Differences in sex and age response to single pill combination based antihypertensive therapy reflecting in blood pressure and arterial stiffness.

OBJECTIVE: There are noticeable sex differences in the treatment response to antihypertensives, with limited data on the response to single pill combinations. The aim of the PRECIOUS trial was to assess the treatment response to perindopril/amlodipine and perindopril/amlodipine/indapamide dual and triple single-pill combination in men and women. METHODS: Four hundred and forty adults with essential hypertension were assessed in the 16-week interventional, open-label, prospective, international, multicentre trial. Based on the previous antihypertensive therapy, patients were assigned to either perindopril/amlodipine 4/5 mg or perindopril/amlodipine/indapamide 4/5/1.25 mg, with the initial dose up-titrated in 4-week intervals in case of uncontrolled blood pressure. An additional analysis was performed for sex- and age-related differences on the blood pressure response and arterial stiffness in men and women aged 35-74 years. RESULTS: Women achieved better overall blood pressure control in all age groups, except for the 35-44 age group. Women presented higher average 24 h aortic augmentation indexes than men, but had more pronounced decreasing trends. The pulse wave velocity was only age-dependent, with reductions slightly greater in women. Both the aortic augmentation index and pulse wave velocity were significantly decreased in all groups compared to baseline. CONCLUSIONS: The results of the PRECIOUS trial contribute significant data to the expanding body of evidence on sex differences in hypertension, including the aspect of age-related changes during the life course of women. The differences between same-aged men and women tend to be smaller with advancing age, but with a greater treatment response in women in all age groups for all observed blood pressure parameters and arterial stiffness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03738761.

Serum Hepatocyte Growth Factor Concentration Correlates with Albuminuria in Individuals with Optimal Blood Pressure and Untreated Arterial Hypertension.

Background/Objectives: Hepatocyte growth factor (HGF) is a protective factor against acute renal injury and chronic renal fibrosis. A positive correlation between HGF and blood pressure (BP) has been established. This study aimed to determine the association between serum HGF concentration and albuminuria in subjects with optimal blood pressure (OBP) and untreated arterial hypertension (UAH), as well as its association with BP levels, serum glucose levels, and inflammatory markers. Methods: Data from 563 subjects were analyzed. Albuminuria was normalized to urine creatinine and expressed as the albumin/creatinine ratio (ACR). HGF, serum glucose, C-reactive protein, and blood leucocyte counts were measured. BP was measured and subjects were divided into optimal blood pressure (BP < 120/80 mmHg, N = 295) and untreated arterial hypertension (BP > 140/90 mmHg, N = 268) groups. Results: The subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total and LDL cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all p < 0.001). A significant positive correlation was found between serum HGF concentration and ACR in both groups. There was no difference or correlation between HGF and BP or inflammatory markers in either group. The multivariate regression analysis identified serum HGF concentration as a strong predictor of ACR increase (Beta = 0.376, p < 0.001). Conclusion: This study found that serum HGF concentration is associated with albuminuria not only in individuals with untreated arterial hypertension, but also in those with optimal blood pressure. The results suggest that serum HGF is an independent predictor of ACR increase in both groups.

Longer Telomere Length in Balkan Endemic Nephropathy Patients Undergoing Chronic Hemodialysis is Associated with Lower Cardiovascular Mortality.

BACKGROUND: Balkan endemic nephropathy (BEN) is characterized with later onset and milder forms of hypertension, and with lower pulse wave velocity (PWV) than other end-stage kidney disease (ESKD). Longer telomeres are associated with better cardiovascular (CV) prognosis. Therefore, we hypothesized that telomere length (TL) could be longer in BEN patients compared to other ESKD patients. METHODS: A total of 124 patients undergoing hemodialysis (HD) (68 BEN, 56 non-BEN) were enrolled and followed-up for 72 months. TL was measured in leukocytes by Southern blot at inclusion. RESULTS: Age and sex-adjusted TL was significantly longer in the BEN group (p<0.001). TL was negatively associated with carotid-femoral PWV in BEN patients. BEN patients had significantly lower CV mortality than non-BEN ESKD patients (p<0.001). In the BEN group shorter TL (1kb change) was the only determinant of shorter survival (HR 0.11). Using the TL threshold defined by ROC analysis (TL < 6.21 kb), we showed in both groups significantly higher CV mortality in the presence of short telomeres (Log-rank (Mantel-p<0.001). CONCLUSIONS: Longer telomeres are associated with less CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. In BEN patients, TL was negatively associated with arterial stiffness and positively associated with survival. This study confirmed our hypothesis that BEN is associated with slower vascular aging and that longer TL may partially explain this phenomenon.

