Assessment of kidney involvement in systemic sclerosis: From scleroderma renal crisis to subclinical renal vasculopathy

Gigante, Antonietta; Leodori, Giorgia; Pellicano, Chiara; Villa, Antonella; Rosato, Edoardo

doi:10.1016/j.amjms.2022.02.014

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…Microvascular damage is a hallmark of SSc and it plays a key role in the pathogenesis of internal organs damage [ 1 ]. Renal scleroderma associated vasculopathy is characterized by increased RRI that over the time leads to parenchymal thickness reduction with atrophy and worsening of renal function, assessed by eGFR [ 44 ]. Renal ischemia–reperfusion injury is the primary cause of AKI, which can cause a significant increase in the expression of NGAL in kidneys with consequent NGAL accumulation in the blood and urine, which can be detected in patients with AKI [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Pellicano,

Colalillo,

De Marco

et al. 2024

Clin Exp Med

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Introduction Systemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost. Methods Twenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2). Results SSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC. Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2. Conclusions SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.

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Section: Discussionmentioning

confidence: 99%

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Pellicano,

Colalillo,

De Marco

et al. 2024

Clin Exp Med

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“…Telangiectasias, pitting scars, periungual microvascular abnormalities (e.g., giant capillaries, hemorrhages, avascular areas, ramified/bushy capillaries) clinically detectable by nailfold videocapillaroscopy (NVC), ischemic digital ulcers (DUs), and pulmonary arterial hypertension (PAH) generally occur later in the disease process, severely affecting patients’ quality of life [ 1 , 2 , 3 ]. Chronic vasculopathy also plays a pivotal role in the most severe SSc-related renal vascular complication, i.e., scleroderma renal crisis (SRC), a clinical condition characterized by poor renal cortical perfusion and rapidly progressive renal failure [ 8 , 9 ]. Cardiac involvement, erectile dysfunction, vascular malformations of the gastrointestinal mucosa, and, to some extent, myopathy are also described as frequent [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

Fioretto

Rosa

Matucci‐Cerinic

et al. 2023

IJMS

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Systemic sclerosis (SSc, scleroderma) is a multifaceted rare connective tissue disease whose pathogenesis is dominated by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and both cutaneous and visceral fibrosis. Microvascular impairment represents the initial event of the disease, preceding fibrosis by months or years and accounting for the main disabling and/or life-threatening clinical manifestations, including telangiectasias, pitting scars, periungual microvascular abnormalities (e.g., giant capillaries, hemorrhages, avascular areas, ramified/bushy capillaries) clinically detectable by nailfold videocapillaroscopy, ischemic digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. Despite a variety of available treatment options, treatment of SSc-related vascular disease remains problematic, even considering SSc etherogenity and the quite narrow therapeutic window. In this context, plenty of studies have highlighted the great usefulness in clinical practice of vascular biomarkers allowing clinicians to assess the evolution of the pathological process affecting the vessels, as well as to predict the prognosis and the response to therapy. The current narrative review provides an up-to-date overview of the main candidate vascular biomarkers that have been proposed for SSc, focusing on their main reported associations with characteristic clinical vascular features of the disease.

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“…Indeed, Bandini et al showed how potentially also the splanchnic vessels in SSc may be non-invasively investigated with abdominal US and color Doppler US, showing that some morphological and functional US parameters of mesenteric arteries of SSc patients are different from healthy controls defining a “bowel vasculopathy” [ 12 ]. In addition, renal arteries seem to be involved in SSc vasculopathy, often sub-clinically, and are characterized by vascular damage and normal renal function and expressed by an increase in intrarenal stiffness [ 13 ]. Finally, Hughes et al have recently described an overlap entity of SSc associated with the presence of antineutrophil cytoplasm autoantibodies (ANCA), which could represent a poor prognostic vascular phenotype [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Peripheral Macrovascular Involvement in Systemic Sclerosis: A Cohort Study by Color and Spectral Doppler Ultrasonography

D’Alessandro

González

Falsetti

et al. 2023

Life

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Objectives: Systemic sclerosis (SSc) is a disease characterized by diffuse sclerosis of skin and organs and small vessel vasculopathy. Despite it, large vessels can also be involved with ulnar artery vasculopathy, revealing as a more frequent feature of SSc. The aim of this paper is to assess the macrovascular involvement of SSc patients through an ultrasound (US) evaluation of radial and ulnar arteries. Methods: Radial and ulnar resistance indices (RIs) and peak systolic velocity (PV) (cm/s) together with clinical features of SSc patients were evaluated. Raynaud phenomenon (RP) and healthy control (HC) groups were used for comparison. Results: Forty-three SSc patients were evaluated. Twelve patients (28%) had ulnar artery occlusions (UAOs). In nine cases (75%), UAOs were bilateral. A high UAO prevalence (42%) was found in SSc patients with late nailfold-video-capillaroscopy (NVC) pattern (p = 0.0264). Patients with UAOs had digital ulcers (DUs) in 10 cases (83.3%). Radial and ulnar PVs were lower in SSc and RP patients than the HC group. Radial and ulnar RIs were higher in SSc and RP patients than the HC group. A decision tree analysis led to the classification of 70% of SSc patients with an ulnar RI > 0.82 and ulnar PV > 2.8 cm/s. The most influential variables on UAO development were interstitial lung disease (ILD) (p = 0.002) and NVC pattern (p = 0.002). A positive correlation was shown between modified Rodnan skin score (mRSS) and ILD (p = 0.283; r = 0.033), mRSS and DU (r = 0.344; p = 0.012) and DU and ILD (r = 0.303; p = 0.024). Male sex was associated with increased UAO frequency (p = 0.042). Conclusions: UAO is a peculiar feature of severe SSc present in 28% of the cases, particularly associated with the presence of ILD and late NVC pattern. In 75% of the cases, UAOs are bilateral. DUs are very frequent in patients with UAOs (83%). The RI evaluated by US could be useful to distinguish SSc from HC patients. US could be a useful tool for assessing high-risk DU development in patients.

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Assessment of kidney involvement in systemic sclerosis: From scleroderma renal crisis to subclinical renal vasculopathy

Cited by 9 publications

References 51 publications

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

Peripheral Macrovascular Involvement in Systemic Sclerosis: A Cohort Study by Color and Spectral Doppler Ultrasonography

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