Extremely high mortality rates among hemodialysis patients with COVID-19 before the era of SARS-CoV-2 vaccination: results from a large database from the North of Poland.

INTRODUCTION: Preliminary reports suggested high incidence and mortality rates of SARS­ CoV 2 infection in patients receiving kidney replacement therapy. OBJECTIVES: We aimed to describe the incidence and outcomes of COVID­ 19 in hemodialysis patients. PATIENTS AND METHODS: We conducted a retrospective multicenter cohort study on the incidence and mortality of COVID­ 19 in hemodialysis patients as compared with the general adult population in the period from the beginning of the pandemic until the commencement of the SARS­ CoV 2 vaccination program. The study population included all patients who were receiving hemodialysis in any of the 14 dialysis units of Pomerania Province, Poland on December 31, 2019 and all individuals who were starting long­ term hemodialysis between January 1, 2020 and January 31, 2021, amounting to a total of 1567 patients. Data on the general population were obtained from reports of the health authorities. RESULTS: The absolute cumulative incidence of SARS­ CoV 2 infection in hemodialysis patients was 22.4%, and after standardization for age it was 3.98-fold higher compared with the general population (P <0.001). The epidemic trajectory of both groups ran in parallel, but the increase and decline in the number of new cases occurred earlier in hemodialysis patients. The fatality rate of COVID­ 19 among hemodialysis patients was 30.4%. It was the highest among the oldest patients, reaching 43.81% in individuals aged 75 years or older (P = 0.003). Age­ standardized fatality and mortality rates in hemodialysis patients were 5.5- and 10.9-fold higher than in controls, respectively (both P <0.001). CONCLUSIONS: The results of this study show the extremely high mortality rate of COVID­ 19 in hemodialysis patients during the first and second waves of the epidemic in Pomerania Province, before the vaccination era.

Serum myelin basic protein as a marker of brain injury in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Myelin basic protein (MBP) is the second most abundant protein in central nervous system myelin. Since the 1980s, it has been regarded as a marker of brain tissue injury in both trauma and disease. There have been no recent reports regarding MBP in aneurysmal subarachnoid haemorrhage (SAH). METHODS: One hundred four SAH patients with ruptured aneurysms underwent endovascular treatment within 24 h of rupture, and 156 blood samples were collected: 104 on days 0-3, 32 on days 4-6 and 20 on days 9-12 post-SAH. MBP levels were assayed using ELISA and compared with the clinical status on admission, laboratory results, imaging findings and treatment outcome at 3 months. RESULTS: MBP levels on days 0-3 post-SAH were significantly higher among poor outcome patients (p < 0.001), non-survivors (p = 0.005), patients who underwent intracranial intervention (p < 0.001) and patients with intracerebral haemorrhage (ICH; p < 0.001). On days 4-6 post-SAH, significantly higher levels were found following intracranial intervention (p = 0.009) and ICH (p = 0.039). There was clinically relevant correlation between MBP levels on days 0-3 post-SAH and 3-month Glasgow Outcome Scale (cc = - 0.42) and also ICH volume (cc = 0.48). All patients who made a full recovery had MBP levels below detection limit on days 0-3 post-SAH. Following endovascular aneurysm occlusion, there was no increase in MBP in 86 of the 104 patients investigated (83%). CONCLUSIONS: The concentration of MBP in peripheral blood after intracranial aneurysm rupture reflects the severity of the brain tissue injury (due to surgery or ICH) and correlates with the treatment outcome. Endovascular aneurysm occlusion was not followed by a rise in MBP in most cases, suggesting the safety of this technique.

Current epidemiology and practice patterns in prevention and treatment of PD-related infections in Poland.

BACKGROUND: Peritoneal dialysis (PD) related infections are associated with technique failure and mortality. The aim of this multicentre study was to examine epidemiology, treatment and outcomes of PD-related infections in Poland as well as practice patterns for prevention of these complications in the context of current ISPD recommendations. METHODS: A survey on PD practices in relation to infectious complications was conducted in 11 large Polish PD centres. Epidemiology of peritonitis and exit-site infections (ESI) was examined in all patients treated in these units over a 2 year period. RESULTS: The study included data on 559 PD patients with 62.4% on CAPD. Practice patterns for prevention of infectious complications are presented. The rate of peritonitis was 0.29 episodes per year at risk, with Gram positive microorganisms responsible for more than 50% of infections and 85.8% effectively treated. Diagnosis and treatment followed ISPD guidelines however most units did not provide an anti-fungal prophylaxis. Although neither of the centres reported routine topical mupirocin on catheter exit-site, the rate of ESI was low (0.1 episodes per year at risk), with Staphylococcus aureus as most common pathogen and full recovery in 78.3% of cases. CONCLUSION: The study shows rewarding outcomes in prevention and treatment of PD-associated infections, mainly due to a thorough compliance with the current ISPD guidelines, although some deviations from the recommendations in terms of practice patterns have been observed. More studies are needed in large numbers of patients to differentiate the importance of specific recommendations and further support the guidelines.

