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.
Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from ...collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).
We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores.
S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort.
We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.
The effects and side effects of medical cannabis are not well-established. In 2018, cannabis was approved as a medical drug in Denmark - giving all doctors the opportunity to subscribe medical ...cannabis to their patients. In this case report a 64-year-old kidney-transplanted woman started cannabis droplets due to chronic back pain, which resulted in increased appetite, weight gain and development of diabetes mellitus. Patients with an increased risk of developing diabetes may be more prone to this under the treatment with cannabis. Further studies are needed.
Abstract Background and Aims The effect of vaccinations against SARS-CoV-2 on risk of infection and subsequent adverse outcomes in patients with kidney dysfunction beyond end-stage kidney disease ...remains uncertain. Based on nationwide data from multiple health care registers, the study aims to evaluate vaccination effect on rates of SARS-CoV-2 infection and subsequent risk of associated mortality in patients with kidney disease beyond end-stage kidney disease. Method A population-based retrospective cohort study on all Danish residents ≥18 years with an eGFR ≤90 ml/min/1.73 m2 identified between February 1st 2021 and June 27th 2022 corresponding to predominance of Alpha-, Delta-, and Omicron-variant. Outcomes compared based on vaccination state (unvaccinated, vaccinated, and booster vaccinated) across predefined eGFR categories (eGFR 60-90 mL/min/1.73 m2; eGFR 45-59 mL/min/1.73 m2, eGFR 30-44 mL/min/1.73 m2; eGFR <30 mL/min/1.73 m2). Risk of infection reported as age- and gender-standardized rate ratios of positive SARS-CoV-2 PCR and subsequent risk of death reported as age- and gender standardized 30-day mortality risk. Standardized risks computed based on hazards obtained in multiple cause-specific Cox regression models. Results A total of 982,047 adults with eGFR ≤90 ml/min/1.73 m2 identified. Gender distribution was 43.9% male, median age was 71 IQR 61–78 years, median eGFR 75 IQR 63-84, and 13.1% diabetes. Population rates of vaccination were 3.5%, 80.1%, and 95.4% for Alpha-, Delta-, and Omicron-variant, with 66.2% booster vaccinated at Omicron-variant baseline (Pfizer BionTech 88.3%, Moderna 9.4%, other vaccinations 2.3%). In total 359,428 SARS-CoV-2 infections were identified (Alpha: n = 7,861, Delta: n = 27,868, Omicron: n = 323,699), corresponding to a crude rate of positive SARS-CoV-2 PCR test of 629.0 per 100,000 person-weeks overall. Vaccination and booster vaccination were associated with progressively lower rate of SARS-CoV-2 infection. Age- and gender-standardized rate ratios are shown in Fig. 1. Overall, mean 30-day risks of death were 7.1‰ 95% CI 6.7-7.6, 3.8‰ 95% CI 3.5-4.0, and 1.4‰ 95% CI 1.3-1.4 in unvaccinated, vaccinated, and booster vaccinated persons, respectively. Vaccination and booster vaccination were associated with benefit on 30-day mortality across all strata of eGFR despite progressive increase in risk of death observed with declining kidney function. Age- and gender standardized 30-day mortality rates following a positive PCR for SARS-CoV-2 across granular eGFR are shown in Fig. 2. Conclusion Based on comprehensive nationwide data covering Alpha-, Delta-, and Omicron-variant predominance in Denmark, vaccination and booster vaccination against COVID-19 were associated with lower rates of SARS-CoV-2 infection and benefit on subsequent risk of 30-day mortality across all strata of eGFR.
Abstract Background and Aims Infection due to the immunosuppressive treatment, is among the most frequent causes of hospitalization and death in patients with ANCA-associated vasculitis (AAV). ...Information on prevailing causal microbial aetiologies is crucial for improving treatment and prevention of such events. Here we examined causal bacteriology, incidence, and risk of blood stream infections (BSIs) in incident and prevalent AAV patients, as compared to the general population. Method All data were retrieved from the Danish nationwide registries and the Danish Microbiology Database. Prevalent patients between 1998-2010 were all included at the same index date 1.1.2010; Incident patients diagnosed after 2010 were included with index being the day of diagnosis. Both groups were followed until first time BSI, death, or a maximum of 12 months. Background controls were matched 1:4 on age and sex. Cumulative incidence was assessed by the Aalen-Johansen estimator, and cox analyses adjusted for age, sex, kidney involvement, hypertension, diabetes, dialysis, and plasma exchange (PLEX), were used to model survival time. Results A total 19 (2.3%) BSIs were identified in 818 prevalent patients, and 55 (5.9%) BSIs in 939 incident patients (P < 0.001). As in the background control group, primary causal microbial agents among prevalent patients were E. coli (26.3%) and S. aureus (21.1%), with an overall Gram-negative predominance (58.8%). E. coli (17.5%) remained the most frequent microbial cause of BSIs in incident patients, however with a relatively higher frequency of gram-positive bacteria (50.9%) dominated by Coagulase-negative Staphylococci (12.3%), Enterococci (14%), and Streptococci (14%). Difference in bacteriology between prevalent and incident patients disappeared when patients on dialysis were excluded, whereas the difference in BSI frequency remained significant (p < 0.001). One-year HR of first-time BSI was significantly higher in patients with AAV as compared to controls (prevalent AAV: HR 3.17 95% CI 1.63-6.18, p < 0.0001; Incident AAV; HR 8.64 95% CI 4.88-15.31, p < 0.0001), with significant difference between incident and prevalent patients (HR 2.73 95% CI 1.39-5.35, p = 0.003). Dialysis (HR 3.15 95% CI 1.86-5.31, p < 0.0001) and PLEX (HR 1.87 95% CI 1.05-3.33, p < 0.033) were solitary risk factors of BSI as well as higher age, hypertension, diabetes, and kidney disease (Figure). Risk of BSI remained significantly increased for both prevalent and incident patients as compared to matched background controls when patients on dialysis were excluded. Conclusion E. coli and S. aureus were predominant causal isolates in prevalent AAV patients and controls, and the gram-positive predominance seen with incident AAV was primarily caused by patients on dialysis. Risk of BSI was higher in incident AAV as compared to prevalent AAV, and the AAV diagnosis was associated with increased risk of BSI at all times, with highest risk initially after first diagnosis. Interventions requiring a central venous catheter were solitary risk factors of BSI.
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
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.
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