Döller D, Sharif A, Tura A, Säemann MD
• PMID: 25777999

Posttransplantation diabetes mellitus (PTDM) is a major complication after renal transplantation due to its negative impact on patient and graft survival, and affects up to 40% of renal transplant recipients. The generation of evidence regarding its optimal treatment is now progressing with some emphasis on early postoperative insulin treatment that targets β-cell failure. This therapy seems to benefit renal transplant patients but contrasts with previous PTDM guidelines that were following treatment of type 2 diabetes mellitus (DM): oral antidiabetics first, insulin last. Similarly, in the current PTDM consensus recommendations, diagnostic procedures are in accordance with the American Diabetes Association (ADA) recommendations for diagnosis of DM. PTDM and type 2 DM, however, are distinct disease entities with different pathophysiological backgrounds. This review will discuss the significance of the standard diagnostic criteria for DM in patients after renal transplantation without prior DM. In particular, the role of glycated hemoglobin (HbA1c) and oral glucose tolerance testing (OGTT) will be reviewed. In addition, the potential role of other glycated proteins and continuous glucose monitoring will be covered, although these parameters are not yet part of the consensus recommendations.

Epub: 23-03-15

More evidence needed before lower dialysate sodium concentrations can be recommended.

• Cite: Hecking M, Rayner H, Port FK
• PMID: 25704046

Epub: 01-03-15

What are the Consequences of Volume Expansion in Chronic Dialysis Patients?: Defining and Measuring Fluid Overload in Hemodialysis Patients.

• Cite: Hecking M, Rayner H, Wabel P
• PMID: 25732408

Epub: 23-02-15

Assessment of beta-cell function and insulin secretion in subjects that underwent renal transplantation.

• Cite: Tura A, Hecking M, Wolzt M, Saemann MD, Pacini G
• PMID: 26736770

In this study we aimed to assess the performance of various indices of beta-cell function derived from oral glucose tolerance test (OGTT) in subjects that underwent renal transplantation. Impaired insulin secretion seems in fact central for development of new onset diabetes after transplantation, but its assessment has not been systematically evaluated. Twenty subjects underwent a 75 g 2h-OGTT for measurement of glucose, insulin, C-peptide. OGTT indices of beta-cell function were either derived by mathematical modeling (yielding the reference index: glucose sensitivity) or were empirical: insulinogenic index (IGI), IGI derived indices, whole shape C-peptide (WHOSH_CP). Indices of beta cell function, showed significant correlation with glucose sensitivity (R(2)=0.40-0.86, all P<;0.003). The majority of beta-cell function indices provided comparable results also when subjects were divided into subgroups according to sex, age, body mass index, mean glycemia. In conclusion, in transplanted subjects OGTT empirical indices are typically acceptable for the estimation of beta-cell function.

Epub: 14-01-15

Antidiabetic therapy in post kidney transplantation diabetes mellitus.

• Cite: Werzowa J, Säemann M, Haidinger M, Krebs M, Hecking M
• PMID: 25641399

Post-transplantation diabetes mellitus (PTDM) is a common complication after kidney transplantation that affects up to 40% of kidney transplant recipients. By pathogenesis, PTDM is a diabetes form of its own, and may be characterised by a sudden, drug-induced deficiency in insulin secretion rather than worsening of insulin resistance over time. In the context of deteriorating allograft function leading to a re-occurrence of chronic kidney disease after transplantation, pharmacological interventions in PTDM patients deserve special attention. In the present review, we aim at presenting the current evidence regarding efficacy and safety of the modern antidiabetic armamentarium. Specifically, we focus on incretin-based therapies and insulin treatment, besides metformin and glitazones, and discuss their respective advantages and pitfalls. Although recent pilot trials are available in both prediabetes and PTDM, further studies are warranted to elucidate the ideal timing of various antidiabetics as well as its long-term impact on safety, glucose metabolism and cardiovascular outcomes in kidney transplant recipients.

Epub: 31-10-14

Bioimpedance spectroscopy for assessment of volume status in patients before and after general anaesthesia.

• Cite: Ernstbrunner M, Kostner L, Kimberger O, Wabel P, Säemann M, Markstaller K, Fleischmann E, Kabon B, Hecking M
• PMID: 25360698

Technically assisted assessment of volume status before surgery may be useful to direct intraoperative fluid administration. We therefore tested a recently developed whole-body bioimpedance spectroscopy device to determine pre- to postoperative fluid distribution.

Epub: 28-10-14

Sex-specific differences in hemodialysis prevalence and practices and the male-to-female mortality rate: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

• Cite: Hecking M, Bieber BA, Ethier J, Kautzky-Willer A, Sunder-Plassmann G, Säemann MD, Ramirez SP, Gillespie BW, Pisoni RL, Robinson BM, Port FK
• PMID: 25350533

A comprehensive analysis of sex-specific differences in the characteristics, treatment, and outcomes of individuals with end-stage renal disease undergoing dialysis might reveal treatment inequalities and targets to improve sex-specific patient care. Here we describe hemodialysis prevalence and patient characteristics by sex, compare the adult male-to-female mortality rate with data from the general population, and evaluate sex interactions with mortality.

Epub: 06-08-14

Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions.

