Changes in renal microcirculation in patients with nephrotic and nephritic syndrome: The role of resistive index.

BACKGROUND: Renal Resistive Index (RRI) is an important and non-invasive parameter of renal damage and it is associated with abnormal microcirculation or to a parenchymal injury. The aim of our study was to compare the RRI in a cohort of patients with renal diseases categorized in three groups: nephrotic syndrome (NS), acute nephritic syndrome (ANS) and patients with urinary abnormalities (UA). METHODS: Four hundred eighty-two patients with median age of 48 years (IQR 34-62) with indications for kidney disease were included in the study. Biochemical analyses, clinical assessment with detection of NS, ANS and UA and comorbidities were reported. Renal Doppler ultrasound with RRI was evaluated in all patients at the time of enrolment. RESULTS: NS was present in 81 (16.8 %) patients while ANS in 81 (16.8 %) and UA in 228 (47.3 %) patients. Patients with ANS showed significant higher RRI compared to both patients with NS [0.71 (IQR 0.67-0.78) vs 0.68 (0.63-0.73), p < 0.001] and UA [0.71 (0.67-0.78) vs 0.65 (0.61-0.71), p < 0.001]; RRI was higher in NS patients than in patients with UA [0.68 (0.63-0.73) vs 0.65 (0.61-0.71), p < 0.001]. Patients with ANS had significantly lower median estimated glomerular filtration rate (eGFR) compared respectively to NS and UA patients [19.7 ml/min vs 54.8 ml/min and vs 72.3 ml/min, p < 0.001], while renal length was significantly higher in patients with NS compared to both patients with ANS and UA [111.88 mm vs 101.98 mm and vs 106.15, p < 0.001]. Patients with ANS had more frequently hematuria and RRI ≥ 0.70 (p < 0.001) compared to both patients with NS and patients with UA. The multiple regression analysis, weighted for age, showed that RRI inversely correlates with eGFR (ß coefficient = -0.430, p < 0.001). CONCLUSIONS: Higher and pathological RRI were found in ANS than NS and UA. Renal resistive index in ANS reflects changes in intrarenal perfusion and microvascular dysfunction related to disease characteristics.

Stem Cells in Kidney Ischemia: From Inflammation and Fibrosis to Renal Tissue Regeneration.

Ischemic nephropathy consists of progressive renal function loss due to renal hypoxia, inflammation, microvascular rarefaction, and fibrosis. We provide a literature review focused on kidney hypoperfusion-dependent inflammation and its influence on renal tissue's ability to self-regenerate. Moreover, an overview of the advances in regenerative therapy with mesenchymal stem cell (MSC) infusion is provided. Based on our search, we can point out the following conclusions: 1. endovascular reperfusion is the gold-standard therapy for RAS, but its success mostly depends on treatment timeliness and a preserved downstream vascular bed; 2. anti-RAAS drugs, SGLT2 inhibitors, and/or anti-endothelin agents are especially recommended for patients with renal ischemia who are not eligible for endovascular reperfusion for slowing renal damage progression; 3. TGF-ß, MCP-1, VEGF, and NGAL assays, along with BOLD MRI, should be extended in clinical practice and applied to a pre- and post-revascularization protocols; 4. MSC infusion appears effective in renal regeneration and could represent a revolutionary treatment for patients with fibrotic evolution of renal ischemia.

In systemic sclerosis, the TAPSE/sPAP ratio can be used in addition to the DETECT algorithm for pulmonary arterial hypertension diagnosis.

