Equine asthma syndrome is a cost-consuming equine respiratory disease of the lower airways in horses. Non-invasive biomarkers from blood or urine are sought. The aim of this study was to assess the circulating immune complexes (CICs) during the exacerbation and remission of an asthma episode—with and without additional treatment and the potential usefulness of CIC levels in the diagnosis, monitoring, and treatment progression. The control group, asthma group, and treated asthma group each contained six horses. The horses were kept in a dusty environment for seven days and then moved to an asthma-friendly environment for over three weeks (the treated group received injections of glucocorticoids). Blood was collected at baseline and on the 1st, 2nd, 3rd, 7th, 14th and 30th days. CICs measured in the time points did not show statistical differences. When CICs were analysed within the groups, there was a significant decrease in CIC in the treated group and a significant increase in CIC in the non-treated group on day 30. CIC did not support the diagnosis procedure of equine asthma syndrome, although it may help in monitoring patients with and without treatment. To the best of the authors’ knowledge, this is the first study to analyse the dynamics of CIC in equine asthma patients during an environmental challenge, remission, and treatment.Non-invasive diagnostic biomarkers of equine asthma syndrome (EAS) from blood or urine are sought. The aim of this study was to assess the absorbance of circulating immune complexes (CICs) during the exacerbation, remission, and treatment of an asthma episode and assess the potential usefulness of CIC levels in the diagnosis and monitoring of the disease. The control group, asthma group, and treated asthma group each contained six horses. Following an initial examination and group classification, the horses were kept in a dusty environment for seven days and then moved to an asthma-friendly environment for three weeks (the treated group received injections of glucocorticoids). Blood was collected at baseline and on the 1st, 2nd, 3rd, 7th, 14th and 30th days. CIC was measured using the modified Haskova method. The time points did not show significant statistical differences. There was a significant decrease in CIC in the treated group, and a significant increase in CIC in the non-treated group on day 30. CIC did not support the EAS diagnosis, although it may help in monitoring patients. To the best of the authors’ knowledge, this is the first study to analyse the dynamics of CIC during environmental challenge, remission, and treatment. Equine asthma syndrome, which appears in light/moderate and severe forms, is most commonly diagnosed in a temperate climate ,2. SeverUnlike human asthma, a type 1 hypersensitivity response is not observed after an environmental challenge in asthmatic horses. Higher histamine activity observed in the lungs of horses approximately five hours after exposure to an allergen suggests a type 3 hypersensitivity response . ResearcNevertheless, a major consequence of T cell activation is neutrophil recruitment into the airways . The subEquine asthma syndrome requires a comprehensive clinical approach based on a detailed history, a thorough clinical examination, and some ancillary tests. Due to quite invasive disease diagnostics, especially in severely asthmatic patients, there is a great need for biomarkers to facilitate a diagnosis based on blood analysis. Lately, researchers have also focused on exhaled breath gas and exhaled breath condensate (EBC) and its chemical and metabolomic analysis ,11,12.Researchers are focusing more on research based on blood analysis, because it is material that is quite easily obtained in field practice. The formation of circulating immune complexes (CICs) is caused by a basic defence response against endo- and exogenous antigens. The CIC aims to eliminate antigens and present them to immunologically competent cells. CIC detection allows the assessment of the immunological status of patients ,14. In hIn the available literature, there are few studies on circulating immune complexes in horses. In recent years, research has been published on the concentration of CICs and antigen masses on a group of 42 healthy horses . Some stThe aim of this study was to assess the serum absorption of circulating immune complexes during the exacerbation and remission of an asthma episode in asthmatic patients with and without additional treatment. In addition, the usefulness of CIC levels in monitoring the disease progression and treatment was assessed.A consent of the Wrocław II Local Ethic Committee was obtained for this study . The owners were informed about the study design and the risks, the owners’ consent was obtained.Eighteen horses were included in the study. The horses were divided into three groups: the control group, untreated asthma patients, and treated asthma patients. The control group (group 1) contained six healthy adult horses: four mares and two geldings, from 4 to 9 years of age. Groups 2 and 3 contained animals diagnosed with severe equine asthma. Group 2 included six adult horses that did not undergo treatment during the study period. There were three mares and three geldings, from 11 to 18 years of age in the group. One of the mares was euthanised due to severe colic with no consent for surgical approach from the owner. Group 3 contained six adult horses, from 4 to 8 years of age, four mares and two geldings. Those animals were treated pharmacologically during the experiment.Only animals with no known comorbidities or pathological symptoms other than asthma (for the asthma groups) were qualified in the study.Each animal underwent a full preliminary procedure, to determine whether the horse was clinically healthy or had severe equine asthma. The animals were firstly qualified for preliminary procedures by the patient history and clinical symptoms. After the full preliminary procedures, only animals that clearly qualified as healthy or with severe equine asthma were included in the study. This procedure consisted of a detailed history, a clinical examination, basic blood tests, arterial blood gasometry, respiratory endoscopy and bronchoalveolar lavage. Samples of 25 mL of venous blood were obtained from the jugular vein using a 1.2 mm needle (18 G) and a 25 mL syringe. The arterial blood samples were obtained from the transverse facial artery with a 0.8 mm (21 G) butterfly needle and a heparinized 2 mL syringe. The arterial blood gas analysis  was performed immediately after blood collection using the Osmotech OPTI Blood Gas Analyser .g. A smear from the sediment was stained according to the May–Grunwald–Giemsa method.The horses were sedated with 0.6–1 mg/kg bw xylazine  and 25–50 μg/kg bw butorphanol . The endoscopy was performed using a 180 cm-long video endoscope with an outside diameter of 9 mm  and a Karl Storz GarstoPack portable light source . During the endoscopy, the appearance of the tracheal mucous membrane, as well as the mucus coloration and amount, were rated. The bronchoalveolar lavage was performed with a special catheter—a bronchoalveolar lavage catheter . A total amount of 300 mL 0.9% sodium chlorate  was passed into the lungs and withdrawn into the syringe. The obtained material (over 50% of the fluid was retrieved from each horse) underwent cytological analysis on the same day, following transportation on ice. The samples were centrifuged for 5 min at 2000× The cytological assessment was based on a 400-cell leukocyte differential percentage count according to the standard equine asthma diagnostic procedure .The clinical and endoscopic score was analysed using the modified Tilley score  Appendi. Only anThe study lasted for over four weeks. During the first seven days, asthma symptoms were exacerbated in the sick animals by an environmental challenge. The control group was kept under the same conditions as the sick animals. During the environmental challenge, the horses were kept in stables for the majority of the day (20–22 h). Straw was used as bedding, the horses were fed poor quality, dusty hay, and dry concentrated feed. Following the period of symptom exacerbation, the horses were kept in asthma-friendly conditions. Asthma-friendly environmental changes were implemented starting from day 8, and the animals were pastured for the majority of the day (8–12 h). Non-dusty bedding was used, and they were fed good quality hay that had been soaked for 20–30 min and wet concentrate feed. The patients were kept in the asthma-friendly environment for over three weeks. In the third group, the horses also received an intravenous treatment, starting from day 8, with steroid drugs containing dexamethasone sodium phosphate, which was initially administered at 0.096 mg/kg (day 8), followed by a second dose at 0.062 mg/kg (day 9) and a third dose at 0.031 mg/kg (day 10) .Blood samples were obtained from the external jugular vein at the beginning of the experiment (T0), 24 h after beginning the environmental challenge (T1), and 48 h (T2), 72 h (T3), 7 days (T7), 14 days (T14) and 30 days after commencing the experiment (T30) . Tubes wThe collected blood was assessed on the day of collection. The remaining blood (both plasma and serum) was centrifuged and divided into 0.6–1.7 mL portions and frozen at −80 °C until further analysis.The venous blood haematology analysis was carried out using the ABC Vet equipment . The biochemistry blood test at the baseline was performed using the Konlab PRIME 30i . The total bilirubin (BILI-T), urea, creatinine, albumin, total protein, glucose, total calcium, iron, sodium, potassium, chloride, magnesium, bile acids, aspirate aminotransferase (ASPAT), alanine aminotransferase (ALAT), gamma-glutamyl transpeptidase (GGTP), and creatinine kinase (CK) parameters