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Background: Percutaneous transluminal renal angioplasty (PTRA) with or without stenting is the gold standard therapy in patients with atherosclerotic renal artery stenosis (aRAS). However, therapeutic success depends on the correct timing of revascularization and the reversibility of the renal damage. Materials and Methods: We report a case series of patients treated with PTRA for renovascular hypertension and ischemic nephropathy. We measured bilateral renal resistive index (RRI), circulating renal stem cells (RSC), and Neutrophil Gelatinase Associated Lipocalin (NGAL) at baseline and after PTRA at different time points to understand their changes in post-revascularization. Results: At baseline, the studied patients (n = 5) had different RSC levels. After PTRAs, all patients showed an improvement in blood pressure, while renal function varied differently within the studied subjects. RRI > 0.75 at baseline and the absence of NGAL decrease after PTRAs were associated with post-PTRA renal function worsening, despite an increase of RSC in all patients. Conclusions: Although limited to a few patients, our observation allowed the exploration of the behaviour of the studied parameters in different degrees of renal ischemia. This revealed different disease models suggesting the importance of further investigations in larger and homogeneous cohorts to confirm that a greater basal RSC percentage, low RRI values before PTRA, and a post-revascularization NGAL reduction could be related to better renal outcomes in aRAS patients.

Introduction/objectives Gastrointestinal tract (GIT) involvement is frequently observed in systemic sclerosis (SSc) and may lead to nutritional impairment. The aim of the study was to assess the prevalence of symptoms related to GIT involvement and to analyze the possible association between gastrointestinal symptoms and low muscularity in SSc patients. Methods Sixty-nine consecutive patients (60 females, median age 53 (IQR 43–63), body mass index (BMI) 23.2 (IQR 20.9–24.6) kg/m2) with diagnosis of SSc admitted to our Scleroderma Unit were enrolled. Clinical status, anthropometric data, and bioelectrical impedance (Inbody 770, USA) analysis-assessed Fat-Free Mass Index (FFMI) were recorded upon enrollment. UCLA questionnaire was used to quantify GIT involvement with seven specific scales. Results Mean FFMI was 16.2 kg/m2 (IQR 15.2–17.6). The median UCLA total score was 0.53 (IQR 0.19–0.89). FFMI showed a significant negative correlation with UCLA total score (r = −0.29, p = 0.016) and UCLA distention/bloating (r = −0.35, p p = 0.039) in SSc patients with lower FFMI [1.75 (IQR 0.75–2.12) vs 0.75 (IQR 0.25–1.75)]. At multiple linear regression model, FFMI showed association with UCLA distention/bloating [beta coefficient − 0.315 (95% CI of beta coefficient: −0.591; −0.039), p = 0.026], BMI [beta coefficient 0.259 (95% CI of beta coefficient: 0.163; 0.355), p = 0.001], and disease duration [beta coefficient − 0.033 (95% CI of beta coefficient: −0.059; −0.007), p = 0.015]. Conclusions In SSc, low FFMI is associated with symptoms related to GIT involvement, in particular with distension/bloating. Key Points• FFMI is associated with symptoms related to GIT involvement.• Low FFMI is associated with symptoms related to UCLA distention/bloating.• Malnutrition is not associated with symptoms related to GIT involvement.

To estimate the prevalence of temporomandibular dysfunction in scleroderma patients according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and to correlate it with disease variables.Temporomandibular dysfunction was evaluated in 75 scleroderma patients and 74 healthy controls using DC/TMD. Gastrointestinal symptoms were evaluated through the University of California Los Angeles (UCLA) score in scleroderma patients.There was no difference of prevalence in temporomandibular dysfunction [30 (40%)Temporomandibular dysfunction prevalence between scleroderma patients and healthy controls is similar. In scleroderma patients, temporomandibular dysfunction reduces oral mobility and opening, which worsens distension/bloating.

