Abstract
Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. ...However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death adjusted hazard ratio (aHR) 0.89, but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.
There is amassed evidence regarding the use of endovascular procedures for the treatment of vascular access stenosis and thrombosis. A review was conducted based on available randomized trials, ...cohort studies and retrospective analyses published after 2000 on endovascular treatment of dysfunctional and thrombosed vascular access, with an aim to illustrate the available device and procedural options. The use of paclitaxel-coated balloons, cutting balloons and covered stents is described in the field of vascular access stenosis. The broad spectrum of available devices and endovascular declotting procedures ranging from thrombolysis to thrombectomy is also discussed. Overall, in this review we demonstrate the increasing role of endovascular procedures in vascular access treatment and the improved patency outcomes provided by the implementation of novel endovascular devices. Moreover, the improvement of post-intervention primary patency rates after endovascular declotting procedures and the shift to more thrombectomy-dependent procedures over time is also highlighted. In conclusion, endovascular treatment of dialysis access stenosis and thrombosis has an established role, owing to the implementation of sophisticated devices, allowing, when needed, the simultaneous treatment of thrombosis and the underlying stenosis.
Purpose
Vascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its ...activation is vitamin K dependent. The aim of this study is to investigate the role of oral vitamin K2 supplementation in the prevention of VC progression in haemodialysis patients.
Methods
We conducted a prospective randomized interventional study in patients on hemodialysis. Patients were randomly assigned to either receiving orally 200 μgr of vitamin K2 (vitamin K2/MK-7, Solgar) every day for 1 year or no treatment. Uncarboxylated MGP (uc-MGP) concentrations were quantified using ELISA at randomization, at 3 and at 12 months. Aortic calcification was evaluated using Agatston score after an abdominal computed tomography scan that was performed at the beginning and at 12 months of follow-up.
Results
There were 102 patients that were randomized. After 1 year of follow-up, 22 patients from the vitamin K2 group and 30 patients from the control group were included in the analysis. After 3 months of treatment, uc-MGP values remained unchanged in the vitK2 group but after 1 year were reduced by 47% (
p
= 0.005). Furthermore, uc-MGP at 1 year was increased by 12% in the control group. At 1 year, vitK2 group had significantly lower values of uc-MGP in comparison to controls (
p
= 0.03). Agatston score was increased significantly both in vitamin K2 and control group at 1 year with no difference between groups.
Conclusions
Oral administration of vitamin K2 in patients on haemodialysis reduced serum uc-MGP levels but did not have an effect in the progression of aortic calcification.
Keratins, the intermediate filaments of the epithelial cell cytoskeleton, are up-regulated and post-translationally modified in stress situations. Renal tubular epithelial cell stress is a common ...finding in progressive kidney diseases, but little is known about keratin expression and phosphorylation. Here, we comprehensively describe keratin expression in healthy and diseased kidneys. In healthy mice, the major renal keratins, K7, K8, K18, and K19, were expressed in the collecting ducts and K8, K18 in the glomerular parietal epithelial cells. Tubular expression of all 4 keratins increased by 20- to 40-fold in 5 different models of renal tubular injury as assessed by immunohistochemistry, Western blot, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The up-regulation became significant early after disease induction, increased with disease progression, was found de novo in distal tubules and was accompanied by altered subcellular localization. Phosphorylation of K8 and K18 increased under stress. In humans, injured tubules also exhibited increased keratin expression. Urinary K18 was only detected in mice and patients with tubular cell injury. Keratins labeled glomerular parietal epithelial cells forming crescents in patients and animals. Thus, all 4 major renal keratins are significantly, early, and progressively up-regulated upon tubular injury regardless of the underlying disease and may be novel sensitive markers of renal tubular cell stress.
