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Objective. The objective of the study was to assess the relationship between selected clinical and biochemical parameters of end stage renal disease (ESRD) patients and arterial calcification. Materials and Methods. The study comprised 59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis). The examined parameters included common carotid artery intima-media thickness (CCA-IMT), BMI, incidence of diabetes and impaired fasting glucose (IFG), dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric dimethylarginine (ADMA), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC) were also measured. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using von Kossa method and alizarin red. Results. Calcification of radial artery was significantly associated with higher prevalence of IFG and diabetes (P = 0.0004) and older age (P = 0.003), as well as higher OPG (P = 0.014) and ADMA concentrations (P = 0.022). Fasting glucose > 5.6 mmol/l (IFG and diabetes) significantly predicted vascular calcification in multiple logistic regression. The calcification was also associated with higher CCA-IMT (P = 0.006) and mortality (P = 0.004; OR for death 5.39 [1.20.24.1] after adjustment for dialysis status and age). Conclusion. Combination of renal insufficiency and hyperglycemic conditions exerts a synergistic effect on vascular calcification and increases the risk of death. [ABSTRACT FROM AUTHOR]

• sTM is a multifunctional molecule released following endothelial injury. • sTM may be closely related to TNF-mediated inflammation in ESRD. • OPN independently predicts sTM concentrations and may be involved in associated tissue remodeling and mineralization processes. • sTM correlates with progression of MAC. • sTM does not correlate with age and other traditional CV risk factors. Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1–3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications. [ABSTRACT FROM AUTHOR]

Introduction: Although filters are still preferred during carotid stenting, proximal protection systems (PPS) are increasingly used during these procedures. PPS seem to be safer than distal systems, especially in symptomatic patients, but evidence supporting their use is limited. Aim: This was a post hoc survey with 30-day mid-term and long-term follow up, which was aimed at assessment of the safety and efficacy of stenting of the internal carotid artery under PPS in symptomatic patients. Material and methods: We analysed the results of stenting in 120 symptomatic patients presenting with at least 60% stenosis. Patients were aged 67.9 ±9.8 years, and 12 patients were older than 80 years. An occlusion of contralateral artery was found in 5 patients and bilateral stenosis in 26 patients. The primary endpoint of this study was the proportion of patients who had new neurological events, including transient ischemic attack and minor or major stroke in 30-day follow-up. The secondary endpoint was a composite of technical and clinical success. During longterm follow-up we assessed new neurological events and stenoses of implanted stents. Results: The incidence of new neurological events during 30-day follow-up was 0.8%. The rate of technical success defined by secondary endpoint was 100%. Mean internal carotid artery stenosis before and after stent implantation was 93.8 ±9% and 8.4 ±6.3%, respectively (p < 0.001). Procedural success was achieved in all cases. During longterm follow-up there were two (1.7%) asymptomatic in-stent stenoses and no (0%) new neurological events. Conclusions: Endovascular management of symptomatic carotid stenosis under PPS is safe, feasible, and appears to be a good alternative to surgical endarterectomy. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) seems to worsen the prognosis of acute ischaemic stroke (AIS) patients treated with mechanical thrombectomy (MT). At the same time, the procedure of MT increases AKI risk by iodinated contrast use. Identification of factors predisposing to AKI after MT is important for recognizing vulnerable patients and successful prevention. Aim: To identify factors associated with the occurrence of AKI during hospitalization in MT-treated AIS patients. Material and methods: The study included all AIS patients treated with MT in the University Hospital in Krakow from 2019 to 2021. The diagnosis of AKI during hospitalisation was based on serum creatinine concentration levels, according to the Kidney Disease Improving Global Outcomes guidelines. We compared patients with and without AKI in terms of age, sex, comorbidities, stroke course and laboratory test results at admission. We identified factors associated with the occurrence of AKI using univariate logistic regression analysis, with significant variables subsequently added to the multivariate analyses. Results: Among 593 MT-treated AIS patients the incidence of AKI during hospitalisation was 12.6%. AKI development was associated with diabetes, chronic kidney disease, total volume of iodinated contrast obtained during hospitalisation, posterior circulation stroke, lack of intravenous thrombolysis, and laboratory test results at admission: haemoglobin, glucose, urea, potassium, and creatinine. Total contrast volume and urea level were the most important independent risk factors associated with occurrence of AKI. Conclusions: AKI is common in MT-treated AIS patients. There is a need to establish a protocol for decreasing the risk of AKI in AIS patients undergoing MT and, in case it occurs, a procedure for its treatment. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β superfamily, participates in processes associated with myeloma development and its end-organ complications. It plays a significant role in both physiological and abnormal erythropoiesis and regulates iron homeostasis through modulation of hepcidin. It is abnormally secreted in marrow stromal cells of patients with multiple myeloma (MM), which may reflect the tumor microenvironment. We analyzed the associations of serum GDF-15 with clinical characteristics of 73 MM patients (including asymptomatic MM) and the laboratory indices of renal function, anemia, and inflammation. Baseline serum GDF-15 was studied as the predictor of two-year survival. We defined five clinically relevant subgroups of patients (symptomatic MM only, patients with and without remission, patients on chemotherapy, and without treatment). Increased GDF-15 concentrations were associated with more advanced MM stage, anemia, renal impairment (lower glomerular filtration and higher markers of tubular injury), and inflammation. Most of the results were confirmed in the subgroup analysis. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin were associated with GDF-15 independently of other variables. In the studied MM patients, GDF-15 did not significantly predict survival (p = 0.06). Our results suggest that serum GDF-15 reflects myeloma burden and shares a relationship with several markers of prognostic significance, as well as major manifestations. [ABSTRACT FROM AUTHOR]

