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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.

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.

Active acromegaly is associated with impaired glucose metabolism, which improves upon treatment. Treatment options include surgery, medical therapy with somatostatin analogues (SSA) and Pegvisomant (PEG), and irradiation. The objective of the study was to describe the differential effect of various treatment regimens on the secretion of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) in patients with acromegaly.23 surgically treated, non-diabetic patients with acromegaly and 12 healthy controls underwent an oral glucose tolerance test (OGTT) and subsequently isoglycaemic intravenous glucose infusion on a separate day. Baseline hormone concentrations, time-to-peak and area under the curve (AUC) on the OGTT-day and incretin effect were compared according to treatment regimens.The patients treated with SSA (N = 15) had impaired GIP-response (AUC, P = 0.001), and numerical impairment of all other hormone responses (P 0.3). Patients co-treated with PEG (SSA + PEG, N = 4) had increased secretion of insulin and glucagon compared to patients only treated with SSA (SSA ÷ PEG, N = 11) (insulinSSA impaired the insulin, glucagon, and incretin hormone secretions. Co-treatment with PEG seemed to counteract the somatostatinergic inhibition of the glucagon and insulin response to OGTT. We speculate that PEG may exert its action through GH-receptors on pancreatic δ-cells. Clinical trial registration NCT02005978.

Background SGLT2 inhibitors, originally developed as glucose-lowering agents for treatment of type 2 diabetes, have been shown to have cardio- and kidney-protective effects among CKD patients with and without diabetes. However, the mechanisms remain largely unknown. Methods Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease (DECODE-CKD) is an investigator-initiated, prospective, single-center, randomized, placebo-controlled trial evaluating the effects of 6 months of treatment with 10 mg of dapagliflozin compared with placebo on cardiac structure and function in 222 adults with CKD. Results The primary objective was to assess whether dapagliflozin improves left ventricular mass index. Secondary and exploratory end points include changes in cardiac and kidney markers, quality of life, depressive symptoms, and cognitive function. Conclusions This is the first study to address the effects of SGLT2 inhibitors on cardiac structure and function in patients with CKD. The results will provide valuable insights into the mechanisms underlying the cardiopro- tective benefits of SGLT2 inhibitors in patients with CKD. Clinical Trial registry name and registration number NCT05359263

Echocardiographic findings in chronic kidney disease (CKD) vary. We sought to estimate the prevalence of abnormal cardiac structure and function in patients with CKD and their association to estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR).We prospectively enrolled 825 outpatients with non-dialysis-dependent CKD, mean age 58± 13 yrs, and 175 matched healthy controls, mean age 60±12 yrs. Echocardiography included assessment of left ventricular (LV) hypertrophy, LV ejection fraction (LVEF), global longitudinal strain (GLS) and diastolic dysfunction according to ASE/EACVI guidelines.LV hypertrophy was found in 9% of patients vs. 1.7% of controls (p=0.005) was independently associated with UACR (p=0.002). Median LVEF was 59.4% (IQR 55.2, 62.8) in patients vs. 60.8% (57.7, 64.1) in controls (p=0.002). GLS was decreased in patients with eGFR60ml/min/1.73m² (-17.6%±3.1%) vs. patients with higher eGFR (19.0%±2.2%, p0.001), who were similar to controls. Diastolic dysfunction was detected in 55% of patients and in 34% of controls.Non-random sampling, cross-sectional analysis.We report lower prevalence of hypertrophy than previous studies, but similar measurements of systolic and diastolic function. Cardiac remodeling in CKD may be influenced by treatment modalities, demographics, comorbidities and renal pathology.

Background Vascular calcification is a known risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, since there is a lack of studies examining several arterial regions at a time, we aimed to evaluate the risk of major adverse cardiovascular events (MACE) and all-cause mortality according to calcium scores in five major arterial sites. Methods This was a prospective study of 580 patients from the Copenhagen CKD Cohort. Multidetector computed tomography of the coronary and carotid arteries, the thoracic aorta, the abdominal aorta and the iliac arteries was used to determine vascular calcification at baseline. Calcium scores were divided into categories: 0, 1–100, 101–400 and >400. Results During the follow-up period of 4.1 years a total of 59 cardiovascular events and 64 all-cause deaths occurred. In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, hypertension, diabetes mellitus, hypercholesterolemia and smoking, only the coronary and carotid arteries, and the thoracic aorta were independent predictors of the designated endpoints. When examining the potential of calcification in the five arterial sites for predicting MACE, the difference in C-statistic was also most pronounced in these three sites, at 0.21 [95% confidence interval (CI) 0.16%–0.26%, P Conclusions The overall results, including data on specificity, suggest that calcium scores of the coronary and carotid arteries have the most potential for identifying patients with CKD at high cardiovascular risk and for evaluating new therapies.

