Search

Morten Baltzer Houlind,1–4 Esben Iversen,1 Baker Nawfal Jawad,1 Thomas Kallemose,1 Mads Hornum5,6 1Department of Clinical Research, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark; 2The Capital Region Pharmacy, Herlev, Denmark; 3Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 4Emergency Department, Copenhagen University Hospital – Amager & Hvidovre, Hvidovre, Denmark; 5Department of Nephrology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark; 6Department of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Morten Baltzer Houlind, Tel +45 28838563, Email morten.baltzer.houlind@regionh.dk View the original paper by Dr Kaas-Hansen and colleagues A Response to Letter has been published for this article

The effect of 10 min of high-intensity cycling exercise on circulating growth hormone (GH), insulin-like growth factors I and II (IGF-I and -II), and insulin-like growth factor binding protein 3 (IGF BP-3) was studied in nine eumenorrheic women (age 19-48 yr) at two different phases of the menstrual cycle. Tests were performed on separate mornings corresponding to the follicular phase and to the periovulatory phase of the menstrual cycle, during which plasma levels of endogenous estradiol (E2) were relatively low (272 +/- 59 pmol/l) and high (1,112 +/- 407 pmol/l), respectively. GH increased significantly in response to exercise under both E2 conditions. Plasma GH before exercise (2.73 +/- 2.48 vs. 1.71 +/- 2.09 micrograms/l) and total GH over 10 min of exercise and 1-h recovery (324 +/- 199 vs. 197 +/- 163 ng) were both significantly greater for periovulatory phase than for follicular phase studies. IGF-I, but not IGF-II, increased acutely after exercise. IGF BP-3, assayed by radioimmunoassay, was not significantly different at preexercise, and exercise, or at 30-min recovery time points and was not different between the two study days. When assayed by Western blot, however, there was a significant increase in IGF BP-3 30 min after exercise for the periovulatory study. These findings indicate that the modulation of GH secretion associated with menstrual cycle variations in circulating E2 affects GH measured after exercise, at least in part, by an increase in baseline levels. The acute increase in IGF-I induced by exercise appears to be independent of the GH response and is not affected by menstrual cycle timing.

Background and aim: Malnutrition in older patients is linked to poor appetite. Cannabis‐based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1‐mg delta‐9‐tetrahydrocannabinol [THC] and 7.5‐mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR‐estimates and measured‐GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods. Methods and objectives: This study is composed of two substudies. Substudy 1 is an investigator‐initiated single‐center, double‐blinded, randomized, placebo‐controlled, superiority, cross‐over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single‐dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1—the difference in energy intake between Sativex® and placebo conditions; substudy 2— the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP‐1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin. [ABSTRACT FROM AUTHOR]

Background: The significance of chronic kidney disease on susceptibility to COVID‐19 and subsequent outcomes remains unaddressed. Objective: To investigate the association of estimated glomerular filtration rate (eGFR) on risk of contracting COVID‐19 and subsequent adverse outcomes. Methods: Rates of hospital‐diagnosed COVID‐19 were compared across strata of eGFR based on conditional logistic regression using a nested case–control framework with 1:4 matching of patients diagnosed with COVID‐19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID‐19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G‐computation of results to determine 60‐day risk standardized to the distribution of risk factors in the sample. Results: Estimated glomerular filtration rate was inversely associated with rate of hospital‐diagnosed COVID‐19: eGFR 61–90 mL/min/1.73m2 HR 1.13 (95% CI 1.03–1.25), P = 0.011; eGFR 46–60 mL/min/1.73m2 HR 1.26 (95% CI 1.06–1.50), P = 0.008; eGFR 31–45 mL/min/1.73m2 HR 1.68 (95% CI 1.34–2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50–4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60‐day risk of death or severe COVID‐19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7–15.0); eGFR 90–61 mL/min/1.73m2 16.1% (95% CI 14.5–17.7); eGFR 46–60 mL/min/1.73m2 17.8% (95% CI 14.7–21.2); eGFR 31–45 mL/min/1.73m2 22.6% (95% CI 18.2–26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1–29.1). Conclusions: Renal insufficiency was associated with progressive increase in both rate of hospital‐diagnosed COVID‐19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID‐19. [ABSTRACT FROM AUTHOR]

Abstract: We hypothesized that a decrease in renal function is seen immediately after heart transplantation (HTX) with little recovery over time. Twelve consecutive patients had their glomerular filtration rate (GFR) measured using 51Cr-ethylenediaminetetraacetic acid (EDTA) measured GFR (mGFR) before transplantation and at 1, 2, 3, and 26 weeks after transplantation. The mGFR decreased by 28% and 24% during the first 3 and 26 weeks, respectively, with mean blood cyclosporine concentration as an independent risk factor for the decrease in mGFR. The identification of cyclosporine A (CsA) as the most important risk factor for the rapid and sustained decrease in renal function supports the need for more studies on renoprotective strategies immediately after HTX. [Copyright &y& Elsevier]

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A-C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) compared with both individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] min) compared with individuals with cirrhosis (5.7 [5.2;6.3] min, P = 0.002) and control individuals (5.7 [5.2;6.3] min, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, CKD, but not liver cirrhosis, leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination., (© 2024 by the American Diabetes Association.)