Clusterin, a New Cerebrospinal Fluid Biomarker in Severe Subarachnoid Hemorrhage: A Pilot Study.

BACKGROUND: Inflammation following subarachnoid hemorrhage (SAH) involves numerous mediators with biomarker properties. Preliminary studies indicated that clusterin, a multifunctional chaperon protein, was a potential biomarker in SAH. We aimed to clarify the status of clusterin in SAH. METHODS: From 27 patients with severe SAH, 47 cerebrospinal fluid (CSF) samples were collected 0-3, 5-7, and 10-14 days after SAH. Control CSF was collected from 25 age- and sex-matched healthy control subjects undergoing spinal anesthesia for minor surgery. Clusterin concentrations were assayed using enzyme-linked immunosorbent assay and compared with inflammatory markers, imaging findings, and treatment outcome. RESULTS: In healthy control subjects, mean CSF clusterin level (1908.5 ng/mL ± 36.0) was significantly higher than in the patient group (P < 0.001). In the patient group, mean clusterin level was 741.1 ng/mL ± 759.2 0-3 days, 601.6 ng/mL ± 507.2 5-7 days, and 639.2 ng/mL ± 446.8 10-14 days after SAH. Clusterin level failed to differentiate between good (Glasgow Outcome Scale 4-5) and poor (Glasgow Outcome Scale 1-3) outcomes 0-3 days and 10-14 days after SAH (P = 0.238 and P = 0.225), but significantly higher levels of CSF clusterin were found 5-7 days after SAH in patients with good outcome (P = 0.017). There was a significant correlation between CSF clusterin level 5-7 days after SAH and Glasgow Outcome Scale at 3 months (correlation coefficient = 0.633). The best correlation was found for World Federation of Neurological Societies scale (correlation coefficient = -0.741). CONCLUSIONS: SAH is associated with immediate decrease in CSF clusterin concentrations. Clusterin level at one point was a good predictor of outcome, and it may serve as a biomarker.

Impact of gender and dialysis adequacy on anaemia in peritoneal dialysis.

PURPOSE: In the general population, haemoglobin (Hb) concentration is higher in men than in women. However, target Hb levels in dialysis patients are set constant regardless of the patient's sex. The aim of this study was to evaluate Hb concentration and the use of erythropoiesis-stimulating agents (ESA) in peritoneal dialysis (PD) patients taking gender and dialysis adequacy into account. METHODS: The study comprised two parts. The first was a cross-sectional analysis of Hb and ESA in 2180 prevalent PD patients. The second included 88 incident PD patients, followed for 36 months. During this time, the major parameters recorded at 12-month intervals included: Hb concentration, weekly ESA, total, renal, and peritoneal Kt/V. Erythropoietin resistance index (ERI) was calculated as the ratio between ESA dose and achieved Hb. RESULTS: In prevalent PD patients, Hb concentration was significantly lower in women, (11.2 ± 1.4 vs. 11.5 ± 1.6 g/dl; p < 0.001), despite higher doses of ESA (2691 ± 1821 vs. 2344 ± 1422; p = 0.001). Hb concentrations were related to dialysis adequacy in both cohorts. However, despite significantly higher Kt/V, women were characterized by a lower Hb level. In incident patients, this association was present throughout the observation period, while the ESA dose in women was significantly higher at every time point. In multiple regression analysis, gender was an independent determinant of ERI (b = 0.34; p < 0.05). CONCLUSIONS: Despite higher dialysis adequacy, Hb concentration in women treated with PD is significantly lower, and the ability to correct it impaired, as compared to men.

Peritoneal dialysis as a treatment option in autosomal dominant polycystic kidney disease.