were assessed.g at 4 °C. The obtained sediment was washed with 2.5% PEG and centrifuged for 15 min at 24,000× g at 4 °C. The sediment was dissolved in 2 mL of a 0.1% sodium hydroxide solution (NaOH). The optical density was measured at a wavelength of 280 nm using the option of a pathlength correction with a µQuantum ELISA-Microplate reader  and the Greiner UV-Star microplate.The detection and quantification of circulating immune complexes was performed using a modified method with polyethylene glycol (PEG) according to Hašková et al. . In ordeThe CICs were precipitated using PEG6000 as described before, in the serum of 6 horses containing different concentrations of CIC—three with elevated  and three with normal levels of CIC . Concentration of CIC in examined samples: No: 1, 0.0192 mg/mL; 2, 0.0378 mg/mL; 3, 0.166 mg/mL; 4, 0.206 mg/mL; 5, 0.016 mg/mL; 6, 0.149 mg/mL.The precipitated CICs were washed twice with 2 mL of 2% PEG6000 solution and centrifuged again. The precipitates were dissolved with NaOH solution or dissociation buffer. The presence of equine IgG in CIC was confirmed using double immunodiffusion, counter-current immunoelectrophoresis, SDS-PAGE gel electrophoresis, and immunoblotting.CICs precipitated from serum samples with PEG were washed twice and solubilized in NaOH. CICs were added to respective wells cut in 1.2% Agar Oxoid gel diluted in 0.15 M veronale buffer, pH 8.2. The central well was filled with goat anti-equine IgG antiserum  The plate was incubated in a wet chamber for 24 h at room temperature and for 24 h at 4 °C. Subsequently, the plates were washed in PBS, dried, and stained with amido-black.IEF was performed in 1.2% Agar Oxoid gel diluted in 0.15 mol veronale buffer, pH 8.2, at stable voltage (100 V) for 75 min. Then, 20 µL of solubilized CIC was mixed with 10 µL of 0.1% sodium dodecyl sulphate solution and incubated for 10 min and then added to the wells at (−). The goat anti-equine IgG antiserum was added to the wells located at a distance of 11 mm to (+). The plate was than incubated in a wet chamber for 24 h at room temperature, washed with PBS for 24 h at 4 °C, dried, and stained with amido-black.g; 4 °C), the precipitates (CIC) were dissolved/resuspended in 200 μL of dissociation buffer . Then, the samples were heated at 100 °C for 5 min and centrifuged for 10 min at 10,000× g. The CIC samples were separated by SDS-PAGE gel electrophoresis in 7% polyacrylamide gels (~50 μg/lane). At the end of the electrophoretic run, separated proteins were stained with Coomassie Brilliant Blue R 250. Gel documentation was made using ChemiDoc XRS+ Instruments (BioRad). The molecular weights of proteins were estimated using Image LabTM software (BioRad) by comparison with standard protein markers (Spectra Multicolor Broad Range Protein Ladder BR or HR).After centrifugation  resuspended in 200 μL of dissociation buffer  were separated by SDS-PAGE gel electrophoresis in 7% polyacrylamide gels and transferred onto nitrocellulose membranes (Sigma Aldrich) . Membrane was blocked using Western blot blocking buffer . The membrane was incubated with the goat anti-equine IgGb  for 90 min at RT. The reaction was developed using ECL substrate (BioRad). The membrane visualisation was performed using Gel Doc XR Instruments (BioRad). The molecular weights of proteins were estimated using Image LabTM software  by comparison with standard protein marker .All statistical analyses were performed using the R statistical package for Windows  using non-parametric tests .The analysis of qualifying tests and the analysis of the differences in the absorbance of CIC between the groups were carried out using the Kruskal–Wallis test, with a post hoc analysis using the Conover method.An analysis of the changes over time was conducted using linear mixed models. In addition, time models for the entire population were created.The severity of the severe equine asthma was assessed according to the modified Tilley et al. scale, using the scored evaluation of clinical symptoms and endoscopic examination . The useThe cytological analysis of the bronchoalveolar lavage fluid, based on the percentage of leukocyte differential counts, showed a significantly increased number of neutrophilic cells in asthmatic horses (treated and untreated asthma groups) and a significantly higher proportion of macrophages in the control group. The results are presented in The arterial blood gas analysis revealed significant differences in the partial oxygen concentration. However, the partial pressure of carbon dioxide and saturation did not differ significantly between the groups. The results are presented in The analysis of the haematologic results from venous blood did not show statistically significant differences between the experimental groups .The analysis of the biochemical results from venous blood did not show statistically significant differences between the experimental groups .At all the time points , there were no significant differences between the groups. The results are presented in p < 0.001)) as well as a significant increase in the OD280 mm absorbance in T30 in the untreated group from T0 median = 0.240  to T30 median = 0.332  (p = 0.016)). In the control group, a significant decrease in the CIC was noted already at T7: from T0 median = 0.248  to T7 median = 0.228  with (p = 0.004), to T14 (p = 0.0302) and T30 (p = 0.0288). The results are presented in The analysis of changes over time showed that there was a significant decrease in the OD280 mm absorbance at the T30 point in the asthma-treated group from T0 median = 0.304  to T30 median = 0.151  ; heavy chain of IgG antibody  and light chain of IgG antibody . Immunoblotting analysis revealed the reactions with a heavy chain of IgG antibodies (data not shown).Research on the development and progression pathomechanisms of asthma, both in humans and in horses, is frequently conducted. This is associated not only with the economic impact of the disease on the sports and racing industry, but also with the fact that horses are a natural animal model in research on asthma in humans. The long life expectancy of these animals (30–35 years) allows for the long-term observation of sick animals, the evaluation of their inflammatory response, and the analysis of airway remodelling secondary to a naturally occurring disease, which is not seen in other animals such as mice or rats .2 reduction in patients with advanced asthma symptoms [All the horses were divided into the experimental groups based on the results of the qualifying diagnostic procedures according to commonly used criteria. No animals with other diseases, such as orthopaedic problems, that could potentially disturb the result of the assessed parameter, were included in the study. The clinical and endoscopic scores were assessed using the modified point scale, according to Tilley et al. . All thesymptoms ,26. Accosymptoms . Due to symptoms . The anisymptoms . The aniCirculating immune complexes form the basis of widespread research. Available scientific reports focus on the total number of complexes, specifically defined types of complexes such as IgE-containing complexes, as well as complex analysis after separation.The clinical significance of the detection of circulating immune complexes has been linked to many health problems, such as allergies, autoimmune diseases, tumours, cardiac, dermatological, endocrinological, haematological nephrological, neurological, ophthalmological, parasitological, pulmonary, reproductive, transplant and infectious diseases .It is believed that long-term therapy with corticosteroid drugs prolongs the circulation of immune complexes and delays their elimination in humans . In the In human medicine, circulating immune complexes were observed in 28% of patients with bronchial asthma and in 20% of patients with atopic asthma . The meaIn children with asthma, an increase in the levels of free and bound CIC IgE with normal concentrations of IgG, IgA and IgM were observed . ElevateThe tests carried out on the clinically healthy horses revealed the content of CIC in the serum in the form of a mean extinction value at E450 nm. In the studied group of horses, this amounted to 0.278 (±0.096). . Due to In the horses with secondary arthritis, 82% had detectable CICs in serum and 77% had them in the synovial fluid. In 64% of patients, the value of CIC was elevated in both serum and synovial fluid . In studIn the presented study, the CIC absorbance did not differentiate patients in the control group from sick animals. It does not correlate with an earlier study performed on Polish Konik horses . This maTo the best of the authors’ knowledge, this is the first study to analyse the dynamics of CIC during an environmental challenge, remission, and treatment. A significant decrease in the absorbance value at the T30 time point in the treated asthma group as well as a significant increase in the absorbance value at T30 in the untreated asthma group were observed. The above results may suggest the utility of the assessment of CIC in monitoring the course of asthma. In human medicine, the usefulness of monitoring CIC levels in response to therapy in various disease entities has been noted, including Hodgkin’s lymphoma, tumours, tuberculosis and borreliosis ,37,38. TBased on the presented study, the following conclusions have been reached: the circulating immune complexes did not show straightforward utility as biomarkers in the laboratory diagnosis of equine asthma; and circulating immune complexes may become a useful parameter in monitoring the progress of asthma therapy in horses. Further research on a larger group of animals in order to determine the possibility of monitoring the progress of therapy in field practice with the help of circulating immune complexes is warranted.