BACKGROUND: AKI involves a rapid decrease in kidney function that may be associated with structural damage. Early markers predicting AKI are emerging, but tools to assess patients’ long-term health risks after AKI are still lacking. Endotrophin (ETP) is a bioactive molecule released during the formation of collagen type VI. We evaluated the potential of circulating ETP as a prognostic biomarker of adverse outcomes after AKI. METHODS: We measured ETP in plasma samples collected 1 year after an episode of AKI, using the PRO-C6 ELISA in 801 patients (393 patients with AKI and 408 controls) from the prospective AKI Risk in Derby (ARID) study (ISRCTN25405995), who were then followed until year 3. Kidney disease progression was defined as ≥25% decline in eGFR combined with a decline in CKD stage. RESULTS: ETP levels were significantly higher in the AKI group compared with controls (P

Aims The aim of this study was to compare short- and long-term risk of sudden cardiac death (SCD) among persons aged 18–49 years with and without chronic kidney disease (CKD). Methods and results Using Danish nationwide health registries, all persons aged 18–49 years diagnosed with earlier stages of CKD or chronic kidney failure from 1 July 1995 through 2009 were identified. Non-exposed subjects matched on sex and birth-year were identified. All SCD in the Danish population aged 18–49 years in 2000–2009 have previously been identified using information from the Danish nationwide health registries, death certificates, and autopsy reports. In total, 9308 incident cases of earlier stage CKD and 1233 incident cases of chronic kidney failure were included. Among patients with earlier stage CKD, the absolute risk of SCD 1, 5, and 10 years after diagnosis was 0.14%, 0.37%, and 0.68%, respectively. Compared with age- and sex-matched subjects the corresponding relative risk (RR) was 20.3 [95% confidence interval (CI) 8.4–48.8], 7.1 (95% CI 4.2–12.0), and 6.1 (95% CI 3.8–9.7), respectively. Among patients with chronic kidney failure, the absolute 1-, 5-, and 10-year risk of SCD was 0.17%, 0.56%, and 2.07%, respectively. The corresponding RR was 12.5 (95% CI 1.4–111.6), 7.9 (95% CI 2.3–27.0), and 10.1 (95% CI 4.5–22.6). Conclusion Persons with earlier stage CKD and chronic kidney failure had increased risk of SCD compared with the background population with a 6- to 20-fold increased risk of SCD. These findings underline the importance of early cardiovascular risk monitoring and assessment in persons with CKD.

Cardiovascular disease is the leading cause of mortality amongst patients with chronic kidney disease (CKD). This is the first study using 3-dimensional echocardiography (3DE) to investigate associations between adverse changes of the left ventricle, and different stages of CKD. Participants were recruited from the Copenhagen CKD cohort study and the Herlev-Gentofte CKD cohort study. Patients were stratified according to GFR category (G1 + 2: eGFR ≥ 60 mL/min/1.73 m

Introduction: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD. Methods: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (μmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM. Findings: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0–1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: −0.1–[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (−7.3 mmol/mol, 95% CI: −10.0–[−4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64). Discussion: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.

