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1.
Sci Transl Med ; 14(649): eabl8503, 2022 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-35704597

RESUMEN

Cyclic GMP-phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and women (45 to 80 years) with long-duration (>3 years) and well-controlled type 2 diabetes mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according to echocardiographic signs of cardiac remodeling. Patients were randomly assigned (1:1) to placebo or oral tadalafil (20 mg, once daily). The primary outcome was to evaluate sex differences in cardiac torsion change. Secondary outcomes were changes in cardiovascular, metabolic, immune, and renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement in cardiac torsion (-3.40°, -5.96; -0.84, P = 0.011) and fiber shortening (-1.19%, -2.24; -0.14, P = 0.027) in men but not women. The primary outcome could not be explained by differences in cGMP concentrations or tadalafil pharmacodynamics. In both sexes, tadalafil improved hsa-miR-199-5p expression, biomarkers of cardiovascular remodeling, albuminuria, renal artery resistive index, and circulating Klotho concentrations. Immune cell profiling revealed an improvement in low-grade chronic inflammation: Classic CD14++CD16- monocytes reduced, and Tie2+ monocytes increased. Nine patients (14.5%) had minor adverse reactions after tadalafil administration. Continuous PDE5 inhibition could offer a strategy to target cardiorenal complications of T2DM, with sex- and tissue-specific responses. Further studies are needed to confirm Klotho and hsa-miR-199-5p as markers for T2DM complications.


Asunto(s)
Diabetes Mellitus Tipo 2 , Disfunción Eréctil , MicroARNs , Carbolinas/farmacología , Carbolinas/uso terapéutico , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/etiología , Femenino , Humanos , Cinética , Masculino , Erección Peniana , Inhibidores de Fosfodiesterasa 5/farmacología , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Tadalafilo/farmacología , Tadalafilo/uso terapéutico , Resultado del Tratamiento , Remodelación Ventricular
2.
Kidney Blood Press Res ; 45(2): 350-356, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32101875

RESUMEN

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.


Asunto(s)
Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Riñón/química , Imagen por Resonancia Magnética/métodos , Esclerodermia Sistémica/diagnóstico por imagen , Adulto , Femenino , Gadolinio/farmacología , Gadolinio/fisiología , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad
3.
J Rheumatol ; 47(4): 567-571, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31203218

RESUMEN

OBJECTIVE: Renal involvement in systemic sclerosis (SSc) ranges from urinary abnormalities, reduction of glomerular filtration rate, and high renal resistive index, to scleroderma renal crisis. Intrarenal resistance indices are considered markers of renal SSc-associated vasculopathy. The aim of this study is to evaluate renal morphological variables, such as renal length, parenchymal thickness, atrophy index, and renal sinus in patients with SSc and to correlate it with renal function and hemodynamic variables. METHODS: There were 92 patients with SSc and 40 healthy controls (HC) enrolled in this study. Doppler and renal ultrasound (US) including renal length, parenchymal thickness, atrophy index, renal sinus, and intrarenal resistive index were measured in patients with SSc and HC. RESULTS: Renal US showed significant differences between HC and patients with SSc. The renal length (mm; 106.7 ± 5.1 vs 102.3 ± 8.4) and renal sinus (70.7 ± 7.9 vs 65.3 ± 7.7 mm) were significantly (p = 0.001) higher in HC than patients with SSc. The parenchymal thickness was significantly (p = 0.004) higher in HC than patients with SSc (18 ± 3.1 vs 16.3 ± 2.5 mm). Pulsatility index, resistive index, and systolic/diastolic ratio were significantly (p < 0.0001) lower in HC than patients with SSc. The renal length was significantly (p = 0.004) higher in diffuse cutaneous SSc (105 ± 8.4) than in limited cutaneous SSc (99.5 ± 7.5). CONCLUSION: In SSc, kidney involvement is subclinical and is related to vascular injury, Raynaud phenomenon, and chronic hypoxia that can modify renal morphology. Serum creatinine is a poor marker of renal damage, and renal US could be a useful tool - together with Doppler - to evaluate renal involvement in a systemic and chronic disease such as SSc.


