IntroductionPatients 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 analysisThe 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 disseminationThe 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 numberNCT04841304.
Arteriovenous fistulas (AVFs) are iatrogenic vascular connections established to allow high‐flow intravascular access for patients with chronic kidney disease requiring hemodialysis. The left‐right ...flow shunt results in changes in extracellular fluid volume and blood pressure‐controlling hormones that could affect the residual kidney function. We present a case where a female patient with a brachiocephalic AVF had a fistula flow of >4 L/min. To reduce the flow, a banding procedure was performed. The patient was examined prior to banding and 1 and 2 weeks thereafter. Banding resulted in a marked decrease in AVF flow from >4 to 1 L/min and was associated with reductions in N‐terminal pro‐brain natriuretic peptide of 51% and 67% at 1‐ and 2‐weeks post‐banding, respectively. Mid‐regional pro‐atrial natriuretic peptide concentrations were reduced post‐banding by 17% after 1 week and 25% after 2 weeks. After 1 week, renin, angiotensin II, and aldosterone levels in plasma decreased transiently by 44%, 47%, and >86%, respectively, and returned to pre‐banding levels after 2 weeks. Creatinine clearance tended to decrease while blood pressure and total body water increased 2 weeks after banding. This indicates that high‐flow AVF is associated with increased natriuretic peptides and hormones of the renin–angiotensin–aldosterone system, that may balance each other regarding fluid retention and hypertension and support remaining kidney function.
A patient with end‐stage kidney disease and an arteriovenous fistula with extreme access flow of >4 L/min underwent flow reduction to 1 L/min by banding. Flow reduction was associated with increased total body water and blood pressure and reduction in natriuretic peptide hormones along with temporary decreased hormones of the renin—angiotensin—aldosterone system and a small decrease in creatinine clearance. This indicates that a high‐flow arteriovenous fistula is associated with hormonal changes that may balance each other regarding fluid retention and hypertension and support remaining kidney function.
Kaposi Sarcoma (KS) is driven by human herpes virus 8 causing vascular proliferation which is induced by loss of immune function most often due to HIV or immunosuppressants. KS occurs with increased ...incidence in kidney transplant recipients, but rarely is disseminated. We report a 64-year-old male who developed severely disseminated KS 5 months after ABO-incompatible kidney-transplantation. No guidelines for chemotherapy exist in this case and reduced kidney function and impaired immune system complicates the use of systemic chemotherapy in kidney transplant recipients. A combination of paclitaxel and gemcitabine followed by two days of hemodialysis treatment was chosen since paclitaxel can be given in full dose independently of kidney function and gemcitabine is metabolised to 2′,2′-difluorodeoxyuridine which is found to be highly dialysable. The present treatment was well tolerated by the patient with one episode of leukopenia and elevated alanine transaminase during treatment which resolved. There were no serious adverse events and the patient obtained a complete remission verified by Positron Emission Tomography CT after ending chemotherapy and at one-year follow up.
Abstract
Background and Aims
Fluid overload is a major challenge in haemodialysis (HD) patients and might cause hypervolaemia. We speculated that HD patients reaching dry weight could have undetected ...hypervolaemia and low haemoglobin concentration (Hb) due to haemodilution.
Method
The study included HD patients (n = 22) and matched healthy controls (n = 22). Blood volume, plasma volume, red blood cell volume, and total haemoglobin mass (Hb mass) were determined using a carbon monoxide (CO)-rebreathing method in HD patients reaching dry weight and controls. Blood volume measurements were also obtained by a dual-isotope labelling technique in a subgroup for validation purposes.
Results
Blood volume was higher in 16 out of the 22 HD patients compared to controls. In the HD group, the median 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) (Table 1). The median 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 HD and control groups, respectively (P < 0.001). Hb was lower in HD patients (P<0.001), whereas no difference in total Hb mass was observed between groups (P = 0.11). Changes in Hb levels during and after dialysis were observed in the HD group and is shown in Fig. 1. A correlation was found between blood volume measured by the CO-rebreathing test and the dual-isotope labelling technique in the control group (r = 0.83, P = 0.015), but not the HD group (r = 0.25, P = 0.60).
Conclusion
The HD group had increased blood volume at dry weight due to high plasma volume, indicating a hypervolaemic state. The total Hb mass was similar between HD patients and controls, unlike Hb, which emphasizes that Hb is an inaccurate marker of anaemia among HD patients.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed, but why precisely SGLT2 inhibition ...has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient's blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper was to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors' physiological effects.
Changes induced by SGLT2 inhibitors on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that include radioisotopes, indocyanine green (ICG) dye, or carbon monoxide (CO). Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled CO. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of CO is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated.
A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors.
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.
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.
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.
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.
Abstract
Background and Aims
Anaemia in long-term haemodialysis (HD) is caused by reduced erythropoietin levels but shortened erythrocyte life span is thought to contribute. However, reduced ...erythrocyte life span has never been documented in patients with type 2 diabetes (T2D) undergoing long-term HD. The aim of the study was to establish if the erythrocyte life span is decreased in in patients with type 2 diabetes (T2D) undergoing long-term HD and to investigate predictors of reduced erythrocyte life span.
Method
Patients with T2D undergoing long-term HD and patients with T2D without nephropathy (control group) (eGFR above 60ml/min) were included. Erythrocyte life span was measured using Chromium-51 (51Cr) labelled erythrocytes. Blood radiotracer activity was measured 6-8 times over 3-5 weeks to calculate the erythrocyte half-life for each patient. Markers for haemolysis, blood pressure and time spend in dialysis were obtained 5 times over 16 weeks and correlated to the erythrocyte half-life.
Results
For patients with T2D undergoing HD (n=13), the median half-life was 34.5 days (30.6 - 40.7) compared with 44.6 days (43.5 - 58.0) in the control group (n=10) corresponding to a 23 % difference (p=0.0003). From the half-life, the median erythrocyte life span was estimated to 49.7 days (44.1-58.6) and 64.2 days (62.6-83.5), respectively. For patients with T2D undergoing HD no correlation was found between the erythrocyte half-life and markers of haemolysis, blood pressure or time spend in dialysis.
Conclusion
The half-life of erythrocytes was reduced by 23 % in patients with T2D undergoing long-term HD compared with a control group. This reflects that erythrocyte life span is reduced in these patients. No specific markers of haemolysis could be correlated to the findings.
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