Background: Estimated GFR (eGFR) has shown poor agreement with measured GFR (mGFR) in several populations. We investigated the impact of age and body composition on the accuracy and precision of eGFR in heart transplant (HTx) recipients., Methods: In a longitudinal, observational, retrospective study design, patients receiving first-time HTx with at least one registered mGFR value within 15 months after HTx and a corresponding plasma creatinine were included. GFR was measured by 51Cr-EDTA and eGFR calculated by creatinine-based CKD-EPI formula., Results: A total of 150 patients with a total of 723 mGFR measurements were included. During the first year after HTx, mean weight increased by 4.2 kg (CI: 3.2 to 5.1) followed by an annual decrease of 0.35 kg/year (Cl: -0.05 to 0.74). mGFR increased by 7.5 mL/min (Cl: 3.2 to 11.8) the first year but was stable hereafter (0.0 mL/min/year; CI: -1.0 to 1.0). The initial weigh gain and increase in mGFR were most pronounced in patients &lt;45 years. Neither eGFR adjusted nor unadjusted for BSA detected the initial increase in mGFR. At 1 year after HTx, limits of agreement on the Bland-Altman plot were -37.2 to 33.1 mL/min with a bias of -2.1 mL/min (Cl: -5.0 to 0.9). In patients &lt;45 years, eGFR significantly overestimated mGFR by 7.1 mL/min (Cl: 1.0 to 13.2) and showed a significant lower precision than patients &gt;45 years. There was no effect of BMI class, weight, BSA, or change in BMI class on the difference between eGFR and mGFR., Conclusion: eGFR is, on average, accurate but imprecise in HTx patients. The agreement is affected by age but not body composition., (© 2024 S. Karger AG, Basel.)

Background: This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments and prognosis of kidney diseases., Methods: Kidney biopsy reports from 1 January 1998 to 31 December 2018 were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values and Cohen's kappa coefficient for the retrieved SNOMED codes were calculated., Results: A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease ( n  = 368), tubulointerstitial disease ( n  = 67), renal vascular disease ( n  = 51), diabetic nephropathy ( n  = 51) and various renal disorders ( n  = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%) and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%) and other renal disorders (17%) showed lower PPV., Conclusions: SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research., Competing Interests: No potential conflicts of interest were reported by M.M., I.B., H.D., J.W.G., H.H., K.H., P.I., K.H.R., M.B.J., D.K., F.H.M., P.R., K.E.O., F.P. and K.D.S. T.K. reports honoraria for education and consultancy from AstraZeneca. R.B. reports honoraria for education and consultancy from AstraZeneca, Bayer, Mundipharma, Vifor and Boehringer Ingelheim. M.H. reports honoraria for advisory boards for AstraZeneca, Bayer, Boeringer Ingelheim, Vifor, GSK and Novo Nordisk A/S, and education for AstraZeneca, Boeringer Ingelheim and Novo Nordisk A/S outside the scope of this manuscript. D.H. reports research grant from Vifor Pharma and Gedeon Richter, and consultancy fees and lecture fees from UCB Nordic, GSK and AstraZeneca., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Subcellular membranes have complex lipid and protein compositions, which give rise to organelle-specific membrane packing, fluidity, and permeability. Due to its exquisite solvent sensitivity, the lipophilic fluorescence dye Nile Red has been used extensively to study membrane packing and polarity. Further improvement of Nile Red can be achieved by introducing electron-donating or withdrawing functional groups. Here, we compare the potential of derivatives of Nile Red with such functional substitutions for super-resolution fluorescence microscopy of lipid packing in model membranes and living cells. All studied Nile Red derivatives exhibit cholesterol-dependent fluorescence changes in model membranes, as shown by spectrally resolved stimulated emission depletion (STED) microscopy. STED imaging of Nile Red probes in cells reveals lower membrane packing in fibroblasts from healthy subjects compared to those from patients suffering from Niemann Pick type C1 (NPC1) disease, a lysosomal storage disorder with accumulation of cholesterol and sphingolipids in late endosomes and lysosomes. We also find small but consistent changes in the fluorescence lifetime of the Nile Red derivatives in NPC1 cells, suggesting altered hydrogen-bonding capacity in their membranes. All Nile Red derivatives are essentially non-fluorescent in water but increase their brightness in membranes, allowing for their use in MINFLUX single molecule tracking experiments. Our study uncovers the potential of Nile Red probes with functional substitutions for nanoscopic membrane imaging., (© 2024. The Author(s).)