Systemic sclerosis (SSc) subclinical renal vasculopathy is characterized by progressive increase of intrarenal stiffness and reduction of parenchymal thickness due to post ischemic fibrosis secondary to the renal Raynaud phenomenon. Aims of this study were to evaluate kinurenic acid (KYNA) serum level in SSc patients and healthy controls (HC) and to assess the role of KYNA in SSc subclinical nephropathy. Serum level of KYNA was evaluated in 52 SSc patients and 20 HC, matched for sex and age. Renal function was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (eGFR) and renal doppler ultrasound was performed to evaluate kidneys' morphology and indices of intrarenal stiffness. The parameters registered were renal longitudinal length, atrophy index (AI), renal sinus, parenchymal thickness, renal resistive index (RRI), pulsatile index (PI) and systolic/diastolic ratio (S/D). SSc patients had lower median value of KYNA than HC [54.43 ng/ml (IQR 44.44-63.64) vs 61.94 ng/ml (IQR 55.23-88.75), p 0.001]. SSc patients with AI ≥ 0.70 had lower KYNA than SSc patients with AI 0.70 [47.85 ng/ml (IQR 41.16-59.91) vs 55.5 ng/ml (IQR 49.99-67.33), p 0.05] and a slightly significant negative linear correlation was found between KYNA and AI (r = - 0.249, p 0.05). SSc patient with RRI ≥ 0.70 had higher KYNA than SSc patients with RRI 0.70 [58.25 ng/ml (IQR 50.49-69.68) vs 50.07 ng/ml (IQR 42.70-56.31), p 0.05] and a significant positive correlation was found between KYNA and RRI (r = 0.318, p 0.05). KYNA may be used as a marker to evaluate the renal involvement in SSc patients.

Systemic sclerosis (SSc) is autoimmune disease characterized by endothelial dysfunction and microvascular damage. Resistin has been implied in microvascular dysfunction. Objective of this study is to evaluate the association between baseline resistin and development of new digital ulcers (DUs) in SSc patients. At baseline, serum resistin has been assessed in 70 female SSc patients and 26 healthy controls (HC). In SSc patients, clinical assessment was performed at baseline and after a 52-weeks follow-up. Serum resistin level was increased in SSc patients compared to HC [5.89 ng/ml (2.5 ng/ml–8.1 ng/ml) vs 2.3 ng/ml (0.4 ng/ml–2.4 ng/ml), p = 0.0004)]. Resistin was lower (p = 0.005) in SSc patients with early capillaroscopic pattern than patients with active or late capillaroscopic pattern [2.49 ng/ml (0.89 ng/ml–5.81 ng/ml) vs 7.11 ng/ml (3.48 ng/ml–11.35 ng/ml) and 6.49 ng/ml (3.35 ng/ml–8.87 ng/ml), respectively]. After a 52-weeks follow-up, 34 (48.6%) patients developed new DUs. Median serum resistin was significantly higher in patients with new DUs than in patients without new DUs [6.54 ng/ml (3.35 ng/ml–11.02 ng/ml) vs 4.78 ng/ml (1.06 ng/ml–7.6 ng/ml), p = 0.019]. Kaplan–Meier curves show a significantly reduced free survival from DUs in patients with increased resistin (p = 0.002). In multivariate analysis, resistin is associated with the development of new DUs. Increased serum resistin level is a predictive marker of new DUs in SSc.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by microvascular damage and fibrosis of the skin and internal organs. Among SSc complications, changes in nutritional status have a negative effect on quality of life and predispose patients to malnutrition. The aim of this exploratory pilot study was to examine whether bioelectrical impedance analysis-derived phase angle (PhA) is a parameter of nutritional status and a marker of mortality in patients with SSc.Consecutive adult patients with SSc were included in the study. Biochemical analyses, anthropometric data, and bioelectrical impedance analysis assessments were recorded at the time of enrollment. The Malnutrition Universal Screening Tool (MUST) and Global Leadership Initiative on Malnutrition (GLIM) were applied to assess nutritional status.A total of 104 patients with SSc (88 women; median age: 55 y [interquartile range (IQR), 45.5- 66 y]) were enrolled. In patients with SSc and high malnutrition risk according to MUST, mean values of PhA were significantly lower than those of patients with SSc and low malnutrition risk (4° [IQR, 3.7°-4.4°] vs 4.6° [IQR, 4.2°-5.1°]; P = 0.004). Patients with SSc and malnutrition according to the GLIM criteria showed significantly lower PhA than patients with SSc but without malnutrition (3.8° [IQR, 3.5°-4.3°] vs 4.6° [IQR, 4.2°-5.1°]; P0.0001). Kaplan-Meier curves demonstrated that overall survival was significantly shorter (34.57 mo [±13.35] vs 48 mo [±0]; P = 0.001) in patients with SSc and PhA3.75°. In the multivariate analysis, only PhA was a predictive factor for death (hazard ratio: 0.283; 95% confidence interval, 0.083-0.965; P = 0.044).The data obtained suggest that lower PhA values in patients with SSc are associated with an increased malnutrition risk with MUST, malnutrition with GLIM, and increased mortality. Additional studies are necessary to confirm these preliminary results.