Introduction: Survival after heart transplantation (HTX) is extended due to continuous improvement of medical care, allowing enough time for coronary artery vasculopathy to develop. Data on the clinical outcome of cardiac transplantation patients after percutaneous coronary intervention (PCI) are still not extensively explored. The aim of our study was to assess whether heart transplantation itself compromises the outcome in patients undergoing percutaneous coronary intervention and to assess survival rates as well as major cardiovascular complications in heart transplant recipients who had undergone PCI.Material and Methods: Thirty-three heart transplant recipients who had undergone PCI in the years 2005 to 2015 in a single center were matched by age, sex and main risk factors of arteriosclerosis with 33 controls without heart transplant history. Mean age of patients was 54.6 ±11.4 years in the HTX group and 58.8 ±10.8 years in controls. Median time from heart transplant to PCI was 13 years (4.4-22 years). Case and control groups did not differ in terms of standard risk factors of coronary artery disease, apart from chronic kidney disease, which was present in 70% of patients after heart transplantation, and dyslipidemia, which was present in 91% of control subjects.Results: Patients after HTX had worse survival compared to controls (p = 0.04). When adjusted for comorbidities in the Cox regression model, there was no significant difference in survival between cardiac transplant recipients and the control group (HR = 1.06; 95% CI: 0.10-11.24). Chronic renal disease was a significant predictor of all-cause mortality (HR = 29.9; 95% CI: 2.3-393). Considering other endpoints, HTX patients had considerably higher incidence of severe bleeding compared to the control group (27% vs. 3%, p < 0.05).Conclusions: There was no significant difference in myocardial infarction rate, revascularization or hospitalization rates. [ABSTRACT FROM AUTHOR]

Principles of treat-to-target (T2T) have been widely adopted in both multinational and regional guidelines for rheumatoid arthritis (RA). Several questionnaire studies among physicians and real-world data have suggested that an evidence–practice gap exists in RA management. Investigating physician adherence to T2T, which requires a process measure, is difficult. Different practice patterns among physicians are observed, while adherence to protocolized treatment declines over time. Rheumatologist awareness, agreement, and claims of adherence to T2T guidelines are not always consistent with medical records. Comorbidities, a difficult disease course, communication barriers, and individual preferences may hinder an intensive, proactive treatment stance. Interpreting deviations from protocolized treatment/T2T guidelines requires sufficient clinical context, though higher adherence seems to improve clinical outcomes. Nonmedical constraints in routine care may consist of barriers in healthcare structure and socioeconomic factors. Therefore, strategies to improve the institution of T2T should be tailored to local healthcare. Educational interventions to improve T2T adherence among physicians may show a moderate, although beneficial effect. Meanwhile, a proportion of patients with inadequately controlled RA exists, while management decisions may not be in accordance with T2T. Physicians tend to be aware of current guidelines, but their institution in routine practice seems challenging, which warrants attention and further study. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of renal significance (MGRS) has introduced a new perspective to several well-known disease entities impacting nephrology, haematology and pathology. Given the constantly changing disease spectrum of these entities, it is clinically imperative to establish diagnostic and treatment pathways supported by evidence-based medicine. MGRS is a disease of the kidney, secondary to plasma cell clonal proliferation or immune dysfunction, requiring therapeutic intervention to eradicate the offending clone. To fully understand the disease(s), it is prerequisite to determine the significance of the findings. The diagnostic work up should be extensive due to the wide heterogeneity of clinical presentation, ultimately necessitating kidney biopsy. Particular patient profiles such as AL amyloidosis, which may be diagnosed through biopsies of other tissues/organs, may be an exception. Treatment decisions should be formulated by multi-disciplinary consensus: nephrologists, haematologists and pathologists. The ultimate goal in managing MGRS is eradication of the offending plasma cell clone which requires targeted chemotherapy and, in eligible cases, haematopoietic stem cell transplantation. We present a review of diagnostic procedures, treatment options and advances in the last few years in the management of MGRS in an effort to acquaint specialists with this new face of several older diseases. [ABSTRACT FROM AUTHOR]

PurposeDisrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin.Patients and methodsThe cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined.ResultsIn total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22;p = 0.016 and beta = 0.26;p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age.ConclusionsOur data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis. [ABSTRACT FROM AUTHOR]