OBJECTIVE: Early detection of pulmonary arterial hypertension (PAH) is crucial for improving patient outcomes. The aim of this study was to compare the positive predictive value (PPV) of the echocardiography-derived tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio with that of the DETECT algorithm for PAH screening in a cohort of SSc patients. METHODS: Fifty-one SSc patients were screened for PAH using the DETECT algorithm and echocardiography. RESULTS: Echocardiography was recommended by the DETECT algorithm step 1 in 34 patients (66.7%). Right heart catheterization (RHC) was recommended by the DETECT algorithm step 2 in 16 patients (31.4%). PAH was confirmed by RHC in 5 patients. The DETECT algorithm PPV was 31.3%. The TAPSE/sPAP ratio was higher in SSc patients not referred for RHC than in SSc patients referred for RHC according to the DETECT algorithm step 2 [0.83 (0.35-1.40) mm/mmHg vs 0.74 (0.12-1.09) mm/mmHg, P < 0.05]. Using a cut-off of 0.60 mm/mmHg, 8 (15.7%) SSc patients had a TAPSE/sPAP ratio of ≤0.60 mm/mmHg. PAH was confirmed by RHC in 5 patients. The PPV of TAPSE/sPAP was 62.5%. In multiple regression analysis, TAPSE/sPAP was associated with age [ß coefficient = -0.348 (95% CI: -0.011, -0.003); P < 0.01], DETECT algorithm step 1 [ß coefficient = 1.023 (95% CI: 0.006, 0.024); P < 0.01] and DETECT algorithm step 2 (ß coefficient = -1.758 [95% CI: -0.059, -0.021]; P < 0.0001). CONCLUSION: In SSc patients with a DETECT algorithm step 2 total score of >35, the TAPSE/sPAP ratio can be used to further select patients requiring RHC to confirm PAH diagnosis.

Assessment of renal microcirculation in biopsy-proven tubulointerstitial nephritis in patients with and without glomerular disease: the role of resistive index.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Maresin1 is a predictive marker of new digital ulcers in systemic sclerosis patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In SSc patients, MaR1 is reduced compared to HC and it is a predictive marker of new DUs.

Diet and Proteinuria: State of Art.

Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy.

CD21low B cells are predictive markers of new digital ulcers in systemic sclerosis.

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 < 0.01]. The 10% cut-off shows good diagnostic accuracy [area under the curve (AUC) = 0.732, confidence interval (CI) = 0.587-0.878; P = 0.01]. Kaplan-Meier curves show a significantly reduced free survival from new digital ulcers in systemic sclerosis patients with CD21low B cells ≥ 10% (p < 0.0001). In multivariate analysis, CD21low B cells ≥ 10%, modified Rodnan skin score (mRSS) and systolic pulmonary arterial pressure (sPAP) are associated with the development of new digital ulcers. We hypothesize that CD21low B cells are a predictive marker of new digital ulcers in systemic sclerosis patients.

Serum and urine free light chains measurements in patients with systemic sclerosis: novel biomarkers for disease activity.

Circulating free light chains (FLCs), considered biomarkers of B cell activity, are frequently elevated in patients affected by systemic inflammatory autoimmune diseases. As the systemic sclerosis (SSc) clinical course can be variable, this study is aimed at evaluating FLCs levels in 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 κ and λ FLC in serum significantly higher than HC (p = 0.0001) alongside the mean values of free κ/λ ratio and κ + λ sum (p = 0.0001). SSc patients showed increased free κ in urine with a κ/λ higher than HC (p = 0.0001). SSc patients with increased κ + λ in serum showed that erythro-sedimentation rate (p = 0.034), C-reactive protein (p = 0.003), DAI (p = 0.024) and DSS (p = 0.015) were higher if compared to SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free κ and DAI (r = 0.29, p = 0.014). In addition, SSc patients with increased free κ in urine had higher DAI (p = 0.048) than SSc patients with normal κ levels. Our results strengthen the role of serum FLC as useful biomarker in clinical practice to early diagnosis and monitor disease activity, showing for the first time that also urine FLC levels correlated with disease activity in SSc patients.

Laser speckle contrast analysis predicts major vascular complications and mortality of patients with systemic sclerosis.

OBJECTIVES: The aim of study was to evaluate peripheral blood perfusion and the proximal-distal gradient (PDG) of the hands as biomarkers of SSc major vascular complications (digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis) and mortality by laser speckle contrast analysis. METHODS: In this retrospective observational study, 176 SSc patients [158 female, median age 53 (51-57) years] and 142 healthy controls [115 female, median age 53 (48-55) years] were enrolled. Clinical data were collected at baseline and annually through 5 years of follow-up. Hand dorsum perfusion images were divided into three regions of interest (ROI): ROI1 included the second, third, and fourth fingers distal to the proximal interphalangeal finger joint; ROI2 included the area between the proximal interphalangeal finger joint and the metacarpophalangeal joint; ROI3 included the hand dorsum. PDG was identified when the perfusion mean difference between ROI1 and ROI2 was >30 perfusion units. RESULTS: Median peripheral blood perfusion was significantly lower for SSc patients than healthy controls. PDG was present in 51.5% of SSc patients and in 98.6% of healthy controls. Using the final multivariate model, nailfold videocapillaroscopy (NVC) pattern [hazard ratio (HR) 0.065 (0.015-0.283), P <0.0001] and PDG [HR 0.376 (0.194-0.727), P <0.01] were found to be risk factors for major vascular complications. By multivariate analysis, age [HR 1.051 (1.014-1.088), P <0.01), NVC pattern [HR 0.001 (0.000-3.111), P >0.05], and PDG [HR 0.207 (0.073-0.589), P <0.01] were found to be risk factors for 5-year SSc mortality. CONCLUSION: PDG predicts major vascular complication and 5-year mortality of SSc patients.

