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Background and objectives For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure-related symptoms differently, but the change in symptoms before and after start of dialysis has not been studied. Therefore, we investigated the course of total and individual symptom number and burden before and after starting dialysis in older patients.Design, setting, participants, & measurements The European Quality (EQUAL) study is an ongoing, prospective, multicenter study in patients >= 65 years with an incident eGFR

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

Abnormal coagulation parameters are often observed in patients with coronavirus disease 2019 (COVID-19) and the severity of derangement has been associated with a poor prognosis. The COVID-19 associated coagulopathy (CAC) displays unique features that include a high risk of developing thromboembolic complications. Viscoelastic tests (VETs), such as thromboelastometry (ROTEM), thromboelastography (TEG) and Quantra Hemostasis Analyzer (Quantra), provide “dynamic” data on clot formation and dissolution; they are used in different critical care settings, both in hemorrhagic and in thrombotic conditions. In patients with severe COVID-19 infection VETs can supply to clinicians more information about the CAC, identifying the presence of hypercoagulable and hypofibrinolysis states. In the last year, many studies have proposed to explain the underlying characteristics of CAC; however, there remain many unanswered questions. We tried to address some of the important queries about CAC through VETs analysis.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Studies addressing the anti-inflammatory properties of citrate dialysate enrolled patients in both hemodialysis (HD) and hemodiafiltration (HDF), the latter not adjusted for adequate convective exchange. This is a potential source of confounding in that HDF itself has anti-inflammatory effects regardless of the buffer, and optimal clinical outcomes are related to the amount of convection. To distinguish the merits of the buffer from those of convection, we performed a 6-month, prospective, randomized, crossover AB-BA study. Comparisons were made during the 3-month study period of on-line HDF with standard dialysate containing three mmol of acetic acid (OL-HDFst) and the 3-month of OL-HDF with dialysate containing one mmol of citric acid (OL-HDFcit). Primary outcome measure of the study was interleukin-6 (IL-6). Klotho, high sensitivity C-reactive protein (hsCRP), fetuin and routine biochemical parameters were also analyzed. We analyzed 47 patients (mean age 64 years, range 27-84 years) enrolled in 10 participating Nephrology Units. Convective volumes were around 25 L/session with 90 percent of sessions > 20 L and s2-microglobulin reduction rate 76% in both HDFs. Baseline median IL-6 values in OL-HDFst were 5.6 pg/ml (25:75 interquartile range IQR 2.9:10.6) and in OL-HDFcit 6.6 pg/ml (IQR 3.4:11.4 pg/ml). The difference was not statistically significant (p 0.88). IL-6 values were lower during OL-HDFcit than during OL-HDFst, both when analyzed as the median difference of overall IL-6 values (p 0.02) and as the median of pairwise differences between the baseline and the 3-month time points (p 0.03). The overall hsCRP values too, were lower during OL-HDFcit than during OL-HDFst (p 0.01). Klotho levels showed a time effect (p 0.02) and the increase was significant only during OL-HDFcit (p 0.01). Citrate buffer modulated IL-6, hsCRP and Klotho levels during high volume OL-HDF. These results are not attributable to differences in the dialysis technology that was applied and may suggest a potential biological effect of citrate on CKD-associated inflammatory state. ClinicalTrials.gov identifier NCT02863016.

BACKGROUND Humoral response after two doses of mRNA-based SARS-CoV-2 vaccines is weak in kidney transplant recipients (KTRs) [1]. Of concern, even a third dose of the mRNA-1273 vaccine induced a suboptimal humoral response in a cohort of KTRs who did not respond after two doses [2]. However, the assessment also of the T-cell immune response of mRNA vaccines in KTRs is limited in the literature [3]. Herein, we report the evaluation of humoral response induced after a third dose of the mRNA-1273 vaccine in a cohort of KTRs and T-cell immune responses in not responders to the third dose. METHODS Observational cohort data were collected from KTRs actively followed up in our outpatient clinic, with no history of COVID-19 infection, who received a third mRNA-1273 vaccine dose, 6 months after the second dose, as per suggested local policy. The primary endpoint was the humoral response provided at least 4 weeks after the third dose compared with the humoral response after the second dose. Anti-S1-RBD IgG antibodies were determined using a fluoroimmunoenzymatic method (Thermo Fisher Scientific), and the quantitative result expressed in BAU/mL (reference interval: 40 Positive; linear range between 0.7 and >1632 according to the manufacturer). In seronegative and borderline KTRs after the third dose, an INFγ-release assay (IGRA) [Euroimmun, Lubeck, Germany] was used to detect T-cell immune responses. A patient result was considered negative, borderline and positive when IFNγ values were respectively 200 mIU/mL. RESULTS Sixty KTRs received a third dose of the mRNA-1273 vaccine. Overall, we obtained the antibody titre in 57 KTRs at a median of 23 days (IQR: 22–31) after the second dose and 23 days (IQR: 21–26) after the third dose. After the second dose, positive antibody titres were detectable in 28 KTRs (49%), and 2 KTRs (4%) had a borderline positivity. While after third dose, positive and borderline antibody responses were observed in 40 (70%) and 4 (7%) KTRs, respectively. Among all 57 KTRs, the median anti-S1-RBD IgG titre significantly increased after the third dose ( 448 versus 39 BAU/mL; P = 0.0018; Mann–Whitney test). While in 28 KTRs already seropositive after the second dose, the median antibody titre increased from 556 to >1632 BAU/mL (P = 0.0285; Mann–Whitney test). Figure 1 shows the kinetics of anti-S1-RBD IgG titres after the second and the third dose for all the 57 KTRs. Among 17 KTRs with negative and borderline humoral responses after the third dose, IFNγ values were positive and borderline in only 1 (6%) and 1 (6%) KTRs, respectively. The median IFNγ value was 22 mIU/mL (IQR: 0–1014). The 34 KTRs receiving mycophenolate mofetil (MMF) were less likely to develop adequate immune responses than the 23 KTRs not receiving MMF; 12 KTRs (35%) receiving MMF had no antibody and IFNγ positive response after the third dose in comparison to 4 KTRs (17%) not receiving MMF, and the median anti-S1-RBD IgG titre beyond the two groups after the third dose was statistically different (205 versus > 1632; P = 0.0046; Mann–Whitney test). CONCLUSIONS In this study, the third dose of the mRNA-1273 vaccine increases the rate of positive antibody responses in non-responders KTRs after the second dose, and improves the magnitude of these responses in already seropositive KTRs. However, a fraction of KTRs still lacks protective antibody titres and T-cell responses after a third dose, with mycophenolate mofetil to be associated with poor immune responses. Alternative vaccination protocols are needed to protect this high-risk group.