Implantable Cardioverter Defibrillators in Prevention of Sudden Cardiac Death in Kidney Transplant Recipients: A Case Series and an Appraisal of Current Evidence.

Background: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of mortality among kidney transplant recipients (KTRs). While implantable cardioverter defibrillators (ICDs) are established for SCD prevention in the general population, data on the benefits in patients with CKD is scarce and controversial, and there is no established general consensus on their use in this group of patients. Furthermore, data for KTRs are lacking. The aim of this study is to present our experience with ICDs in KTRs and evaluate the outcomes in this population. Methods: We retrospectively analyzed medical records of KTRs who received a kidney allograft between October 1973 and December 2023 and received ICDs for the prevention of SCD. Results: Of 2282 KTRs, 10 patients (0.44%) underwent an ICD implantation with an average age of 60.6 years at the time of implantation; 9 were male. Primary prevention of SCD was the most common indication, with only one patient receiving an ICD following sudden cardiac arrest. The female patient received an ICD while on dialysis, and the rest of the patients received ICDs in the posttransplant period with an average time of 9.1 years after KT. Kidney allograft function was reduced in all patients at the time of the ICD implantation with an average estimated glomerular filtration rate (eGFR) of 44 mL/min/1.73 m2. No ICD-related complications were recorded. Six patients are alive with an average follow-up of 5.2 years. Conclusions: ICD implantation in carefully selected KTRs may offer survival benefits and can be a valuable tool in preventing SCD. Larger studies are needed to confirm these findings and establish clear guidelines for ICD use in this specific population.

SGLT2 Inhibitors and Their Effect on Urolithiasis: Current Evidence and Future Directions.

Urolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach for UL treatment. These inhibitors may help reduce the risk of urolithiasis, particularly in patients with diabetes, by improving glycemic control and altering urinary chemistry, which are crucial factors in stone formation. However, the changes in urinary composition induced by SGLT2 inhibitors might also increase the risk of uric acid stone formation. This review evaluates the potential of SGLT2 inhibitors in managing UL, highlighting both the benefits and the risks. While these inhibitors show promise in reducing new and recurrent urinary stones in patients with diabetes, data on their effects in patients without diabetes who form stones are limited. Current human evidence largely comes from post hoc analyses of randomized controlled trials (RCTs) and large-scale database studies, with only one study providing detailed stone composition data. Experimental studies in animal models and cell lines have focused on calcium oxalate (CaOx) stones, showing that SGLT2 inhibitors specifically target CaOx stone formation and related renal inflammation. Although primarily studied for CaOx stones, their potential impact on other calcium-containing stones, such as calcium phosphate, remains promising. Further research is needed to explore their therapeutic potential and optimize treatment strategies.

A Comparative Analysis of the SARC-F Questionnaire and the Malnutrition-Inflammation Score for Sarcopenia Risk Assessment and Negative Outcome Probability in Chronic Hemodialysis Patients.

Background/Objectives: Protein-energy wasting (PEW) and sarcopenia are common in chronic hemodialysis (HD) patients, leading to numerous complications and increased mortality. This study aimed to compare the reliability of the SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls) and the Malnutrition-Inflammation Score (MIS) in assessing sarcopenia and predicting negative outcomes in HD patients. Methods: This cross-sectional study enrolled 109 HD patients. Nutritional assessments were performed, and blood samples were taken for routine blood laboratory investigations. The MIS was used as a scoring system to represent the severity of PEW, while the SARC-F was applied as an indicator of sarcopenia risk and general functional capacity. A multivariable logistic regression was conducted to analyze the association of several predictors with a negative cross-sectional outcome (death). Results: Patients with SARC-F scores ≥ 4 and MISs ≥ 6 were older, had significantly lower albumin and prealbumin levels, and more severe anemia. They were also more likely to report weight loss and poor appetite. A higher MIS was closely associated with unfavourable nutritional status according to the International Society of Renal Nutrition and Metabolism (ISRNM) criteria for PEW. However, in 71.25% of patients with satisfactory functional capacity (SARC-F scores 0-3), some form of PEW was still observed. After performing logistic regression modelling, only the MIS remained strongly associated with the probability of a negative outcome. Conclusions: The SARC-F alone often did not correspond to an increased sarcopenia risk or clear clinical and biochemical indicators of PEW in HD patients. When assessing nutritional risk in this group, it is recommended to use more detailed tools, such as the MIS, to ensure the accurate identification of those at the highest risk for negative outcomes.

Specific antigen-based stratification of membranous nephropathy in patients after haematopoietic stem cell allotransplantation - a case series and literature review.

