Far infrared treatment on the arteriovenous fistula induces changes in sVCAM and sICAM in patients on hemodialysis.

INTRODUCTION: There is a substantial risk of developing stenosis and dysfunction in the arteriovenous fistula (AVF) in patients on hemodialysis (HD). Far infrared radiation (FIR) is a non-invasive local intervention with a potentially beneficial effect on AVF patency. The underlying mechanism is not clear. It was hypothesized that a single FIR treatment reduces factors of inflammation and promotes endothelial vasodilators in the AVF. METHODS: Forty HD patients with an AVF were included in an open-label intervention study. Patients were randomized to receive either FIR (FIR group) or no FIR (control group). Blood samples were drawn directly from the AVF and from a peripheral vein in the non-AVF arm before (T0) and 40 min after (T40) treatment during a HD session. The changes [median (interquartile range)] in circulating factors of inflammation, endothelial function and vasoreactivity during FIR were measured. RESULTS: In the AVF a single FIR treatment during dialysis resulted in a significantly diminished decrease in soluble vascular cell adhesion molecule, sVCAM [-31.6 (-54.3; 22.1) vs -89.9 (-121.6; -29.3), P = .005] and soluble intercellular adhesion molecule, sICAM [-24.2 (-43.5; 25.3) vs -49 (-79.9; -11.6), P = .02] compared with the control group. Other factors, such as interleukins, nitrite, nitrate and tumor necrosis factor 1, also declined during dialysis, but with no significant differences related to FIR in either the AVF or the non-AVF arm. CONCLUSION: A single FIR treatment attenuated the decrease in sVCAM and sICAM in the AVF compared with a control group during HD. Findings do not support the hypothesis of a vaso-protective effect of FIR. The long-term effects of FIR on the AVF are unknown.

The New Nordic Renal Diet Induces a Pronounced Reduction of Urine Acid Excretion and Uremic Toxins in Chronic Kidney Disease Patients (Stage 3 and 4).

OBJECTIVE: Metabolic acidosis and the uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with increased risks of kidney disease progression, muscle catabolism, cardiovascular disease, and mortality in patients with chronic kidney disease (CKD). The New Nordic Renal Diet (NNRD) is a plant-focused meal pattern, with reduced phosphorus and protein content compared to an average Danish diet. Due to a higher amount of plant-based products, we hypothesized that NNRD would reduce renal excretion of acids and uremic toxins. Thus, we evaluated the effects of NNRD on metabolic acidosis and uremic toxins in patients with moderate CKD, stages 3-4. DESIGN AND METHODS: This post hoc analysis is based on a randomized controlled crossover trial comparing 1 week of the NNRD to a control 1-week period of an average Danish diet, in patients with CKD stages 3 and 4. Urine pH and urine excretion of bicarbonate, ammonium, titratable acids, IS, and PCS alongside plasma total CO2 (tCO2) were measured at days 1, 4, and 7 in 18 patients. RESULTS: After 7 days on NNRD 24-hour urine net acid excretion was decreased by 80% (P < .001), 24-hour urine excretion of ammonium and bicarbonate decreased by 34% (P < .001), and increased by 678% (P < .001), respectively, compared with the control period. Plasma tCO2 was increased by 8% (P = .005). Moreover, 24-hour urine excretion of PCS and IS were reduced by 31% (P = .018) and 29% (P < .001), respectively. CONCLUSION: One week of NNRD in patients suffering from moderate CKD effectively improved metabolic acidosis with a marked reduction in urine net acid excretion that included a large increase in urine bicarbonate excretion. In addition, NNRD reduced urinary excretion of the uremic toxins PCS and IS. These results encourage further investigations of the long-term effects of NNRD on renal protection in patients with CKD.

The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis.

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.

Adrenal insufficiency in kidney transplant patients during low-dose prednisolone therapy: a cross-sectional case-control study.