Purpose: Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the 'inflamed' (vulnerable) plaques by scintigraphy using IL-2 labelled with Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. Methods: A total of 28 patients (18 men, 10 women, aged 55.2 ± 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. Results: Increased Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 ± 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine ( R = 0.22, p = 0.037), apolipoprotein B (apoB) ( R = 0.31, p = 0.008), apoB to apoA-I ratio ( R = 0.29, p = 0.012) and triglyceride concentration ( R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 ± 0.5 vs 2.16 ± 0.68, p = 0.025) was revealed as well as a difference between values of T/nT ratio in groups of patients with values of apoB, soluble CD40 ligand and asymmetric dimethylarginine above and below median (3.18 ± 0.52 vs 2.16 ± 0.68, p = 0.031). No statistically significant association was found between T/nT ratio and mean value of either IMT or classic cardiovascular risk factors. Conclusion: Scintigraphy with the use of Tc-HYNIC-IL-2 can be a tool for inflamed atherosclerotic (vulnerable) plaque visualization within CCA in ESRD patients. Quantitative results of carotid artery scintigraphy with Tc-HYNIC-IL-2 correlate with serum concentration of selected cardiovascular risk markers. [ABSTRACT FROM AUTHOR]

Purpose: Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the 'inflamed' (vulnerable) plaques by scintigraphy using IL-2 labelled with Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. Methods: A total of 28 patients (18 men, 10 women, aged 55.2 ± 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. Results: Increased Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 ± 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine ( R = 0.22, p = 0.037), apolipoprotein B (apoB) ( R = 0.31, p = 0.008), apoB to apoA-I ratio ( R = 0.29, p = 0.012) and triglyceride concentration ( R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 ± 0.5 vs 2.16 ± 0.68, p = 0.025) was revealed as well as a difference between values of T/nT ratio in groups of patients with values of apoB, soluble CD40 ligand and asymmetric dimethylarginine above and below median (3.18 ± 0.52 vs 2.16 ± 0.68, p = 0.031). No statistically significant association was found between T/nT ratio and mean value of either IMT or classic cardiovascular risk factors. Conclusion: Scintigraphy with the use of Tc-HYNIC-IL-2 can be a tool for inflamed atherosclerotic (vulnerable) plaque visualization within CCA in ESRD patients. Quantitative results of carotid artery scintigraphy with Tc-HYNIC-IL-2 correlate with serum concentration of selected cardiovascular risk markers. [ABSTRACT FROM AUTHOR]

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate—eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin—NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = −0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = −0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = −0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = −0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a common plasma cell malignancy, which is responsible for significant mortality, often related to severe renal impairment (RI). Kidney injury can limit therapeutic choices and may often translate into poor outcomes, but it remains potentially reversible in a proportion of patients. The most accessible, conventional markers of RI are subject to several shortfalls, among which are the delayed onset following kidney insult, multiple interfering factors, and lesser sensitivity to mild changes in glomerular filtration. Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have accumulated large interest in MM-RI due to being very sensitive markers of renal injury, as well as indicators of tubular-glomerular axis impairment. Of interest, recent data suggest that prediction of acute kidney injury may be aided by urinary tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), which both act to induce G1 cell cycle arrest, reflective of a state of pre-injury, and thus may be superior to other measures of kidney insult (NGAL, kidney injury molecule ((KIM-1)). Moreover, TIMP-2 seems to be a biomarker dedicated to distal tubular cells, whereas insulin-like growth factor-binding protein 7 (IGFBP7) secretion has been found in proximal tubule cells. IGFBP7 can also identify a subsection of the normal proximal nephron, even, maybe the one that is responding to insult. They may be adopted into a conceptual screening panel for MM-RI. Unfortunately, no biomarker is ideal (influence of non-renal, biologic factors), and novel measures are limited by economic constraints, availability, lack of standardization. With the emergence of more advanced diagnostic and prognostic MM models, markers reflective of disease processes (including RI) are of high interest. Candidate molecules also include peptidome markers. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a malignancy of clonal plasma cells accounting for approximately 10% of haematological malignancies. MM mainly affects older patients, more often males and is more frequently seen in African Americans. The most frequent manifestations of MM are anaemia, osteolytic bone lesions, kidney failure and hypercalcemia. The anaemia develops secondary to suppression of erythropoiesis by cytokine networks, similarly to the mechanism of anaemia of chronic disease. The concomitant presence of kidney failure, especially chronic kidney disease (CKD) and MM per se, leading to anaemia of chronic disease (ACD) in combination, provoked us to pose the question about their reciprocal dependence and relationship with specific biomarkers; namely, soluble transferrin receptor (sTfR), growth differentiation factor 15 (GDF15), hepcidin 25 and zonulin. One or more of these are new biomarkers of ferric management may be utilized in the near future as prognostic predictors for patients with MM and kidney failure. [ABSTRACT FROM AUTHOR]