Background: Although kidney insufficiency has been shown to be associated with increased risk of myocardial injury, benefit of coronary angiography (CAG) and revascularization remains uncertain, with implications on management strategies and outcomes. We aimed to compare rates of CAG and revascularization and subsequent risk of cardiovascular and kidney outcomes in hospitalized patients with myocardial injury and kidney dysfunction., Methods: Retrospective cohort study encompassing hospitalized patients with myocardial injury i.e. elevated troponin I or T and an eGFR ≤60 ml/min/1.73 m 2 identified between 2011 and 2021 in Danish national registers. 30-day odds for CAG were computed across granular eGFR-categories based on multiple logistic regression. Standardized one-year risks of cardiovascular and kidney outcomes including mortality were determined based on hazards obtained in multiple Cox regression., Results: A total of 52,798 patients with myocardial injury were identified. CAG was performed in 14.3 % (n = 7549). 30-day odds ratios for CAG were 0.64 [0.60-0.68], 0.38 [0.34-0.42], 0.18 [0.14-0.22], and 0.35 [0.30-0.40] in patients with eGFR 31-45 ml/min/1.73 m 2 , eGFR 15-30 ml/min/1.73 m 2 for eGFR<15 ml/min/1.73 m 2 and chronic dialysis, respectively (eGFR 46-60 ml/min/1.73 m 2 as reference). Median follow-up was 4.1 years. One-year mortality risk differences associated with CAG and revascularization (no CAG as reference) were -7.8 [-7.0; -8.7] and -9.1 [-8.4; -9.9] for eGFR 46-60 ml/min/1.73 m 2 ; -7.0 [-5.7;-8-3] and -8.0 [-6.6; -9.5] for eGFR 31-45 ml/min/1.73 m 2 ; -5.4 [-3.0; -7.2] and -5.2 [-2.2; -8.3] for eGFR 15-30 ml/min/1.73 m 2 ; -8.8 [-3.1; -13.7] and -5.4 [3.1; -13.4] for eGFR<15 ml/min/1.73 m 2 ; and -4.9 [-0.1; -9.7] and -4.2 [1.5; -9.2] for chronic dialysis, respectively., Conclusion: Probability of CAG following myocardial injury declined with progressive kidney dysfunction. Overall, CAG was associated with lower mortality irrespective of kidney function and subsequent revascularization., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit., Methods and Analysis: The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient., Ethics and Dissemination: The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals., Trial Registration Numbers: NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00., Competing Interests: Competing interests: CDP has received speaker honoraria or consultancy fees from AstraZeneca and Astellas. Support for attending meetings and travel from Boehringer Ingelheim. CDP also has an ongoing collaboration with Vifor Pharma including donation of a research grant unrelated to this study. DH has received speaker and consultancy fees from AstraZeneca, GlaxoSmithKline and UCB Nordic. ELFB has received a donation of a research grant from AstraZeneca unrelated to this study. ELG has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Novo Nordisk, MSD, Lundbeck Pharma and Organon. He is an investigator in clinical studies sponsored by AstraZeneca, Idorsia or Bayer and has received unrestricted research grants from Boehringer Ingelheim. IB has received speaker honoraria from Amgen and Bayer. JBO has received speaker honoraria or consultancy fees from Bayer, Bristol-Myers Squibb, Organon and Pfizer. LB has received consultancy fees from AstraZeneca, Astellas, Vifor Pharma, Pfizer and Novartis. LK has received speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis and Novo Nordisk. MH has received speaker and consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Vifor and GSK within the last 3 years. ML has received speaker and consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and GlaxoSmithKline. NC has received speaker honoraria from AstraZeneca and Bristol-Myers Squibb. RB has received speaker honoraria or consultancy fees from AstraZeneca, Bayer and Boehringer Ingelheim. She is an investigator in clinical studies sponsored by Boehringer Ingelheim, AstraZeneca or Bayer and has received unrestricted research grants from Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project., Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m 2 ; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease., Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P  < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) ( P  = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P  = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P  < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P  < 0.05). These vascular changes were independent of differences in age., Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health., (© 2024 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed, but why precisely SGLT2 inhibition has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient's blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper was to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors' physiological effects., Summary: Changes induced by SGLT2 inhibitors on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that include radioisotopes, indocyanine green (ICG) dye, or carbon monoxide (CO). Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled CO. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of CO is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated., Key Messages: A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors., (© 2023 S. Karger AG, Basel.)