Summary The objective of this study was to evaluate the predictive role of CD21low B cells as markers of new digital ulcers in systemic sclerosis patients. Peripheral blood B cell subpopulations and clinical assessments have been evaluated in 74 systemic sclerosis patients at baseline and after a 12‐month follow‐up. After a 12‐month follow‐up, 23 (31.1%) systemic sclerosis patients developed new digital ulcers. The median percentage of CD21low B cells was significantly higher in patients with than without new digital ulcers [10.1 (4.3–13.6) versus 4.8 (3.5–7.4); p, CD21low B cells are increased in SSc patients. CD21low B cells are higher in SSc patients with major vascular complications. CD21low B cells may be a possible predictive marker of new DUs.

Objective In Systemic Sclerosis (SSc), vasculopathy is the background of major vascular complications (MVCs), like digital ulcers (DUs), pulmonary arterial hypertension (PAH) and scleroderma renal crisis (SRC). We aimed to identify the predictors and to test the primary preventive effect of vasoactive/vasodilating drugs (VVD) for the development of MVCs in SSc MVCs-naive patients. Methods patients fulfilling the ACR/EULAR 2013 classification criteria for SSc without history of MVCs were eligible. Data about clinical manifestations, laboratory and instrumental assessments and treatments were retrospectively collected at baseline and latest available follow-up. Results 134 SSc patients were enrolled (mean age 56.5 years ± 14.2, females 88.1%, limited subset 61.9%, ACA positivity 60.4%). In a mean of 43 ± 19 months of follow-up 12 (9.0%) patients developed at least 1 MVC (10 DU, 2 PAH and 1 SRC). Dyspnoea and arthritis at baseline were independent predictors for MVCs development (p = 0.012, and p = 0.002 respectively). No primary preventive effect of VVD on MVCs development was found. However, sildenafil reduced the renal resistive index increase (p = 0.042) and alprostadil slowed the DLco decline (p = 0.029). Both iloprost and angiotensin-receptor blockers (ARBs) delayed MVCs development, while angiotensin converting enzyme inhibitors (ACEi) determined an earlier onset of such MCVs. Conclusions in SSc patients, our data confirm the role of arthritis and dyspnea as independent predictors of major vascular complications, in particular in MVCs-naive patients. Prostanoids, sildenafil and ARBs, even in absence of a primary preventive action, might help in slowing disease progression and postponing the onset of MVCs.

Subclinical nephropathy is underestimated in systemic sclerosis (SSc). Study aim is to evaluate the role of renal resistance indices (RRI) and estimated glomerular filtration rate (eGFR) assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) as predictive markers of mortality during 10 years of follow-up in SSc patients.181 SSc patients (60 years, 152 females) were enrolled. At baseline, the GFR was estimated in 181 SSc patients and RRI was measured in 122 SSc patients. During a follow-up of 10 years we recorded the main complications of disease, date and causes of death.eGFR shows a linear negative correlation with RRI. RRI showed a correlation with systolic pulmonary artery pressure (sPAP). Overall survival is lower in SSc patients with eGFR60 ml/min and RRI ≥0.70 than in SSc patients with eGFR≥60 ml/min (p0.0001) and with RRI0.70 (p0.01) both for mortality due to SSc and all causes. In multivariate analysis, eGFR60 ml/min [HR 6.429, 95%CI (1.006-41.08), p0.05] and forced vital capacity (FVC) [HR 0.954, 95%CI (0.911-1), p0.05] are predictive markers of mortality due to SSc, while eGFR [HR 3.617, 95%CI (1.370-9.554), p0.01], RRI [HR 0.210, 95% CI (0.068-0.649), p0.01], age [HR 1.062, 95%CI (1.023-1.103), p0.01], FVC [HR 0.967, 95%CI (0.946-0.989), p0.01] and disease activity index (DAI) [HR 1.663, 95%CI (1.262-2.191), p0.0001] are predictive markers of mortality due to all causes.We demonstrate that eGFR is a predictive marker of mortality due to SSc and to all causes, conversely RRI is predictive marker of mortality due to all causes.