BACKGROUND Adults receiving haemodialysis (HD) have a higher mortality risk when infected with SARS-CoV-2 and less intense humoral response after two doses of mRNA vaccines compared with healthy subjects [1], leading the Italian authorities to recommend a third dose as a priority in this high-risk population. Here we investigated the humoral response to the third dose of the mRNA-1273 vaccine in a cohort of HD patients. METHODS Observational cohort data were collected from our HD centre. A third dose of the mRNA-1273 vaccine was proposed to all HD patients regardless of the anti-S1-RBD IgG titres measured at a median two weeks before the scheduled injection, and regardless of previously developed COVID-19. All patients received two doses of the mRNA-1273 vaccine in March-April 2021. As per the suggested policy, the third dose was administrated 6 months after the second dose. The primary endpoint was the humoral response at least four weeks after the third dose of vaccine compared with the anti-S1-RBD IgG titre measured two weeks before the vaccine administration. Anti-S1-RBD IgG titres were determined using a fluoroimmunoenzymatic method (Thermo Fisher Scientific), and the quantitative result expressed in BAU/mL (reference interval: 40 Positive; linear range between 0.7 and >1632 according to the manufacturer). RESULTS Among the 66 HD patients who received two mRNA-1273 doses, 2 (3%) developed COVID-19 after the second dose of vaccine, and two patients refused the third injection. Thus, 64 patients received the third dose (Figure 1). At baseline, anti-S1-RBD IgG titres were measured at a median of 12 days (IQR 10–15) before the third vaccine dose. The median level of anti-S1-RBD IgG was 208 BAU/mL (IQR 0.7–>1632). Negative, borderline and positive responses were observed in 16 (24.2%), 2 (3%) and 48 (72.7%) patients, respectively. After the third vaccine dose, anti-S1-RBD IgG titres were measured at a median of 43 days (IQR 40–49). The median anti-S1-RBD IgG titre significantly increased after the third dose (>1632 versus 142; P CONCLUSIONS In this study, a third dose of the mRNA-1273 vaccine substantially increased antibody levels in HD patients, consolidating the humoral response against SARS-CoV-2 in a population known to have a rapid antibody decline after vaccination [1,3]. Furthermore, the third dose allowed seroconversion in those patients without a protective antibody titre after about 6 months of the conventional vaccination schedule. Thus, intensification of the vaccination protocol appears to be a reliable strategy for strengthening protection against SARS-CoV-2 in HD patients.

BACKGROUND Advance care planning (ACP) enables competent patients to define goals and preferences for future treatments and care, to discuss these goals and preferences with relatives, and if appropriate to record these preferences [1]. After many years of political and social debates, in December 2017 the first advance directive and care planning legislation was approved in Italy. In the last years, several national recommendations released by political institutions and medical associations have underlined the importance of conducting ACP with chronic patients, included dialyses patients. Nevertheless, citizens’ awareness of these issues is scarce as well as the integration of the ACP process into clinical routine [2]. METHOD Since November 2020, our nephrology unit adopted a protocol aimed to conduct ACP interventions with dialysis patients. Firstly, all patients were informed about the possibility to taking part in one or more ACP conversations with their nephrologist. Secondly, a semi-structured guide to the conversation was created in order to support physicians in conducting the ACP intervention. The guide is divided into three sections: (1) exploring patient's understanding of the disease and his/her hopes and life goals; (2) patient's social relationships; (3) preferences for future treatments and care (e.g. CPR, dialysis, palliative care, etc). Finally, patients along with nephrologist and their relatives can document their preferences. RESULTS Of 110 haemodialysis patients, 40 treated in our centre asked for an ACP intervention and filled-in an advance directive. Specifically, no patients required an immediate discontinuation of dialysis; nevertheless, 70% of them stated that would not like to continue with dialysis in case he/she was no longer able to self-determine (e.g. permanent loss of capacity to communicate with others). Most of patients (90%) have appointed a personal representative (usually their partner). In the eventuality of cardiac arrest, 55% of patients asked for cardiopulmonary resuscitation. Pain control and palliative care was the overall most cited topic. The fear of being a burden on family members has been frequently expressed by not independent patients. Regarding the last phase of life, 75% of patients expressed the desire to stay at home, the others in hospice. CONCLUSION ACP process is very recent in Italy and not well known by patients and healthcare providers (HCPs). As a result, discussions about future treatments and care are rarely included in the clinical routine with haemodialysis patients. Training of HCPs on these issues as well as the use of procedures tailored to the Italian context for conducting ACP interventions is needed.