PURPOSE: When choosing a dialysis option for ADPKD patients, peritoneal dialysis (PD) is often discouraged, due to its potential drawbacks: risk of abdominal hernias and dialysis fluid leaks, risk of peritonitis and insufficient dialysis adequacy. The present study was designed to compare the outcomes and dialysis efficacy in ADPKD patients treated with PD, in comparison with non-ADPKD subjects. METHODS: This study was a retrospective analysis of the data from the national PD registry in which 106 ADPKD and 1606 non-ADPKD incident PD patients were evaluated. Data on dialysis adequacy, risk of dialysis-associated complications, as well as patient and technique survival were compared between the groups. RESULTS: The ADPKD patients did not differ from the non-ADPKD controls in terms of dialysis adequacy. After a median observation time of 32 months, there were no differences in patient or technique survival. The risk of abdominal hernias and dialysis fluid leaks was twice as high in ADPKD subjects, compared to the non-ADPKD group. However, these complications did not result in a need for a permanent transfer to hemodialysis. CONCLUSIONS: Dialysis adequacy, and patient and technique survival are similar in the ADPKD and non-ADPKD patients treated with PD. PD seems a feasible treatment option for end-stage renal failure in the course of ADPKD.

Plasma total homocysteine is a determinant of carotid intima-media thickness and circulating endothelial progenitor cells in patients with newly diagnosed hypertension.

BACKGROUND: Accumulating evidence suggests that elevated plasma homocysteine (Hcy), prevalent in hypertensive patients, affects oxidant/antioxidant balance of the body, and is linked to the development of atherosclerosis, inflammation, and endothelium injury. Our objective was to examine a hypothesis that Hcy is a predictor of total antioxidant status (TAS) and endothelial progenitor cells (EPCs), important in the repair of injured endothelium, in hypertensive patients. METHODS: This study was conducted with newly diagnosed essential hypertension patients (n=42) and healthy controls (n=20). Anthropometric and biochemical characteristics, including plasma Hcy, lipids, TAS, and C-reactive protein (CRP) were quantified. Intima-media thickness (IMT) was assessed in carotid arteries. Blood derived EPCs were quantified using an in vitro culture assay. RESULTS: Hcy, IMT, and CRP were significantly elevated while TAS and EPCs were significantly lower in hypertensive patients compared with controls. In multivariate regression analysis Hcy was a predictor of IMT of carotid artery and EPCs number. CONCLUSIONS: Our results suggest that Hcy might increase carotid artery IMT by reducing EPCs numbers. Possible involvement of Hcy in the reduction of EPCs number in hypertensive patients might be in part mediated by Hcy influence on the TAS.

Plasma tissue factor and tissue factor pathway inhibitor in patients with primary glomerulonephritis.

OBJECTIVE: Nephrotic syndrome (NS) is associated with numerous blood coagulation abnormalities and a marked predisposition to thromboembolism. Fibrin formation within the glomeruli occurs in various forms of human and experimental glomerulonephritis and may play an important role in progressive glomerular injury. The aim of this study was to measure the plasma concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) and intravascular thrombin generation markers and to analyze their relationships in patients with primary glomerulonephritis. MATERIAL AND METHODS: The study population comprised 57 patients (mean age 35.2 years; range 18-63 years) with primary glomerulonephritis: 36 with NS (NS group) and 21 without (non-NS group). The control group consisted of 24 sex- and age-matched healthy volunteers. TF and TFPI antigen, prothrombin fragment F 1+2 (PF 1+2) and thrombin-antithrombin III complex (TAT) concentrations in plasma were estimated using commercially available kits. RESULTS: Serum TF and TFPI concentrations in both the NS and non-NS groups were higher than those observed in the control group. Moreover, there were significant differences in TF and TFPI concentrations between the NS and non-NS groups. TF:TFPI ratios in both the examined groups were constant and significantly higher than those in the control group. Positive correlations between TF and both PF 1+2 and TAT concentrations in the total cohort of patients were shown. Furthermore, a positive correlation between TF and TFPI concentrations was observed. CONCLUSIONS: Our data support the hypothesis concerning activation of coagulation pathways in patients with primary glomerulonephritis. An inadequate TFPI concentration as a result of an elevated TF:TFPI ratio characterizes not only patients with clinical manifestations of NS but also patients with mild proteinuria.

[Can platelets be synthetized from nucleotides?]. / Czy plytki krwi sa zdolne do syntezy nukleotydów?