Objectives: The authors aimed to evaluate the role of N-terminal proANP (NT-proANP) and of NT-proBNP circulating levels as predictive markers of death due to systemic sclerosis (SSc).Methods: The a...

Introduction: Contrast-induced acute kidney injury (CIAKI) is one of the main causes of acute renal failure in hospitalized patients, following the administration of iodinated contrast medium used for CT scans and angiographic procedures. CIAKI determines a high cardiovascular risk and appears to be one of the most feared complications of coronary angiography, causing a notable worsening of the prognosis with high morbidity and mortality. Aim: To evaluate a possible association between the renal resistive index (RRI) and the development of CIAKI, as well as an association with the main subclinical markers of atherosclerosis and the main cardiovascular risk factors. Materials and Methods: We enrolled 101 patients with an indication for coronary angiography. Patients underwent an assessment of renal function (serum nitrogen and basal creatinine, 48 and 72 h after administration of contrast medium), inflammation (C reactive protein (CRP), serum calcium and phosphorus, intact parathormone (iPTH), 25-hydroxyvitaminD (25-OH-VitD), serum uric acid (SUA), total cholesterol, serum triglycerides, serum glucose and insulin). All patients also carried out an evaluation of RRI, intima-media thickness (IMT), interventricular septum (IVS) and the ankle-brachial index (ABI). Results: 101 patients (68 male), with a mean age of 73.0 ± 15.0 years, were enrolled for the study; 35 are affected by type 2 diabetes mellitus. A total of 19 cases of CIAKI were reported (19%), while among diabetic patients we reported an incidence of 23% (8 patients). In our study, patients with CIAKI had significantly higher RRI (p < 0.001) and IMT (p < 0.001) with respect to the patients who did not develop CIAKI. Furthermore, patients with CIAKI had significantly higher CRP (p < 0.001) and SUA (p < 0.006). Conclusions: We showed a significant difference in RRI, IMT, SUA and CRP values between the population developing CIAKI and patients without CIAKI. This data appears relevant considering that RRI and IMT are low-cost, non-invasive and easily reproducible markers of endothelial dysfunction and atherosclerosis.

Interleukin (IL)-33 is part of the IL-1 family of cytokines and soluble suppression of tumorigenicity 2 (sST2) is part of the family of IL-1 receptors. In systemic sclerosis (SSc), IL-33 and sST2 are involved in cardiac manifestations such as diastolic dysfunction (DD), autonomic dysfunction (AD) and right ventricular–pulmonary arterial coupling assessed by tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP). Serum levels of IL33 and sST2 were assessed in 50 SSc patients and 14 healthy controls (HC). Clinical assessment, echocardiography and heart rate variability (HRV) analysis were performed in SSc patients. Serum levels of IL-33 and sST2 were significantly higher in SSc patients than HC. A linear positive correlation between modified Rodnan skin score and IL33 was observed. Serum values of sST2 were higher in SSc patients with DD than in patients without DD [15403 pg/ml (12,208–19,941) vs 8556 pg/ml (6820–11,036), p r = − 0.281, p r = 0,349, p r = − 0.398, p

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Gastrointestinal tract (GIT) involvement may lead to malnutrition, which can in turn negatively affect morbidity, mortality, and quality of life. The aim of the study was to assess the prevalence of malnutrition in SSc patients with both the European Society of Clinical Nutrition and Metabolism (ESPEN) and the Global Leadership Initiative on Malnutrition (GLIM) criteria and to assess whether it relates with disease activity and severity.Adult SSc patients were included in the study. Biochemical analyses, disease activity index (DAI), disease severity scale (DSS), anthropometric data, and body composition parameters for GLIM and ESPEN assessment were recorded at enrollment.One hundred and two SSc patients were enrolled (86 females, mean age 55 ± 14 years). The prevalence of malnutrition was 8.8% (9 of 102), according to ESPEN, and 16.6% (17 of 102), according to GLIM criteria. GLIM severity grading of malnutrition was moderate in 12.7% (13 of 102) and severe in 3.9% (4 of 102) . In SSc patients with malnutrition according to GLIM criteria, DAI and DSS were significantly higher than in SSc patients without malnutrition (P.0001), whereas no association was observed between malnutrition and DAI or DSS when using the ESPEN criteria.Prevalence of malnutrition is higher with GLIM than with ESPEN criteria. Irrespective of the method used, prevalence of malnutrition in SSc is lower than one would expect in a chronic, autoimmune disease with GIT involvement.