Introduction: Fluid overload is a major challenge in hemodialysis patients and might cause hypervolemia. We speculated that hemodialysis patients reaching dry weight could have undetected hypervolemia and low hemoglobin (Hb) concentration (g/dL) due to hemodilution., Methods: The study included hemodialysis patients (n = 22) and matched healthy controls (n = 22). Blood volume, plasma volume, red blood cell volume, and total Hb mass were determined using a carbon monoxide (CO)-rebreathing method in hemodialysis patients reaching dry weight and controls. Blood volume measurements were also obtained by a dual-isotope labeling technique in a subgroup for validation purposes., Findings: In the hemodialysis group, the median specific blood volume was 89.3 mL/kg (interquartile range [IQR]: 76.7-95.4 mL/kg) and was higher than in the control group (79.9 mL/kg [IQR: 70.4-88.0 mL/kg]; p < 0.037). The median specific plasma volume was 54.7 mL/kg (IQR: 47.1-61.0 mL/kg) and 44.0 mL/kg (IQR: 38.7-49.5 mL/kg) in the hemodialysis and control groups, respectively (p < 0.001). Hb concentration was lower in hemodialysis patients (p < 0.001), whereas no difference in total Hb mass was observed between groups (p = 0.11). A correlation was found between blood volume measured by the CO-rebreathing test and the dual-isotope labeling technique in the control group (r = 0.83, p = 0.015), but not the hemodialysis group (r = 0.25, p = 0.60)., Discussion: The hemodialysis group had increased specific blood volume at dry weight due to high plasma volume, suggesting a hypervolemic state. However, correlation was not established against the dual-isotope labeling technique underlining that the precision of the CO-rebreathing test should be further validated. The total Hb mass was similar between hemodialysis patients and controls, unlike Hb concentration, which emphasizes that Hb concentration is an inaccurate marker of anemia among hemodialysis patients., (© 2023 International Society for Hemodialysis.)

Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves. Patients were assessed pre-transplant and in three post-transplant periods: 0-45, 46-365 and >365 days. A higher PRS was significantly associated with increased odds of pre-transplant T2DM. However, no improvement was observed for pre-transplant T2DM prediction when comparing PRS combined with non-genetic risk scores to using non-genetic risk scores alone. This was also true for predictions of PTDM in all three post-transplant periods. This study demonstrated that polygenic risk was only associated with the risk of T2DM among SOT recipients prior to transplant and not for PTDM. Combining PRS with a clinical model of non-genetic risk scores did not significantly improve the predictive ability, indicating its limited clinical utility in identifying patients at high risk for T2DM before transplantation, suggesting that non-genetic or different genetic factors may contribute to PTDM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 dos Santos, Leung, Thorball, Ledergerber, Fellay, MacPherson, Hornum, Terrones-Campos, Rasmussen, Gustafsson, Perch, Sørensen, Ekenberg, Lundgren, Feldt‐Rasmussen and Reekie.)