BACKGROUND Nephrotic syndrome is associated with many solid tumours and haematologic malignancies. Membranous nephropathy (MN) is the most commonly reported paraneoplastic glomerulonephritis; about 10% (rate 5–20%) of adults with MN have been reported to have a malignancy [1]. Less frequently, minimal change disease, focal segmental glomerular sclerosis, membranoproliferative and crescentic glomerulonephritis, IgA nephropathy [1] and thrombotic microangiopathy [2] have been associated with cancer. Differentiating primary from secondary glomerular disease in patients with malignancy can be difficult. The probability of a secondary form is higher when the appearance of proteinuria or nephrotic syndrome precedes by few months or develops within a year of cancer diagnosis. The suspicion of paraneoplastic nephropathy is even stronger when tumour remission is associated by significant fall in proteinuria and when recurrence of malignancy is followed by the development of clinical glomerular disease. Solid tumour most commonly associated with glomerular diseases (mainly MN) is lung cancer, followed by prostate and colorectal cancer. Paraneoplastic glomerular diseases are rarely linked to breast cancer. In two reviews, breast cancer was reported only in 3% (5 out of 159 patients) [1] and 8% (6 out of 85 patients) of patients with MN and solid tumours. Breast cancer is the most common malignancy in women, while it is a rare disease in men. Male breast cancers account for less than 1% of all diagnosed cases, and the mean age is usually over 60 years [1]. METHODS We report the case of a breast cancer in a man associated with a paraneoplastic nephrotic syndrome. A 76-year-old man was managed at our renal department since 2016 for chronic kidney disease. He was overweight and affected by non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease. Since 2016 to December 2020, he had stable renal function with serum creatinine levels ranging from 2.5 to 3.0 mg/dL and a normal urinary protein excretion rate (100–150 mg/24 h). In March 2021, the patient developed a right periareolar breast swelling, pain and erythema with yellowish nipple discharge. In the same period, a full-blown nephrotic syndrome with heavy proteinuria (8 g/24 h) was observed, and serum creatinine increased to 3.5–4.0 mg/dL. Immunological blood tests were negative, including anti-PLA2R and anti-THSD7A antibodies. A kidney biopsy could not be performed due to bilateral renal cysts. Mammogram examination and ultrasound imaging revealed ductal ectasia and microscopic calcifications at the site of right breast lesion, so a diagnosis of cancer was made. RESULTS In September 2021, the patient underwent radical right mastectomy and histopathological examination confirmed early-stage breast cancer (pT1a, pN0, Mx R0, ER 100%, PgR 0, Ki67 5%, CerbB2 neg). In the following month, the 24-h urinary protein excretion markedly reduced to 1.4 g and the nephrotic syndrome resolved completely, confirming its secondary origin. CONCLUSIONS Paraneoplastic nephrotic syndrome is a rare complication of cancer. Its recognition and detection of an undiagnosed malignancy could be life-saving. To our knowledge, this is the first case reported in literature of paraneoplastic nephrotic syndrome in a man affected by breast cancer.

Introduction: Poor medication adherence in CKD patients is associated with high mortality and morbidity and can reach up to 80%. The most effective interventions to increase patients’ adherence to treatments are conducted by a multi-professional team and with the active participation of patients and their families. Narrative evidence-based medicine has been proved as a useful methodology in the care of chronic patients also in promoting their adherence to treatments. Methods: Around 50-70% of CKD patients treated in our centre will follow clinical protocol based on a narrative medicine approach: (1) patients will be invited to write a brief history related to their experience with the CKD and treatments; (2) screening for depression (HADS; PHQ-9); (3) intervention of pharmaceutical counselling aimed to explore patients’ behaviours about taking their medications; (4) sharing of decision-making: the results of the narrative histories and of questionnaires will be discussed with the patients; (5) psychoeducational groups. Results: The pilot phase of the project will last 6 months. During these months, patients will be monitored for biochemical (e.g. anemia) and anthropometric (e.g. blood pressure) parameters and depression. Medical visits or diagnostic tests missed by patients will also be recorded. Conclusions: The development of an active role of patients in taking care of themselves is one of the main challenge of clinical nephrology. The present project aims to implement in the clinical routine a protocol based on the narrative medicine approach in which the biological, psychological and social needs of CKD patients are considered and discussed with them.

