Myocardial work in chronic kidney disease: insights from the CPH-CKD ECHO Study.

BACKGROUND: Myocardial work is a novel echocardiographic measure that offers detailed insights into cardiac mechanics. We sought to characterize cardiac function by myocardial work in patients with chronic kidney disease (CKD). METHODS: We prospectively enrolled 757 patients with non-dialysis-dependent CKD and 174 age- and sex-matched controls. Echocardiographic pressure-strain loop analysis was performed to acquire the global work index (GWI). Linear regressions were performed to investigate the association between estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) to GWI. RESULTS: Patients with CKD had a mean age of 57 years, 61% were men, and median eGFR was 42 mL/min/1.73 m2. Overall, no difference in GWI was observed between patients and controls (1879 vs. 1943 mmHg%, p = 0.06). However, a stepwise decline in GWI was observed for controls vs. patients with CKD without left ventricular hypertrophy vs. patients with CKD and left ventricular hypertrophy (GWI, 1943 vs. 1887 vs. 1789 mmHg%; p for trend = 0.030). In patients with CKD, eGFR was not associated with GWI by linear regression. However, diabetes modified this association (p for interaction = 0.007), such that per 10 mL/min/1.73 m2 decrease in eGFR, GWI decreased by 22 (9-35) mmHg% (p = 0.001) after multivariable adjustments in patients without diabetes, but with no association between eGFR and GWI in patients with diabetes. No association was observed between UACR and GWI. CONCLUSION: Patients with CKD and left ventricular hypertrophy exhibited lower myocardial work compared to matched controls. Furthermore, decreasing eGFR was associated with decreasing myocardial work only in patients without diabetes. No association to UACR was observed.

Renal Disease in Metabolic Syndrome: the Hidden Role of Intrarenal Ischemia.

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/m2; (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.

The role of aetiology in cardiac manifestations of chronic kidney disease: the CPH-CKD ECHO study.

PURPOSE: We investigated the associations between cardiac parameters and aetiologies of CKD in an exploratory study. METHODS: The study population consisted of 883 participants, 174 controls and 709 patients with aetiologies of CKD including diabetic nephropathy/renovascular KD in diabetes mellitus, hypertensive/renovascular nephropathy, tubulointerstitial nephritis, glomerulonephritis/vasculitis, polycystic KD (PKD), and CKD of unknown origin. Echocardiographic measures included left ventricular (LV) ejection fraction, global longitudinal, area, and radial strain, E/e' ratio, and LV mass index. These were compared between each aetiological group and controls in unadjusted and adjusted analysis. RESULTS: In unadjusted analysis, patients with diabetic nephropathy/renovascular KD in diabetes mellitus, had impaired LV ejection fraction (Median [IQR]: 56% [49.9,60.69] vs. 60.8% [57.7,64.1]), global longitudinal (mean ± SD: 13.1 ± 3.5% vs. 15.5 ± 2.6%), area (24.1 ± 5.8% vs. 28.5 ± 4.2%), and radial strain (36.2 ± 11.2% vs. 44.1 ± 9.7%), and increased LV mass index (89.1 g/m2 [71.8,104.9] vs. 69,0 g/m2 [57.9,80.8]) and E/e' ratio (10.6 [8.5,12.6] vs. 7 [5.8,8.3], p < 0.001 for all) compared with controls. Associations were similar for CKD of unknown origin. Patients with hypertensive/renovascular nephropathy had impaired global longitudinal and area strain, and higher E/e' ratio. Patients with glomerulonephritis/vasculitis had higher LV mass index, while patients with PKD had better global longitudinal strain than controls. All findings remained significant in adjusted analysis, except for the impaired global longitudinal strain in hypertensive/renovascular nephropathy. CONCLUSION: Glomerulonephritis/vasculitis, hypertensive/renovascular nephropathy, CKD of unknown origin, and diabetic nephropathy/renovascular KD in diabetes mellitus were increasingly associated with adverse cardiac findings, while PKD and tubulointerstitial nephritis were not. Aetiology might play a role regarding the cardiac manifestations of CKD.

Oral anticoagulation for stroke prevention in atrial fibrillation and advanced kidney disease.