BACKGROUND: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.

Assessment of Salt, Potassium, and Iodine Intake in the Croatian Adult Population Using 24 h Urinary Collection: The EH-UH 2 Study.

Cardiovascular diseases, which are the leading cause of death in Croatia, are linked to the high prevalence of hypertension. Both are associated with high salt intake, which was determined almost two decades ago when Croatian Action on Salt and Health (CRASH) was launched. The main objective of the present study was to evaluate salt, potassium, and iodine intake using a single 24 h urine sample in a random sample of the adult Croatian population and to analyse trends in salt consumption after the CRASH was intensively started. METHODS: In this study, we analysed data on 1067 adult participants (mean age 57.12 (SD 13.9), men 35%). RESULTS: Mean salt and potassium intakes were 8.6 g/day (IQR 6.2-11.2) and 2.8 g/day (IQR 2.1-3.5), respectively, with a sodium-to-potassium ratio of 2.6 (IQR 1.8-3.3). We detected a decrease of 17.6% (2 g/day less) in salt consumption compared with our previous salt-mapping study. However, only 13.7% and 8.9% met the WHO salt and potassium recommended targets of 5 g/day and 3.5 g/day, respectively. Salt intake was higher, and potassium ingestion was lower, in rural vs. urban regions and in continental vs. Mediterranean parts of Croatia. Moderate to severe iodine insufficiency was determined in only 3% of the adult participants. CONCLUSION: In the last fifteen years, salt consumption has been significantly reduced in the Croatian adult population because of the intensive and broad CRASH program. However, salt intake is still too high, and potassium ingestion is too low. Salt reduction programs are the most cost-effective methods of cardiovascular disease prevention and merit greater consideration by the government and health policy makers.

Factors Associated with Hyperpolypharmacy and Complex Medication Regimens in Kidney Transplant Recipients.

Background: Kidney transplantation is considered the best modality for renal replacement therapy. The use of immunosuppressive therapy and pre-existing and newly developed comorbidities predispose these patients to the use of a large number of medications. (Hyper)polypharmacy is associated with worse adherence and negative outcomes. This study aims to explore the factors correlated with hyperpolypharmacy and complex medication regimens in kidney transplant recipients. Methods: This is a cross-sectional study of outpatient kidney transplant recipients. Collected data include demographic data, complete chronic medication lists, medical history, and graft function. Linear and logistic regression were used to identify factors associated with hyperpolypharmacy and complex medication regimens. Medication regimen complexity was quantified by the Medication Regimen Complexity Index (MRCI). Results: Overall, 224 kidney transplant recipients were included, with an average time since transplantation of 8 years. Hyperpolypharmacy was present in more than two-thirds of patients; the average number of different medications was 12; and the mean MRCI score was 21.4, ranging from 6 to 50. Hypertension was almost universally present, while other frequently prescribed medication groups were hypolipemics, medication for bone-mineral metabolism disorders, gout, and antihyperglycemics. Conclusions: Factors independently associated with hyperpolypharmacy and complex medication regimens were found to be age and graft function. Studies investigating interventions aimed at reducing medication complexity and increasing adherence should focus on older patients with worse graft function.

Improving blood pressure and dyslipidemia control by increasing health literacy in Croatia-missions 70/26 & Do you know what is your number.

PURPOSE: In 2022 hypertensive disease was the second cause of death in Croatia. The crude prevalence of hypertension is increasing and still majority of hypertensive patients did not reach blood pressure and cholesterol goals Low awareness, and small number of treated and controlled patients point on poor adherence and even worse clinical inertia. MATERIALS AND METHODS: Croatian Hypertension League (CHL) has started the permanent public health action Hunting the Silent Killer aiming to increase health literacy. In 2023 we decided to intensify program with two missions - '70/26', and 'Do you know what is your number?' aiming to achieve target values in 70% and in 50% of patients treated for hypertension and dyslipidaemia, respectively, by 2026. For the health care workers, the program will primarily involve digital education, and 'School of Communication in Hypertension'. In the second arm of the program, we will advise patients and general population to visit our educational website with important and useful information on how to improve bad lifestyle, how to proper measure blood pressure, why is it important to sustain in taking drugs etc. In 2026, the CHL will organise field research to assess the success of programs using the same methodology as we used in previous EH-UH studies. CONCLUSION: We will monitor and analyse trends in the management and control of patients treated for hypertension and dyslipidaemia. This will enable us to make an evidence-based conclusion how successful we were in increasing health literacy.