Chronic Kidney Disease is a worldwide public health problem that affects millions of people from all racial and ethnic groups. Identification of a Chronic Kidney Disease is a major risk factor for cardiovascular morbidity and mortality and is attributed to hyperuricemia. Evidences show that high serum uric acid contribute directly to glomerulosclerosis, interstitial fibrosis and atherosclerosis that correction of hyperuricemia associated with Chronic Kidney Disease will slow the progression of chronic renal failure. This study is done to correlate between serum uric acid level and estimated glomerular filtration rate in chronic kidney disease patients.A hospital based cross-sectional study on chronic kidney disease patients including 57 patients on conservative treatment attending Bir Hospital with diagnosis of chronic kidney disease was performed. Detailed clinical history, examination and investigations including uric acid were done. Chronic Kidney Disease staging was done according to estimated glomerular filtration rate estimated by Cockcroft-Gault equation. Prevalence rate of hyperuricemia in Chronic Kidney Disease and its stages were calculated and compared with each other.A total of 57 Chronic Kidney Disease cases were enrolled, with male to female ratio of 2:1 and mean age 51.63±17.75 years. Hyperuricemia was present in 55 (96.49%) of study population. Though prevalence of hyperuricemia increased with Chronic Kidney Disease stage, there was no significant difference in mean value of uric acid in different stages. Hyperuricemia and stages of Chronic Kidney Disease had negative correlation which was statistically significant.Hyperuricemia is highly prevalent among Chronic Kidney Disease patients with conservative management. The severity of hyperuricemia increases as Chronic Kidney Disease stage progresses. Kidney damage refers to a broad range of abnormalities of kidney resulting in decline of excretory, endocrine and metabolic functions. KDIGO refers to a eGFR<60 ml/min/1.73m4 Evidence reported on an association of uric acid with hypertension and renal disease.5 It is a potent antioxidant outside cell, pro-oxidant inside cell and induce stimulation of NADPH oxidases with mitochondrial dysfunction.6 It leads to arteriosclerosis, glomerular hypertension and glomerulosclerosis and progress CKD.7Chronic hyperuricemia is strongly associated with chronic tubulointerstital disease and decreased renal function.This study is done to know the prevalence of high serum uric acid level in chronic renal disease and to correlate between severity of the renal disease and serum uric acid level.It is a hospital based cross-sectional study. It comprises 57 patients with CKD on conservative management who attended Department of Nephrology, Bir Hospital from May 2015 to April 2016. The study was performed after approval from the Institutional Review Board at our hospital and taking written, informed consent from all the patients. All cases of CKD stage- 3,4,5 who were on conservative management were included. Excluded cases were: 1. Renal transplant patients, 2. Patients on uric acid lowering drugs, 3. CKD patients on hemodialysis and 4. Patients not willing to give consent.Non-random sampling technique was applied. Patients admitted and attending outpatient department in hospital with clinical, biochemical and sonographic evidence of CKD were taken. Sample size was calculated using following formula:n= required sample sizeZa= z deviated corresponding to desired reliability level (1.96)8P= estimated proportion in the population (10.6%)Q= 100-P (if P is in %)d = maximum tolerable error (10%)WhereCKD staging is done as following  . A detaData was tabulated and interim analysis was performed after the reports of 10 cases are available. All the analysis were carried out using standard statistical software SPSS 20 version and Microsoft Excel. Results are presented in tables, graphs and diagrams. Results were expressed as mean±SD. Prevalence rate of hyperuricemia in CKD and its stages were calculated and compared with each other. Statistical analyses included the unpaired t-test (for continuous measures) and the Chi-square tests for categorical assessed. For the purpose of this study a 95% confidence interval was accepted and a P<0.05 was taken as significant.Out of 57 patients, 38 were male and 19 were female. The mean age for the total number of patients was 51.63 years. Hyperuricemia was present in 55 (96.49%) of the patients .The mean uric acid level in men was 9.38±1.403 mg/ dl and mean uric acid level in female population was 8.86±1.13 mg/dl .The mean uric acid level in stage 3 CKD in female population was 12 mg/dl and in men population was 8.67 mg/dl. In stage 4 CKD mean uric acid level in female was 8.76 mg/dl and in men was 9.24 mg/dl and in stage 5 CKD mean uric acid level in female was 8.55 mg/dl and in men was 10.15 mg/dl .Of the study population 15 (26.31%) had hypertension, 6 (10.52%) had hypertension and DM, 18 (31.6%) had hypertension and smoking, 2 (3.5%) had DM, 9 (15.8%) had hypertension, DM and smoking and 2 (3.5%) were only smokers .2. The mean serum uric acid of the study participants was 6.5±1.9 mg/dl.9This study has evaluated prevalence of hyperuricemia in Chronic Kidney Disease. Patients in a cohort of 57 subjects, out of which 38 patients (66.7%) were male and 19 patients (33.3%) were females. In this study, hyperuricemia was present in 96.49% of study population while 3.51% has normal serum uric acid. The mean serum uric acid in the study population was 9.213 mg/dl. Similar study done by Jolly ES et al. in which a 1078 participants was analysed in Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study in which the participants were followed for 4 years. Sixty three (13%) of the participants had CKD. The mean age of the participants having CKD was 63 years. Forty seven (63%) of them had HTN and 7 (9%) had DM. BMI of the CKD patients was 28.5 kg/m10In the study done by Paudel YP et al. at Kist Medical College and Teaching Hospital in Kathmandu involving 150 CKD patients, found 57% male, 43% female, mean age was 48.62±18.09 years. The mean uric acid level was 5.96±2.22mg/dl. In this study, the prevalence of hyperuricemia in various stage was CKD stage 3–24.6%, stage 4–40.4% and stage 5–35% study population. There is no significant difference in the mean value of serum uric acid in the various stages of CKD.11Similar study done by Adejumo OA et al, prevalence of hyperuricemia in stage 3 CKD patients was 33.4%, stage 4–40.8%and stage 5–21.7%. In this study, mean creatinine level of the patient was 4.1298 mg/ dl. The mean systolic BP was 156.3860 mm of Hg and mean diastolic BP was 93.7544 mm of Hg. Out of 120 patients, 57 of the patients had high serum uric acid level. The prevalence of hyperuricemia was 47.5%.12 The association was more pronounced in hypertensive subjects compared to normotensive individuals. In this study the most common cause for CKD was hypertension 57.89% of studied population had HTN. Hypertension and DM both were present on 27.31% of the patient. DM alone was present on 3.5% of the patients. The remaining 12.28% of the patient had other causes for CKD. In the study done by Adejumo OA et al. involving 120 patients the causes of CKD were that 37.8% of the patient had hypertensive nephropathy, 30% had diabetic nephropathy, 27.5% had chronic glomerulonephritis and 5.8% had other causes for CKD.Most of the patients in our study were hypertensive, so it can be concluded that hyperuricemia may lead to the progession of CKD faster in hypertensive patients. Study done by Sedaghat S et al. in a prospective cohort showed that high levels of serum uric acid are associated with faster decline in eGFR and increased incidence of CKD.This study showed that hyperuricemia is highly prevalent among CKD patients with conservative management. Though this study showed increasing prevalence of hyperuricemia with increasing stage of CKD (stage III to V), the mean value of uric acid did not show significant difference among different stages. Further studies without above mentioned limitation and including larger group are needed.None.


In emergency medicine, blood pressure is often measured by an oscillometric device using an upper arm cuff. However, measurement accuracy of this technique in patients suffering from hypotensive shock has not been sufficiently evaluated. We designed a prospective observational study investigating the accuracy of an oscillometric device in hypotensive patients admitted to the resuscitation area of the emergency department. Patients admitted to the resuscitation area of a university hospital, who were equipped with an arterial catheter and found to be hypotensive  < 60 mmHg) were eligible for the study. Blood pressure was measured simultaneously via upper arm cuff and invasively under routine clinical conditions. After data extraction, Bland–Altman analysis, correlation coefficient and percentage error of mean and systolic blood pressure pairs were performed. We analysed 75 simultaneously obtained blood pressure measurements of 30 patients in hypotension, 11 (37%) were female, median age was 76.5 years (IQR 63–82). Oscillometric MAP was markedly higher than invasive MAP with a mean of the differences of 13 ± 15 mmHg (oscillometric—invasive), 95% limits of agreement − 16 to 41 mmHg, percentage error was 76%. In 64% of readings, values obtained by the upper arm cuff were not able to detect hypotension. Oscillometric blood pressure measurement is not able to reliably detect hypotension in emergency patients. Therefore, direct measurement of blood pressure should be established as soon as possible in patients suffering from shock. Shock is defined as a “life threatening, generalised form of acute circulatory failure associated with inadequate oxygen utilisation by the cells” . The preThe reference method for arterial blood pressure in critical conditions is the direct measurement by an arterial catheter. However, usually only critically ill patients in the resuscitation area or on intensive care unit (ICU) are equipped with an arterial catheter. In emergency medicine, both in and out of the hospital, a patient’s blood pressure is measured noninvasively via an upper arm cuff. The noninvasive determination of blood pressure can be performed either manually or automatically. Automatic devices nowadays are commonly based on an oscillometric algorithm embedded in the device. Big database analyses showed that oscillometric techniques fail to reliably reflect very low or very high blood pressure values by overestimating low values and underestimating high values . HoweverThe aim of this prospective observational study was to investigate the accuracy of noninvasive oscillometric