BACKGROUND: Maintenance immunosuppressive regimens after renal transplantation (RTx) most often include prednisolone, which may induce secondary adrenal insufficiency, a potentially life-threatening side effect to glucocorticoid (GC) treatment due to the risk of acute adrenal crisis. We investigated the prevalence of prednisolone-induced adrenal insufficiency in RTx patients receiving long-term low-dose prednisolone treatment. METHODS: We performed a case-control study of patients on renal replacement therapy differing in terms of GC exposure. The study included 30 RTx patients transplanted >11 months before enrolment in the study and treated with prednisolone (5 or 7.5 mg prednisolone/day for ≥6 months) and 30 dialysis patients not treated with prednisolone. Patients underwent testing for adrenal insufficiency by a 250-µg Synacthen test performed fasting in the morning after a 48-h prednisolone pause. Normal adrenal function was defined as P-cortisol ≥420 nmol/L 30 min after Synacthen injection. This cut-off is used routinely for the new Roche Elecsys Cortisol II assay and is validated locally based on the Synacthen test responses in 100 healthy individuals. RESULTS: Thirteen RTx patients {43% [95% confidence interval (CI) 27-61]} had an insufficient response to the Synacthen test compared with one patient in the control group [3% (95% CI 0.6-17)] (P = 0.0004). Insufficient responses were seen in 9/25 and 4/5 RTx patients treated with 5 and 7.5 mg prednisolone/day, respectively. CONCLUSIONS: We found a high prevalence of adrenal insufficiency among RTx patients receiving low-dose prednisolone treatment. We therefore advocate for increased clinical alertness towards prednisolone-induced adrenal insufficiency in RTx patients and thus their potential need of rescue GC supplementation during stress.

Short-term effect of the New Nordic Renal Diet on phosphorus homoeostasis in chronic kidney disease Stages 3 and 4.

BACKGROUND: The New Nordic Diet is a food concept favouring organically produced food items, fruits, vegetables, whole grains and fish. We investigated the short-term effects of a modified phosphorus-reduced New Nordic Renal Diet (NNRD) in chronic kidney disease (CKD) patients on important parameters of phosphorus homoeostasis. METHODS: The NNRD contained a total of 850 mg phosphorus/day. A total of 18 patients, CKD Stages 3 and 4 were studied in a randomized crossover trial comparing a 1-week control period of the habitual diet with a 1-week period of the NNRD. Data were obtained at baseline and during 1 week of dietary intervention (habitual diet versus NNRD) by collecting fasting blood samples and 24-h urine collections. The primary outcome was the difference in the change in 24-h urine phosphorus excretion from baseline to Day 7 between the NNRD and habitual diet periods. Secondary outcomes were changes in the fractional excretion of phosphorus, fibroblast growth factor 23 (FGF23) and plasma phosphate. RESULTS: As compared with the habitual diet, 24-h urine phosphorus excretion was reduced in the NNRD by 313 mg/day (P < 0.001). The mean baseline phosphorus was 875 ± 346 mg/day and was decreased by 400 ± 256 mg/day in the NNRD and 87 ± 266 mg/day in the habitual diet. The 24-h urine fractional excretion of phosphorus decreased by 11% (P < 0.001) and FGF23 decreased by 30 pg/mL (P = 0.03) with the NNRD compared with the habitual diet. Plasma phosphate did not change. CONCLUSION: This study demonstrates that dietary phosphorus restriction in the context of the NNRD is feasible and has positive effects on phosphorus homeostasis in CKD patients.

The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis.

BACKGROUND: The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis. METHODS: Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models. RESULTS: One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996-2012 and 2002-2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70-4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02-1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54-3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78-5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death. CONCLUSION: All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population.

The New Nordic Diet: phosphorus content and absorption.