Background: The net benefit of oral anticoagulation (OAC) with vitamin K antagonists or direct oral anticoagulants in patients with advanced chronic kidney disease and atrial fibrillation remains uncertain. Objectives: We examined the use, efficacy, and safety of OAC in patients with estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2 (including dialysis-treated patients) and atrial fibrillation. Methods: In a retrospective cohort study, patients diagnosed with atrial fibrillation and eGFR of <30 mL/min/1.73 m2 were identified in national Danish registers between 2010 and 2022. Initiation of OAC was identified based on redemption of a relevant prescription. One-year risks of thromboembolic event, major bleeding, and death associated with OAC and no treatment were computed and standardized to the distribution of risk factors in the sample based on hazards determined in multiple Cox regression models adjusted for age and sex. Results: A total of 3208 patients were included (mean age 80 years, 52.8% males, 20.9% chronic dialysis). OAC was initiated in 1375 (42.9%) patients, of whom 48.1% were vitamin K antagonists and 51.9% were direct oral anticoagulants. One-year risks in nontreated and anticoagulated patients were 4.8% (95% CI, 3.8%-5.7%) and 3.6% (95% CI, 2.8%-4.6%; P = .028) for thromboembolic event, 7.6% (95% CI, 6.6%-8.7%) and 10.5% (95% CI, 9.3%-12.1%; P < .001) for major bleeding, and 36.3% (95% CI, 34.2%-38.3%) and 29.6% (95% CI, 27.6%-31.6%; P < .001) for death, respectively. Conclusion: In a retrospective study on patients with advanced chronic kidney disease and atrial fibrillation, OAC was associated with overall decreased 1-year risk of thromboembolic event and death offset by increased 1-year risk of major bleeding.

Post-intervention Adherence to the New Nordic Renal Diet among patients with chronic kidney disease, stages 3 and 4.

The New Nordic Renal Diet (NNRD) is a meal pattern reduced in phosphorus, protein, and sodium for patients with moderate chronic kidney disease. The NNRD showed improvements in metabolic, and physiological outcomes after 26-weeks intervention. In the original study, participants were randomized to NNRD (n = 30), or control (habitual diet) (n = 30). The aim of this study was to explore adherence to the NNRD 3 months after cessation of intervention (follow-up). Fifty-seven participants completed the follow-up visit, which consisted of fasting blood samples and 24 h urine samples. At follow-up, there was no longer a significant reduction in 24 h urine phosphorus excretion in the NNRD group. From intervention to follow-up, 24 h urine phosphorus increased by 63 mg in the NNRD group, vs. -24.1 mg in the control group, between-group difference 87.1 mg (-10.1, 184.3, p = 0.08). Our findings show that more active intervention is needed to support adherence and maintain beneficial effects of the NNRD.

Plasma activin A rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease.

Background: Plasma (p-)activin A is elevated in chronic kidney disease-mineral and bone disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined whether p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality and CKD-MBD complications in CKD patients. Methods: The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with estimated glomerular filtration rate (eGFR), coronary and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen-Johansen or Kaplan-Meier estimator, with subsequent multiple Cox regression analyses. Results: P-activin A was increased by CKD stage 3 (124-225 pg/mL, P < .001) and correlated inversely with eGFR (r = -0.53, P < 0.01). P-activin A was associated with all-cause mortality [97 events, hazard ratio 1.55 (95% confidence interval 1.04; 2.32), P < 0.05] after adjusting for age, sex, diabetes mellitus (DM) and eGFR. Median follow-up was 4.36 (interquartile range 3.64-4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A. Conclusion: P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM and eGFR. No association with MACE, vascular calcification or BMD was demonstrated.

Predicting type 2 diabetes risk before and after solid organ transplantation using polygenic scores in a Danish cohort.

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.

Cardiac arrhythmia and hypoglycaemia in patients receiving haemodialysis with and without diabetes (the CADDY study): protocol for a Danish multicentre cohort study.

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.

Non-adherence, medication beliefs and symptom burden among patients receiving hemodialysis -a cross-sectional study.

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.

Health effects of the New Nordic Renal Diet in patients with stage 3 and 4 chronic kidney disease, compared with habitual diet: a randomized trial.