In light of the existing knowledge platelets are not able to de novo synthesis of nucleotides. However single report exists about the possession by thrombocytes of the full enzymatic complex, which is essential to such synthesis. An aim of our study was the estimation of the platelets nucleotide pool of patients subjected to immunossuppresion therapy using azathioprine and mycophenolate mofetil, drugs known to block enzymes of de novo synthesis pathways. Fifty-nine patients enrolled to a study were divided to three groups: hemodialysed patients (n = 28), patients after kidney transplantation receiving azathioprine (n = 16) and kidney transplanted patients receiving mycophenolate mofetil (n = 16). Platelets nucleotides concentration was measured using HPLC. In the group of patients after the kidney transplantation receiving AZA concentration of adenine and guanine nucleotides in thrombocytes were statistically lower both with relation to hemodialysed as and with relation to the healthy group. Similarly platelets of patients after the kidney transplant receiving MMF characterized lower adenine and guanine nucleotides concentration comparatively to hemodialyzed patients. One showed also lower ADP, GDP and AMP concentration with relation to of the healthy volunteers. One from possible reasons of the obtainment of above results can be the possession by platelets enzymes, which are vital to de novo nucleotides synthesis.

Mycophenolate mofetil treatment following renal transplantation decreases GTP concentrations in mononuclear leucocytes.

MMF (mycophenolate mofetil) has been proven to provide an effective immunosuppression by non-competitive selective reversible inhibition of IMPDH (inosine monophosphate dehydrogenase), the enzyme playing a crucial role in GTP biosynthesis. However, the exact metabolic changes induced by inhibition of IMPDH in target cells of the immune system have been the subject of recent debate. The aim of the present study was to evaluate whether MMF treatment produced sustained changes in the guanosine nucleotide pool of MNLs (mononuclear leucocytes) in vivo. Sixty-two renal failure patients were divided into three groups: chronic renal failure patients undergoing haemodialysis (CRF-HD; n=20) and two groups of patients after renal transplantation, the first on AZA (azathioprine; TN-AZA; n=23) and the second treated with MMF (TN-MMF; n=19). In addition, MNLs from 25 healthy subjects were analysed as controls. Anion-exchange HPLC was used to quantify purine and pyrimidine nucleotides in MNLs. We report a significant decrease in GTP and the total MNL guanine nucleotide pool in the TN-MMF group (P<0.05) compared with control, CRF-HD and TN-AZA groups, although no significant differences were found between any of the other groups. Adenine nucleotide concentrations in MNLs were decreased in the TN-AZA group, but not in the TN-MMF group compared with the CRF-HD group and controls. There were no differences in CTP concentrations, but UTP concentrations were decreased in the CRF-HD, TN-AZA and TN-MMF groups compared with controls. MMF caused a significant and sustained decrease in the guanine nucleotide pool in MNLs from renal transplant recipients. This decrease contrasts with the elevation in GTP reported in erythrocytes of MMF-treated patients.

Mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, causes a paradoxical elevation of GTP in erythrocytes of renal transplant patients.

The immunosuppressant MMF (mycophenolate mofetil) has increasingly replaced AZA (azathioprine) in renal transplantation. MMF is a prodrug of MPA (mycophenolic acid), which inhibits lymphocyte IMPDH (inosine monophosphate dehydrogenase), thereby drastically decreasing GTP concentrations essential to lymphocyte proliferation in vitro and in vivo. Erythrocyte GTP concentrations are commonly elevated in severe renal disease, but normalize following successful engraftment. Consequently, elevated GTP in renal transplant recipients might signal impending loss of immunosuppression and graft failure. In the present study, we compared erythrocyte nucleotides and plasma metabolites in two groups of 25 patients after renal transplantation, both receiving prednisolone and cyclosporin A, but one group receiving MMF and the other AZA. No patients had recent allograft biopsy evidence of rejection. Erythrocyte GTP concentrations at MMF commencement were 50.4+/-23.4 micromol/l. An increase occurred during the first 3 months after transplant when MMF was used de novo, stabilizing at 146.7+/-62.9 micromol/l after 4 months. This was significantly higher (P=2.5 x 10(-6)) than erythrocyte GTP (40.4+/-15.9 micromol/l) in the AZA group, which was essentially unchanged from values immediately after successful transplantation. The effect of MMF on erythrocyte GTP levels was reversible, since GTP levels fell when MMF therapy was terminated. The results demonstrate paradoxically high GTP concentrations in erythrocytes of renal transplant patients receiving MMF. MPA may stabilize reticulocyte IMPDH, allowing the protein to persist during erythropoiesis. This behaviour is in marked contrast with the decrease in GTP levels seen in white blood cells of patients on chronic MMF therapy.