PURPOSE: High phosphorus content in the diet may have adverse effect on cardiovascular health. We investigated whether the New Nordic Diet (NND), based mainly on local, organic and less processed food and large amounts of fruit, vegetables, wholegrain and fish, versus an Average Danish Diet (ADD) would reduce the phosphorus load due to less phosphorus-containing food additives, animal protein and more plant-based proteins. METHODS: Phosphorus and creatinine were measured in plasma and urine at baseline, week 12 and week 26 in 132 centrally obese subjects with normal renal function as part of a post hoc analysis of data acquired from a 26-week controlled trial. We used the fractional phosphorus excretion as a measurement of phosphorus absorption. RESULTS: Mean baseline fractional phosphorus excretion was 20.9 ± 6.6 % in the NND group (n = 82) and 20.8 ± 5.5 % in the ADD group (n = 50) and was decreased by 2.8 ± 5.1 and 3.1 ± 5.4 %, respectively, (p = 0.6) at week 26. At week 26, the mean change in plasma phosphorus was 0.04 ± 0.12 mmol/L in the NND group and -0.03 ± 0.13 mmol/L in the ADD group (p = 0.001). Mean baseline phosphorus intake was 1950 ± 16 mg/10 MJ in the NND group and 1968 ± 22 mg/10 MJ in the ADD group and decreased less in the NND compared to the ADD (67 ± 36 mg/10 MJ and -266 ± 45 mg/day, respectively, p < 0.298). CONCLUSION: Contrary to expectations, the NND had a high phosphorus intake and did not decrease the fractional phosphorus excretion compared with ADD. Further modifications of the diet are needed in order to make this food concept beneficial regarding phosphorus absorption.

Parathyroid hormone-related peptide plasma concentrations in patients on hemodialysis.

BACKGROUND: Uremic patients develop hyperplasia of the parathyroid glands due to disturbances in the mineral metabolism. The hyperplastic parathyroids are associated with significant expression of parathyroid hormone (PTH)-related peptide (PTHrP). PTHrP has been shown to have an autocrine/paracrine function in the parathyroids, but it is still uncertain if PTHrP is a secretory product of the gland and thereby possess endocrine actions. In cells of severe adenomatous secondary hyperparathyroidism PTHrP and PTH have been found to be co-localized in the same secretory granules. PTH and PTHrP act through the same receptor, the PTH1R, and it has been shown experimentally that PTHrP enhances the PTH secretory response to hypocalcemia, indicating a link between the two hormones. METHODS: Together with a number of parameters involved in mineral homeostasis plasma PTHrP was measured before hemodialysis in 90 patients and in 15 healthy subjects. Plasma PTH was determined in order to examine the possible relationship between the two peptides. RESULTS: In hemodialysis patients mean plasma PTHrP, 4.2 ± 2.1, was significantly lower than that of healthy subjects, 8.3 ± 1.1 pmol/L, p < 0.0001. No relationship was found between plasma PTHrP and PTH in hemodialysis patients. Gender, PTX, specific treatments and diagnoses had no impact on PTHrP concentrations. CONCLUSION: Thus PTHrP is measurable in hemodialysis patients, but its secretion might not be part of a regulated mineral homeostatic process and may not derive from the uremic hyperplastic parathyroid glands.

Intravascular volumes and the influence on anemia assessed by a carbon monoxide rebreathing method in patients undergoing maintenance hemodialysis.

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.

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.

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial.

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.

Stable incidence and survival of arteriovenous fistulas over 39 years: A long-term national cohort study.

INTRODUCTION: The age and number of comorbidities in the hemodialysis population has increased over time. This may influence the construction and survival of the arteriovenous fistula (AVF). The present study explored the incidence and survival of AVFs over a period of 39 years. METHODS: A retrospective cohort study was conducted based on Danish registries. Incident hemodialysis patients between 1977 and 2015 were included. The incidence of AVF and factors associated with the construction of an AVF were described. Risk factors for AVF survival and repair were explored by Kaplan Meier and Cox proportional hazard analysis. RESULTS: The total number of arteriovenous accesses (AVF and arteriovenous grafts) were 10,187 and there were 4201 central venous catheters (CVC). No significant difference in the proportion of AVFs during the 39 years was seen. Age and renal diagnosis did not influence the proportion of AVFs. Patients with CVCs were found to have a significantly higher prevalence of comorbidities (p < 0.01). AVF survival remained stable during the 39 years. The first constructed AVF had the best survival, 35% still functioning after 15 years. Factors such as brachiocephalic AVF, female sex, and diabetic nephropathy increased the risk of AVF failure (Odds Ratio (OR): 2.46, 95% Confidence Interval (CI) (2.29-2.65), 1.17 (1.10-1.25), and 1.21 (1.12-1.3)), respectively. CONCLUSION: Despite an older dialysis population, the proportion and survival of the AVF in the Danish dialysis population has not changed, probably because of increased awareness of AVF as the first choice of vascular access and improved surveillance, surgery, and repair.

