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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.
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Glomerulonefritis Membranosa , Trasplante de Células Madre Hematopoyéticas , Humanos , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Adulto , Persona de Mediana Edad , Leucemia Mieloide Aguda/terapia , Síndrome Nefrótico/etiologíaRESUMEN
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.
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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.
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Dislipidemias , Alfabetización en Salud , Hipertensión , Humanos , Croacia , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Dislipidemias/terapia , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Presión Sanguínea/efectos de los fármacos , Masculino , FemeninoRESUMEN
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.
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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 24âh 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.
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Arterias , Determinación de la Presión Sanguínea , Presión Sanguínea , Humanos , Determinación de la Presión Sanguínea/métodos , Arterias/fisiología , Presión Sanguínea/fisiología , Hemodinámica/fisiologíaRESUMEN
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.
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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.
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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.
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Cloruro de Sodio Dietético , Croacia , Humanos , Cloruro de Sodio Dietético/administración & dosificación , Industria de Alimentos , Femenino , Política Nutricional , Masculino , Dieta Hiposódica , Promoción de la Salud/métodos , PanRESUMEN
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.
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Nefrectomía , Síndrome Nefrótico , Humanos , Nefrectomía/efectos adversos , Síndrome Nefrótico/complicaciones , Riñón/fisiopatología , Diálisis Renal/efectos adversos , Trasplante de Riñón , Masculino , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Persona de Mediana EdadRESUMEN
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.
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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.
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Diagnóstico Precoz , Nefrólogos , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/diagnóstico , Europa Oriental/epidemiología , Europa (Continente)/epidemiologíaRESUMEN
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.
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Ablación por Catéter , Diabetes Mellitus , Hipertensión , Enfermedades Metabólicas , Humanos , Croacia/epidemiología , Médicos de Familia , Estudios Prospectivos , Consenso , Arteria Renal/cirugía , Hipertensión/diagnóstico , Hipertensión/cirugía , Riñón , Desnervación/métodos , Simpatectomía/efectos adversos , Simpatectomía/métodos , Presión Sanguínea , Resultado del Tratamiento , Ablación por Catéter/efectos adversosRESUMEN
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.
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Hipertensión , Humanos , Hipertensión/terapiaRESUMEN
Aristolochia clematitis L. is a perennial herbaceous plant distributed throughout Europe, Asia Minor and Caucasus. It has been used as a medicinal plant since antiquity but not in recent times because it contains poisonous aristolochic acid, causing progressive kidney failure. The aim of this work was to study Aristolochia clematitis ecology on the basis of vegetation plots from the European Vegetation Archive, and to investigate the differentiation of its ecological niche using a co-occurrence-based measure of ecological specialization (ESI). The ecological niche was studied on three spatial scales: on the entire distribution area, its differentiation across 200 × 200 km grid cells and the differences between three central and three marginal regions. Our results suggest that Aristolochia clematitis has a very broad ecological niche occurring in a range of different habitats and climatic conditions, with a trend of a niche width decrease with the distance from the geographical center. The plant prefers more stable communities with less anthropogenic influence moving towards the margin of the distribution area. Specialization towards the marginal area is a result of evolutionary history, which refers to the recent anthropogenically induced spread from its original home range. A high incidence of Aristolochia clematitis in the vegetation of arable lands and market gardens as well as anthropogenic herbaceous vegetation in the distribution center corresponds to the geographical incidence of Balkan Endemic Nephropathy.
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BACKGROUND: The effectiveness of the COVID-19 vaccine may differ in hemodialysis patients. The aim of this prospective multicenter study was to determine the degree of serological response to the SARS-CoV-2 vaccine in the population of dialysis patients and its association with later SARS-CoV-2 infections. METHODS: A blood sample was taken for the determination of COVID-19 serological status (IgG antibodies) in 706 dialysis patients 16 weeks after vaccination with the second dose (Pfizer-BioNTech). RESULTS: Only 314 (44.5%) hemodialyzed patients had a satisfactory response to the COVID-19 vaccine. Eighty-two patients (11.6%) had a borderline response, while 310 patients (43.9%) had an unsatisfactory (negative) post-vaccinal antibody titer. A longer dialysis vintage had an increased odds ratio (OR) of 1.01 for the occurrence of COVID-19 positivity after vaccination. In the group of subsequently positive patients, 28 patients (13.6%) died from complications of COVID-19. We have found differences in mean survival time between patients with and without appropriate responses to vaccination in favor of patients with a satisfactory serological response. CONCLUSIONS: The results showed that the dialysis population will not have the same serological response to the vaccine as the general population. The majority of dialysis patients did not develop a severe clinical picture or die at the time of positivity for COVID-19.