Rationale & Objective: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers., Study Design: Cross-sectional diagnostic test substudy of a randomized clinical trial., Setting & Participants: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021., Tests Compared: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, β-trace protein (BTP) and/or β 2 -microglobulin (B2M)., Outcome: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE)., Results: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m 2 ). Among the creatinine-based equations, the 2009 CKD-EPI cr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPI comb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPI comb , the CKD-EPI panel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%)., Limitations: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status., Conclusions: The 2009 CKD-EPI cr , 2021 CKD-EPI comb , and CKD-EPI panel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement., Funding: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark)., Trial Registration: Registered at ClinicalTrials.gov with registration number NCT03741283., Plain-Language Summary: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as β-trace protein and β 2 -microglobulin did not further improve accuracy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients receiving haemodialysis are at increased risk of arrhythmias and sudden cardiac death, but data on arrhythmia burden and the pathophysiology remain limited. Among potential risk factors, hypoglycaemia is proposed as a possible trigger of lethal arrhythmias. The development of implantable loop recorders (ILR) and continuous glucose monitoring (CGM) enables long-term continuous ECG and glycaemic monitoring. The current article presents the protocol of a study aiming to increase the understanding of arrhythmias and risk factors in patients receiving haemodialysis. The findings will provide a detailed exploration of the burden and nature of arrhythmias in these patients including the potential association between hypoglycaemia and arrhythmias., Methods and Analysis: The study is an investigator-initiated, prospective, multicentre cohort study recruiting 70 patients receiving haemodialysis: 35 with diabetes and 35 without diabetes. Participants are monitored with ILRs and CGM for 18 months follow-up. Data collection further includes a monthly collection of predialysis blood samples and dialysis parameters. The primary outcome is the presence of clinically significant arrhythmias defined as a composite of bradycardia, ventricular tachycardia, or ventricular fibrillation. Secondary outcomes include the characterisation of clinically significant arrhythmias and other arrhythmias, glycaemic characteristics, and mortality. The data analyses include an assessment of the association between arrhythmias and hypoglycaemia and hyperglycaemia, baseline clinical variables, and parameters related to kidney failure and the haemodialysis procedure., Ethics and Dissemination: The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-20069767). The findings will be presented at national and international congresses as well as in international peer-reviewed scientific journals., Trial Registration Number: NCT04841304., Competing Interests: Competing interests: DHK has received speaker honoraria from Bayer A/S outside the submitted work. SZD is a consultant to Cortrium and Vital Beats and a member of Bristol Myers Squibb/Pfizer advisory board and has received speaker honoraria from Bristol Myers Squibb/Pfizer and Bayer. TB is a member of Medtronic and AstraZeneca advisory board and has received speaker honoraria from AstraZeneca outside the submitted work. ML is a member of advisory board at AstraZeneca, Bayer A/S Denmark, Boehringer Ingelheim, GlaxoSmithKline and received speaker honoraria from AstraZeneca, Bayer A/S Denmark and Boehringer Ingelheim. KN holds stocks in Novo Nordisk; has been a paid consultant for Novo Nordisk and Medtronic; has received speaker honorarium and honorarium for Advisory Board to her institution from Medtronic, Novo Nordisk, Convatec, and her institution has received research funding from Zealand Pharma, Novo Nordisk, Medtronic and Dexcom. TPA holds stocks in Novo Nordisk A/S. JHS is a member of Medtronic advisory board and has received speaker honoraria and research grants from Medtronic outside the submitted work. MH has served on scientific advisory boards for the following companies outside the scope of this study: Astra Zeneca A/S, Boehringer Ingelheim A/S, GSK A/S and CSL Vifor Pharma A/S; has served as moderator of a symposium and an educational meeting for Astra Zeneca A/S; has received research grants from the A.P. Møller Foundation, Augustinus Foundation, Helen Bjørnow Foundation, Lundbeck Foundation and has a Twinning Horizon Europe Grant. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Non-adherence to medication is a common and complex issue faced by individuals undergoing hemodialysis (HD). However, more knowledge is needed about modifiable factors influence on non-adherence. This study investigated the prevalence of non-adherence, medication beliefs and symptom burden and severity among patients receiving HD in Denmark. Associations between non-adherence, medications beliefs and symptom burden and severity were also explored., Method: A cross-sectional questionnaire-based multisite study, including 385 participants. We involved patient research consultants in the study design process and the following instruments were included: Medication Adherence Report Scale, Beliefs about Medication Questionnaire and Dialysis Symptom Index. Logistic regression analysis was performed., Results: The prevalence of non-adherence was 32% (95% CI 27-37%) using a 23-point-cut-off. Just over one third reported being concerned about medication One third also believed physicians to overprescribe medication, which was associated with 18% increased odds of non-adherence. Symptom burden and severity were high, with the most common symptoms being tiredness/ lack of energy, itching, dry mouth, trouble sleeping and difficulties concentrating. A high symptom burden and/or symptom severity score was associated with an increased odd of non-adherence., Conclusion: The study found significant associations between non-adherence and, beliefs about overuse, symptom burden and symptom severity. Our results suggest health care professionals (HCP) should prioritize discussion about medication adherence with patients with focus on addressing patient-HCP relationship, and patients' symptom experience. Future research is recommended to explore the effects of systematically using validated adherence measures in clinical practice on medication adherence, patient-HCP communication and trust. Additionally, studies are warranted to further investigate the relationship between symptom experience and adherence in this population., Trial Registration: NCT03897231., (© 2023. The Author(s).)

Background: Cardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels., Methods: In a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m 2 between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort., Results: We included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6-10.0) and 7.4% (95% CI 7.3-7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1-3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes., Conclusions: Diabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD., (© 2023. The Author(s).)

Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation. P-ETP and U-ETP/Cr at D1 (P-ETP AUC = 0.86, p < 0.0001; U-ETP/Cr AUC = 0.70, p = 0.0002) were independent markers of delayed graft function (DGF) and P-ETP at D1 had an odds ratio of 6.3 ( p < 0.0001) for DGF when adjusted for plasma creatinine. The results for P-ETP at D1 were confirmed in a validation cohort of 146 transplant recipients (AUC = 0.92, p < 0.0001). U-ETP/Cr at M3 was negatively associated with kidney graft function at M12 ( p = 0.007). This study suggests that ETP at D1 can identify patients at risk of delayed graft function and that U-ETP/Cr at M3 can predict the future status of the allograft. Thus, measuring collagen type VI formation could aid in predicting graft function in kidney transplant recipients.