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.

Cutaneous vascular calcifications in patients with chronic kidney disease and calcific uremic arteriolopathy: a cross-sectional study.

INTRODUCTION: Calcific uremic arteriolopathy is a life-threatening cutaneous condition in patients with chronic kidney disease. Often, clinical diagnosis is accompanied by histopathologic evaluations demonstrating vascular calcium deposits. We aimed to investigate the presence of cutaneous calcifications in non-lesional tissue in patients with chronic kidney disease, and the relation to systemic vascular calcification. METHODS: We investigated the presence of cutaneous vascular calcifications in non-lesional skin biopsies from patients with current or previous calcific uremic arteriolopathy and patients with different stages of chronic kidney disease without calcific uremic arteriolopathy, and explored their association with vascular calcification in other vascular beds. Systemic vascular calcification was examined by mammography and lumbar X-ray. RESULTS: Thirty-nine adults were enrolled (current or previous calcific uremic arteriolopathy, n = 9; end-stage chronic kidney disease, n = 12; chronic kidney disease stage 3b-4, n = 12; healthy controls, n = 6). All calcific uremic arteriolopathy patients had end-stage kidney disease. Cutaneous vascular calcifications were not present in any of the non-lesional skin punch biopsies. Breast arterial calcification was demonstrated in patients with calcific uremic arteriolopathy (75%) and chronic kidney disease (end-stage 67% and stage 3b-4 25%, respectively), but in none of the controls. All chronic kidney disease patients had systemic calcification on lumbar X-ray (median score 21, 22, and 15 in patients with calcific uremic arteriolopathy, end-stage kidney disease and chronic kidney disease stage 3b-4). The serum calcification propensity was significantly different between groups. DISCUSSION: Despite a high burden of systemic vascular calcification, cutaneous calcium deposits in non-lesional tissue could not be demonstrated histopathologically in patients with chronic kidney disease (with or without current or previous calcific uremic arteriolopathy). Further studies to determine whether these findings are representative or attributed to other factors are warranted.

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.

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.

Hemoglobin A1c and Fructosamine Evaluated in Patients with Type 2 Diabetes Receiving Peritoneal Dialysis Using Long-Term Continuous Glucose Monitoring.

INTRODUCTION: Shortened erythrocyte life span and erythropoietin-stimulating agents may affect hemoglobin A1c (HbA1c) levels in patients receiving peritoneal dialysis (PD). We compared HbA1c with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with type 2 diabetes receiving PD. METHODS: Fourteen days of CGM (Ipro2, Medtronic) were performed in 23 patients with type 2 diabetes receiving PD and in 23 controls with type 2 diabetes and an estimated glomerular filtration rate over 60 mL/min/1.73 m2. Patients were matched on gender and age (±5 years). HbA1c (mmol/mol), its derived estimate of mean plasma glucose (eMPGA1c) (mmol/L), and fructosamine (µmol/L) were measured at the end of the CGM period and compared with the mean sensor glucose (mmol/L) from CGM. RESULTS: In the PD group, mean sensor glucose was 0.98 (95% con-fidence interval (CI): 0.43-1.54) mmol/L higher than the eMPGA1c compared with the control group (p = 0.002) where glucose levels were nearly identical (-0.05 (95% CI: -0.35-0.25) mmol/L). A significant association was found between fructosamine and mean sensor glucose using linear regression with no difference between slopes (p = 0.89) or y-intercepts (p = 0.28). DISCUSSION/CONCLUSION: HbA1c underestimates mean plasma glucose levels in patients with type 2 diabetes receiving PD. However, the clinical significance of this finding is undetermined. Fructosamine seems to more accurately reflect glycemic status. CGM or fructosamine could complement HbA1c to increase the accuracy of glycemic monitoring in the PD population.