A decreased glomerular filtration rate (GFR) is a risk factor for cardiovascular disease even after adjustment for conventional risk factors. The myocardial performance index (MPI) is defined as (isovolumetric relaxation time (IVRT) + isovolumetric contraction time (IVCT))/ejection time (ET). It has been shown to be an independent predictor of cardiovascular events. We hypothesized the MPI could prove valuable for assessing cardiac risk in subjects of the general population with decreased estimated GFR (eGFR). MPI was measured in 1915 subjects from a large general population prospective cohort study using color tissue Doppler imaging (TDI) M-mode through the mitral valve. We compared the prognostic capabilities of the MPI between subjects with eGFR ≥ 75 mL/min/1.73 m2 and subjects with eGFR < 75 mL/min/1.73 m2 using multivariable adjusted Cox regression models. The composite endpoint was heart failure, myocardial infarction or cardiovascular death. Mean age was 58 years (SD 16.2), 58% were women, 42% had hypertension and 8.3% diabetes. During a median follow-up time of 12.4 years [IQR 10.6–12.7 years] 269 participants reached the combined endpoint. eGFR modified the prognostic capability of MPI (p-value for interaction < 0.001): After multivariable adjustment, MPI remained an independent predictor of the composite endpoint only in participants with eGFR < 75 mL/min/1.73 m2: HR 1.18 (95% CI 1.02–1.38), p = 0.03, vs. in subjects with eGFR ≥ 75 mL/min/1.73 m2: HR 1.14 (95% CI 0.94–1.39), p = 0.17. These results suggest the MPI could be particularly valuable for identifying elevated cardiac risk in individuals from the general population with decreased eGFR.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Except for SGLT2 inhibitors and GLP-1R agonists, there have been few changes in DKD treatment over the past 25 years, when multifactorial intervention was introduced in patients with type 2 diabetes mellitus (T2DM). The unmet clinical need is partly due to the lack of animal models that replicate clinical features of human DKD, which has raised concern about the utility of these models in preclinical drug discovery. In this review, we performed a comprehensive analysis of rodent models of DKD to compare treatment efficacy from preclinical testing with outcome from clinical trials. We also investigated whether rodent models are predictive for clinical outcomes of therapeutic agents in human DKD.

Background Patients with chronic kidney disease (CKD) and arterial calcification are considered at increased risk of adverse cardiovascular outcomes. However, the optimal site for measurement of arterial calcification has not been determined. The primary aim of this study was to examine the pattern of arterial calcification in different stages of CKD. Methods This was an observational, cross-sectional study that included 580 individuals with CKD stages 1–5 (no dialysis) from the Copenhagen CKD Cohort. Calcification of the carotid, coronary and iliac arteries, thoracic and abdominal aorta was assessed using non-contrast multidetector computed tomography scans and quantified according to the Agatston method. Based on the distribution of Agatston scores in the selected arterial region, the subjects were divided into calcium score categories of 0 (no calcification), 1–100, 101–400 and > 400. Results Participants with CKD stages 3–5 had the highest prevalence of calcification and the highest frequency of calcium scores > 400 in all arterial sites. Calcification in at least one arterial site was present in > 90% of patients with CKD stage 3. In all five CKD stages prevalence of calcification was greatest in both the thoracic and abdominal aorta, and in the iliac arteries. These arterial sites also showed the highest calcium scores. High calcium scores (> 400) in all five arterial regions were independently associated with prevalent cardiovascular disease. In multivariable analyses, after adjusting for cardiovascular risk factors, declining creatinine clearance was associated with increasing calcification of the coronary arteries (p = 0.012) and the thoracic aorta (p = 0.037) only. Conclusions Arterial calcification is highly prevalent throughout all five CKD stages and is most prominent in both the thoracic and abdominal aorta, and in the iliac arteries. Follow-up studies are needed to explore the potential of extracardiac calcification sites in prediction of cardiovascular events in the CKD population.