Obesity is a heterogenous condition with multiple different phenotypes. Among these a particular subtype exists named as metabolically healthy obesity (MHO). MHO has multiple definitions and its prevalence varies according to study. The potential mechanisms underlying the pathophysiology of MHO include the different types of adipose tissue and their distribution, the role of hormones, inflammation, diet, the intestinal microbiota and genetic factors. In contrast to the negative metabolic profile associated with metabolically unhealthy obesity (MUO), MHO has relatively favorable metabolic characteristics. Nevertheless, MHO is still associated with many important chronic diseases including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease as well as certain types of cancer and has the risk of progression into the unhealthy phenotype. Therefore, it should not be considered as a benign condition. The major therapeutic alternatives include dietary modifications, exercise, bariatric surgery and certain medications including glucagon-like peptide-1 (GLP-1) analogs, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and tirzepatide. In this review, we discuss the significance of MHO while comparing this phenotype with MUO., Competing Interests: Declaration of Competing Interest D.H.vR. has acted as a consultant for and received honoraria from Boehringer Ingelheim-Eli Lilly Alliance, Merck, Sanofi, and AstraZeneca, and has received research operating funds from Boehringer Ingelheim-Lilly Diabetes Alliance, AstraZeneca, and Merck. All honoraria are paid to his employer. Other authors declare that they have no conflict of interest., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: Hemodialysis (HD) induces several physiological changes that can affect plasma glucose levels in patients with diabetes and in turn their glycemic control. Studies using continuous glucose monitoring (CGM) to assess glucose variations on dialysis days compared with nondialysis days report conflicting results. Here, we used CGM to examine glucose variations induced by HD in patients with type 2 diabetes., Methods: Patients with type 2 diabetes undergoing maintenance HD were included. CGM (Ipro2®, Medtronic) was performed at baseline and Week 4, 8, 12, and 16 for up to 7 days at each visit. CGM profiles on days where participants received HD were compared with days without HD using a linear mixed model., Findings: Twenty-seven patients were included. The median number of CGM days performed was 8 (interquartile range [IQR] 6-10) for dialysis days and 16 (IQR 12-17) for nondialysis days. The median sensor glucose was 9.4 (95% confidence interval [CI] 8.8-10.2) mmol/L on dialysis days compared with 9.5 (95% CI 8.9-10.2) mmol/L on nondialysis days (p = 0.58). Nocturnal mean sensor glucose was higher on dialysis days compared with nondialysis days: 8.8 (95% CI 8.0-9.6) mmol/L versus 8.4 (95% CI 7.7-9.2) mmol/L (p = 0.029)., Discussion: Similar median sensor glucose values were found for days on and off HD. Nocturnal glucose levels were modestly increased on dialysis days. Our findings indicate that antidiabetic treatment does not need to be differentiated on dialysis versus nondialysis days in patients with type 2 diabetes undergoing maintenance HD., (© 2023 The Authors. Hemodialysis International published by Wiley Periodicals LLC on behalf of International Society for Hemodialysis.)

Background and Objective: Adrenalectomy for primary aldosteronism (PA) has been associated with decreased kidney function after surgery. It has been proposed that elimination of excess aldosterone unmasks an underlying failure of the kidney function. Contralateral suppression (CLS) is considered a marker of aldosterone excess and disease severity, and the purpose of this study was to assess the hypothesis that CLS would predict change in kidney function after adrenalectomy in patients with PA., Design and Patients: Patients with PA referred for adrenal venous sampling (AVS) between May 2011 and August 2021 and who were subsequently offered surgical or medical treatment were eligible for the current study., Results: A total of 138 patients were included and after AVS 85/138 (61.6%) underwent adrenalectomy while 53/138 (38.4%) were treated with MR-antagonists. In surgically treated patients the estimated glomerular filtration rate (eGFR) was reduced by 11.5 (SD: 18.5) compared to a reduction of 5.9 (SD: 11.5) in medically treated patients (p = .04). Among surgically treated patients, 59/85 (69.4%) were classified as having CLS. After adrenalectomy, patients with CLS had a mean reduction in eGFR of 17.5 (SD: 17.6) compared to an increase of 1.8 (SD: 12.8) in patients without CLS (p < .001). The association between CLS and change in kidney function remained unchanged in multivariate analysis. Post-surgery, 16/59 (27.1%) patients with CLS developed hyperkalemia compared to 2/26 (7.7%) in patients without CLS (p = .04)., Conclusion: This retrospective study found that CLS was a strong and independent predictor of a marked reduction of eGFR and an increased risk of hyperkalemia after adrenalectomy in patients with PA., (© 2022 John Wiley & Sons Ltd.)