Dyslipidemia is common in kidney transplant recipients owing to the disturbance of lipid metabolism caused by chronic kidney disease and the effect of immunosuppression on lipid metabolism. Patients ...receiving treatment with mammalian target of rapamycin inhibitors show more prominent lipid disorders, which are attributed mainly, but not only, to adipocyte lipid uptake disruption, lipolysis promotion and lipogenic gene expression enhancement. Dyslipidemias in kidney transplant recipients predispose these patients to an increased risk of developing cardiovascular disease; thus, current guidelines recommend treatment initiation with a statin, regardless of low-density lipoprotein cholesterol (LDL-C) concentration, with ezetimibe as a secondary option for patients who do not tolerate such therapy or for those with inadequate response. Treatment with pro-protein convertase subtilisin/kexin type 9 inhibitors such as alirocumab, although effectively reducing LDL-C in patients with chronic kidney disease, has not been evaluated in kidney transplant recipients. In this case report, we present a case of a female kidney transplant recipient who developed substantial dyslipidemia after everolimus initiation. This case was resistant to treatment with simvastatin/ezetimibe combination, and the patient subsequently received alirocumab. Our patient showed a mean reduction of 46.6% in LDL-C during an 18-month period after alirocumab initiation, which is comparable to the results of studies on patients with or without renal impairment. Furthermore, treatment with alirocumab proved to be well tolerated without adverse effects or interactions with the immunosuppression regimen.
Pediatric obesity and type 1 diabetes mellitus (T1DM) represent two common chronic diseases associated with chronic inflammation, endothelial dysfunction and long-term complications. The aim of the ...present study was to assess the possible diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation and impaired endothelial function, in children with the diseases. In this cross-sectional study, children and adolescents with T1DM (
N
= 41) or obesity (
N
= 37), aged < 18 years old, and without proteinuria were included, together with children of similar age and without evident morbidity that served as controls (
N
= 42). Serum samples were obtained during standard outpatient follow up and the urokinase-type plasminogen activator receptor (suPAR) concentrations were measured using a commercially available sandwich ELISA kit (DUP00, R&D systems). Clinical and biochemical indices that were also assessed include body mass index (BMI) z-score, Tanner stages, glycosylated haemoglobin (HbA1c), fasting lipid profile and serum creatinine. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls. Also, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359,
p
< 0.001) and serum creatinine levels (Spearman rho −0.334,
p
= 0.005), and a positive correlation with BMI z-score (Spearman rho 0.354,
p
= 0.009) in the whole cohort.
Conclusion
: Serum suPAR may be a useful predictive marker of inflammation or endothelial dysfunction for children with obesity and T1DM, as well as a promising therapeutic target. Further studies are needed in order to clarify whether the reported differences in suPAR levels could reflect a greater impairment of the inflammation status and endothelial function in children with obesity compared to children with T1DM.
What is Known:
• Paediatric obesity and type 1 diabetes are characterised by chronic inflammation and metabolic dysregulation.
• Urokinase plasminogen activator receptor (uPAR) has been proposed as a useful biomarker for chronic inflammation and cardiovascular risk in adults.
What is New:
• Serum suPAR levels were increased in children and adolescents with obesity compared to those with T1DM and healthy controls; thus, obesity may affect the inflammatory status and endothelial function to a higher degree than T1DM during childhood.
• Serum suPAR may serve as a diagnostic and predictive marker of inflammation and endothelial dysfunction for children and adolescents with obesity and T1DM.
Keratins are the main components of the cell cytoskeleton of epithelial cells. Epithelial cells under stressful stimuli react by modifying their keratin expression pattern. Glomerular diseases are ...pathological conditions that may lead to loss of kidney function if not timely diagnosed and treated properly. This study aims to examine glomerular and tubular keratin expression in podocytopathies, ANCA-associated vasculitis, and IgA nephropathy and how this expression correlates to clinical outcomes. We included 45 patients with podocytopathies (minimal change disease and focal segmental glomerulosclerosis), ANCA-associated vasculitis, and IgA nephropathy, with or without crescentic lesions, and healthy controls. All tissues were assessed by photon microscopy and immunohistochemistry. Biopsy sections were examined for keratins 7, 8, 18, and 19 expression in the glomerular and tubulointerstitial areas separately. Moreover, we examined how keratin expression was correlated with long-term kidney function outcomes. All four studied keratins had significantly increased glomerular expression in patients with ANCA vasculitis compared to controls and MCD patients. Tubular expression of keratins 7, 8, and 19 was related to kidney outcome in all groups. Patients with crescents had higher expression of all keratins in both glomeruli and tubulointerstitium. The presence of tubular atrophy, interstitial fibrosis, mesangial hyperplasia, and interstitial inflammation did not affect keratin expression. Keratins, an abundant component of renal epithelial cells, have the potential to be featured as a biomarker for kidney function prognosis in patients with glomerular diseases.