BACKGROUND AND AIMS Non-alcoholic fatty liver disease (NAFLD) is suggested as being a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally parallel to the increasing incidences of obesity and type 2 diabetes. As diabetes remains the leading cause of CKD the co-existence of NAFLD, CKD and type 2 diabetes needs to be explored. Here, we evaluated the prevalence of hepatic steatosis in patients with type 2 diabetes and CKD and patients with type 2 diabetes without CKD. METHOD This cross-sectional study included 50 patients with type 2 diabetes and CKD stages 3–5 and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy (1H-MRS) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) by the multi-echo Dixon-technique in a 3 Tesla full-body MRI scanner. Hepatic steatosis was defined as ≥ 5.56% liver fat. Further, continuous glucose monitoring (CGM) was performed for 4 days. RESULTS Mean age 72.0 ± 4.9 years and body mass index (BMI) 28.6 ± 3.5 kg/m2 in patients with CKD, and mean age 65.9 ± 7.8 years and BMI 27.0 ± 4.0 kg/m2 in patients without CKD with a predominance of men in both groups. Hepatic steatosis was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (P = 0.68). Median (IQR) values of percentage liver fat were 4.7% (3.0–8.5) and 4.1% (2.9–7.7) in patients with and without CKD, respectively, corresponding to 5.3% higher levels of hepatic fat percentage in patients with CKD [95% confidence interval (CI) −23; 45, P = 0.75]. Mean sensor glucose from CGM was 9.0 ± 1.6 mmol/L and 8.7 ± 1.8 mmol/L in patients with and without CKD, respectively (P = 0.47). There was no statistically significant difference between the two groups regarding the percentage of time spent in different CGM ranges: time-below-range, 10.0 mmol/L (P = 0.20). Pooled data from both groups showed no significant association between the mean sensor glucose from CGM and hepatic fat percentages (P = 0.38). CONCLUSION These findings do not support any association between hepatic steatosis and CKD stages 3–5 in patients with type 2 diabetes.

BACKGROUND AND AIMS Chronic kidney disease (CKD) and diabetes are both well-established risk factors for cardiovascular mortality. However, the risk of cardiovascular mortality and the impact of diabetes for those who have already reached advanced CKD are poorly examined. We examined the risk of cardiovascular mortality among persons with advanced CKD with and without diabetes. METHOD In a nationwide registry-based retrospective matched cohort study, we identified all Danish persons aged ≥ 18 years with advanced CKD between 2002 and 2018. Persons were included in the study at first measured estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2. We excluded persons having a major cardiovascular event or dying < 30 days after inclusion. Non-exposed persons with eGFR ≥ 30 mL/min/1.73m2 (with and without diabetes) were matched on birthyear and sex in a ratio of 4:1. By using the Danish Register of Medicinal Product Statistics, persons with diabetes were identified. Information regarding mortality was obtained from the Danish Registry of Causes of Death. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized absolute risk of cardiovascular mortality adjusted for age, sex and prior cardiovascular disease and subsequently stratified by age group (18–49, 50–59, 60–69, 70–79, 80 years or older). RESULTS We included 135 824 persons with advanced CKD. Overall, 52% were women and the mean age was 76 years. There were 31 991 (23.6%) with diabetes, of whom 2512 (7.9%) had type 1 diabetes. The mean duration of diabetes was 9.7 years. Figure 1 depicts the standardized absolute risk of cardiovascular mortality. Estimations stratified by age groups are shown in Table 1. For persons with diabetes, the standardized absolute risk (95% CI) of cardiovascular mortality was 13.4% (11.5–15.1) in persons aged 18–49 years 5 years after diagnosis, rising to 35.7% (34.7–36.6) in persons aged ≥ 80 years. Compared with age- and sex matched persons, the corresponding relative risk [95% confidence interval (CI)] was 38.0 (29.9–48.1) in persons aged 18–49 years, declining to 1.8 (1.7–1.8) in persons aged ≥ 80 years. Among persons without diabetes, the standardized absolute risk (95% CI) 5 years after diagnosis was 5.2% (4.5–5.8) in persons aged 18–49 years, rising to 33.6% (33.1–34.0) in persons aged ≥ 80 years. The corresponding relative risk was 14.6 (11.7–18.4) and 1.7 (1.6–1.7), respectively, compared with matched persons. Comparing persons with diabetes to persons without diabetes, the relative risk (95% CI) of cardiovascular mortality 5 years after diagnosis was 2.6 (2.2–3.2), 1.8 (1.6–2.9), 1.4 (1.3–1.5), 1.2 (1.1–1.2), 1.1 (1.0–1.1) for age group 18–49, 50–59, 60–69, 70–79, ≥80 years, respectively. CONCLUSION Persons with advanced CKD have, independently of age, a much higher risk of cardiovascular mortality compared with the background population and in the age groups ˂70 years this is even more outspoken in persons with concomitant diabetes. These data highlight the importance of early cardiovascular risk assessment for this population.