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0–100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was –0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03–1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.

Immunocompromised patients, including solid organ transplant recipients (SOTRs), were not included in the two large trials of Pfizer/BioNTech and Moderna mRNA vaccines, and therefore, safety and efficacy data are lacking in this population. Recently, immunogenicity, at a median of 29 days, after dose 2 of the mRNA SARS-CoV-2 vaccines have been studied among 658 SOTRs. 46% of participants did not mount anti spike antibody responses suggesting that such patients may remain at high risk for COVID-19 despite vaccination.

Background and Aims Advance care planning (ACP) enables competent patients to define goals and preferences for future treatments and care, to discuss these goals and preferences with relatives, and if appropriate to record these preferences. After many years of political and social debates, in December 2017 the first advance directive and care planning legislation was approved in Italy. Nevertheless, citizens’ awareness of these issues is scarce as well as the integration of the advance care planning process into clinical routine. The latest data reported to the Italian Parliament by the Ministry of Health indicated that advance directives have been completed by 62030 people, approximately 1.1% of Italian adult population. However, during the last months, the COVID-19 pandemic solicited taking steps towards promoting an advance care planning culture. Indeed, the need of proposing ACP to patients have been recently stressed both by medical associations and national and local institutional documents. Method Since November 2020, our nephrology unit adopted a protocol approved by Ethical committee by Physician Order of Florence, aimed to conduct ACP interventions with dialysis patients. Firstly, all patients were informed about the possibility to taking part in one or more advance care planning conversations with their nephrologist. Secondly, a semi-structured guide to the conversation was created in order to support physicians in conducting the ACP intervention. Finally, patients along with nephrologist and their relatives, could documented their preferences for future treatments and care. Results From November to March only one patient asked to receive an ACP intervention. However, since COVID-19 spread in Italy last March, the number of patients who demanded ACP raised up. In the period from April to July, 15 out of 110 hemodialysis patients treated in our center asked for an ACP intervention and filled-in an advance directive. Specifically, no patients required an immediate discontinuation of dialysis, nevertheless 80% of them stated that would not like to continue with dialysis in case he/she was no longer able to self-determine (e.g. permanent loss of capacity to communicate with others). All patients except one have appointed a personal representative (usually their partner). In the eventuality of cardiac arrest, 60% of patients asked for cardiopulmonary resuscitation. Finally, all patients expressed the wish to spend the last days of life at home. Conclusion The COVID-19 pandemic raised up the number of dialysis patients who required to taking part in a advance care planning intervention. In this sense, the pandemic can be an opportunity for consolidate advance care planning in Italy as well as in other countries, where these interventions are not well known by people and not yet regularly offered in the clinical routine. Using a semi-structured interview for the ACP interview can help the nephrologist to discuss future care and end-of-life topics with their patients.

Anticoagulant drugs (i.e., unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants) are widely employed in preventing and treating venous thromboembolism (VTE), in preventing arterial thromboembolism in nonvalvular atrial fibrillation (NVAF), and in treating acute coronary diseases early. In certain situations, such as bleeding, urgent invasive procedures, and surgical settings, the evaluation of anticoagulant levels and the monitoring of reversal therapy appear essential. Standard coagulation tests (i.e., activated partial thromboplastin time (aPTT) and prothrombin time (PT)) can be normal, and the turnaround time can be long. While the role of viscoelastic hemostatic assays (VHAs), such as rotational thromboelastometry (ROTEM), has successfully increased over the years in the management of bleeding and thrombotic complications, its usefulness in detecting anticoagulants and their reversal still appears unclear.

Background and Aims Poor medication adherence in CKD patients can reach up to 80%. Non-adherence is associated with high mortality and morbidity and it is a negative criterion for the inclusion in the transplant waiting list. Poor adherence increases also the costs for health care in terms of diagnostic procedures, dialysis in emergency, etc. Therefore, to increase patients’ adherence to medical treatments is one of the priority of clinical nephrology. According to the WHO adherence behaviors are associated to several factors (e.g. organization of health services, doctor-patient relationship, patients’ psychosocial factors). The most efficacy interventions descried in the literature to increase patients’ adherence to treatments are conducted by a multi-professional team and with the active participation of patients. In the last years, narrative evidenced-based medicine has been proved as a useful methodology in the care of chronic patients also in promoting adherence to treatments. Aim of this clinical project is to obtain the best control of the evolution of chronic kidney disease through a multidisciplinary approach of narrative medicine. Method Within the pre-dialysis service of the Division of Nephrology and Dialysis Firenze 2, it has been integrated the clinical care for CKD patients with a protocol based on a narrative medicine approach (Fig.1). The clinical protocol is composed by the following procedures: Results This project begun around 2 months ago. In this period 15 patients were met, collecting stories by 12 of them (80%). Most of the stories were rich of contents and useful from a medical point of view. None patients refuse the medical consultation at the presence of psychologist, and 5 of them asked for psychotherapy sessions. In line with the literature, 30% of patients presented symptoms of depression. Due to logistic reasons we are going to start the pharmacy counseling intervention at the end of January. All patients were grateful to have been included in this protocol. In the following months we will be able to assess the impact of this protocol in terms of medical outcome. Conclusion To promote an active role of patients in taking care of themselves and follow medical prescriptions, it has been implemented a clinical protocol based on narrative medicine approach in which the biological, psychological and social needs of patients are considered and discussed with them. The empirical results obtained in these first months indicate a positive response from patients in terms of wish to write the experience with the disease and to receive the medical visit with the nephrologist at the presence of a psychologist.