BACKGROUND: Chronic kidney disease (CKD) leads to an accumulation of waste products and causes adverse cardiometabolic effects. OBJECTIVES: We investigated the health effects of the New Nordic Renal Diet (NNRD), a novel meal pattern reduced in phosphorus, protein, and sodium. METHODS: A 26-wk randomized trial compared the NNRD with a habitual diet. The NNRD group received weekly home deliveries of food and recipes. Monthly study visits included fasting blood samples, 24-h urine samples, blood pressure, and anthropometric measurements. Intention-to-treat analysis used linear mixed-effects models. RESULTS: Sixty patients, mean estimated glomerular filtration rate (eGFR) 34 mL/min/1.73 m2 and body mass index of 25-27 kg/m2, were included and 58 completed. Metabolic syndrome was present in 53% (NNRD group) and 57% (control group). The NNRD group (n = 30) reduced their 24-h urine phosphorus excretion by 19% (-153 mg; 95% confidence interval [CI]: -210, -95), control group (n = 30) (no change), between-group difference -171 mg (95% CI: -233, -109; P < 0.001). Proteinuria was reduced by 39% in the NNRD group (-0.33 g/d; 95% CI: -0.47, -0.18), control group (no change), between-group difference -0.34 g/d (95% CI: -0.52, -0.17; P < 0.001). Plasma urea was reduced by -1.5 mmol/L in the NNRD group (95% CI: -2.1, -0.9), control group (no change), between-group difference -1.4 mmol/L (95% CI: -2.0, -0.7; P < 0.001). Systolic blood pressure fell by -5.2 mmHg in the NNRD group (95% CI: -8.4, -2.1), control group (no change), between-group difference -3.9 mmHg (95% CI; -7.6, -0.2; P = 0.04). The NNRD group lost -1.7 kg (95% CI: -2.6, -0.8), control group (no change), between-group difference -2.0 kg (95% CI: -3.0, -1.0; P < 0.001). There were no effects on eGFR during the 26-wk intervention. CONCLUSION: NNRD in moderate CKD reduces phosphorus excretion, proteinuria, systolic blood pressure, and weight, mainly by reducing abdominal fat. This trial was registered at clinicaltrials.gov as NCT04579315.

Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease.

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 <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) >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 < 0.0009 and p < 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.

Performance of Panel-Estimated GFR Among Hospitalized Older Adults.

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, ß-trace protein (BTP) and/or ß2-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/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel 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-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel 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 ß-trace protein and ß2-microglobulin did not further improve accuracy.

Cardiovascular mortality in patients with advanced chronic kidney disease with and without diabetes: a nationwide cohort study.

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/1.73m2 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.

Glucose variability in maintenance hemodialysis patients with type 2 diabetes: Comparison of dialysis and nondialysis days.

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.

Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease.

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.

Glucose metabolism, gut-brain hormones, and acromegaly treatment: an explorative single centre descriptive analysis.

PURPOSE: 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. METHODS: 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. RESULTS: 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) (insulinAUC mean ± SEM, SSA + PEG 49 ± 8.3 nmol/l*min vs SSA ÷ PEG 25 ± 3.4, P = 0.007; glucagonAUC, SSA + PEG 823 ± 194 pmol/l*min vs SSA ÷ PEG 332 ± 69, P = 0.009). GIP secretion remained significantly impaired, whereas GLP-1 secretion was numerically increased with PEG (SSA + PEG 3088 ± 366 pmol/l*min vs SSA ÷ PEG 2401 ± 239, P = 0.3). No difference was found in patients treated with/without radiotherapy nor substituted or not with hydrocortisone. CONCLUSION: SSA 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.

Can the Use of Continuous Glucose Monitoring Improve Glycemic Control in Patients with Type 1 and 2 Diabetes Receiving Dialysis?

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.

Coronary and extra-coronary artery calcium scores as predictors of cardiovascular events and mortality in chronic kidney disease stages 1-5: a prospective cohort study.

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 < .001], 0.26 (95% CI 0.22%-0.3%, P < .001) and 0.20 (95% CI 0.16%-0.24%, P < .001), respectively. This trend also applied to all-cause mortality. 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.