This review summarises the current knowledge of electroconvulsive therapy (ECT) which is still the most potent and fast-acting antidepressant intervention. The modern procedure is safe when general precautions are taken. Cognitive side effects are transient in most patients, and concerns about side effects should not prevent relevant use. Due to the prognostic benefits of rapid remission, ECT should, in relevant patients, be considered early in the treatment course. Patients should be offered maintenance pharmacotherapy, and, in high-risk cases, tapering of the acute ECT course or maintenance ECT, in order to reduce the risk of relapse.

Background: Patients undergoing lung transplantation (LTx) experience a rapid decline in glomerular filtration rate (GFR) in the acute postoperative period. However, no prospective longitudinal studies directly comparing the performance of equations for estimating GFR in this patient population currently exist. Methods: In total, 32 patients undergoing LTx met the study criteria. At pre-LTx and 1-, 3-, and 12-weeks post-LTx, GFR was determined by51 Cr-EDTA and by equations for estimating GFR based on plasma (P)-Creatinine, P-Cystatin C, or a combination of both. Results: Measured GFR declined from 98.0 mL/min/1.73 m2 at pre-LTx to 54.1 mL/min/1.73 m2 at 12-weeks post-LTx. Equations based on P-Creatinine underestimated GFR decline after LTx, whereas equations based on P-Cystatin C overestimated this decline. Overall, the 2021 CKD-EPI combination equation had the lowest bias and highest precision at both pre-LTx and post-LTx. Conclusions: Caution must be applied when interpreting renal function based on equations for estimating GFR in the acute postoperative period following LTx. Simplified methods for measuring GFR may allow for more widespread use of measured GFR in this vulnerable patient population.

BACKGROUND: Calcium channel blockers may ameliorate the decline in renal function caused by calcineurin inhibitors in lung transplantation (LTX) recipients. We hypothesized that pre-operative and 12-week post-operative treatment with the calcium channel blocker felodipine would reduce the decline in glomerular filtration rate (GFR).METHODS: In this prospective, randomized, double-blind trial, 39 LTX recipients were transplanted and received placebo (n = 19; GFR, 102 ml/min/1.73 m2 [range, 91-113 ml/min/1.73 m2]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m2 [range, 88-104 ml/min/1.73 m2]). Pre-operative treatment was titrated post-operatively to 10 mg or the maximum tolerable dose. The primary end-point was the change in GFR using Cr-51-labeled EDTA from LTX to 12 weeks thereafter, and follow-up was 52 weeks.RESULTS: The treatment group showed an absolute mean decline in GFR of 31 ml/min/1.73 m2 (95% CI: -40 to 22 ml/min/1.73 m2), whereas that of the placebo group was 48 ml/min/1.73 m2 (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m2). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m2 (95% CI: 4-29 ml/min/1.73 m2; p = 0.01). Half of the patients were unable to complete the 3-month primary follow-up, and the analysis includes these patients by intention-to-treat. After 52 weeks (40 weeks after termination of treatment), the treatment effect was maintained at 12 ml/min/1.73 m2 (95% CI: 0-24 ml/min/1.73 m2, p = 0.05). The number of days with registered hypotension was significantly higher in the felodipine group than in the placebo group (39 days vs 13 days, rate ratio: 2.9 [95% CI: 1.5-5.3]).CONCLUSIONS: Use of felodipine in select patients was associated with greater preservation in renal function early (90 days) after LTX. The observed benefits were attenuated by 1 year, although trends in better renal function were noted.

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 (

Post-transplant diabetes mellitus (PTDM) is associated with a higher risk of adverse outcomes. We aimed to describe the proportion of patients with diabetes prior to solid organ transplantation (SOT) and post-transplant diabetes mellitus (PTDM) in three time periods (early-likely PTDM: 0–45 days; 46–365 days and >365 days) post-transplant and to estimate possible risk factors associated with PTDM in each time-period. Additionally, we compared the risk of death and causes of death in patients with diabetes prior to transplant, PTDM, and non-diabetes patients. A total of 959 SOT recipients (heart, lung, liver, and kidney) transplanted at University Hospital of Copenhagen between 2010 and 2015 were included. The highest PTDM incidence was observed at 46–365 days after transplant in all SOT recipients. Age and the Charlson Comorbidity Index (CCI Score) in all time periods were the two most important risk factors for PTDM. Compared to non-diabetes patients, SOT recipients with pre-transplant diabetes and PTDM patients had a higher risk of all-cause mortality death (aHR: 1.77, 95% CI: 1.16–2.69 and aHR: 1.89, 95% CI: 1.17–3.06 respectively). Pre-transplant diabetes and PTDM patients had a higher risk of death due to cardiovascular diseases and cancer, respectively, when compared to non-diabetes patients.