Background and Aims Obesity, hypertension, smoke, high dietary salt intake and physical inactivity are the main modifiable risk factors for chronic kidney disease, that affects about 9-10% of Italian people. About daily salt intake, the World Health Organization recommends a maximum consumption of 5 grams of salt per day. In Italy, most people consume too much salt – on average 8-10 grams per day or around twice the recommended maximum level of intake. Aim of this study was to investigate dietary habits and lifestyle of the heterogeneous students population of “Scuola Carabinieri di Firenze” (attended by people coming from all Italian regions) and their relations with urinary abnormalities. Method from November 2018 to March 2019 we collected anamnestic and anthropometric data, blood pressure measurements and body cellular mass (BCM) of 257 young subjects (152 males, 105 females; mean age 32 + 11 yy). We determinated sodium, chlorine and protein excretion on a spot urine sample in addition to plasma creatinine levels. Statistical analyses were performed using SPSS. Results We analyzed preliminary data of urinary sodium excretion (UNa), proteinuria (Up) and hematuria (Urbc) of all the subjects. Fifty-five percent of them had a UNa higher than 100 mmol/L (approximately equivalent to a dietary salt intake of 6 grams/day). In these subjects with higher salt consumption, Up and Urbc, measured by urine dipstick, were detectable in 32% and 21% respectively. In subjects with lower salt intake (less than 6 grams/day), Up and Urbc were 0% and 5% respectively. To determine if there was an association between our variables, we used Pearson correlation coefficient. We found that UNa was directly related to Up (r 0.26, p 0.002), age (r 0.22 p 0.011) and diastolic blood pressure (DBP, r 0.22, p 0.012). We also found that poor exercise (r -0.15, p 0.7) and low lean body mass percentage (r -0.15, p 0.7) were inversely related to UNa. Conclusion high dietary salt intake is associated with elevated blood pressure and proteinuria in a young and “healthy” population. Hypertension and proteinuria are both known risk factors for the development of chronic kidney disease. Wrong dietary habits and lifestyles must be detected and corrected in order to prevent nephropathy onset.

Introduction: CKD is associated with a reduction of patients’ health-related quality of life. Considering the time spent in dialysis, satisfaction with care is essential for patients QOL. Objective: Since the possible association between satisfaction with the dialysis care and QOL has never been studied, in this study, we explore this plausible link. Methods: One hundred three patients on hemodialysis (HD) and peritoneal dialysis (PD) filled-in patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). QOL was assessed by Kidney Disease Quality of Life-36 and satisfaction by Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) questionnaire. The analysis was conducted on patient-level, considering for single patient sociodemographic characteristics and presence of depression/anxiety. One-way ANOVA was used to compare QOL mean scores for patients who answered “excellent” and for those who answered “other ratings” in CHOICE questionnaire and the Pearson χ2 test to compare the patients’ characteristics between these 2 groups of patients. Results: The analysis showed a significant positive association between PREM and PROM scores for 8 out of 23 CHOICE items. Six of them were related to the figure of nephrologist, 1 to dialysis access site, and 1 to the social worker support. Significant association (p < 0.05) were between frequency of seeing nephrologist and physical component plus mental component, accuracy of information from nephrologist and burden of disease, accuracy of instructions from nephrologist and burden of disease, coordination between nephrologist and other physicians plus mental component, attention to cleanliness of access site and mental component, amount of dialysis information from staff and burden of disease, information from staff when choosing between HD or PD and physical component plus burden of disease, and ease of seeing social worker and burden of disease. Conclusions: The study provides support for the relationship between the care satisfaction and QOL, highlighting the central role of the nephrologist-patient communication in the QOL of dialysis patients.

Background: Depression is the most common psychiatric disorder in long-term dialysis patients and a risk factor for morbidity and mortality. Although there is a relevance of the issue in the dialysis setting, we still know little about possible relationships between depression and uraemia-related biochemical abnormalities. Our aims were to evaluate (1) the prevalence of depression in our haemodialysis (HD) and peritoneal dialysis (PD) population using a validated and easy-to-implement screening tool and (2) the association between depression and the main uraemia-related clinical and biochemical parameter changes. Methods: In this monocentric cross-sectional study, all patients of our centre with at least 3 months of dialysis were screened by Patient Health Questionnaire-9 (PHQ-9), a self-administered depression-screening questionnaire validated in dialysis setting. The impact of depressive symptoms on daily life was also assessed. We then analysed relationships between the PHQ-9-derived depressive score, functional impairment score, demographic, clinical and laboratory variables. Results: In our cohort of 145 patients, depressive symptoms were found in 69 patients (46%). Stratifying for severity, mild, moderate and severe grade accounted for 31, 13 and 2% respectively. Depressive symptoms affected 36% of patients on PD versus 52% of patients on HD. Moreover, the PD patients had significantly less functional impairment derived from depressive symptoms than the HD patients. Simple and multiple regression analysis identified serum phosphorus as the only uraemia-related laboratory parameter that was high statistically associated with depressive score. Conclusions: Using a reliable, simple and fast tool, we found that depressive symptoms affect almost half of dialysis patients, particularly so the HD cohort. Severity of depressive symptoms seems related to serum levels of phosphorus possibly because depression affects compliance to therapy.