Estimated glomerular filtration rate is a marker of mortality in the European Scleroderma Trials and Research Group (EUSTAR) database.

OBJECTIVES: The study aim was to evaluate the estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with respect to mortality in SSc patients from the European Scleroderma Trials and Research Group (EUSTAR) database. METHODS: SSc patients from the EUSTAR database who had items required for the calculation of eGFR at a baseline visit and a second follow-up visit available were included. A cut-off eGFR value of 60 ml/min was chosen for all SSc patients, and 30 ml/min for those with scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the use of eGFR as a predictive factor of mortality. RESULTS: A total of 3650 SSc patients were included in this study. The median serum level of creatinine and the mean of eGFR were 0.8 mg/dl (interquartile range = 0.6-0.9) and 86.6 ± 23.7 ml/min, respectively. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR < 60 ml/min compared with patients with eGFR ≥ 60 ml/min [OS at 5 years 0.763 (95% CI: 0.700, 0.814) vs 0.903 (95% CI: 0.883, 0.919; P < 0.001)]. In multivariable analysis, OS was associated with male gender (P < 0.01), systolic pulmonary arterial pressure (sPAP) (P < 0.001) and eGFR (P < 0.001). The cumulative incidence of deaths due to SSc was associated with increased sPAP (P < 0.001) and reduced eGFR (P < 0.05). The OS at 5 years of 53 SRC patients was not significantly different between SSc patients with eGFR > 30 ml/min and those with eGFR <30 ml/min. CONCLUSION: eGFR represents a predictive risk factor for overall survival in SSc. The eGFR, however, does not represent a risk factor for death in SRC.

Color Doppler Ultrasonography of digital arteries and digital ulcers development in systemic sclerosis.

BACKGROUND: 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. METHODS: 36 SSc patients were examined using nailfold videocapillaroscopy (NVC) and CDUS of PPDA. RESULTS: 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. CONCLUSIONS: RI of PPDA in association with NVC could be used to evaluate SSc patients with increased risk of new DUs development.

Renal resistive index in IgA nephropathy and renal scleroderma vasculopathy.

BACKGROUND: Renal Ultra-Sound (US) and Doppler US provide measurements which reflect changes in renal and systemic haemodynamic. The renal resistive index (RRI), obtained through the Doppler spectrum analysis of renal small arteries, is altered in several pathologic conditions. Glomerulonephritis cause minor RRI changes, while renal scleroderma vasculopathy (RSV) leads to significant RRI modifications. The aim of our study was to assess RRI in IgA nephropathy (IgAN) and RSV in a retrospective observational study and to investigate determinants of the RRI in these groups of patients. METHODS: We enrolled 61 IgAN patients [23 female, median age 41 (33-58) years] and 80 SSc patients [71 female, median age 52 (43-60) years]. RRI was evaluated in all patients at the time of enrolment. Laboratory tests and clinical assessment were evaluated in all patients. RESULTS: IgAN patients showed lower RRI values than RSV patients [0.70 (0.65-0.73) vs 0.66 (0.62-0.72), p < 0.01], while no significant difference in longitudinal length was observed. Median age was significantly lower in IgAN patients than in RSV patients [41 (33-58) vs 52 (43-60), p < 0.05] while IgAN patients showed a higher prevalence of high blood pressure than RSV patients (39.3% vs 13.8%, p < 0.01). The multiple regression analysis, weighted for age, showed that RRI inversely correlates with estimated glomerular filtration rate (ß coefficient = -0.524, p < 0.0001). CONCLUSION: Higher RRI were found in RSV patients than IgAN patients. IgAN is characterized mainly by glomerular injury, not leading to major RRI changes.

Ischemic Nephropaty: The Role of the Renal Artery Stenosis Revascularization on Renal Stem Cells.