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DOCUMENT REVIEWERS: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).
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Hipertensión , Humanos , Italia , España , Francia , Países Bajos , Hipertensión/tratamiento farmacológico , Europa (Continente)RESUMEN
Chronic kidney disease (CKD) is a very common chronic non-communicable disease. Phosphate and calcium metabolism disorders are one of the most common features of CKD. Sevelamer carbonate is the most widely used non-calcium phosphate binder. Gastrointestinal (GI) injury associated with sevelamer use is a documented adverse effect but is underrecognized as a cause of gastrointestinal symptoms in patients with CKD. We report a case of a 74-year-old woman taking low-dose sevelamer with serious gastrointestinal adverse effects causing colon rupture and severe gastrointestinal bleeding.
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OBJECTIVES: In this study, we investigated whether SARS-CoV-2 stimulates autoantibody production. METHODS: The study included 91 patients hospitalized due to COVID 19, with no previous history of immunological diseases. Immunofluorescence assays were performed to detect antinuclear antibodies (ANAs) and antineutrophil cytoplasmic antibodies (ANCAs), along with tests for specific autoantibodies. RESULTS: The median age (57% male) was 74 years (range 38-95 years). Autoantibodies were positive in 67 (74%), ANA in 65 (71%), and ANCA in 11 (12%) patients. Female gender (p = 0.01), age (p = 0.005), and Charlson comorbidity index (p = 0.004) were significant predictors for the development of ANA/ANCA antibodies (p = 0.004). Nuclear mitotic apparatus (NuMA)-like, positivity was the strongest predictor of acute kidney injury (AKI), together with noninvasive ventilation and eGFR (χ2 = 49.01, P < 0.001). CONCLUSION: Positive autoantibodies in a large proportion of patients suggest a role of autoimmunity in the pathophysiology of acute COVID-19 disease. NuMA was the strongest predictor of AKI.
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Lesión Renal Aguda , COVID-19 , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Autoanticuerpos , Anticuerpos Anticitoplasma de Neutrófilos , SARS-CoV-2RESUMEN
Cystinuria is a rare genetic disorder inherited by an autosomal recessive pattern which affects the transmembrane transporter for the base amino acid cystine. It has a general prevalence of 1 in 7000 with demographic variations. Patients with cystinuria have excessive urinary excretion of cystine, which can lead to the formation of stones. Up to 70% of patients will develop chronic kidney disease that can progress even to end-stage renal disease. Symptoms usually start in the first two decades of life with a typical presentation consisting of flank pain and renal colic, usually accompanied by urinary tract infection and deterioration of kidney function. Men are typically affected twice as often as women and have a more severe clinical course. Diagnosis is made by spectrophotometric analysis of the stones that are collected after spontaneous expulsion or medical intervention. Genetic testing is not mandatory but is recommended in uncertain cases or as a part of genetic counseling. Treatment consists of diet modification, alkalization of urine, and thiol-based therapies if other measures fail to prevent stone formation. In pregnancy, cystinuria with the formation of cystine stones represents a therapeutic challenge and requires a multidisciplinary approach consisting of an uro-nephrology team and a gynecologist. We present the case of a 34-year-old woman with cystinuria on whom the diagnosis was made by analysis of the expulsed stone. While her previous pregnancies were without complications, her third pregnancy was accompanied by frequent urinary tract infections, acute worsening of kidney function, and urological interventions during pregnancy due to the formation of new stones. Despite the complicated course, the pregnancy was successfully carried to term with the delivery of a healthy female child.
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Although changes in dietary sodium intake alter blood pressure (BP) in salt-sensitive individuals, pathophysiological mechanisms are still unknown. It has been reported that uromodulin is involved in sodium tubular transport, and genome-wide association studies pointed to UMOD gene as one of the most important gene candidates for arterial hypertension. Our aim was to analyze urinary uromodulin, salt intake and BP in 326 young middle-aged subjects (mean age 36±8 years, 49.4% male). In a subgroup of 175 individuals, ambulatory blood pressure monitoring and echocardiogram were performed. Uromodulin was determined by ELISA. According to the JNC-7 criteria, subjects were classified as optimal BP (n=103, men 72%), prehypertension (PHT) (n=143, men 43%) and hypertension (HT) (n= 80, men 38%). There were no differences in age, salt intake, estimated glomerular filtration rate, sodium excretion and uromodulin among BP groups. However, in PHT subjects, uromodulin was positively associated with fractional sodium excretion and negatively with 24-h sodium excretion and diastolic BP dip. These findings point to the effect of uromodulin on sodium reabsorption along the nephron and consequently circadian BP alteration in prehypertensives.