Background: Hemoglobin A1c (HbA1c) is an unreliable glycemic marker in the dialysis population, and alternative methods of glycemic monitoring should be considered. Continuous glucose monitoring (CGM) measures interstitial glucose, an indirect measure of plasma glucose, and allows for estimating mean sensor glucose, glucose variability, and time in ranges. Thus, CGM provides a more nuanced picture of glycemic variables than HbA1c, which only informs about average glucose and not variation in glucose or hypoglycemia., Summary: In non-dialysis patients with type 1 and type 2 diabetes, CGM metrics are increasingly used to estimate glycemic control and are associated with improvements in glucose levels. Although a clear link has not yet been established between some CGM variables and the development of late diabetic complications, CGM use could be an important step forward in improving glycemic control in patients receiving dialysis. The ability to detect and prevent hypoglycemia while optimizing glucose levels could be particularly valuable. However, long-term CGM use has not been evaluated in the dialysis population, and the practical burden and cost associated with CGM use may be a limitation. We discuss the strengths and limitations of using CGM in the dialysis population with type 1 and type 2 diabetes., Key Messages: CGM circumvents the pitfalls of HbA1c in dialysis patients and provides detailed measures of the mean sensor glucose, glucose variability, and time in ranges. Guidelines recommend a minimum of 50% time spent in the target range (3.9-10.0 mmol/L) and less than 1% below range (<3.9 mmol/L) for patients receiving dialysis but remain to be evaluated in the dialysis population. CGM can be a valuable tool in reducing overall glucose levels and variations while detecting hypoglycemia, but the practical burden of CGM use and cost may be a limitation., (© 2022 S. Karger AG, Basel.)

Background: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population., Methods: Cross-sectional study including patients with type 2 diabetes with CKD stages 3-5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate &lt;60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) &gt;0.675., Results: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p &lt; 0.0009 and p &lt; 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007)., Conclusion: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively., (© 2023 S. Karger AG, Basel.)

Background: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD., Methods: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3-5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction ≥5.6% according to guidelines., Results: Mean age was 72 ± 4.9 years in patients with CKD and 65.9 ± 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 ± 3.5 kg/m2 and 27 ± 4.0 kg/m2 in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0-8.5) and 4.1% (2.9-7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI -23; 45, p = 0.7463)., Conclusion: These findings do not support any association between NAFLD and CKD (stages 3-5) in patients with type 2 diabetes., (© 2023 S. Karger AG, Basel.)

Nicotinamide adenine dinucleotide (oxidized form, NAD + ) is a critical coenzyme, with functions ranging from redox reactions and energy metabolism in mitochondrial respiration and oxidative phosphorylation to being a central player in multiple cellular signaling pathways, organ resilience, health, and longevity. Many of its cellular functions are executed via serving as a co-substrate for sirtuins (SIRTs), poly (ADP-ribose) polymerases (PARPs), and CD38. Kidney damage and diseases are common in the general population, especially in elderly persons and diabetic patients. While NAD + is reduced in acute kidney injury (AKI) and chronic kidney disease (CKD), mounting evidence indicates that NAD + augmentation is beneficial to AKI, although conflicting results exist for cases of CKD. Here, we review recent progress in the field of NAD + , mainly focusing on compromised NAD + levels in AKI and its effect on essential cellular pathways, such as mitochondrial dysfunction, compromised autophagy, and low expression of the aging biomarker αKlotho (Klotho) in the kidney. We also review the compromised NAD + levels in renal fibrosis and senescence cells in the case of CKD. As there is an urgent need for more effective treatments for patients with injured kidneys, further studies on NAD + in relation to AKI/CKD may shed light on novel therapeutics.

Summary: A 72-year-old man with type 2 diabetes volunteered to participate in the control group of a clinical study. The study evaluated non-alcoholic fatty liver disease in patients with kidney disease. The patient was followed at a gastroenterology department due to Crohn's disease and post-operative bile acid malabsorption. The patient had no symptoms or biochemical findings suggesting liver disease. Surprisingly, a transient elastography (FibroScan®) suggested advanced fibrosis with a median of 16.1 kPa. A liver biopsy showed non-alcoholic steatohepatitis (NASH)-cirrhosis. The diagnosis was only made incidentally and highlights how NASH-cirrhosis may be overlooked due to the lack of symptoms., Learning Points: Clinicians treating high-risk populations, including patients with type 2 diabetes and/or components of the metabolic syndrome, should be aware of the frequently occurring co-existence with non-alcoholic fatty liver disease (NAFLD) and especially non-alcoholic steatohepatitis (NASH). Liver enzymes may be in the normal range even in people with steatosis, NASH, or even cirrhosis. The diagnosis of NAFLD should include evaluation of hepatic fibrosis as this is the most important prognostic factor for liver-related complications and mortality. Guidelines about systematic screening for NAFLD in patients with type 2 diabetes are incongruent.