This study aims to evaluate the role of fat free mass index (FFMI) and phase angle (PhA) as markers to predict occurrence of new digital ulcers in systemic sclerosis (SSc) patients.Body composition evaluation from bioelectrical impedance and clinical assessment were performed in SSc patients at enrollment and after 12 months follow-up.Seventy-nine SSc patients (67 female) with a mean age of 53 ± 13 years were enrolled. In SSc patients with a digital ulcers history, FFMI value is lower (p 0.05) and phase angle (PhA) value is higher (p 0.01) than SSc patients without a digital ulcers history. After 12 months of follow-up, 30 patients (38%) presented at least one new episode of digital ulcers. Patients with reduced FFMI had a relative risk of 6.7 for new digital ulcers (CI 2.1-21.8, p 0.001). Patients with reduced PhA had a relative risk of 10.1 for new digital ulcers (CI 3.5-29.5, p 0.0001). In multivariate analysis, FFMI and PhA were associated with major vascular complication (digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis). FFMI loss, assessed as delta between follow-up and baseline, is higher in SSc with short duration (≤ 3 years) than SSc patients with long duration [0.4 (0-0.50) vs - 0.10 (- 0.2-0)].In SSc patients, reduction of the FFMI and PhA represents after 12 months a risk factor for development of new digital ulcers and major vascular complication. Key Points • Fat free mass index represents a risk factor for development of digital ulcers • Phase angle represents a risk factor for development of digital ulcers • Body compositions in systemic sclerosis are a marker of activity disease.

Interstitial lung disease (ILD) remains a major cause of morbidity and mortality in systemic sclerosis (SSc). Study aim is to characterize and quantify SSc-ILD by using Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER). Secondly, our objective is to evaluate which radiological pattern is predictive of lung function decline at 12 months follow-up. In the prospective study (IRB 5435), 66 SSc patients underwent high-resolution computerized tomography (HRCT) at baseline. HRCT was performed according to standard protocol using a CT 64GE light speed VCT power scanner. CALIPER classified lung parenchyma on volume units. Every volume unit was classified into radiological parenchymal patterns (honeycombing, reticular and ground glass). Pulmonary function tests (PFTs) were performed at baseline and after 12 months of follow-up. Cigarette smoking and other lung diseases unrelated to SSc are exclusion criteria. CALIPER analysis showed normal lung parenchyma 87.4 ± 9.8%, ground glass 2.8 ± 5.3%, reticular 4 ± 5.7%, and honeycombing 1 ± 1%. In multiple regression analysis, FEV1 (p 0.0001), FVC (p = 0.001), and DLCO (p 0.0001) measurements at baseline showed a negative correlation with the reticular pattern percentage. At follow-up, DLCO reduction showed a positive correlation (p 0.001) with the percentage of ground glass pattern (r = 0.33, beta coefficient = 0.51). In the ROC curve analysis, ground glass score is a good predictor (0.75, p = 0.009; 95% CI 0.59-0.91) of DLCO worsening, defined as a decrease of more than 10% of DLCO. Using a cutoff ≥ 4.5 for ground glass score, the RR for DLCO worsening is 6.8 (p 0.01; 95% CI 1.6-29.2). The results of this study show that CALIPER is useful not only for quantifying lung damage but also for assessing worsening PFTs, but larger studies are needed to confirm these preliminary data.Key Points• At baseline reticular pattern showed negative correlation with PFTs• At follow-up ground glass pattern predicts worsening of DLCO• CALIPER is a useful to quantify lung damage.