BACKGROUND Aim of this study was to evaluate the early and mid-term outcomes of drug-coated balloons (DCBs) in hemodialysis patients with recurrent stenosis of arteriovenous fistula and previously treated with plain balloon angioplasty (PBA). METHODS Between July 2013 and June 2016 38 hemodialysis patients with recurrent stenosis of arteriovenous fistula underwent endovascular treatment with a DCB at our center. All patients were previously treated at the target lesion with a PBA. The intervals in months between the standard PBA and the procedure with DCB (time PBA-DCB) and between the procedure with DCB and the restenosis at the target lesion (time DCB-restenosis) were evaluated and compared with T-test. Estimated outcomes at 2 years in terms of patient survival, primary patency, primary assisted patency, secondary patency, and freedom from target lesion restenosis were assessed with Kaplan-Meier curves. RESULTS Intraprocedural technical success was obtained in 97.4% of the cases. During the follow-up (mean duration 14.3 months, range 2-33) 19 patients (50%) developed a restenotic lesion at the target lesion with an estimated 2-year freedom from target lesion restenosis of 32.8%. Mean time PBA-DCB was 6.4 months, and the mean time DCB-restenosis was 7.9 months with a statistically significant difference at T-test (P

Background: Estimated glomerular filtration rate (eGFR) is a predictor of outcome among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), but which estimation formula provides the best long-term risk stratification in this setting is still unclear. We compared the prognostic performance of four creatinine-based formulas for the prediction of 10-year outcome in a NSTE-ACS population treated by percutaneous coronary intervention. Methods: In 222 NSTE-ACS patients submitted to percutaneous coronary intervention, eGFR was calculated using four formulas: Cockcroft–Gault, re-expressed modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-Epi), and Mayo-quadratic. Predefined endpoints were all-cause death and a composite of cardiovascular death, non-fatal reinfarction, clinically driven repeat revascularisation, and heart failure hospitalisation. Results: The different eGFR values showed poor agreement, with prevalences of renal dysfunction ranging from 14% to 35%. Over a median follow-up of 10.2 years, eGFR calculated by the CKD-Epi and Mayo-quadratic formulas independently predicted outcome, with an increase in the risk of death and events by up to 17% and 11%, respectively, for each decrement of 10 ml/min/1.73 m2. The Cockcroft–Gault and MDRD equations showed a borderline association with mortality and did not predict events. When compared in terms of goodness of fit, discrimination and calibration, the Mayo-quadratic outperformed the other formulas for the prediction of death and the CKD-Epi showed the best performance for the prediction of events (net reclassification improvement values 0.33–0.35). Conclusions: eGFR is an independent predictor of long-term outcome in patients with NSTE-ACS treated by percutaneous coronary intervention. The Mayo-quadratic and CKD-Epi equations might be superior to classic eGFR formulas for risk stratification in these patients.

We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

Benefits and risks of angiotensin converting enzyme inhibitors (ACE-I) in advanced chronic kidney disease (CKD) are controversial. We tested the role of ACE-I in slowing the progression of renal damage in a real-world elderly population with CKD stage 5. We evaluated all patients consecutively referred to our CKD stage 5 outpatient clinic from January 2002 to December 2013. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m2. We retrieved parameters of interest at baseline and assessed eGFR reduction rate during follow-up. We estimated GFR by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. Mean age of the 342 subjects analyzed was 72 years and eGFR 10 ml/min/1.73 m2. In the 188 patients on ACE-I at baseline, the subsequent annual rate of eGFR reduction was less than a third of that found in the 154 patients off ACE-I. Across phosphate quartiles, baseline eGFR significantly decreased while its annual reduction rate significantly increased. Of the original cohort, 60 patients (17 %) died, 201 (59 %) started dialysis and 81 (24 %) were still in conservative treatment at the end of the study. Multivariate analysis identified age, phosphate, proteinuria, baseline eGFR and its rate of progression as independent risk factors directly or inversely predictive of progression to dialysis. ACE-I use significantly reduced by 31 % the risk of dialysis. Our study shows that proteinuria independently predicts further renal damage progression even in end-stage renal disease patients not yet in dialysis. In our cohort of elderly patients with very advanced CKD, ACE-I was effective in slowing down further renal damage progression.