Glucagon is a major regulator of metabolism and drugs targeting the glucagon receptor (GCGR) are being developed. Insight into tissue and cell-specific expression of the GCGR is important to understand the biology of glucagon and to differentiate between direct and indirect actions of glucagon. However, it has been challenging to localize the GCGR in tissue due to low expression levels and lack of specific methods. Immunohistochemistry has frequently been used for GCGR localization, but antibodies targeting G-protein-coupled-receptors may be inaccurate. We evaluated all currently commercially available GCGR antibodies. The antibody, ab75240 (Antibody no. 11) was found to perform best among the twelve antibodies tested and using this antibody we found expression of the GCGR in the kidney, liver, preadipocytes, pancreas, and heart. Three antibody-independent approaches all confirmed the presence of the GCGR within the pancreas, liver and the kidneys. GCGR expression should be evaluated by both antibody and antibody-independent approaches., (© 2022. The Author(s).)

Hyperreflective dots are a common but highly variable feature of optical coherence tomography (OCT) scans of the retina. We studied the spatial characteristics and perfusion of hyperreflective dots using both structural and angiographic OCT B-scans of the macula in 16 eyes in 8 healthy subjects and 8 patients with diabetic retinopathy without macular edema. Hyperreflective dots were manually graded in a 1000 µm parafoveal area by number, diameter, location and perfusion status and traced through adjacent B-scans at 11 µm intervals to determine their length. Thereby, this study defined a procedure to identify granular and elongated hyperreflective elements and differentiate between presumably perfused and occluded capillaries. The latter were only found in the diabetic patients. This classification can potentially be automated to non-invasively identify capillary non-perfusion in vivo., Competing Interests: The authors declare no conflict of interest.

Background: Post-transplantation anemia (PTA) is frequent among solid organ transplant recipients and has been associated with increased morbidity and mortality. However, the prevalence and impact of PTA in lung transplant recipients is still not elucidated., Methods: We performed a retrospective cohort study of adult Danish lung transplant recipients between January 2010 and December 2019. The prevalence and severity of PTA were determined during the first three years post-transplantation. Associations between PTA and selected risk factors were established using uni- and multivariate logistic regression models., Results: A total of 278 patients were included. At one and three years post-lung transplantation the prevalence of PTA was 75% and 52%, respectively. Male sex was associated with increased odds of PTA at all time points (aOR ranging from 2.3, 95% CI 1.1-4.6, P = 0.02 to 5.9, 95% CI 2.6-14, P < .001). Cystic fibrosis was also associated with anemia at one-year post-transplantation (aOR 4.3, 95% CI 1.2-17, P = 0.03). We found no strong associations between PTA and renal function or viral infections. Excess mortality in recipients with moderate or severe anemia compared to patients with mild or no anemia was borderline statistically significant at one-year post-lung transplantation (aHR 2.0, 95% CI 0.9-4.4, P = 0.07)., Discussion: Post-transplantation anemia is very common in Danish lung transplant recipients. Male sex and cystic fibrosis are independent risk factors for development of anemia. Further investigation on PTA, the underlying mechanisms, and its clinical impact is needed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and represents a wide spectrum ranging from mild steatosis to non-alcoholic steatohepatitis with or without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far there has been scarce evidence of the prevalence of NAFLD among patients with CKD. We investigated the prevalence of moderate-severe hepatic steatosis graded according to the definition of NAFLD in a cohort of patients with CKD., Methods: Hepatic liver fat content was evaluated by computed tomography (CT) scan in 291 patients from the Copenhagen CKD Cohort Study and in 866 age- and sex-matched individuals with normal kidney function from the Copenhagen General Population Study. Liver attenuation density <48 HU was used as a cut-off value for moderate-severe hepatic steatosis., Results: The prevalence of moderate-severe hepatic steatosis was 7.9 and 10.7% (P = 0.177) among patients with CKD and controls, respectively. No association between liver fat content and CKD stage was found. In the pooled dataset from both cohorts, adjusted odds ratios for moderate-severe hepatic steatosis among persons with diabetes, overweight and obesity were 3.1 [95% confidence interval (CI) 1.6-5.9], 14.8 (95% CI 4.6-47.9) and 42.0 (95% CI 12.9-136.6), respectively., Conclusions: In a cohort of 291 patients with CKD, kidney function was not associated with the prevalence of moderate-severe hepatic steatosis as assessed by CT scan., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA. All rights reserved.)