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage and fibrosis of the skin and internal organs. The major complications are lung fibrosis, pulmonary artery hypertension, scleroderma renal crisis, and cardiac involvement. Objective: The aim of this study was to assess renal and cardiac involvement in asymptomatic SSc patients using renal Doppler ultrasound (RDU) and cardiac magnetic resonance (CMR). Materials and Methods: We enrolled 26 consecutive SSc patients (21 female) according to 2013 ACR/EULAR criteria. Biochemical analysis, clinical evaluation, RDU with intrarenal hemodynamic parameters (renal resistive index [RRI], pulsatility index [PI], systolic/diastolic [S/D] ratio), and CMR with late gadolinium enhancement (LGE) were investigated at the time of enrollment. Results: The median PI value was significantly (p = 0.007) higher in SSc patients with LGE than in SSc patients without LGE (1.37 [1.28–1.58] vs. 1.12 [1.06–1.26]). The median RRI value was significantly (p = 0.002) higher in SSc patients with LGE than in SSc patients without LGE (0.68 [0.65–0.73] vs. 0.64 [0.63–0.65]). The median S/D ratio was significantly (p = 0.02) higher in SSc patients with LGE than in SSc patients without LGE (3.12 [2.83–3.76] vs. 2.78 [2.64–2.84]). Conclusions: Our study, although performed on a small SSc population, showed RRI and LGE as markers of vascular and fibrotic damage. Early detection of cardiorenal involvement in SSc patients without symptoms is important to avoid further complications.

ObjectiveThere is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.MethodsA multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.ResultsThe overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.ConclusionOur study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

INTORDUCTION Aldosterone is known to play important role in developing cardiovascular, metabolic, renal damage in hypertensive patients. AIM Aim of study was to evaluate parameters obtained by eco-color Doppler study, as non-invasive and easly performed method in asyntomatic patients with Essential Hypertension (EH) and Primary Aldosteronism (PA), without overt organ damage. METHODS From April 2019 to March 2020 we consecutively enrolled 73 hypertensive subjects (48 males, 25 women), distinguished in two groups: 30 EH patients (mean age 49.5 ± 18.7 years) and 43 PA patients (mean age 53.1 ± 11.6 years)] [23 with aldosterone-secreting adrenal adenoma (APA), 20 with idiopathic aldosteronism (IHA)]. RESULTS PA group showed higher renal filtration rate and 24-h urinary excretion of albumin respect to EH; moreover, in PA we found higher Pulsatility Index, altered percentage of Renale Resistance Index, Atrophy Index, and reducted parietal thickness than EH. The correlation study showed that plasma aldosterone were positively correlated with pulsatility index in PA group (right r = 0.35; p < 0.05; left r = 0.36; p < 0.05). CONCLUSION parameters obtained through the intra-renal eco-color Doppler examination, easly performed and non-invasive, can be useful in the early-stage identification of subclinical microvascular alterations, especially in PA, condition characterized by increased risk of cardio-vascular remodelling and metabolic alterations.

Renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status and it is associated with changes in renal function. Aim of the study was to assess RRI in biopsy-proven tubulointerstitial nephritis (TIN) in patients with and without glomerular disease.132 consecutive patients underwent to native renal biopsy with diagnosis of isolated TIN or in association with glomerulonephritis. Estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion and renal ecocolorDoppler ultrasonography with RRI assessment were performed at time of enrollment.Patients with isolated-TIN had significantly higher RRI than both patients with non-immunoglobulin A glomerulonephritis (non-IgA-TIN) [0.73 (0.68-0.77) vs 0.64 (0.60-0.67), p 0.001] and patients with IgA nephropathy (IgAN) [0.73 (0.68-0.77) vs 0.66 (0.60-0.71), p 0.01]. Patients with isolated-TIN had mainly RRI ≥ 0.70 (n = 15, 65.2%) with the respect to patients with non-IgA-TIN (n = 7, 12.3%) and patients with IgAN (n = 17, 32.7%). A negative linear correlation was found between RRI and hemoglobin (r = 0.233, p 0.01) and between RRI and eGFR (r = 0.537, p 0.001).Tubulointerstitial damage is the most accurate histological lesion that correlates with eGFR and renal impairment. RRI can be a useful parameter to detect tubulointerstitial lesions.

Nephroangiosclerosis (NAS) associated with hypertension continues to be one of the most causes of end stage renal diseases in Europe, but it is still poorly studied. The prevalence of NAS shows a large variability due to the difference among different countries regarding clinical presentations and the indication to perform renal biopsy. The study aimed to investigate the prevalence in biopsy-proven NAS patients and the association with hypertension and/or glomerulonephritis (GN). We included all patients referred for native kidney biopsy between 2003–2021 at Policlinic Umberto I of Rome. From 837 patients who underwent renal biopsy NAS was diagnosed in 80 (10.5%) patients. Serum creatinine was significantly higher in NAS [2.07 mg/dl (IQR 1.13–5.2) vs 1.1 mg/dl (IQR 0.8–2.1), p 0.05). IgA nephropathy, focal segmental glomerulosclerosis and membranous nephropathy were the most frequent GN associated. In conclusion no specific feautures are reported in NAS with and without hypertension. More informations on the phenotype, clinical presentation and markers are needed to improve histological and clinical diagnostics.