Effectiveness of cinacalcet in patients with recurrent/persistent secondary hyperparathyroidism following parathyroidectomy: results of the ECHO study.

BACKGROUND: Progressive secondary hyperparathyroidism (sHPT) is characterized by parathyroid gland hyperplasia which may ultimately require parathyroidectomy (PTX). Although PTX is generally a successful treatment for those patients subjected to surgery, a significant proportion develops recurrent sHPT following PTX. ECHO was a pan-European observational study which evaluated the achievement of KDOQI(TM) treatment targets with cinacalcet use in patients on dialysis. Previously published results showed that cinacalcet plus flexible vitamin D therapy lowered serum PTH, phosphorus and calcium in the clinical practice with similar efficacy as seen in phase III trials. METHODS: This subgroup analysis of ECHO describes the real-world cinacalcet treatment effect in patients with recurrent or persistent sHPT after PTX (n = 153) compared to sHPT patients without prior history of PTX (n = 1696). RESULTS: Both groups of patients had substantially elevated serum PTH with comparable sHPT severity at baseline. After 12 months of cinacalcet treatment, 20.3% (26/128) of patients with prior PTX and 18.2% (253/1388) of patients without prior PTX achieved serum PTH and Ca × P values within the recommended KDOQI(TM) target ranges. CONCLUSIONS: Our data support the successful use of cinacalcet in patients with recurrent/persistent sHPT after PTX.

Study protocol: long-term effect of the New Nordic Renal Diet on phosphorus and lipid homeostasis in patients with chronic kidney disease, stages 3 and 4: a randomised controlled trial.

INTRODUCTION: Chronic 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 ANALYSIS: This 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 DISSEMINATION: The 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 NUMBER: ClinicalTrials.gov (wwwclinicaltrialsgov) Registry (NCT04579315). PROTOCOL VERSION: The 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.

Reduced erythrocyte lifespan measured by chromium-51 in patients with type 2 diabetes undergoing long-term hemodialysis.

INTRODUCTION: A reduced erythrocyte lifespan potentially explains the low hemoglobin A1c values found in hemodialysis patients. However, data supporting this notion in patients with type 2 diabetes is unclear. We evaluated the erythrocyte lifespan in patients with type 2 diabetes undergoing long-term hemodialysis and investigated potential predictors of erythrocyte lifespan. METHODS: Long-term hemodialysis patients with type 2 diabetes and type 2 diabetes patients without nephropathy (estimated glomerular filtration rate > 60 mL/min/1.73 m2 ) were included. The erythrocyte lifespan was measured using chromium-51 (51 Cr)-labeled erythrocytes. Blood radiotracer activity was measured six to nine times over a period of 3-5 weeks to determine the erythrocyte lifespan of each patient. Biochemical markers were obtained five times over 16 weeks and associated with the erythrocyte lifespan. FINDINGS: Type 2 diabetes patients undergoing hemodialysis (N = 13) had a significantly shorter median erythrocyte lifespan of 49.7 (interquartile range [IQR] = 44.1-58.6) days compared with 64.2 (IQR = 62.6-83.5) days in the control group (N = 10) (P ˂ 0.001) with a difference between medians of 14.5 (95% confidence interval = 8.1-38.8) days. In the hemodialysis group, no association could be detected between the erythrocyte lifespan and markers of hemolysis, level of inflammation, or urea. DISCUSSION: A reduced erythrocyte lifespan was detected in type 2 diabetes patients undergoing long-term hemodialysis. This may contribute to the reduced hemoglobin A1c values observed in the type 2 diabetic hemodialysis population. An association could not be detected between the erythrocyte lifespan and biochemical markers of hemolysis or inflammation.