Background Hospitalized patients are at an increased risk of developing kidney disease after discharge, often despite the absence of any clinical indicators during hospitalization. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation that can be measured from routine blood samples. We determined whether elevated suPAR during hospitalization is associated with a decline in estimated glomerular filtration rate (eGFR) after discharge. Methods This was a retrospective longitudinal cohort study of patients without detectable kidney disease presenting to the emergency department on two separate occasions during a 3-year period. The association between suPAR and a decline in eGFR was assessed by linear mixed models for repeated measures adjusting for age, sex, C-reactive protein, sodium, diabetes, hypertension and cardiovascular disease. Results In total, 5124 patients (median age 65.9 years, 51.0% female) were included. The median suPAR was 2.9 ng/mL, the median time to readmission was 144 days and the expected rate of eGFR decline over this period was 5.1 mL/min/1.73 m2/year. Adjusting for other risk factors, patients with suPAR Conclusions A higher suPAR level was associated with accelerated eGFR decline among patients presenting to the emergency department, suggesting that routine suPAR measurements may have utility for the early detection of kidney disease.

Background: Cardiovascular disease is the leading cause of mortality amongst patients with chronic kidney disease (CKD). This is the first study using 3-dimensional echocardiography (3DE) to investigate associations between adverse changes of the left ventricle, and different stages of CKD. Methods: Participants were recruited from the Copenhagen CKD cohort study and the Herlev-Gentofte CKD cohort study. Patients were stratified according to GFR category (G1+2: eGFR≥60mL/min/1.73m 2 , G3: eGFR = 30-59mL/min/1.73m 2 , and G4+5: eGFR≤29mL/min/1.73m 2 ), and according to albuminuria (A1: UACR300 mg/g). Echocardiograms were analysed for left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), and global strain measures. In adjusted analysis, eGFR groups were adjusted for confounders and albuminuria category, while albuminuria groups were adjusted for confounders and GFR category. Results: The study population consisted of 662 outpatients with CKD and 169 controls. Mean age was 57±13 years, and 61% were males. Mean LVEF and global longitudinal strain (GLS) were increasingly impaired across eGFR groups: LVEF = 60.1%, 58.4%, and 57.8% ( p =0.013), GLS = -16.1%, -14.8%, and -14.6% ( p 2 , 88.1g/m 2 , and 92.1g/m 2 ( p =0.007) from A1-3. Adjusted analysis confirmed reduced LVEF in G3 compared with G1+2, and increased LVMi in A3 compared with A1. Conclusion: Increasingly impaired eGFR was associated with adverse changes in LV systolic function, while albuminuria was associated with adverse changes in LV mass assessed by 3DE. Their associations were independent of each other.

The relationship between chronic kidney disease (CKD) and cardiovascular events is well-established. Clinically recognised risk factors of cardiovascular disease cannot fully explain this association. The objective of the present cross-sectional study was to investigate associations between serum metabolites and prevalent cardiovascular disease, as well as subclinical cardiovascular disease measured as coronary artery calcium score (CACS) in patients with CKD.More than 200 preselected metabolites were quantified using nuclear magnetic resonance spectroscopy in 725 patients and 174 controls from the Copenhagen CKD Cohort. CACS was determined by computed tomography.Mean age of patients was 57.8 years, and 444 (61.3%) were men. Most of patients had hypercholesterolemia, and 133 (18.3%) had type 2 diabetes. Overall, 85 metabolites were significantly associated with prevalent cardiovascular disease in a model adjusted for eGFR, age, and sex, as well as Bonferroni correction for multiple testing (p 0.001). After further adjusting for diabetes, BMI, smoking, and cholesterol-lowering medication, the significance was lost for all but six metabolites (concentration of ApoA-1, cholesterol in total HDL and HDL2, total lipids and phospholipids in large HDL particles, and the ratio of phospholipids to total lipids in smaller VLDL particles). Of the 85 metabolites associated with prevalent cardiovascular disease, 71 were also associated with CACS in a similar pattern. Yet, in the model adjusted for all seven cardiovascular risk factors, only serum glucose levels and the ratio of triglycerides to total lipids in larger LDL particles remained significant.In patients with CKD, associations with prevalent cardiovascular disease were mainly found for HDL-related metabolites, while CACS was associated with glucose levels and increased triglycerides to total lipids ratio in LDL particles.

