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Background: Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19. Methods: We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed. Results: The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2–0.3]; P Conclusions: Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure–lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic.

Background: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19. Aims: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19. Methods: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020. Results: 1729 patients (median interquartile range age 63 [50–75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, β-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3–9.6), male sex (OR, 1.4; 95% CI, 1.1–2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1–2.1), and HF (OR, 2.3; 95% CI, 1.5–3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3–0.6), β-blockers (OR, 0.6; 95% CI, 0.4–0.9), statins (OR, 0.5; 95% CI, 0.3–0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4–0.9) was associated with lower risk of death. Conclusions: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.

OBJECTIVE Introduction: Index of microcirculatory resistance assessment is an invasive method of measuring coronary microcirculation function. Association between impaired microcirculatory function and higher rate of cardiovascular events was proven. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio seem to be a promising parameters to predict coronary microcirculatory disease in patients with chronic coronary syndrome. The aim: To determine neutrophil-lymphocyte ratio and platelet-lymphocyte ratio levels in patients with coronary microcirculatory disease and potential association with clinical outcome. PATIENTS AND METHODS Material and methods: 82 consecutive patients with mean age of 67 years, 67% male, were tested for presence of coronary microcirculatory disease using index of microcirculatory resistance. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were calculated based on admission full blood count. Follow-up with major adverse cardiac and cardiovascular events registration was performed (median 24 months). RESULTS Results: The study showed significantly higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with coronary microcirculatory disease compared to control group (3.58±2.61 vs 2.54±1.09 and 164±87.9 vs 124±36.6 respectively). Higher level of platelet-lymphocyte ratio in patients with coronary microcirculatory disease results in worse MACCE-free survival. Optimal cut-off values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio to detect coronary microcirculatory disease were 3.2 and 181.3, respectively. CONCLUSION Conclusions: Higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with increased index of microcirculatory resistance value. Platelet-lymphocyte ratio may be used as a predictor of worse outcome in patients with coronary microcirculatory disease.

Background and Aims Zonulin is a haptoglobin 2 precursor, that regulates the intestinal permeability. As a double-chain form it takes part in scavenging haemoglobin. Chronic inflammation is common complication of chronic kidney disease which affects iron metabolism. The most frequent manifestation of multiple myeloma is anaemia in up to 73% of patients. Serum concentrations of zonulin are associated with inflammation process, age, kidney failure and iron status and anaemia. The aim of the study was to analyse zonulin as a marker of anaemia in MM patients and investigate its relationship with acclaimed parameters of renal failure, inflammation, bone metabolism and stages of MM. Method The studied group of seventy-three patients with MM (67 symptomatic, 6 smoldering) included 35 women and 38 man, with mean age 69 ± 10 years. Median (IQR) of time from initial MM diagnosis was 36 (17; 69) months. Forty patients were in ISS stage 1, 15 in stage 2, and 12 in stage 3 at the time of blood collection. Remission of MM was diagnosed in 52 patients and stable or progressive disease in 21. Twenty-six patients had eGFR Results Median (IQR) serum zonulin in the studied group was 23.9 (19.9; 27.4) ng/ml. There were no differences in zonulin concentrations between patients with smoldering versus symptomatic MM (p=0.4), with ISS 1 to 3 (p=0.7), with remission versus stable or progressive MM (p=0.9), or with eGFR Conclusion Zonulin as a biomarker may promote diagnosis of etiology and management of MM-associated anaemia, which can contribute to biomarker-targeted therapeutic interventions. Early treatment may result in improved life expectancy in patients with MM and increase their quality of life.