We report the case of a 65-year-old man with acute GFR decline to 37 mL/min and uncontrolled high blood pressure. He was suspected for renovascular hypertension and underwent a renal color Doppler ultrasound scan that detected a bilateral atherosclerotic renal artery stenosis. A digital selective angiography by percutaneous transluminal angioplasty and stenting (PTRAs) was successfully performed. Blood pressure rapidly normalized, GFR increased within a few days, and proteinuria disappeared thereafter. These clinical goals were accompanied by a significant increase of circulating renal stem cells (RSC) and a slight increase of resistive index (RI) in both kidneys. This single observation suggests the need for extensive studies aimed at evaluating the predictive power of RI and RSC in detecting post-ischemic renal repair mechanisms.

CD21low B cells in systemic sclerosis: A possible marker of vascular complications.

OBJECTIVES: To evaluate expansion of CD21low B cells and their role in B cell homeostasis, apoptosis, clinical manifestations and serum vascular endothelial growth factor (VEGF) in systemic sclerosis (SSc). MATERIALS AND METHODS: B-cells subpopulations and apoptosis have been assessed in 74 SSc patients and 20 healthy donors. Renal Doppler ultrasound, echocardiography, pulmonary function test and VEGF were performed. RESULTS: SSc patients with expanded CD21low B cells (SSc-CD21low) show a distinct B cell profile with increased memory B cells compared to patients without CD21low B cells (SSc-CD21+). Renal resistive index, systolic pulmonary arterial pressure and FVC/DLCO ratio were significantly higher in SSc-CD21low group than SSc-CD21+, DLCO was lower in SSc-CD21low group than SSc-CD21+. We found a positive linear correlation between CD21low and sPAP, RI and FVC/DLCO ratio whereas a negative correlation was observed between CD21low and DLCO and VEGF levels. CONCLUSIONS: CD21low B cells are increased in SSc patients with visceral vascular manifestations.

Reduced ventilatory efficiency during exercise predicts major vascular complications and mortality for interstitial lung disease in systemic sclerosis.

OBJECTIVES: Major vascular complication, such as digital ulcers (DUs), pulmonary arterial hypertension (PAH) and scleroderma renal crisis (SRC) are hallmarks of systemic sclerosis (SSc). Interstitial lung disease (ILD) is the major cause of mortality in SSc. The aim of study is to identify cardiopulmonary exercise testing (CPET) variables that predict MVC and mortality for ILD in SSc patients. METHODS: In this cohort study, 45 SSc patients underwent clinical evaluation, echocardiography, pulmonary function tests (PFTs), high resolution computerised tomography (HRCT) and CPET. PFTs and echocardiography were performed annually for a 5-year follow-up. RESULTS: 16 (35.6%) SSc patients had MVC: 14 new DUs (31.1%), 1 PAH (2.2%) and 1 SRC (2.2%). At univariate regression analysis, mRss [HR 1.099 (1.008-1.199), p<0.05], NVC patterns (active and late) [HR 0.032 (0.004-0.250), p<0.001], V'E/V'CO2 slope [HR 1.123 (1.052-1.198), p<0.001] were predictive of new onset of MVC. In multivariate analysis, NVC patterns (active and late) (HR 0.044 (0.004-0.486), p<0.05), V'E/V'CO2 (HR 1.094 (1.020-1.198), p<0.05) were predictive of new onset of MVC. The 5-year mortality for ILD is 8.9%. In univariate analysis, DLco [(HR 0.927(CI 0.874- 0.983), p<0.05], V'E/V'CO2 slope and lung parenchymal with radiological patterns of ILD [(1.2.02 (CI 1.018-1.419), p<0.05], represent risk factors for 5-year mortality for ILD [HR 1.142 (1.030-1.267), p<0.05]. In multivariate analysis, only V'E/V'CO2 slope [1.268 (CI 1.003-1.602), p<0.05] represents a risk factor for 5-year mortality for ILD. CONCLUSIONS: V' E/V' CO2 slope is a prognostic marker of MVC and five-year mortality for ILD.

Late Gadolinium Enhancement in Cardiac Magnetic Resonance Imaging Is Associated with High Renal Resistive Index in Patients with Systemic Sclerosis.

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.

Reduction in Heart Rate Variability in Autosomal Dominant Polycystic Kidney Disease.

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.

In systemic sclerosis, microvascular and hands digital arteries damage correlates with serum levels of endostatin.