blood pressure measurement in hypotensive patients admitted to the emergency department. The local ethics committee  approved the study under the Protocol Number 751-15 on 8th February 2016. The need for written informed consent prior to study inclusion was waived due to the emergency setting and the purely observational character of the investigation. In the follow up, subjects who survived and regained consciousness by hospital discharge were asked to participate in the study and to give written informed consent. For the others, it was presumed that there was no objection to participation  in the correct size  and, as soon as possible invasively via arterial cannulation of the radial, brachial or femoral artery, according to the decision of the anaesthesiologist in charge. Noninvasive blood pressure measurement was set up by a trained nurse, who also checked correct zeroing and flushing of the invasive blood pressure measurement as well as the correct position of the pressure transducer at level of the right atrium. In case of cannulation of the radial or brachial artery, the nurse ensured that the upper arm cuff was placed at the contralateral arm. The interval for automatic oscillometric measurements was standardly set at 3 min. All measurements were performed in a supine position. No study-specific intervention took place. All vital parameters of the patients including blood pressure values were stored in the bedside computer. When direct blood pressure measurement was established, the simultaneously recorded blood pressure values were extracted from the bedside computer, screened for hypotensive intra-arterial values, checked for plausibility  and artefacts  according to a predefined protocol, and analysed. All plausible values were included as long as the patient remained hypotensive, leading to a different number of measurements per patient (e.g. in case of refractory hypotension). The patient monitors in the resuscitation areas were checked for calibration and other technical errors by qualified technicians according to German regulations.Patients’ demographic data were extracted from the medical records and the patient data management system , as were patients’ arterial lactate level, pH and base excess.A previous study comparing oscillometric and invasive blood pressure found a mean difference of 8 mmHg at the hypotension threshold of 60 mmHg mean arterial pressure . The staFor data analysis, we used the software Excel  and R . Simultaneously obtained mean and systolic arterial blood pressure values of each patient were analysed by the Bland–Altman method accounting for repeated measurements, resulting in bias (± SD) and 95% limits of agreement (bias ± SD × 1.96) . This anSubgroup analyses were not performed due to the small number of patients included.Patients’ characteristics were calculated as absolute and relative frequencies, and median and interquartile range , as were laboratory values from blood gas analysis.To summarise the endpoint, we aimed to investigate the accuracy of noninvasive intermittent blood pressure measurement via an oscillometric upper arm cuff in 30 patients suffering from shock treated in the resuscitation area in a clinical method comparison study using invasive blood pressure measurement as the reference method.Within the study period 33 patients with simultaneous invasive and noninvasive blood pressure measurement who had a mean arterial pressure below 60 mmHg were admitted to the emergency department. Figure Invasive blood pressure was measured in 19 (63%) cases in the radial artery, in 9 (30%) in the femoral and in 2 (7%) in the brachial artery.Seventy-seven simultaneous invasive and noninvasive measurements were recorded during hypotension. After screening for artefacts and excluding these values, 75 data sets of blood pressure measurement were analyzed. The number of measurements per patient ranged from 1 to 10 . Invasive mean arterial pressure was 51 ± 8 mmHg (30–60 mmHg), whereas noninvasively obtained mean arterial pressure was 64 ± 15 mmHg (27–116 mmHg). The correlation of invasive versus noninvasive mean arterial pressure values resulted in a correlation coefficient of 0.26 (p = 0.024) . The correlation coefficient for systolic arterial pressure was 0.29 (p = 0.010) (Fig. We aimed to investigate the reliability of blood pressure measurement using an oscillometric device in unstable emergency patients. Our data show that it is not possible to reliably detect hypotension in the majority of patients with shock using the tested noninvasive oscillometric device.In our hypotensive patient cohort, oscillometric measurements provided values of mean arterial pressure that were on average 13 mmHg higher than values obtained by invasive blood pressure measurement, which is considered the reference standard. This finding is in accordance with other results investigating oscillometric determination of blood pressure retrospectively , 13. WaxThe reason for overestimation in hypotension may lie within the embedded measurement algorithm of oscillometric devices: They analyse oscillations of the vessel during compression, transmitted through the air-filled occluding cuff. Most commonly, mean arterial pressure is set at the greatest amplitude of oscillations whereas systolic and diastolic pressure are determined by the means of proprietary envelope curves applied to the individual course of oscillations during the measurement cycle. However, the algorithms were often developed in normotensive individuals and analyse oscillations with amplitudes of 1–5 mmHg at the most . In patiTimely and accurate detection of hypotension in the emergency department is of great importance for several reasons. First, algorithms for rapid response teams base the distinction between unstable or stable amongst other factors on presence of hypotension . Second,There are limitations of our study. The study did not follow a strict protocol with respect to number of measurements per patient or site of arterial cannulation, because it was designed to catch realistic clinical conditions. Due to the emergency setting, there was no testing for a possible blood pressure difference between arms. Different arterial cannulation sites may introduce bias, however differences between radial and femoral mean arterial pressure are clinically not relevant . AnotherThe strength of our study is the prospective approach of an emergency patient cohort suffering from shock. Data of patients in profound shock are difficult to obtain as therapeutic efforts must be made immediately in this critical state. In addition, we studied all patients in the supine position and checked for adequate positioning of pressure transducer and cuff at the mid-chest level. Another strength is that we only analysed data pairs in true hypotensive state that were not affected by artefacts. Finally, invasive arterial measurements were used as reference method which is regarded as gold standard in other critical conditions such as cardiac surgery or critical care medicine.In conclusion, oscillometric blood pressure measurement is not able to reliably detect hypotension in emergency patients. Therefore, direct measurement of blood pressure should be established as soon as possible to guide vasopressor and fluid therapy in patients suffering from shock. Larger clinical trials are needed to further investigate the impact of oscillometric and invasive blood pressure monitoring in emergency patients with shock on therapeutic decisions and patient’s outcome.


These limitations are particularly relevant in patients undergoing desensitization or positive crossmatch kidney transplantation. In this article, I discuss Banff criteria for these ABMR categories, with a focus on patients with pre-transplant DSA, and offer a framework for considering the continuum of allograft injury associated with donor specific antibody in these patients.Antibody mediated rejection (ABMR) in the kidney can show a wide range of clinical presentations and histopathologic patterns. The Banff 2019 classification currently recognizes four diagnostic categories: 1. Active ABMR, 2. Chronic active ABMR, 3. Chronic (inactive) ABMR, and 4. C4d staining without evidence of rejection. This categorization is limited in that it does not adequately represent the spectrum of antibody associated injury in allograft, it is based on biopsy findings without incorporating clinical features (e.g., time post-transplant,  Since its initial meeting in 1991, the Banff classification for allograft pathology has become the most commonly used classification system for renal allograft pathology. Pathologists, HLA laboratory directors, nephrologists, surgeons, and researchers gather every other year to discuss recent advances in the field and to revise the classification system, and a meeting report with consensus opinion is published. The Banff schema first recognized antibody mediated rejection (ABMR) as a diagnostic entity in 2001 (published in 2003), making use of the complement split product C4d as an immunophenotypic marker of ABMR on biopsy  kidney transplants, to progressive graft dysfunction or proteinuria years post-transplant. ABMR features are also seen commonly on protocol biopsies from patients who have preformed (pre-transplant) DSA; these patients have stable graft function and no proteinuria . There aand ABMR –5. The cAs of 2019, the Banff schema recognizes four diagnostic categories: 1. Active ABMR, 2. Chronic active ABMR, 3. Chronic (inactive) ABMR, and 4. C4d staining without evidence of rejection, The first category, “active ABMR”, requires 3 diagnostic criteria: histologic evidence of acute tissue injury, evidence of current or recent antibody interaction with the endothelium , and serologic evidence of DSA . Histologically, microvascular inflammation (MVI), also known as capillaritis, qualifying for this category is a glomerulitis (g) score + peritubular capillaritis (ptc) score of 2 or greater. Other acute tissue injury patterns are acute tubular injury, thrombotic microangiopathy, and less commonly arterial lesions of endothelialitis, fibrinoid necrosis, or transmural inflammation. Chronic active ABMR has a similar three criteria, but with histologic evidence of chronic tissue injury, such as transplant glomerulopathy (TG) attributable to ABMR. Chronic (inactive) ABMR shows histologic evidence of chronic tissue injury, but without capillaritis and without C4d deposition in peritubular capillaries.The final category is peritubular capillary C4d staining without evidence of rejection, previously referred to as “accommodation” . This caThe Banff 2019 category of “active” ABMR (previously known as “acute” or “acute/active” ABMR) by itself encompasses a wide variety of clinicopathologic