Background and Aims Transgelin (SM22) is a cytoskeletal actin-binding protein involved in differentiation of smooth muscle cells, osteoblasts and adipocytes. It is present in fibroblasts, some epithelium, immune cells and acts as a tumor suppressor. It was found as a marker of interstitial fibrosis and glomerulosclerosis. Transgelin upregulation depends on the etiology of the disease in various cells (glomerular parietal or visceral, or tubular interstitial cells). Elevated SM22 expression was detected in glomerular and in tubulointerstitial injury. Among patients with multiple myeloma (MM) up to 50% suffer from renal insufficiency (RI) in early stages. Free light chains (FLCs), potential nephrotoxic substances, where lambda light chains are more commonly associated with renal damage, appear to have a prognostic value in MM and indicate the stages of MM. The aim of the study was to analyse the utility of transgelin in case of renal impairment in MM patients and investigate its relationship with acclaimed parameters of renal failure and markers of MM stages. Method The analysis included 126 patients (73 women and 53 men) in mean age 66 ± 10 years. Symptomatic MM was diagnosed in 119 patients, including 84 (67%) with ISS stage 1, 20 (16%) with stage 2 and 15 (12%) with stage 3; 7 (6%) patients had smoldering MM. Mean baseline eGFR (CKD-EPICr) was 74 ± 24 ml/min/1.73 m2 and 31 (25%) patients had eGFR Results Median serum transgelin in the whole studied group was 84.1 (IQR: 65.4; 116.4) ng/ml. Transgelin concentrations were higher in men (median 96.2 versus 78.8 ng/ml; p=0.022) and in patients with smoldering MM (median 149.2 versus 82.4 ng/ml; p=0.003). Transgelin did not differ according to ISS stage (p=0.3) or disease state (regression, stable disease or progression) (p=0.3). Significant correlations were detected between transgelin and serum creatinine (R=0.29; p=0.001), eGFR (CKD-EPICr) (R=-0.25; p=0.007), uric acid (R=0.19; p=0.036), alanine (R=0.18; p=0.048) and aspartate (R=0.26; p=0.003) aminotransferases, ferritin (R=-0.22; p=0.049), hepcidin (R=-0.25; p=0.033), and urine cystatin C (R=0.19; p=0.042). Moreover, after exclusion of patients with smoldering MM, transgelin significantly correlated with serum FLC lambda (R=0.18; p=0.047) and serum periostin (R=-0.22; p=0.013). After median follow-up of 21 (IQR: 15; 24) months, eGFR decreased in 47 (37%) of patients and increased in 71 (56%) patients (no follow-up data were available in 8, i.e. 6% of patients). Patients in whom eGFR decreased had higher transgelin (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 follow-up (R=0.37; p Conclusion Transgelin may be useful in investigating renal damage because of its proven role in regulation of fibrosis, especially in kidney. As a biomarker it may indicate diagnosis and etiology of MM-related chronic kidney disease, which can lead to beginning of early therapeutic interventions and improved overall survival and quality of life in patients with MM. Moreover, elevated transgelin at the beginning of the disease may induce future development of chronic kidney disease.

Background and Aims Urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) seem to be novel kidney injury related biomarkers, especially in tubular cells damage. Free light chains (FLCs) are associated with renal failure in multiple myeloma (MM) and appear to have a prognostic value and indicate stages in MM. The aim of the study was to investigate the correlation between new biomarkers and acclaimed parameters of renal failure and markers of MM stages and prognosis. Method The study included 124 patients with MM in the mean age of 66 +/- 10 years, with median time from MM diagnosis of 30 (lower; upper quartile 14; 63) months. There were 7(6%) patients with smoldering MM, 80(65%) with ISS stage 1, 22 (18%)with stage 2 and 15 (12%) with stage 3 MM. Mean eGFR was 71 +/- 25 ml/min/1.73 m2 and 30 (24%) patients had eGFR Results Except for urine cystatin C and urine TIMP-2, all the studied markers were higher among patients with eGFR Serum and urine IGFBP-7 and urine NGAL were also higher among patients with ISS grade 3 comparing to the rest of the group (p=0.008, p Conclusion Urine TIMP-2 and IGFBP-7 may be useful in investigating tubular renal damage in patients with chronic kidney injury among patients with MM. This can lead to noninvasive biomarker-targeted diagnostic interventions and contribute to early beginning of treatment that may improve life expectancy quality of life in MM.

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima-media thickness (CCA-IMT). Moreover, we studied the relationship between OPG levels and all-cause and cardiovascular (CV) mortality during a 5-year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C-reactive protein, interleukin-6, tumor necrosis factor receptor II (TNFRII), transforming growth factor-β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA-IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39-20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA-IMT values (OR 6.56; 95%CI 1.06-40.6; P = 0.036). OPG levels above the median were associated with higher CCA-IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84-72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA-IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow-up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA-IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all-cause mortality in CKD patients with advanced medial arterial calcification.

Introduction: The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end-stage renal disease (ESRD). There is an ongoing search for novel biomarkers of CV disease in this population. Objectives: We aimed to investigate the associations of matrix proteoglycans (PGs) and glycosaminoglycans (GAGs), collagen, and arterial calcifications with selected serum and plasma markers of endothelial dysfunction, inflammation, oxidative stress, and bone turnover in patients with ESRD. Patients and methods: We enrolled 47 adult patients (32 men) with stage 5 CKD. The following parameters were investigated: fibrinogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor 1 (PAI-1), stromal cell-derived factor 1α (SDF-1α), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high-sensitivity C-reactive protein (hs-CRP), ferric reducing ability of plasma, 2,2-diphenyl-1-picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin-A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor β (TGF-β), hepatocyte growth factor, secreted protein acidic and rich in cysteine, as well as matrix metalloproteinase 2. Radial artery specimens were stained with alizarin red for calcifications, alcian blue for PGs and GAGs, and sirius red for collagen. Results: We observed positive correlations between PG and GAG, collagen, and calcification staining. The most intense (grade 3) alcian blue staining was significantly correlated with diabetes as well as higher levels of Ca×Pi product, hs-CRP, fibrinogen, SDF-1α, PAI-1, and sTM. However, PAI-1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca×Pi product, and hs-CRP levels. Conclusions: Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF-1α, PAI-1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers. biomarkers end‑stage renal disease glycosaminoglycans plasminogen activator inhibitor 1 proteoglycans

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.