Background. In patients on on-line convective treatments, given the considerable quantity of dialysis fluid re-infused, the small amount of acetate present in bicarbonate dialysis fluid as a pH stabilizing factor may allow a significant transfer of that anion to the patient, possibly inducing cytokine activation. Methods. To verify this hypothesis, we performed on-line haemodiafiltration (OL-HDF) with (3 mmol/l) and without acetate in dialysis fluid in a cross-over randomized order on 12 prevalent patients. Results. In comparison with the pre-treatment values, plasma acetate levels were unchanged during and after acetate-free OL-HDF, while they were 5–6 times higher in the course of OL-HDF containing acetate in dialysis fluid; plasma acetate levels returned to basal values 2 h after the end of the procedure. The total increase of bases in the patient attributable to acetate was 36%. Plasma bicarbonate values at the end of treatment were significantly lower in treatments without acetate, as compared to those with acetate. Interleukin-6 plasma levels were super-imposable at the beginning and in the course of the two methods compared, but there was a tendency towards a greater increase at an interval of 2 h following OL-HDF with acetate. Conclusions. Our preliminary results confirm the assumption that body gain of acetate is particularly high in convective treatments, while acetate-free OL-HDF slows down acetate burden. Clinical advantages due to these effects should be evaluated in properly designed prospective studies.

Parameters derived by ultrasonic myocardial characterization in dialysis patients are associated with mortality.BackgroundAutopsy studies have shown that hypertrophic hearts of uremic patients have peculiar characteristics. Changes in tissue structure are detectable by ultrasound as changes in echo reflectivity.MethodsWe studied 96 dialysis patients, 18 hypertensive subjects with normal renal function and 52 healthy subjects. The echo pattern of interventricular septum was assessed by videodensitometry (VDT) (i.e., a computer-assisted quantitative analysis of gray levels). For each pixel a numerical value from 0 (black) to 255 (white) was assigned. From the resulting histogram of gray level frequency distribution, we obtained indexes of central tendency (reflectivity) and of homogeneity of distribution (uniformity).ResultsFor the same septum thickness, dialysis patients showed a significantly greater reflectivity (87 ± 19 and 70 ± 17) (P < 0.001) and lower uniformity (137 ± 32 and 184 ± 71) (P < 0.007) compared with hypertensives. Hypertensive patients showed VDT parameters similar to control subjects in spite of significantly higher septum thickness (P < 0.003). Followed up after 5 years, dialysis patients with a reduced homogeneity of distribution of gray levels (lower uniformity) showed a significantly shorter survival (HR by Cox 2.5, 95% CI 1.21-5.27).ConclusionFor a similar degree of cardiac hypertrophy, dialysis patients differed widely from hypertensives in their VDT parameters. By contrast, the hypertensive heart differed from the normal heart in the degree of hypertrophy but not in terms of VDT parameters. VDT parameters are independent predictors of all-cause mortality in dialysis patients.

Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/day ratio in nondiabetic, cardiovascular events-free hemodialysis patients. Background The use of 24-hour ambulatory blood pressure monitoring is increasing in end-stage renal disease (ESRD) patients but the prediction power for cardiovascular complications of time-averaged ambulatory blood pressure components has been little investigated in these patients. Methods We analyzed the prognostic power of 24-hour ambulatory blood pressure monitoring for all-cause and cardiovascular mortality in 168 nondiabetic, events-free hemodialysis patients selected from a total dialysis population of about 450 patients. Results During the follow-up period (38 ± 22 months), 48 patients died, 29 of them of cardiovascular causes. On univariate Cox regression analyses, the night/day systolic ratio resulted to be the sole blood pressure indicator to be associated with all-cause and cardiovascular mortality while left ventricular hypertrophy (LVH) was a strong predictor of these outcomes. In multivariable Cox models not including LVH, the night/day systolic ratio maintained an independent prognostic value for incident outcomes. However, when both risk factors, LVH and night/day systolic ratio, were introduced into Cox models, LVH was no longer a significant predictor while the night/day systolic ratio became a predictor of marginal statistical significance. Conclusion The night/day ratio emerges as the sole ambulatory blood pressure monitoring-derived indicator providing significant prognostic information in patients with ESRD. However, this indicator as well as LVH loses substantial prediction power in statistical models including both risk factors. The results suggest that the night/day systolic ratio and LVH provide overlapping prognostic information, a phenomenon in keeping with the hypothesis that they represent a common pathway leading to adverse outcomes in ESRD.

The optimal timing of dialysis initiation is still unclear. We aimed to ascertain whether a strict clinical follow-up can postpone need for dialysis in chronic kidney disease (CKD) stage 5 patients. We reviewed records of all consecutive adult patients attending our conservative CKD stage 5 outpatient clinic from 2001 to 2010. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m2. Characteristics of subjects, including comorbidities, were assessed at baseline; blood pressure and serum markers of uremia were assessed both at first and last visit. GFR was estimated by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. In the 312 patients analyzed baseline eGFR was 9.7 ± 2.7 ml/min, which declined by 1.93 ± 4.56 ml/min after 15.6 ± 18.2 months. Age was inversely related to eGFR decline (r −0.27, p = 0.000). During conservative follow-up 55 subjects (18 %) died. In comparison with those eventually entering dialysis, deceased subjects were older and had a longer follow-up with no CKD progression. Multivariate analysis identified age, proteinuria and lower baseline K values as the only independent determinants of death. One hundred ninety-four subjects (66 %) started dialysis with an average eGFR of 6.1 ± 1.9 ml/min. During 35.8 ± 24.7 months of dialysis follow-up, 84 patients died. Multivariate analysis identified age as the main determinant of death (hazard ratio [HR] for every year 1.07, 95 % confidence interval [CI] 1.04–1.11, p 0.000). Patients starting dialysis with eGFR below the median, e.g.