features. Patients undergoing +XM kidney transplants are at increased risk of early acute ABMR within the first month post-transplant . This tyHistologically, these cases of early acute ABMR with high serum DSA levels often show an “ATN-like” (acute tubular necrosis) phenotype (Banff “grade 1”) with few marginated inflammatory cells (particularly neutrophils) in glomerular and peritubular capillaries, along with glomerular thrombi see , 17, 18.As these biopsies show evidence of complement activation, colleagues at Mayo Clinic conducted a pilot study of +XM kidney transplant recipients using a terminal complement inhibitor, eculizumab, to prevent early acute ABMR . CompareAfter the first few months post-transplant, patients with pre-transplant DSA may develop a more indolent form of ABMR, characterized histologically by mild to moderate capillaritis involving the glomeruli, peritubular capillaries, or both . These findings are commonly observed on protocol biopsies from patients with normal graft function and no proteinuria, ranging from 3 months to 5 years post-transplant , 22–24. It is unclear how patients with MVI on biopsy, with or without early TG, should be treated. Since C4d is generally not diffusely positive, we can hypothesize that: (1) the corresponding serum DSA levels are low, and thus likely not responsive to plasmapheresis; and (2) the mechanism of injury may not be complement-mediated, at least not in the way early acute ABMR is complement-mediated. Supporting (2), a subset of patients showed endothelial injury changes and developed MVI, and even TG, even while receiving the terminal complement inhibitor eculizumab , 25. Trede novo DSA status, and other clinical information such as acute kidney injury or protocol biopsy would inform pathologists and nephrologists as to a better classifying diagnosis along this spectrum of antibody associated disease.According to the Banff classification, MVI (with the threshold of g + ptc >/= 2) is an “active” ABMR lesion. The current Banff schema thus may place some cases of early acute ABMR in the same category as a 2 year post-transplant protocol biopsy with mild glomerulitis and peritubular capillaritis and is C4d negative. See Figure 2de novo DSA timing of the biopsy post-transplant, presence of concurrent cellular rejection, and immunosuppressive medication non-adherence , or transplant arteriopathy. Of these, TG is the best characterized lesion of chronic ABMR. By definition, TG is a pattern of injury with glomerular basement membrane duplication in the absence of subendothelial immune complex deposits. TG is most commonly due to chronic ABMR, but the pattern may also be related to chronic thrombotic microangiopathy and/or hepatitis C infection . Biopsiedherence –29. Whildherence , 28. OthThe current Banff classification lumps TG cases together in one diagnostic category, but TG has a variable prognosis. An outcomes-based approach may be used: a study looked at an “archetype” classification, incorporating clinical, histologic, and immunologic features, which placed patients with TG into different prognostic or outcomes groups . These cThe Banff schema also has a category of chronic (inactive) ABMR. This category may be theoretical, since DSA and its resultant effects do not seem to disappear at any point post-transplant, at least with current therapies . Biopsies from patients with advanced chronic kidney disease due to ABMR generally show capillaritis as long as capillaries exist. Occasional transplants show such significant loss of peritubular capillaries that the capillaries simply no longer exist to show capillaritis Figure 2At the 2013 Banff conference in Comandatuba, Bahia, Brazil, a new Banff Working Group was formed, the “Clinical and Laboratory Assessment of Highly Sensitized Patients Working Group”, later referred to as the “Antibody-Mediated Injury Working Group” . This Wonever had DSA testing results when interpreting the kidney transplant biopsy. Recall that DSA information is central to Banff ABMR diagnosis, although not necessarily required for all kidney transplant biopsy diagnoses. 40% of pathologists agreed that the time post-transplant influenced their ABMR diagnosis and 58% agreed that they consider allograft dysfunction in considering a diagnosis. One of the main concerns identified was the dichotomous nature (active and chronic active ABMR) of the Banff ABMR categories. These results reflect the reality of renal pathology practice, and the recognition that the Banff schema does not reflect the full range of ABMR.Our Working Group then conducted a follow up survey in 2019 of pathologists and transplant clinicians to address additional questions raised by the first clinical practices survey . We founAnother concern that some survey respondents raised was that the Banff ABMR classification changed too frequently for practical use . A recenBesides determining the “ideal” histologic criteria and cut-off points for different categories of ABMR, the Banff schema should also take into account problems with reproducibility of the Banff scores. Recognizing problems with the Banff “antibody” scores reflecting microvascular inflammation and transplant glomerulopathy as currently defined, a number of studies have looked at reproducibility and methods to improve the scoring and the relation between antibody scores and graft outcome –38.In a study we conducted at Mayo Clinic, colleagues and I reviewed a set of biopsies from patients with preformed DSA, and evaluated them for the “antibody” scores of g, ptc, and cg (transplant glomerulopathy) . This stA randomized, multi-center clinical trial was conducted to determine the safety and efficacy of the C5 complement inhibitor drug, eculizumab, to prevent early acute ABMR in positive-crossmatch kidney transplant patients, following an initial pilot study at Mayo Clinic with positive results , 20. TheLike all of medical renal pathology, the renal transplant biopsy diagnosis is a clinicopathologic diagnosis. The renal pathologist identifies the histologic pattern, and then the disease, and then ideally the cause of that disease. For example, a biopsy shows a pattern of acute tubular injury with calcium oxalate crystals, the disease is acute oxalate nephropathy, and the cause is enteric hyperoxaluria due to Roux-en-Y gastric bypass. Just as renal pathologists use a clinical history of diabetes to diagnose diabetic glomerulosclerosis, a history of a vasculitic rash to diagnose Henoch-Schoenlein purpura, a history of antibiotic exposure to diagnose acute allergic interstitial nephritis, or a history of autoimmune pancreatitis and sialadenitis to diagnose IgG4-related tubulointerstitial nephritis, we similarly use the clinical history and laboratory results to make a diagnosis on transplant biopsies. While there is value in reproducible histologic scoring systems with outcomes measures (such as the Oxford classification for IgA nephropathy), we should not expect any classification system to assign an accurate diagnosis based on histology alone, and particularly in the transplant, where most “native” kidney diseases may occur, and in addition, those diseases specific to the transplant may also occur.What are potential ways to address many of these concerns? First, the Banff diagnostic categories should recognize and incorporate the broad range of clinicopathologic phenotypes of ABMR. Different patterns of rejection occur in different settings  and at different times post-transplant, and so the clinical setting is useful for a more accurate histopathologic diagnosis. In addition to the ABMR spectrum in An “archetypes” approach, as has been evaluated in TG , could bABMR in the kidney shows a wide range of clinicopathologic features that are not adequately represented in the current Banff diagnostic classification. For current clinical practice and clinical trials, we need to re-assess the usefulness of the current ABMR categories, and more accurately reflect the spectrum of antibody-associated injury and their prognostic categories.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical characteristics. Primary non function (PNF) and delayed graft function (DGF) rates, dialysis need, hospitalization duration, and patient and graft survival rates were compared. The estimated glomerular filtration rate (eGFR) was measured throughout the follow-up. Better clinical outcomes were achieved with EPD than with DCD despite similar graft and patient survival rates The total warm ischemia time (WIT) was longer in the DCD group than in the EPD group. Pure WIT was the highest in the class II group. The DGF rate was higher in the DCD group than in the EPD group. PNF rate was similar in the groups. Dialysis need was the greatest and hospitalization the longest in the class II DCD group. eGFR was lower in the class II DCD group than in the EPD group. Our results indicate good clinical outcomes of kidney transplants from DCD despite the long “no-touch period” and show that ECMO in the procurement phase improves graft outcome, suggesting EPD as a source for pool expansion.  Organ shortage remains the main obstacle in kidney transplantation, thus there is an urgent need for donor pool expansion. Donation after circulatory death (DCD) serves as an additional organ source and has become the current medical practice, despite each country having its own DCD protocol according to its own legislation and healthcare facilities . A majorECLS is an advanced resuscitation technique that ensures blood circulation in asystolic patients. It is a total-body cardiopulmonary by-pass system, applied to allow brain perfusion while cardiac activity restoration is attempted in case of severe heart or lung failure . If resuTo our knowledge, there are no studies on EPD as a new potential donor category. Here we report our pragmatic experience over 11 years, comparing graft outcomes achieved with EPD to those achieved with DCD.A total of 58 patients transplanted with kidneys harvested from DCD 36) and donors on EPD (22) between January 2008 and December 2019 were studied. There were 31 donors from DCD (10 recipients received kidneys from five DCD donors), and 21 donors on EPD (2 recipients received kidneys from one donor on EPD). The transplants were performed in three different kidney transplant centers: Foundation IRCCS Policlinico San Matteo Hospital (Pavia), Niguarda Ca’ Granda Hospital (Milan), and San Raffaele Hospital (Milan). The study protocol was approved by the ethics committee (p-20200027199) and fully complied with the 2000 Declaration of Helsinki . An observation period of 20 min (“no-touch” period), as Italian law imposes, was employed to ensure the irreversibility and permanence of patient’s circulatory death. In cases of donors