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

Aims Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients. Methods Seventy patients were enrolled (64 women and six men; mean age 56.7 ± 14 years) with a disease duration of 11.1 ± 8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan-Meier and Cox regression analyses. Results Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development. Conclusion Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.

The aim was to evaluate the longitudinal association between basal serum adiponectin and repeated measurements of skin thickness during 12 months of follow-up in systemic sclerosis (SSc) patients. We enrolled SSc patients with disease duration > 2 years in a prospective observational study. Skin thickness was measured at baseline and after 12 months of follow-up with modified Rodnan skin score (mRSS). Baseline serum adiponectin was determined using a commercial ELISA kit. We enrolled 66 female SSc patients (median age 54 years, IQR 42–62 years). The median disease duration was 12 (IQR 8–16) years and median baseline serum adiponectin was 9.8 (IQR 5.6–15.6) mcg/mL. The median mRSS was 10 (IQR 6–18) at baseline and 12 (IQR 7–18) at follow-up. A significant correlation was observed between baseline serum adiponectin and disease duration (r = 0.264, p < 0.05), age (r = 0.515, p < 0.0001), baseline mRSS (r = −0.303, p < 0.05), and mRSS at follow-up (r = −0.322, p < 0.001). In multiple regression analysis, only mRSS at follow-up showed an inverse correlation with baseline serum adiponectin (β = −0.132, p < 0.01). The reduction in serum adiponectin levels is correlated with skin thickness.

Introduction: Cardiovascular disease is one of the main causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Autonomic dysfunction is associated with an increased risk for all cardiovascular events in the general population and can be evaluated with heart rate variability (HRV). Objective: To evaluate HRV in ADPKD patients with mild hypertension versus hypertensive patients with organ damage and healthy controls (HC). Materials and Methods: We have enrolled 65 patients: 21 ADPKD patients (10 males), 20 patients with hypertension (14 males), and 24 HC (10 males). Biochemical analysis, clinical evaluation, anthropometric data, intima-media thickness, 24-h ECG Holter recording, and echocardiography were investigated at the time of enrollment. Results: No significant differences in HRV parameters were found between ADPKD with mild hypertension and hypertensive patients with organ damage. The median of HRV variables in time domain as SDNN (global autonomic activity) was significantly lower in ADPKD and hypertensive patients than HC (p < 0.05). In the frequency domain analysis, low frequency (LF), which mainly reflects the sympathetic component, showed higher values in ADPKD and hypertensive patients than HC during the night (p < 0.01). During the night, the sympathovagal balance, LF/high frequency (HF), showed higher values in ADPKD and hypertensive patients than HC (p < 0.0001). Conversely, LF day was lower in ADPKD and hypertensive patients than HC (p < 0.01). HF, which mainly reflects the parasympathetic component, was lower in ADPKD and hypertensive patients during the night than HC (p < 0.0001). Conclusions: HRV reduction is present in ADPKD patients with mild hypertension in the absence of organ damage. The evaluation of sympathovagal balance can provide novel information on the cardiovascular risk in ADPKD patients in addition to classical risk factors.

Digital ulcers (DUs) are one of the main causes of disability among systemic sclerosis (SSc) patients. The inflammation plays a crucial role in mediating the pathophysiological process underlying SSc. Objective of this study was to evaluate Maresin1 (MaR1) serum levels in SSc patients and in healthy controls (HC). Secondary aims were to evaluate the relationship between MaR and diseases variables and to assess the predictive role of MaR1 in the development of new digital ulcers (DUs) during 18 weeks follow-up.MaR1 serum level was evaluated in 55 SSc patients and 24 HC. In SSc patients, clinical assessment was performed at baseline and after 18 week follow-up by the same-blinded observer on serum MaR1 levels.MaR1 was significantly lower in SSc patients than in HC [367 pg/ml (IQR 304-468.3 pg/ml) vs 467.7 pg/ml (IQR 422-522 pg/ml), p 0.001]. During follow-up, six patients (10.9%) developed DUs. MaR1 was higher in SSc patients with new DUs than in patients without new DUs [518.2 pg/ml (IQR 468.2-596.5 pg/ml) vs 355 pg/ml (IQR 299.8-444.7 pg/ml), p 0.01]. Free survival from new DUs is significantly lower in SSc patients with increased MaR1 serum level than in SSc patient with normal MaR1 serum level. In multivariate analysis, serum level of MaR1 393.2 pg/ml is a predictive marker for new DUs.In SSc patients, MaR1 is reduced compared to HC and it is a predictive marker of new DUs.