Hypertension is the most compelling cause of death in Croatia with increasing prevalence.Still 50.1% of treated hypertensive patients and more than 70% of patients with dyslipidaemia in Croatia are uncontrolled.Programs 70/26 and Do you know your number aimed to achieve 70% and 50% control of hypertensive and dyslipidaemia patients, respectively, by 2026.To accomplish these goals, health literacy of healthcare workers, patients, and general population we will try to improve mostly using digital education and by organising schools of communication.

Combination of SGLT2 Inhibitors and GLP-1 Receptor Agonists in PTDM Treatment in Kidney Transplant Recipients: Synergistic Effect With Added Value in Terms of Nephroprotection.

Post-transplantation diabetes mellitus, obesity, and metabolic syndrome are common complications after kidney transplantation. Data on using novel agents, including SGLT2 inhibitors and GLP-1 receptor agonists, in kidney transplant recipients are scarce and practice guidelines are lacking. According to available data, GLP-1 receptor agonists are efficient in terms of weight loss and glycemia control. Although improvement or no change of eGFR was observed, recently published data suggest their protective effect on graft function. Trials on SGLT2 inhibitors demonstrate improved glycemia control, weight, and blood, and stable kidney function. Given the different mechanisms of action, it has been postulated that a combination of SGLT2 inhibitors and GLP-1 receptor agonist could have beneficial effects in treating diabetes. There is some evidence in the literature postulating the beneficial effects of this treatment combination on cardiovascular outcomes in the general population and only one case emphasizing nephroprotective effect. Data on simultaneous use of SGLT2 inhibitors and GLP-1 receptor agonists in kidney transplant recipients is lacking and, here, we bring our experience.

Exploring Acute Pancreatitis in Kidney Transplant Recipients: A Multicentre Retrospective Cohort Analysis of Incidence, Causes, and Clinical Outcomes.

Background: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. Methods: We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. Results: Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. Conclusions: Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required.

Estimated Pulse Wave Velocity and All-Cause and Cardiovascular Mortality in the General Population.

Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 - 0.402 × age + 4.560 × 10-3 × age2 - 2.621 × 10-5 × age2 × MBP + 3.176 × 10-3 × age × MBP - 1.832 × 10-2 × MBP. MBP= (DBP) + 0.4(SBP - DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118-8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.

Blood pressure measurement and assessment of arterial structure and function: an expert group position paper.

Measuring blood pressure (BP) and investigating arterial hemodynamics are essential in understanding cardiovascular disease and assessing cardiovascular risk. Several methods are used to measure BP in the doctor's office, at home, or over 24 h under ambulatory conditions. Similarly, several noninvasive methods have been introduced for assessing arterial structure and function; these methods differ for the large arteries, the small ones, and the capillaries. Consequently, when studying arterial hemodynamics, the clinician is faced with a multitude of assessment methods whose technical details, advantages, and limitations are sometimes unclear. Moreover, the conditions and procedures for their optimal implementation, and/or the reference normality values for the parameters they yield are not always taken into sufficient consideration. Therefore, a practice guideline summarizing the main methods and their use in clinical practice is needed. This expert group position paper was developed by an international group of scientists after a two-day meeting during which each of the most used methods and techniques for blood pressure measurement and arterial function and structure evaluation were presented and discussed, focusing on their advantages, limitations, indications, normal values, and their pragmatic clinical application.

Residual Renal Function: A Double-Edged Sword.

INTRODUCTION: Nephrotic syndrome may persist despite end-stage kidney disease and result in dyslipidaemia, thrombosis and a significantly increased cardiovascular risk. Treatment of refractory nephrotic syndrome includes surgical bilateral nephrectomy, renal artery embolization and pharmacologic nephrectomy. CASE PRESENTATION: We present a case of a haemodialysis patient with refractory nephrotic syndrome who underwent pharmacologic nephrectomy. The procedure decreased the patient's cardiovascular risk and enabled the patient to become a candidate for kidney transplantation. CONCLUSION: In certain situations residual renal function may be harmful. In such instances, nephrectomy should be considered. Pharmacologic nephrectomy using nephrotoxic drugs is a non-invasive approach with least potential complications.

Croatian Action on Salt and Health (CRASH): On the Road to Success-Less Salt, More Health.

The World Health Organization recommends adjusting salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as a priority and the most cost-effective intervention. In 2006, the main aim of the Croatian Action on Salt and Health was to decrease salt intake by 16% because of its critical intake and consequences on human health. We have organized educative activities to increase awareness on salt harmfulness, define food categories of prime interest, collaborate with industries and determine salt intake (24 h urine sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014-2022, salt in semi-white bread was reduced by 14%, 22% in bakery and 25% in the largest meat industry. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced by 15.9-1.8 g/day (22.8% men, 11.7% women). In the last 18 years, a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with the food industry was established and regulatory documents were launched. However, salt intake is still very high, underlying the need for continuation of efforts and even stronger activities.