on EPD, death certification was based on neurological criteria; brain death was declared according to international standardized methods . Once thThen all kidneys were placed in a hypothermic perfusion machine  except for the first three procured at the Pavia center, which were preserved in static cold storage because HPM was not yet available.To avoid PNF, the kidneys were evaluated per donor history, macroscopic appearance, histological criteria and, most importantly, perfusion parameters . In partThe kidneys were also evaluated using perfusion parameters: systolic perfusion pressure was set at 35–40 mmHg. Renal resistance (RR) values were machine-calculated in real-time, as a ratio between the mean perfusion pressure (mmHg) and the flow through the kidney (ml/min); values were recorded every 60 s throughout the perfusion. The perfusion liquid used was a modified Beltzer solution . The perfusion temperature was set at 4–6°C. When the RR value fell below 0.4 mmHg/ml/min, the kidneys were considered suitable for transplantation. In contrast if the RR value remained high after 6 h of perfusion, the kidneys were considered unsuitable for transplantation and discarded, regardless of the biopsy result. The kidneys were detached from the HPM just a few minutes before starting vascular anastomoses.Donor-related variables included: age, body mass index (BMI), sex, death causes, comorbidities, and Maastricht criteria for DCD.Donors on EPD were distinguished by EPDn and EPDc depending on the death certification.The recipients were divided into: Maastricht class II DCD, class III DCD, and EPDc and EPDn, according to the donor type. Recipient-related variables included: age, BMI, sex, dialytic age (months), human leukocyte antigen (HLA) match, maximum panel reactive antibody, comorbidities and, primary renal disease.- Total WIT: time elapsed between the moment of cardiac arrest and the beginning of organ preservation by NRP.-Pure WIT or no-flow period: asystolic period without any resuscitation maneuvers. This time comprised the first variable period of no flow, the duration of which depends on the celerity in beginning cardiopulmonary resuscitation and a second unchanged period which corresponds to a 20 min recording of EKG.-The low-flow period: period in which organ blood perfusion was maintained using cardiopulmonary resuscitation, advanced cardiac life support, and chest compression in an attempt to save the patient’s life.-The no-touch period: stand-off time without any intervention to certify the patient’s death per circulatory death criteria.-Cold ischemia time (CIT): time from the beginning of organ perfusion, using cold preservation solutions during the organ retrieval surgery, until the end of graft perfusion through HPM.The total WIT of the EPD group did not include the total-body ECMO time.Data related to these time intervals, RR, and flow parameters during hypothermic perfusion were collected.(1) machine perfusion pump parameters: persistent flow rate of <60 ml/min and/or resistance index of>0.4 mmHg/ml/min;(2) vascular thrombosis identified upon biopsy analysis performed before hypothermic perfusion; and(3) Remuzzi score >4.Donor kidneys were discarded according to one of the following criteria:Anti-thymocyte globulin or basiliximab was administered as immunosuppression induction therapy. Additionally, methylprednisolone (500 mg/day) was administered intravenously on the first day; its dose was progressively decreased until day 6. Oral methylprednisolone (16 mg) administration was introduced on post-transplant day 7 and reduced every 3 months, to reach a maintenance dose of 4 mg/day. It was discontinued after 1 year . Mycophenolate mofetil was administered at a daily dose of 1–2 g. Tacrolimus or cyclosporine was started on day 1 at 0.1–0.15 mg/kg/day or 6–8 mg/kg/day, respectively. The dose was adjusted to achieve a therapeutic target blood trough level . Maintenance immunosuppression regimens consisted of calcineurin and/or mTOR inhibitors, mycophenolate mofetil, and methylprednisolone. Immunosuppressor trough levels were reduced based on transplant age.The kidney recipients were followed up for 1–11 years. HLA mismatch between donors and recipients was categorized according to differences at the HLA-A, HLA-B, HLA-DR, and HLA-DQ loci.Routine blood tests and serum levels of immunosuppressive drugs were regularly assessed. Follow-up ceased due to patient death, PNF, or graft failure.-PNF was defined as the immediate failure of the graft function, requiring permanent dialysis or a re-transplantation;-DGF was defined as a need for dialysis within the first week after transplantation, DGF duration was measured as the number of dialysis sessions-Dialysis need was defined as the number of dialysis sessions required after transplantation;-Length of hospital stay in the post-transplant period was determined based on the number of days; and-Graft survival rate was defined as the time from transplantation to graft nephrectomy, return to dialysis, or re-transplantation. It did not cover patient death with a functioning graft.The following end points were evaluated after transplantation:Incidences of PNF, DGF, and acute rejection were retrospectively analyzed in all groups of patients. Acute rejection biopsies were classified according to the Banff 2013 classification .In addition, severe post-operative complications such as viral and bacterial infections, severe bleeding, renal vein/artery thrombosis, stenosis of the bladder-ureter anastomosis, allograft rupture, lymphorrhagia, and urine leakage were analyzed retrospectively.Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (expressed in milliliters per minute and adjusted for body surface area), was determined on days 7, 1, 3, 6, and 12 months after transplantation and every year throughout the follow up period.A percutaneous renal graft biopsy was performed 2 or 3 weeks after transplantation when DGF persisted. Furthermore, a biopsy was performed for patients presenting with an abrupt decrease or a lengthy deterioration of renal function, significant proteinuria, or finally, the appearance of specific antibodies against the donor during the follow-up period.Parametric variables are expressed as mean and standard deviation or standard error values and non-parametric variables as medians and interquartile ranges. The categorical variables are expressed as percentages. Chi-square or Fisher test was used for comparative analysis of categorical variables. Differences in eGFR were evaluated using repeated-measures ANOVA.p < 0.05.Patient and graft survival rates were estimated using the Kaplan-Meyer method, the differences were compared using the log rank test. All tests were two-tailed and considered statistically significant at From September 2008 to December 2019, 58 kidney transplants were performed; of which 36 kidneys came from DCD and 22 kidneys from EPD. According to the Maastricht DCD criteria, 18 donors each belonged to classes II and III. In the EPD group, death was certified by circulatory criteria in seven donors and by neurological criteria in 15 donors.p = 0.7).As shown in p < 0.0001).As shown in p < 0.0001). TB ECMO time was similar in the two EPD subgroups (EPDc and EPDn).Similarly, pure WIT was the longest in the class II DCD group and the shortest in the EPDn group .PNF occurred in two patients, one in the class II DCD group (2.7%) and the other in the EPDc group (4.5%). In both cases, renal biopsy revealed ischemic coagulation necrosis.p < 0.0001), while the DGF rate was higher in the class II DCD group than in the EPD group   .p < 0.05)  .During the follow-up period, the highest eGFR was observed in the EPD group, but it was not significantly different from that in the class III DCD group . InteresGraft survival and patient survival were similar in the DCD and EPD groups, as shown by Kaplan-–Meier curves in Causes of death are described in The rates of post-transplant complications causing graft loss did not differ among the DCD (11%) and EPD (4.5%) groups.In the DCD group, three grafts were explanted because of renal vein thrombosis, severe hemorrhage secondary to a mycotic aneurysm, or severe life-threatening sepsis requiring immunosuppressive therapy suspension.The surgical complication rate was higher in the DCD group than in the EPD group: lymphocele was observed in four DCD recipients (11.1%), urinary leakage in two DCD recipients (5.5%), and perirenal hematoma in two EPD (9%) and one DCD recipient (2.7%).Kidney acute rejection (Banff 2a) occurred in only one patient belonging to the EPD group.We report the renal transplantation results after 11 years of follow-up, by comparing the outcomes for EPD and DCD grafts. Our data showed excellent clinical outcomes in the recipients belonging to all groups. EPD was revealed to be a novel and promising category of donor, that has not been taken into consideration previously.The EPD recipients achieved better outcomes than the DCD recipients. They showed better renal function, lower DGF rates, reduced dialysis need, shorter post-transplant hospital stays, and lower short- and long-term medical and surgical complication rates. However, the two groups of recipients showed no differences in PNF or graft and patient survival rates. Several factors, both immunological and non-immunological, are known to affect DGF occurrence and influence graft outcomes.The emergence of new therapies as well as the advancements in mesenchymal stem cell and growth factor therapies and drug monitoring have improved the graft outcomes –17, but 2 value ranging from 98 to 100%, good gas exchange, and a normothermic body temperature), which ensure good tissue perfusion  and a low-flow time (up to a maximum of 120 min), during which a basic level of oxygenated blood circulation is restored by means of a cardiac compressor and mechanical ventilation.Maastricht class III DCD typically includes an unpredictable agonal phase (maximum 2 h) following the WLST and a no-flow period while the EKG is recorded. Therefore, WIT consists of the time of the agonal phase plus the no-touch period. EPD is a type of donor resulting from an unsuccessful ECMO treatment after an irreversible cardiac arrest. In this setting, the patient’s death can be certified by either cardiac (EPDc) or neurological criteria (EPDn). The first choice requires recording a 20 min EKG (no-touchperiod). In contrast, if the patient’s death is certified by the neurological criteria the no-touch period can be avoided. After death determination, all types of donors undergo regional normothermic perfusion aimed at preserving the abdominal organs until harvesting. The removed organ is subsequently stored in the mechanical pulsatile perfusion machine until transplantation.