OBJECTIVE: In SSc, vascular injury leads to endothelial dysfunction with reduced capillary blood flow and tissue hypoxia. In SSc, the angiogenesis is impaired and implicated in the microvascular damage. In severe vascular damage, VEGF is reduced and endostatin is increased. The aim of this study was to evaluate the correlation between endostatin serum levels and microvascular and digital arteries damage. METHODS: Seventeen patients with SSc were enrolled in this study. Serum endostatin levels were determined. All patients underwent a NVC, CDUS, and LDPI. RESULTS: The serum level of endostatin significantly (P < .05) increased with NVC progression damage. The mean perfusion significantly (P < .05) decreased with NVC progression damage. Multiple regression analysis showed a significant correlation between endostatin serum level and RI (r = .34, P < .05), PI (r = .60, P < .01), S/D ratio (r = .76, P < .0001), and mean perfusion (r = -.68, P < .001). Endostatin serum levels significantly (P < .05) increased with progression of CDUS damage. CONCLUSIONS: Increased serum endostatin levels are associated with digital vascular damage. In patients with SSc, endostatin is a marker of skin perfusion and digital arteries damage of hands.

Parasympathetic activity increases with digital microvascular damage and vascular endothelial growth factor in systemic sclerosis.

OBJECTIVES: The imbalance between angiogenic and angiostatic factors with derangement of the microvasculature are hallmarks of systemic sclerosis (SSc). Raynaud's phenomenon in SSc probably is due to the impaired neuroendothelial control mechanisms between vasoconstriction and vasodilatation. The aim of this study is to evaluate autonomic nervous system function using heart rate variability (HRV) analysis and to correlate with vascular endothelial growth factor (VEGF). METHODS: Twenty-seven SSc patients were enrolled. HRV was measured and markers of global sympathetic and parasympathetic system, respectively standard deviation of normal-to-normal RR intervals (SDNN) and square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) were evaluated. Serum VEGF levels and nailfold videocapillaroscopy (NVC) were performed. RESULTS: A linear positive correlation was observed between RMSSD and VEGF (p<0.01, r=0.55), and RMSSD and disease duration (p< 0.01, r=0.54). The RMSSD median value was significantly increased (p< 0.05) with NVC damage progression. The RMSSD median value was significantly (p<0.05) higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [44 (39.4-60.2) vs 24.6 (23-37.1)]. CONCLUSIONS: In our study parasympathetic modulation increases in relation to VEGF. When microcirculation is modified with capillaroscopic pattern progression and DUs, autonomic system seems to stimulate vasodilatation trough parasympathetic system. We can conclude that parasympathetic activity increases with digital microvascular damage and promotes VEGF release.

Effects of autonomic dysfunction on exercise tolerance in systemic sclerosis patients without clinical and instrumental evidence of cardiac and pulmonary involvement.

OBJECTIVES: Autonomic dysfunction (AD) in systemic sclerosis (SSc) was already confirmed through heart rate variability (HRV) analysis. Cardio-pulmonary exercise testing (CPET) is a useful tool in early detection of exercise tolerance in SSc patients. Aim of the study was to assess the relationships existing between AD and exercise tolerance. METHODS: Thirty-two [4 M, 28 F; median age: 47.5 (20-65) years] consecutive SSc patients were enrolled. All patients underwent pulmonary function testing, incremental symptom-limited CPET and twenty-four hours ECG Holter recording with HRV analysis in time and frequency domain. Multiple regression analysis was performed in order to identify independent HRV predictors of exercise tolerance and cardiac efficiency during the effort. RESULTS: HRV analysis showed significant differences in power in low and high frequency (LF and HF, respectively) and their ratio (LF/HF) compared to healthy controls. Nocturnal ratio be- tween power in low and high frequency at HRV (LF/HFnight) was shown to be the only independent positive predictor of maximal work load (R2=18.6%, p=0.014) and maximal oxygen consumption (V' O2 peak) expressed both as absolute value (R2=24.2%, p=0.004) and as corrected for body weight (R2=21.6%, p=0.007). A positive linear relationship was also found between nocturnal LF (LFnight) and the oxygen uptake/work rate (V'O2/W) slope (R2=15.8%, p=0.024). CONCLUSIONS: In SSc patients without cardiopulmonary involvement AD is associated with better exercise tolerance and cardiac function during physical effort. Further studies are needed to confirm these results.