The aim of this study was to evaluate the role of Color Doppler Ultrasonography (CDUS) of proper palmar digital arteries (PPDA) as predictive marker of new digital ulcers (DUs) in systemic sclerosis (SSc) patients during 5 years follow-up.36 SSc patients were examined using nailfold videocapillaroscopy (NVC) and CDUS of PPDA.Fourteen (38.9%) patients had chronic or acute occlusions (C and D pattern) on CDUS evaluation. Using a cut-off of 0.70, 21 (58.3%) patients had a Resistive Index (RI) ≥0.70. Nineteen (52.8%) patients developed new DUs during the follow-up. The median value of RI was higher in SSc patients with DUs than in SSc patients without DUs [0.73 (IQR 0.70-0.81) vs 0.67 (IQR 0.57-0.70), p 0.0001]. The Kaplan-Meier analysis showed a free survival from new DUs higher (p 0.01) in SSc patients with Pattern A and B than SSc patients with Pattern C and D. The Kaplan-Meier curves showed that free survival from new DUs is lower (p 0.001) in SSc patients with increased RI (≥0.70) than in SSc patients with normal RI. In multivariate analysis with two co-variates, RI ≥ 0.70 [HR 5.197 (1.471-18.359), p 0.01] and NVC late scleroderma pattern [HR 7.087 (1.989-25.246), p 0.01] were predictive markers of new DUs.RI of PPDA in association with NVC could be used to evaluate SSc patients with increased risk of new DUs development.

Free light chains (FLC), considered a biomarker of B cell activity, are frequently elevated in different systemic inflammatory-autoimmune diseases. As systemic sclerosis (SSc) clinical course may be variable, this study aimed to assess FLCs levels in serum and urine of affected individuals, as biomarkers of disease activity. We assessed FLC levels in serum and urine of 72 SSc patients and 30 healthy controls (HC). Results were analyzed in comparison with overall clinical and laboratory findings, disease activity index (DAI) and disease severity scale (DSS). SSc patients displayed increased levels of k and λ FLC in serum, significantly higher than HC (p=0.0001) alongside with the mean levels of free k/λ ratio and of the k+λ sum (p=0.0001). In addition, SSc patients had significant higher levels in the urine of free k and of k/λ ratio than HC (p=0.0001). SSc patients with increased k+λ sum in serum showed a statistically higher levels of erythro-sedimentation rate (p=0.034), C-reactive protein (p=0.003), higher DAI (p=0.024) and DSS (p=0.015) than SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free k and DAI (r=0.29, p=0.014). SSc patients with increased free k in urine had statistically higher DAI (p=0.048) than SSc patients with normal level of free k. The significant increased levels of FLC correlated with disease activity in SSc patients. Our results strengthen the role of FLC as useful biomarkers in clinical practice to early diagnosis and monitor disease activity with an improvement of SSc patients’ management.

The spectrum of kidney involvement in systemic sclerosis (SSc) includes scleroderma renal crisis, widely recognized as the most severe renal-vascular complication, but also several forms of chronic renal vasculopathy and reduced renal function are complications of scleroderma. Scleroderma renal crisis, myeloperoxidase-antineutrophil cytoplasmic antibody associated glomerulonephritis, penicillamine-associated renal disease, abnormal urinalysis, alteration of vascular endothelial markers, scleroderma associated-vasculopathy with abnormal renal resistance indices and cardiorenal syndromes type 5 were also reported in SSc patients. A frequent form of renal involvement in SSc patients is a subclinical renal vasculopathy, characterized by vascular damage and normal renal function. Indeed, asymptomatic renal changes, expressed by increase of intrarenal stiffness, are often non-progressive in SSc patients but can lead to a reduction in renal functional reserve. The purpose of this review is to provide an assessment of kidney involvement in SSc, from SRC to subclinical renal vasculopathy.