Calcimimetics are effective in lowering serum parathyroid hormone (PTH) levels in hyperparathyroidism (HPT). However, they failed to reduce PTH levels in the long term in the setting of primary malignant HPT. A haemodialysis patient suffering from severe longstanding secondary HPT underwent total parathyroidectomy with autotransplantation of parathyroid tissue in her left arm. In the following years, she developed a severe HPT sustained by cancerous transformation of the parathyroid transplanted tissue and resistant both to pharmacological and repeated surgical treatments. The calcimimetic 'cinacalcet' was able to effectively reduce serum PTH levels over a 3-year follow-up and to induce disappearance of the neoplastic lesion on radionuclide imaging. Biochemical control of HPT was associated with a remarkable improvement in cardiac function.

Histological changes of the myocardium occur with aging due to an increase in collagen content, hypertrophy of fibers, and patchy fibrosis. Quantitative analysis of conventional echocardiographic images provides an in vivo assessment of myocardial structure by the evaluation of the gray level distribution; with this technique, a relation between myocardial fibrosis and pathological ultrasonic response has been documented. The aim of this study was to evaluate the relation between ultrason-ically assessed myocardial structure and age in a normal population. Seventy-eight subjects (47 men; mean age, 51 years; age range, 23–87 years) without apparent cardiovascular and systemic disease underwent conventional two-dimensional echocardiographic examinations. Still frames at end-diastole from apical four-chamber view were digitized and converted in matrices of 256 × 256 pixels. First-order statistical analysis was performed to describe a region of interest in the interventricular septum. The following parameters were studied: mean (gray level amplitude), standard deviation (overall contrast), uniformity (tonal organization), and entropy (tendency of gray levels to be spread). Myocardial structure was assessed in 75 of 78 subjects, divided into three groups: I, age 23–40 years; II, age 41–65 years; and III, > 65 years. Significant differences for all the parameters were found between the age groups. Age correlated directly with mean and entropy (r = 0.77 and 0.69, respectively) and inversely with uniformity (r = 0.70). Our results suggest that quantitative echocardiography can reveal age-related changes in myocardial structure that are characterized by a greater echogenicity and loss in tonal organization, possibly due to increased collagen content within the fibers.

Background. Late potentials (LP) on the signal-averaged electrocardiogram (SAECG) are predictive of malignant ventricular arrhythmias and sudden cardiac death in patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction, both regional and global, as well as supraventricular and ventricular arrhythmias are reported in a high percentage of patients with end-stage renal failure (ESRF). The aim of the study was to assess the prevalence of LP and the effects of haemodialysis on the SAECG of ESRF patients. Methods. SAECG was recorded immediately before and within 30min after the end of dialysis in 48 patients in sinus rhythm, free of conduction disturbances on ECG and of signs of congestive heart failure. Serum electrolytes were sampled together with the SAECG recordings. An echo-Doppler exam was performed within 2 weeks of the study. SAECGs were adequate for analysis in 45/48 patients. LP were present when at least two of the following criteria were fulfilled: QRS duration ≤ 115 ms, LAS 40 ≤38 ms, RMS 40 ≥ 38 μV at 40 Hz high pass bidirectional filter, and noise

Multiple solitary plasmacytoma (MSP) is a rare plasma cell dyscrasia, characterised by multiple lesions of neoplastic monoclonal plasma cells. It differs from multiple myeloma by the lack of hypercalcaemia, renal insufficiency, anaemia and pathological monoclonal plasmocytosis on a random bone biopsy. We present the case of an MSP described for the first time in a patient on peritoneal dialysis. There are only few cases of MSP described in literature, and we performed a review of these cases trying to systematise the topic. The increasing clinical use of CT, MRI and positron emission tomography will enhance in the future the correct diagnosis of MSP.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase implicated in several age-related biological mechanisms such as telomere shortening and cell senescence. We tested the hypothesis that ADMA blood level is an independent predictor of mortality in elderly. This is a longitudinal population-based cohort study. Participants are a representative cohort of 1,025 men and women (age range 65–102 years) living in Chianti area, Tuscany, Italy. The plasma ADMA was measured by liquid chromatography–tandem mass spectrometry. During the follow-up (95 ± 32 months), 384 individuals died, of whom 141 (37 %) died of cardiovascular (CV) causes. In adjusted analyses, the plasma ADMA was the strongest predictor of all-cause mortality (HR (0.1 μMol/L) 1.26, 95 % CI 1.10–1.44, P 60 μMol/L. Notwithstanding the association of ADMA with all-cause mortality was robust, this biomarker failed to add predictive power to a simple model based on the risk factors in the elderly (area under the ROC curve 0.85 ± 0.01 vs. 0.84 ± 0.01). ADMA is a strong independent predictor of mortality in the older population, and l-arginine modifies the effect of ADMA on survival. The mechanisms for this association should be targeted by future studies.