Digital health is defined as the use of information and communications technologies to manage patients and their health and promote their wellness by making communication between caregivers and patients more efficient . The broOmboni, the most popular digital health application for hypertension management is blood pressure telemonitoring, which has been shown to improve blood pressure control, increase treatment adherence, and favor intensification and optimization of antihypertensive medications. Among the available telemedicine solutions, those based on m-health, providing medication tracking and reminding, teleconsultation, and cuffless blood pressure measurement seem to be the most promising tools.As highlighted in the review by Bard et al., the recent introduction of cuffless blood pressure measurement solutions has the potential to allow a more extensive adoption of blood pressure telemonitoring by enhancing patient autonomy, favoring self-management, and providing physicians with a more complete picture of their patients' blood pressure profile. Although cuffless tools based on applications that enable smartphones to measure blood pressure or rely on wearables are very promising, their routine use is challenged by several potential drawbacks, including a lack of accepted validation schedules, the need to calibrate through conventional means, questionable accuracy, and lack of comparability with office or cuff-based home blood pressure measurement  and healthy lifestyle measures (smoking cessation and cardiac rehabilitation) than patients who received only clinic visits over the same period. Patients rated virtual visits with a high level of satisfaction.A typical digital health application is represented by remote video consultation between doctor and patient  . Kamel eIn conclusion, the articles presented in this Research Topic confirm that digital health, particularly telemedicine and m-health, is transforming the management of cardiovascular conditions such as hypertension, atrial fibrillation, coronary artery disease, and heart failure by healthcare professionals and patients alike. The current COVID-19 health emergency has accelerated this digitalization of healthcare systems, dramatically reducing the occurrence of face-to-face contact between patients and their healthcare managers . WhetherSO prepared the editorial. RJM and BB critically revised its content. All authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.SO was a scientific consultant of Biotechmed Ltd., a provider of telemedicine services. RJM was working with Omron to develop and evaluate the Hypertension Plus Telemonitoring system. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Regardless of albuminuria, women lost 0.93 (0.40–1.46) fewer glomerular filtration units per year than men. A total of 17% of the participants experienced rapid deterioration of renal function, 75.2% of whom were men, with differential risk factors between sexes—severe macroalbuminuria > 300 mg/g for men OR [IQ] 2.40 [1.29:4.44] and concomitant peripheral vascular disease 3.32 [1.10:9.57] for women. Overall mortality of 23% was detected (38% of which was due to cardiovascular etiology). We showed that kidney function declined faster in men, with different risk factors compared to women. Patients with T2D and kidney involvement have very high mortality and an important cardiovascular burden. This cohort is proposed as a great tool for scientific collaboration for studies, whether they are focused on T2D, or whether they are interested in comparing differential markers between diabetic and non-diabetic populations. The GenoDiabMar registry is a prospective study that aims to provide data on demographic, biochemical, and clinical changes in type 2 diabetic (T2D) patients attending real medical outpatient consultations. This registry is also used to find new biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. With this purpose, longitudinal serum and urine samples, DNA banking, and data on 227 metabolomics profiles, 77 immunoglobulin G glycomics traits, and other emerging biomarkers were recorded in this cohort. In this study, we show a detailed longitudinal description of the clinical and analytical parameters of this registry, with a special focus on the progress of renal function and cardiovascular events. The main objective is to analyze whether there are differential risk factors for renal function deterioration between sexes, as well as to analyze cardiovascular events and mortality in this population. In total, 650 patients with a median age of 69 (14) with different grades of chronic kidney disease—G1–G2 (eGFR > 90–60 mL/min/1.73 m Diabetes mellitus is of pandemic proportions, affecting more than 450 million people worldwide, of whom up to 95% have type 2 diabetes . The maiIn recent decades, the improvement in prevention strategies and therapeutic interventions has led to a significant reduction in most diabetes complications. However, this is not so evident in the case of diabetic kidney disease (DKD), which remains the leading cause of end-stage renal disease (ESRD) in Western countries ,6. When In past years, high-throughput techniques have shown the feasibility of finding new biomarkers of early kidney dysfunction, as well as providing valuable information on the metabolic pathways involved in the physiopathology of DKD and other diabetic micro- and macrovascular complications ,22,23,24The analysis of hundreds of metabolites, protein glycosylation profiles, genetic variants, or emerging biomarkers requires large-sample-size cohorts in order to robustly detect associations. GenoDiabMar is a detailed cohort useful as a tool to improve and expand knowledge on different pathophysiological pathways involved in diabetic complications, and enables the replication of results obtained in different populations to generate collaborative research. We present the GenoDiabMar registry, created with the aim of providing data on demographic, biochemical, and longitudinal clinical changes in a population of T2D patients attending a real medical outpatient consultation. Moreover, this registry is used to find new emerging biomarkers related to the micro- and macrovascular complications of T2D, with a particular focus on diabetic nephropathy. In this study, we analyzed the clinical and analytical characteristics at baseline and during the almost 5-year follow-up of this population. We assessed whether there were differential risk factors between the sexes in the evolution of renal function, as well as CV events and mortality associated with this population.2 and normal urine albumin to creatinine ratio < 30 mg/g), and if renal damage was present at any time. Additional information is available in the The GenoDiabMar registry was designed as a prospective study, and has currently collected information regarding 650 Caucasian adults with T2D recruited from the nephrologist consultant of Hospital del Mar and six primary care centers from the Hospital del Mar health area, Litoral-Mar, Barcelona, Spain. The inclusion criteria were adults over 45 years old, diagnosed with T2D at least 10 years before the first study visit, if there was no renal disease—defined as glomerular filtration rate (eGFR) > 60 mL/min/1.73 mBetween February 2012 and July 2015, 650 T2D patients underwent a basal in-person medical visit (V1) performed by a nephrologist and a nurse. Medical history, demographics, physical examination, and laboratory data were registered along with collection of blood and urine samples. In addition, an annual follow-up of all participants included at the baseline visit was performed in order to obtain complete analytical and clinical parameters, including new cardiovascular events and changes in the status of diabetic retinopathy and nephropathy, as well as mortality, by consulting participants´ electronic clinical reports. Between March 2017 and February 2020, living patients with functioning kidneys who did not require renal replacement therapy underwent the second in-person visit (V2). Again, analytical, and clinical data, including changes in treatments, were registered. The second biological samples for the biobank were collected on this second visit, performed an average of 4.7 (0.65) years from the baseline visit. At the first visit, each participant completed a comprehensive questionnaire about their medical history, including information related to the presence and type of diabetes mellitus in their family history. A complete list of data and samples available at the baseline visit, last visit, and annually during the follow-up are summarized in At baseline (V1) and at the last visits (V2), fasting venous blood and urine samples were collected. Serum, urine, DNA, and whole blood samples were stored in freezers of the Nephropathies Research Group (GREN) at the Institut Hospital del Mar d´Investigacions Mèdiques (IMIM)  and the 2 and albuminuria > 300 mg/g, or albuminuria 30–299 mg/g and DR, regardless the eGFR. Patients were classified based on their degree of kidney disease following the KDIGO guidelines as grade 1–2 if eGFR > 90–60 mL/min/1.73 m2, grade 3 if eGFR = 59–30 mL/min/1.73 m2, grade 4 if eGFR = 29–15 mL/min/1.73 m2, and grade 5 if eGFR < 15 mL/min/1.73 m2  vs. 63.4 [41.7:86.4] mL/min/1.73 m2), but the rate of loss of kidney function was significantly lower in women, losing 0.93 (0.40–1.46) fewer glomerular filtration units per year than men, regardless of albuminuria . The overall mean annual glomerular filtration loss was −1.2  per year, separated by sex.Multivariate logistic regression model showing the variables of risk of undergoing a rapid decline in renal function, defined as a loss of >5 ml/min/mp < 0.001). Although this registry was initially started with the objective of studying new biomarkers of kidney injury in T2D, it is a well-characterized population that has detailed information on other micro- and macrovascular diabetic complications, which we also analyzed. Thus, during the follow-up period, 135 patients (22.1%) endured one or more CV events, of whom 33.3% fulfilled the established criteria for DKD and 18.4% did not match the DKD criteria at baseline  started renal replacement therapy, and 10 were lost to follow-up , with patients who sometimes may be excluded from other types of clinical trials or studies, with strict inclusion criteria. This allows us to obtain evidence that is closer to routine clinical practice.The characteristics of the evolution of renal function and the differences found between the sexes in morbimortality are similar to those described in the literature ,43,44 foThe absolute value of macrovascular events is not high compared to other large-population cohorts. However, since this cohort has patients with a high burden of disease, recruited from real consultations—which allows us a more reliable and closer follow-up of the clinical events—the relative values and percentages of events and complications are similar to or even higher than those observed in other, larger cohorts. As stated, it is important to join efforts in conducting collaborative studies to minimize statistical power problems and, although a single registry may not have enough events, management through meta-analysis of results and validation of data in external cohorts is postulated as a mandatory scientific practice. In this study, we have shown that diabetic patients with kidney disease, beyond classic antihypertensive or lipid-lowering treatments and acceptable metabolic control, have a very high mortality—mainly associated with cardiovascular events. The physicians attending this kind of patient—general practitioners, endocrinologists, cardiologists, or nephrologists—must be especially aware and approach these patients in a multidisciplinary manner. The low percentage of patients in this cohort under treatment with drugs that have demonstrated cardio- and nephroprotection (SGLT2i or GLP1-AR) is remarkable. Although we know that this trend is changing, we must continue efforts to implement these drugs in routine clinical practice. In addition, the main strengths of this cohort are that it includes a collection of baseline and longitudinal follow-up biological samples, and covers the entire spectrum of kidney disease, including patients from grade 1 CKD to patients on renal replacement therapy. As these are patients from medical consultations belonging to our healthcare area, we have detailed and precise information about them, and we can ensure good monitoring capacity. One of the limitations of the study is the generalizability of the findings, which is limited to Caucasian subjects. The results of our study may be validated in multiethnic cohorts in order to evaluate their applicability in broader populations with T2D. We do not have urine samples from all of the participants, and lack information regarding diet and lifestyle. Moreover, we have not conducted kidney histological studies in most of the patients to ensure the renal disease etiology. Since no other reliable and non-invasive markers have been established, we cannot overcome this limitation but, in order to minimize misdiagnosis, medical history—including ultrasonography and fundoscopy studies—was reviewed by two nephrologists. In addition, to date, the registry has only ensured the extraction of DNA from the samples, but they have not yet been sequenced. With current technology, the statistical power of the cohort would be insufficient to propose GWAS-type studies without a prior hypothesis. However, once the population has been sequenced, studies aimed at validating predetermined genetic variants could be considered, as well as potential replication studies.We presented a registry of patients from real nephrology and primary care medical outpatient consultations, from which we have registered several clinical and analytical variables for 5 years. In addition, the registry includes serum and urine biobanks, DNA banks, and data on metabolomics, glycomics, and other biomarkers already analyzed. We consider this cohort to be a great potential tool for scientific collaboration for studies, whether they are focused on T2D, or whether they are interested in comparing differential markers between diabetic and non-diabetic populations. Furthermore, as we have shown in other collaborative projects, the GenoDiabMar registry can meet the criteria to replicate or meta-analyze results obtained in other cohorts. It should be noted that this registry is part of The Consortium of Metabolomics Studies (COMETS), whose main objective is to create a collaborative network to identify metabolomic markers associated with different phenotypes and pathologies . This descriptive publication of our GenoDiabMar registry should engage researchers in collaborative efforts to advance knowledge of the etiology, diagnosis, treatment, and prognosis of T2D complications. In this spirit, we invite researchers—including those without data of their own—to join us with scientific collaboration proposals.