Background:
Patients with refractory to optimal pharmacological treatment heart failure (HF) require frequent hospitalization. Peritoneal dialysis (PD) has been part of the management of such ...patients mainly for promoting ultrafiltration and management of overhydration independently of kidney function. The aim of this study was to evaluate the efficacy of PD, especially the use of icodextrin solutions and intermittent PD, in the hospitalization rate and cardiac functional status of patients with HF.
Methods:
We conducted a retrospective study involving patients with New York Heart Association (NYHA) class IV HF and preserved renal function (estimated glomerular filtration rate (eGFR) > 25 ml/min), who were refractory to conservative treatment. Clinical data on weight loss, hospitalization rate before and after PD initiation, cardiac functional status, and technique complications during a 6-month observational period were analyzed.
Results:
PD treatment was performed in 32 patients with a mean age of 63.8 ± 11.9 years and a follow-up of 20.78 ± 14.24 months. Hospitalizations were significantly reduced from 20.7 ± 13.7 to 7.7 ± 8.9 days/patients at 6 months. All patients showed improvement in NYHA class as well as in left ventricular ejection fraction. Overall, eGFR showed a significant decrease but only six patients reached end-stage renal disease. Complications included 18 cases of peritonitis. PD was well tolerated and no patient dropped out of the method. Survival rate reached 72% at 12 months but mortality rate was high with 23 patients dying at 16.65 ± 12.3 months after the initiation of treatment. Patients survival was not influenced by the type of PD modality or weight reduction achieved.
Conclusions:
PD showed to be a viable option for the treatment of patients with refractory HF leading to a better cardiac functional status and diminishing the number of hospital admissions.
Normal saline (N/S) and Ringer's-Lactate (L/R), are administered in everyday clinical practice. Despite that, N/S increases the risk of sodium overload and hyperchloremic metabolic acidosis. In ...contrast, L/R has lower sodium content, significantly less chloride and contains lactates. In this study we compare the efficacy of L/R versus N/S administration in patients with prerenal acute kidney injury (AKI) and pre-established chronic kidney disease (CKD).
In this prospective open-label study we included patients with prerenal AKI and previously known CKD stage III-V without need for dialysis. Patients with other forms of AKI, hypervolemia or hyperkalemia were excluded. Patients received either N/S or L/R intravenously at a dose of 20 ml/kg body-weight/day. We studied kidney function at discharge and at 30 days, duration of hospitalization, acid-base balance and the need for dialysis.
We studied 38 patients and 20 were treated with N/S. Kidney function improvement during hospitalization and at 30 days after discharge, was similar between the two groups. Duration of hospitalization was also similar. Anion-gap improvement as expressed with Δanion-gap between discharge and admission day was higher in those patients that received L/R in comparison to those that received N/S and pH increase (ΔpH) was slightly higher in the L/R group. No patient required dialysis.
Administration of L/R or N/S to patients with prerenal AKI and pre-established CKD had no significant difference in short or long term kidney function but L/R showed a better profile in acid-base balance improvement and Cl
overload in comparison to N/S.
Patients on maintenance hemodialysis show lower serological response to mRNA vaccines. Main causes that contribute to this phenomenon are uremic milieu and older age. However, there are no data on ...the impact of body composition parameters to humoral response.
In this retrospective study, we used data from adult patients on maintenance hemodialysis who received vaccination with 2 doses of BNT162b2. Quantitative determination of antibodies to SARS-CoV-2 spike (S) protein receptor binding domain was performed using the Elecsys immunoassay. Antibody levels higher than 0.8 and 264 U/mL were considered positive and protective, respectively. Body composition parameters were assessed using multifrequency bioelectrical impedance spectroscopy.
Overall, 49 patients were included in the study. Three weeks after the 1
vaccination, 34% of patients, and 3 weeks and 3 months after the 2
vaccination, 100% of patients had detectable titers. Protective titer was developed in 43% of patients 3 weeks after the 2
vaccination and then decreased to 24% 3 months after the 2
vaccination. More years on dialysis were correlated to the absence of protective titers. Higher prediction marker values correlated to poor antibody response, and phase angle was negatively associated with the development of protective titers. Patients with protective titers at 3 months after the 2
vaccination had significantly lower prediction marker and higher phase angle values.
Parameters of body composition correlate and affect antibody response in patients on hemodialysis. The main observation is that immunogenicity of mRNA vaccines is influenced by phase angle and prediction marker.
PDF