Immunomodulatory Effect of COVID-19 on HLA-Antibody Profile in Renal Transplant Recipients.

Background/Objectives: The novel coronavirus disease 2019 (COVID-19) has led to significant morbidity and mortality among kidney transplant recipients. SARS-CoV-2 has been hypothesized to cause an unusual immunological dysregulation triggering alloimmunity and leading to graft rejection. Methods: This prospective observational cohort study assessed 321 kidney transplant recipients who had COVID-19 infection. After the infection, patients' sera were tested for the presence of anti-HLA de novo DSA and non-DSA specificities. Logistic regression analysis and a stepwise multivariable logistic regression analysis were used to analyze the independent risk factors associated with the development of antibodies, adjusting for known confounders. The variables evaluated were acute COVID-19 characteristics (i.e., presentation, and need for hospitalization), demographic characteristics (i.e., age, gender, and primary renal disease), clinical characteristics (i.e., various comorbidities), and post-COVID-19 sequelae. Results: Anti-HLA de novo DSA developed in 18.7% of patients, while anti-HLA class I and class II non-DSA antibodies developed de novo in 84 (26.3%) and 83 (25.9%) patients, respectively. The development of DSA, HLA-DQ, and HLA-DR antibodies was predicted by the history of graft rejection. Obesity appeared to be protective against the emergence of de novo DSA. De novo DSA and HLA-DR antibody formation was positively linked with intravenous immunoglobulin use, CMV-hyperimmune globulin use, and decreased doses of immunosuppression during acute infection. Better allograft function during the acute disease was a protective factor against the formation of HLA-DQ and HLA-DR antibodies. Positive predictors of de novo DSA development were graft biopsy and the reactivation of EBV after infection. Conclusions: These findings suggest that the SARS-CoV-2 virus has an immunomodulatory effect and may be associated with an increased mortality in this population.

The Importance of Early Diagnosis and Intervention in Chronic Kidney Disease: Calls-to-Action from Nephrologists Based Mainly in Central/Eastern Europe.

BACKGROUND: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases. SUMMARY: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care. KEY MESSAGES: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.

Renal Denervation in the Treatment of Resistant Hypertension and Difficult-to-Control Hypertension - Consensus Document of the Croatian Hypertension League - Croatian Society of Hypertension, Croatian Cardiac Society, Croatian Endovascular Initiative, Croatian Society for Diabetes and Metabolic Diseases, Croatian Renal Association, and Croatian Society of Family Physicians of the Croatian Medical Association.

Renal denervation (RDN) as a method of treating arterial hypertension (AH) was introduced in Croatia in 2012. A multidisciplinary team and a network of hospitals that diagnose and treat patients with severe forms of AH were established, and a very strict diagnostic-treatment algorithm was prepared. At monthly meetings patients with truly resistant hypertension who were candidates for RDN were discussed. According to the 2021 ESH position statement and 2023 ESH guidelines, RDN is considered an alternative and additional, not a competitive method of treating patients with various forms of AH which must be performed by following a structured procedure and the patient's preference should be considered. In view of the changes in the global scientific community, the Croatian Hypertension League brings this consensus document on RDN conducted with radiofrequency-based catheter, the only currently available method in Croatia. In this document, exclusion and inclusion criteria are shown, as well as three groups of patients in whom RDN could be considered. The new diagnostic-treatment algorithm is prepared and follow-up procedure is explained. In Croatia, RDN is reimbursed by the national insurance company, thus pharmacoeconomic analyses is also shown. Criteria required by an individual centre to be approved of RDN are listed, and plans for prospective research on RDN in Croatia, including the Croatian registry for RDN, are discussed.

The Hypertension Excellence Centre programme of the European Society of Hypertension - current status, activities and reshaping for the future.

PURPOSE: To describe the history of the Excellence Centre (EC) programme of the European Society of Hypertension (ESH) since the beginning in 2006, its achievements, and its future developments. MATERIALS AND METHODS: We list the number of ECs per country, the research projects performed so far, and the organisational steps needed to reshape the EC programme for the future. RESULTS: In August 2023, the ESH EC programme includes 118 registered ECs in 21 European and 7 non-European countries. Updates about the formal steps for application, re-application, transfer of EC and retirement of EC heads are given. CONCLUSIONS: The EC programme of the ESH has been a success from the beginning. Further refinements will make it fit for the next decades.