In patients with myeloproliferative neoplasms (MPN) and in patients with kidney dysfunction, a higher rate of thrombosis has been reported compared with the general population. Furthermore, MPN patients are more prone to develop kidney dysfunction. In our study, we assessed the importance of specific risk factors for kidney dysfunction and thrombosis in MPN patients. We found that the rate of thrombosis is correlated with the degree of kidney dysfunction, especially in myelofibrosis. Significant associations for kidney dysfunction included arterial hypertension, MPN treatment, and increased inflammation, and those for thrombosis comprised arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The identified risk factor associations varied between MPN subtypes. Our data suggest that kidney dysfunction in MPN patients is associated with an increased risk of thrombosis, mandating closer monitoring, and, possibly, early thromboprophylaxis.2)) into eGFR1 , eGFR2 , and eGFR3 . A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia , polycythemia vera , and myelofibrosis  were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m Patients with myeloproliferative neoplasms (MPNs) are at increased risk of developing myelofibrosis as well as vascular complications such as thrombosis or severe hemorrhage ,3,4,5,6,n = 559) were excluded, resulting in a study sample size of 1420 patients.The present retrospective multicenter study is a secondary analysis of existing data collected in the ongoing prospective MPN bioregistry study of the German Study Group for MPN (GSG-MPN bioregistry), which has recruited patients since 2012. A total of 1979 MPN patients from 52 centers, included between 2012 and December 2019, were screened. Diagnosis of ET, PV, or MF  was required, as defined by the World Health Organization (WHO) classifications of 2008 , 2001 , blood cell parameters (leukocytes (G/L), platelets (G/L), monocytes (G/L), neutrophils (G/L)), JAK2V617F and CALR status, and parameters of proliferative activity and inflammation , C-reactive protein , uric acid (mg/dL)). For each risk factor, median values were used in order to classify patients into a high or a low group. Additionally, MPN duration, MPN-specific therapy ), and antithrombotic therapy were documented. Finally, the time from diagnosis to last follow-up (FU) or date of death was assessed for survival analysis in relation to kidney dysfunction, and the Eastern Cooperative Oncology Group Performance Status (ECOG PS) was collected as a quantification of patients’ capability to engage in activities of daily living (ADL).2) [Kidney function was calculated using the simplified Modification of Diet in Renal Disease (MDRD) formula to obtain the eGFR (mL/min/1.73 m2) :eGFR = 12, which persists over 3 months, CKD is confirmed, regardless of the presence of albuminuria [2; eGFR2: 60–89 mL/min/1.73 m2; and eGFR3: <60 mL/min/1.73 m2, respectively. As an indicator of age-independent kidney function, the serum creatinine level was used.According to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines , CKD is uminuria . In the 2-test  or Wilcoxon–Mann–Whitney/Kruskal–Wallis test, as appropriate. Univariate and multiple logistic regression analyses were applied for associations, expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs), between the occurrence of thrombosis, severe bleeding, and decreased kidney function in relation to the above-mentioned risk factors. Age and sex were not included in the regression analyses of kidney function, since they are components of the eGFR formula. Risk factors with significance shown in univariate analyses were included in the basic models in multiple regression analyses. In order to evaluate and quantify progression of kidney function in relation to MPN duration, logistic regression models were used. The impact of kidney function on overall survival was estimated according to Kaplan–Meier and assessed by log-rank testing and Cox regression models. Data analysis was performed using SAS software 9.4. [p < 0.05. Multiple comparisons were adjusted by Bonferroni correction.Descriptive data are presented as percentage or median including quartiles  and were analyzed using χare 9.4. . StatistAmong the 1420 patients, 39% of the patients had ET, 34% had PV, and 28% had MF; 49% of the patients were male, with the expected lower percentage in ET and higher percentage in MF . JAK2V612, respectively, at baseline (time of inclusion into the registry or routine follow-up) , 60–89 (eGFR2), and <60 (eGFR3) mL/min/1.73 mllow-up) . Median T and PV A. A totaT and PV . In the In In the total cohort, diabetes mellitus, arterial hypertension, and hyperlipidemia were significantly more prevalent in eGFR3 than in eGFR2 or eGFR1 groups . HoweverAs expected, the proportion of patients with elevated uric acid levels was higher in eGFR3 than in eGFR1 , in keepOverall, elevated leukocyte, neutrophil, and monocyte counts were significantly associated with decreased kidney function, while elevated platelet counts were less frequent in these patients . DiffereThe presence of the JAK2V617F mutation has been associated with an increased risk of thrombosis in ET ,35, and A longer MPN duration was found in eGFR3 than in eGFR2 and eGFR1. When patients were categorized into two groups above and below the median duration of 42 months, more patients with a longer duration fell into eGFR3 and eGFR2 compared with eGFR1 C. AdjustP). MF, co-existing diabetes mellitus, hyperlipidemia, leukocytes > 8.4 G/L, neutrophils > 5.48 G/L, monocytes > 0.55 G/L, LDH > 267.5 U/L, CRP levels > 1.4 mg/L, and treatment with RUX and anagrelide/IMIDs/interferon showed significant ORs when contrasting eGFR3 to eGFR2 or eGFR1. As stated above, MPN duration > 42 months was associated with kidney dysfunction. Arterial hypertension, uric acid levels > 5.7 mg/dL, and HU treatment were significant risk factors in all eGFR groups. Associations of age and sex with kidney function were not examined, since these factors are part of the eGFR formula. In multiple logistic regression analysis, HU treatment was significantly associated with kidney dysfunction ), treatment with HU only, RUX only, and multiple lines of MPN therapies were associated with kidney dysfunction . Signifip = 0.0174) but not in PV or MF.In order to evaluate the association of kidney dysfunction with patients’ survival, we analyzed overall survival after MPN diagnosis in the two creatinine groups (>0.9 mg/dL and ≤0.9 mg/dL) A–C. Over2. Compared with the general population [2, respectively). The fraction of patients with kidney dysfunction (eGFR < 60 mL/min/1.73 m2) was 22.3% in our cohort and 29% [In this retrospective multicenter analysis of the German GSG-MPN bioregistry, the majority of patients had an eGFR between 60 and 89 mL/min/1.73 mpulation ,40,41, mpulation , while apulation   to milder (eGFR ≥ 60 mL/min/1.73 m2) kidney dysfunction, the most relevant factors accompanying decreased function were co-existing diabetes mellitus, arterial hypertension, hyperlipidemia, elevated levels of uric acid, leukocytes, neutrophils, monocytes, LDH, CRP, and MPN therapy , the reason for this being unclear. Moreover, when correlating MPN-specific therapy to median eGFR, we detected a lower median eGFR in the treated patients compared with WW management in ET and MF but not in PV, suggesting that treatment of PV was beneficial for kidney function. This is in line with previous data showing that treatment of PV improved kidney function and suggests that PV-related non-diabetes factors, such as microcirculatory disturbance and arterial hypertension, play a prominent role in the pathophysiology of CKD in PV .As expected from studies in the general population , higher In the overall population, JAK2V617F positivity was not different between eGFR groups . HoweverAs expected, the prevalence of thrombosis was higher in our MPN cohort  in comparison to general population-based analyses ,15,16,18In our cohort, more patients with impaired kidney function received therapy than those with normal kidney function , and theAn elevated creatinine level was associated with a lower survival rate in ET but not PV or MF A–C, suggTo our knowledge, this is the largest MPN cohort analyzed for renal dysfunction to date, and, importantly, it reflects real world data from current practice. Nevertheless, our study has some limitations: (a) We have only one measurement of serum creatinine; the other parameters were extracted from patients’ records and only the life-time prevalence of thrombosis was documented. Therefore, no rigorous cause-effect relationships between MPN, CKD, and thrombosis can be demonstrated statistically. However, the assumed relationships between MPN, CKD, and thrombosis in our study are supported by prior research relevant in the context (see above). Nevertheless, paired measurements of creatinine and related parameters at predefined time points, i.e., before and at the time of diagnosis, during FU, and the date of thrombosis, should be analyzed in future prospective studies. (b) Furthermore, additional parameters for kidney dysfunction such as albumin, serum cystatine C , and addOur large registry-based multicenter study revealed an increased prevalence of kidney dysfunction in MPN patients compared with the general population and, in addition, we demonstrated a higher proportion of thromboses in patients with more severe kidney dysfunction. It was shown that MF has a higher impact on kidney function compared with ET or PV. The lower frequency of CKD in PV patients receiving MPN treatment may imply a beneficial impact of MPN treatment on kidney function. In conclusion, our results suggest that MPN patients with renal dysfunction may require closer monitoring and, possibly, earlier thromboprophylaxis and MPN-directed treatment. Nevertheless, future research should focus on the acquisition of longitudinal data, which is required to confirm the findings of the present study.