Introduction This study examined the prevalence of microvascular and macrovascular complications in people receiving dialysis with and without diabetes and investigated independent risk factors for foot ulcers and lower‐extremity amputations. Methods We performed a cross‐sectional study of 119 individuals with diabetes and 219 individuals without diabetes receiving chronic dialysis during June 2019 at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Effects of diabetes and other risk factors were assessed by log‐binomial regression. Prevalence data were compared with a historical control group of 38 individuals with diabetes receiving dialysis examined in 2004 in the same department. Results We found that persons with diabetes had a twofold higher risk ratio of current (unadjusted risk ratio 2.2 [95% CI 1.1, 4.7]) and previous foot ulcer (2.5 [1.7, 3.7]) and a fourfold higher risk ratio of lower‐extremity amputation (4.2 [2.1, 8.6]) in comparison with persons without diabetes (all p, Over the past decades, there has been a general improvement in the prognosis of people with diabetes; however, it is unclear what the consequences of these improvements are in relation to complications among people receiving dialysis. This study examined the prevalence of micro‐ and macrovascular complications in people receiving dialysis with and without diabetes, and found that individuals with diabetes had a higher prevalence of foot ulcer, amputation and myocardial infarction compared to individuals without diabetes.

The current understanding of molecular mechanisms driving diabetic kidney disease (DKD) is limited, partly due to the complex structure of the kidney. To identify genes and signalling pathways involved in the progression of DKD, we compared kidney cortical versus glomerular transcriptome profiles in uninephrectomized (UNx) db/db mouse models of early-stage (UNx only) and advanced [UNxplus adeno-associated virus-mediated renin-1 overexpression (UNx-Renin)] DKD using RNAseq. Compared to normoglycemic db/m mice, db/db UNx and db/db UNx-Renin mice showed marked changes in their kidney cortical and glomerular gene expression profiles. UNx-Renin mice displayed more marked perturbations in gene components associated with the activation of the immune system and enhanced extracellular matrix remodelling, supporting histological hallmarks of progressive DKD in this model. Single-nucleus RNAseq enabled the linking of transcriptome profiles to specific kidney cell types. In conclusion, integration of RNAseq at the cortical, glomerular and single-nucleus level provides an enhanced resolution of molecular signalling pathways associated with disease progression in preclinical models of DKD, and may thus be advantageous for identifying novel therapeutic targets in DKD., Summary: Combining single-nucleus RNAseq with glomerular and cortical gene expression profiling can link kidney transcriptome signatures to specific cell types in an advanced mouse model of hypertension-accelerated diabetic kidney disease.

Introduction The clinical-histologic correlation in diabetic nephropathy is not completely known. Methods We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). Results Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% 10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III. Conclusions Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes., Graphical abstract

IntroductionChronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. New Nordic Renal Diet (NNRD) is a new dietary concept designed by the present research group that aims to offer patients with moderate CKD a whole food approach with a markedly reduction in dietary phosphorus intake, corresponding to 850 mg/day. The present protocol describes a randomised controlled trial aiming to test the long-term effects of dietary intervention with NNRD versus a non-restricted habitual diet on important parameters of phosphorus and lipid homeostasis.Methods and analysisThis trial will be executed at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Sixty patients aged >18 years with CKD stages 3 and 4 (estimated glomerular filtration rate between 15 and 45 mL/min) will be recruited and randomly assigned to the intervention or control group. The other inclusion criterion includes a medically stable condition for at least 2 months prior to the start of the study. Exclusion criteria are treatment with phosphate binders, metabolic disorders that require specific dietary regulation, pregnancy and breast feeding, any types of food allergies or those who are vegans. The observation period is 26 weeks including seven study visits at the outpatient clinic combined with a weekly telephone consultation in both groups. A follow-up visit 3 months after study completion finalises the intervention. The primary outcome is the difference in the change in 24-hour urine phosphorus excretion from baseline to week 26 between the two study groups. Secondary outcomes include changes in phosphate-related and lipid metabolism-related blood and urine biochemistry, blood pressure and body composition. Moreover, we wish to explore adherence to the diet as well as quality of life.Ethics and disseminationThe study has been approved by the Scientific Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. The results of the studies will be presented at national and international scientific meetings, and publications will be submitted to peer-reviewed journals.Trial registration numberClinicalTrials.gov (wwwclinicaltrialsgov) Registry (NCT04579315).Protocol versionThe protocol, version 2, has been approved by the Ethical Committee Denmark on 18 September 2020. The protocol has also been approved by Data Protection Regulation and Data Protection Law on 15 September 2020. This study protocol is in accordance with the Standard Protocol Items: Recommendations for International Trials.

Context The insulin-stimulating and glucagon-regulating effects of the 2 incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), contribute to maintain normal glucose homeostasis. Impaired glucose tolerance occurs with high prevalence among patients with end-stage renal disease (ESRD). Objective To evaluate the effect of the incretin hormones on endocrine pancreatic function in patients with ESRD. Design and Setting Twelve ESRD patients on chronic hemodialysis and 12 matched healthy controls, all with normal oral glucose tolerance test, were included. On 3 separate days, a 2-hour euglycemic clamp followed by a 2-hour hyperglycemic clamp (3 mM above fasting level) was performed with concomitant infusion of GLP-1 (1 pmol/kg/min), GIP (2 pmol/kg/min), or saline administered in a randomized, double-blinded fashion. A 30% lower infusion rate was used in the ESRD group to obtain comparable incretin hormone plasma levels. Results During clamps, comparable plasma glucose and intact incretin hormone concentrations were achieved. The effect of GLP-1 to increase insulin concentrations relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (50 [8–72]%, P = 0.03). Similarly, the effect of GIP relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (34 [13–50]%, P = 0.005). Glucagon was suppressed in both groups, with controls reaching lower concentrations than ESRD patients. Conclusions The effect of incretin hormones to increase insulin release is reduced in ESRD, which, together with elevated glucagon levels, could contribute to the high prevalence of impaired glucose tolerance among ESRD patients.

Objective Increasing the amounts of functionally competent brown adipose tissue (BAT) in adult humans has the potential to restore dysfunctional metabolism and counteract obesity. In this study, we aimed to characterize the human perirenal fat depot, and we hypothesized that there would be regional, within-depot differences in the adipose signature depending on local sympathetic activity. Methods We characterized fat specimens from four different perirenal regions of adult kidney donors, through a combination of qPCR mapping, immunohistochemical staining, RNA-sequencing, and pre-adipocyte isolation. Candidate gene signatures, separated by adipocyte morphology, were recapitulated in a murine model of unilocular brown fat induced by thermoneutrality and high fat diet. Results We identified widespread amounts of dormant brown adipose tissue throughout the perirenal depot, which was contrasted by multilocular BAT, primarily found near the adrenal gland. Dormant BAT was characterized by a unilocular morphology and a distinct gene expression profile, which partly overlapped with that of subcutaneous white adipose tissue (WAT). Brown fat precursor cells, which differentiated into functional brown adipocytes were present in the entire perirenal fat depot, regardless of state. We identified SPARC as a candidate adipokine contributing to a dormant BAT state, and CLSTN3 as a novel marker for multilocular BAT. Conclusions We propose that perirenal adipose tissue in adult humans consists mainly of dormant BAT and provide a data set for future research on factors which can reactivate dormant BAT into active BAT, a potential strategy for combatting obesity and metabolic disease., Graphical abstract Image 1, Highlights • Dormant brown adipose tissue (BAT) dominates the perirenal adipose depot of adult humans. • Multilocular BAT accumulates adjacent to local sympathetic sources. • Dormant BAT displays a transcriptomic signature distinct from multilocular BAT and white adipose tissue. • Brown fat precursor cells are present in human dormant perirenal BAT. • SPARC is associated with a dormant BAT phenotype.

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 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.