INTRODUCTION Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. OBJECTIVES We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). PATIENTS AND METHODS The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor 1α (SDF1α), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. RESULTS Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and SDF1α levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between SDF1α and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. CONCLUSIONS Circulating ADMA levels indicate medial arterial calcification in patients with CKD.

Background: The survival rate of elderly hemodialyzed (HD) patients is commonly thought to be poor. In a prospective, single center, non-interventional, observational study, the cause of all-cause and cardiovascular (CV) and heart failure (HF) mortality in this patient group were examined and compared with a younger cohort (below 60 years). Material/Methods: The study included 223 patients (90 women and 133 men) with age ranging from 34.5 to 75.0 years treated with HD. Median duration of HD was 70.0 months (24.0-120.0). Mortality data was collected over a period of six years. We divided patients into groups

INTRODUCTION Hepatocyte growth factor (HGF) is a regenerative protein involved in tissue protection and endothelial repair in response to injury. OBJECTIVES The aim of the study was to assess the effect of increased HGF levels on total and cardiovascular (CV) mortality in patients on peritoneal dialysis (PD) during 6‑year follow‑up. PATIENTS AND METHODS The study included 55 patients (mean age, 53 years; median duration of PD, 24 months). The ejection fraction (EF) and calcium score (CaSc) were measured. White blood cell (WBC) count and albumin, calcium (Ca), phosphorus (Pi), intact parathormone (iPTH), and high‑sensitivity C‑reactive protein (hsCRP) levels were measured. Serum levels of HGF, interleukin (IL) 6, and IL‑18 were determined using enzyme‑linked immunosorbent assays. RESULTS Of all patients, 45% died within 6 years, including 80% from CV complications. HGF significantly correlated with the total (hazard ratio [HR], 1.97; P = 0.03) and CV (HR, 2.04; P = 0.04) mortality in a univariate Cox regression model. This was confirmed by a multiple model including age, dialysis duration, residual renal function (RRF), albumin, Ca × Pi, EF, and CaSc (HR, 2.24; P = 0.02 and HR, 2.58; P = 0.02 for total and CV mortality, respectively). Factors negatively affecting patients' survival included WBC count, hsCRP, IL‑6, and CaSc, while higher albumin levels and EF were associated with longer overall survival. HGF positively correlated with WBC count (r = 0.30, P = 0.01), hsCRP (r = 0.25, P = 0.04), IL‑6 (r = 0.46, P = 0.0004), CaSc (r = 0.29, P = 0.03), and mean arterial pressure (r = 0.25; P = 0.04) and negatively with RRF (r = -0.31, P = 0.02). CONCLUSIONS Increased concentrations of proinflammatory cytokines and an association between HGF levels and CaSc may indicate higher total and CV mortality in patients on PD.

Background Patients with end-stage renal disease (ESRD) suffer from markedly increased cardiovascular morbidity and mortality. Common carotid artery (CCA) intima-media thickness (IMT) assessment and CCA plaque identification using ultrasound are well-recognized tools for identification and monitoring of atherosclerosis. A new method for monitoring the inflammatory status of plaque, namely radiolabeled interleukin-2 (IL-2) scintigraphy, was proposed recently. The aim of this pilot study was to perform 123I-labeled-IL-2 carotid plaque scintigraphy in ESRD patients treated with peritoneal dialysis and to correlate obtained results with ultrasound assessment of CCA and selected inflammatory markers. Methods CCA-IMT was measured and CCA plaques were identified by ultrasound in 10 patients (5 women, 5 men; mean age 62.4 ± 10.4 years; median peritoneal dialysis duration 32.5 months, range 12 – 55 months) with advanced cardiovascular comorbidity. Following CCA ultrasound, 123I-labeled IL-2 carotid plaque scintigraphy was performed. Several biomarkers of inflammation and atherosclerosis were also measured in all patients. Results Mean target/non-target ratio for focal 123I-IL-2 uptake within the plaque was 3.15 ± 0.54, and mean IMT from the site of the scintigraphy analysis was 0.975 ± 0.337 mm. Highly significant correlation was found between CCA-IMT and a target/non-target ratio for focal 123I-IL-2 uptake in a corresponding artery ( R = 0.92, p = 0.01). However, no significant correlations were found between target/non-target ratio for focal 123I-IL-2 uptake and levels of measured biomarkers. Conclusions Our preliminary results suggest potential for identification of an inflamed (vulnerable) plaque using IL-2 scintigraphy in ESRD patients with cardiovascular comorbidities.