• Cite: Sharif A, Hecking M, de Vries AP, Porrini E, Hornum M, Rasoul-Rockenschaub S, Berlakovich G, Krebs M, Kautzky-Willer A, Schernthaner G, Marchetti P, Pacini G, Ojo A, Takahara S, Larsen JL, Budde K, Eller K, Pascual J, Jardine A, Bakker SJ, Valderhaug TG,
• PMID: 25307034

A consensus meeting was held in Vienna on September 8-9, 2013, to discuss diagnostic and therapeutic challenges surrounding development of diabetes mellitus after transplantation. The International Expert Panel comprised 24 transplant nephrologists, surgeons, diabetologists and clinical scientists, which met with the aim to review previous guidelines in light of emerging clinical data and research. Recommendations from the consensus discussions are provided in this article. Although the meeting was kidney-centric, reflecting the expertise present, these recommendations are likely to be relevant to other solid organ transplant recipients. Our recommendations include: terminology revision from new-onset diabetes after transplantation to posttransplantation diabetes mellitus (PTDM), exclusion of transient posttransplant hyperglycemia from PTDM diagnosis, expansion of screening strategies (incorporating postprandial glucose and HbA1c) and opinion-based guidance regarding pharmacological therapy in light of recent clinical evidence. Future research in the field was discussed with the aim of establishing collaborative working groups to address unresolved questions. These recommendations are opinion-based and intended to serve as a template for planned guidelines update, based on systematic and graded literature review, on the diagnosis and management of PTDM.

Epub: 14-02-14

Recovery time, quality of life, and mortality in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

• Cite: Rayner HC, Zepel L, Fuller DS, Morgenstern H, Karaboyas A, Culleton BF, Mapes DL, Lopes AA, Gillespie BW, Hasegawa T, Saran R, Tentori F, Hecking M, Pisoni RL, Robinson BM
• PMID: 24529994

There is limited information about the clinical and prognostic significance of patient-reported recovery time.

Epub: 06-07-13

Significance of interdialytic weight gain versus chronic volume overload: consensus opinion.

• Cite: Hecking M, Karaboyas A, Antlanger M, Saran R, Wizemann V, Chazot C, Rayner H, Hörl WH, Pisoni RL, Robinson BM, Sunder-Plassmann G, Moissl U, Kotanko P, Levin NW, Säemann MD, Kalantar-Zadeh K, Port FK, Wabel P
• PMID: 23838386

Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as >15% above 'normal' extracellular fluid volume, equivalent to >2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of 'nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.

Epub: 06-10-10

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation.

• Cite: Haidinger M, Werzowa J, Voigt HC, Pleiner J, Stemer G, Hecking M, Döller D, Hörl WH, Weichhart T, Säemann MD
• PMID: 20925938

New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.

Epub: 16-04-09

Late onset Pneumocystis pneumonia in renal transplantation after long-term immunosuppression with belatacept.

• Cite: Haidinger M, Hecking M, Memarsadeghi M, Weichhart T, Werzowa J, Hörl WH, Säemann MD
• PMID: 19210692

Interference with T-cell function increases the risk of infections, especially during the early post-transplant period. Belatacept, a costimulation blocker, is currently being tested in phase III clinical trials. Here we report a renal transplant recipient who received belatacept and developed severe Pneumocystis jirovecii pneumonia (PCP) with fatal superinfections 4 years post transplant. Cytomegalovirus infection preceded PCP, which typically occurs in overimmunosuppressed patients, but has not yet been reported under T-cell costimulation blockade in transplant patients. This case illustrates the possibility of excessive immunosuppression even with a lymphocyte-specific regimen.

Epub: 16-03-08

Analysis of liver function in renal transplant recipients undergoing C2-monitoring for cyclosporine.

• Cite: Hecking M, Kainz A, Schillinger M, Posch C, Birsan T, Rasoul-Rockenschaub S, Böhmig GA, Schmaldienst S, Watschinger B, Hörl WH, Mühlbacher F, Säemann MD
• PMID: 17903183

There exists no systematic evaluation of liver function in renal allograft recipients undergoing C2-monitoring with Neoral [cyclosporine A (CsA)-microemulsion]. In the present cohort analysis, we compared the hepatic profiles of C2-monitored (n = 80), C0-monitored (n = 81), and non-CsA-treated renal allograft recipients (n = 29), transplanted between 1/1999 and 2/2004 in our institution. While the C2-targets were set in accordance with (n = 72) or below (n = 8) the consensus on Neoral (1500 +/- 200 ng/ml), non-CsA-patients received FK506 (n = 29), partially in combination with rapamycin (n = 13) as primary immunosuppression. Analysis of maximum hepatic laboratory parameters and also repeated measures by anova within 30 days post-transplant revealed highly significant elevations of direct, indirect and total bilirubin, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase (P < 0.001) in the C2-group, in comparison with the C0- and the non-CsA-group. Bilirubin-levels were by far the most affected of all hepatic parameters, and correlated with C2-levels (r2 = 0.62). Seventeen CsA-patients had excessive bilirubin-elevations (>4 mg/dl) and were therefore considered to be 'CsA-sensitive' [14 C2-patients (17% of all C2-patients), 3 C0-patients (4% of all C0-patients)]. Bilirubin- and the other parameter elevations in these patients were reversible upon withdrawal or lowering of CsA. Most 'CsA-sensitive' patients (n = 12, 70%) displayed pre-transplant hepatic impairment, indicating a pre-existing liver instability. Collectively, our data emphasize the need for increased awareness toward individual predispositions for CsA-sensitivity.