Asunto(s)
Enfermedad de Raynaud , Esclerodermia Sistémica , Tasa de Filtración Glomerular , Hemodinámica , Humanos , Riñón/diagnóstico por imagen , Riñón/fisiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagen
4.
Int J Rheum Dis ; 22(6): 1029-1035, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30989785

RESUMEN

AIM: Autonomic dysfunction (AD) is an early feature of systemic sclerosis (SSc). A regular endothelial function is a prerequisite for normal response of the myocardial blood flow (MBF) to cold pressure test (CPT). The aim of the study was to evaluate the relation between MBF and AD at rest and after CPT in asymptomatic SSc patients. METHODS: Twenty SSc patients and 10 age-, sex- and body mass index-matched healthy controls underwent cardiac magnetic resonance at rest and after CPT. All subjects underwent 24 hours ambulatory 3-channel electrocardiogram Holter to evaluate AD by heart rate variability. RESULTS: We did not observe any significant difference in MBF (mL/g/min) at rest and after CPT between SSc patients and healthy controls. Delta of MBF (difference between MBF after CPT and rest MBF) was lower (P = 0.039) in SSc patients than healthy controls (0.28 [0.04-0.40] vs 0.33 [0.24-0.54]). The low frequency/high frequency (LF/HF) was higher (P = 0.002) in SSc patients than healthy controls (3 [1.7-6] vs 1.8 [1.1-2.8]). The high frequencies (HF), modulated mainly by paraympathetic system, was lower (P = 0.003) in SSc patients than healthy controls (30 [16-42] vs 36.5 [24-44]). Sympathetic hyperactivity, due to reduction of parasympathetic activity (HF), is present in SSc patients. A negative correlation was observed between Delta of MBF and LF/HF (r = -0.572, P = 0.0031). CONCLUSION: AD, characterized by sympathovagal imbalance due to a reduced parasympathetic tone with high LF/HF ratio, could be responsible for the reduced myocardial vasodilatory response after CPT.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Sistema Nervioso Autónomo/fisiopatología , Circulación Coronaria , Cardiopatías/diagnóstico por imagen , Corazón/diagnóstico por imagen , Corazón/inervación , Imagen por Resonancia Cinemagnética , Imagen de Perfusión Miocárdica/métodos , Esclerodermia Sistémica/complicaciones , Adulto , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Estudios de Casos y Controles , Femenino , Cardiopatías/etiología , Cardiopatías/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/fisiopatología , Vasodilatación , Adulto Joven
5.
J Scleroderma Relat Disord ; 4(1): 71-76, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35382150

RESUMEN

Introduction: Since female sexual dysfunction in systemic sclerosis women is multifactorial, we can assume that vascular damage may play a role in pathogenesis. The aim of the study was to evaluate the clitoral blood flow, by Echo color Doppler, and to correlate it whit serum levels of vascular endothelial growth factor and endostatin. Methods: A total of 15 systemic sclerosis women and 10 healthy controls matched for sex and age were enrolled in this study. Serum VEGF165 and endostatin levels were determined in systemic sclerosis patients by commercial enzyme-linked immunosorbent assay kit. Clitoral blood flow was measured by Doppler indices of clitoral artery: pulsatile index, resistive index, and systolic/diastolic ratio were measured. Sexual dysfunction was assessed by Female Sexual Function Index. Results: Vascular endothelial growth factor (pg/mL) and endostatin (ng/mL) median values were significantly higher in systemic sclerosis women than healthy controls. Resistive index and systolic/diastolic ratio median values were significantly higher in systemic sclerosis women than healthy controls. Negative correlation exists between serum levels of vascular endothelial growth factor and resistive index (r = -0.55, p < 0.05). Positive correlation was observed between serum levels of endostatin and resistive index (r = 0.70, p < 0.01) and systolic/diastolic ratio (r = 0.77, p < 0.01). Discussion: We can suppose that clitoral blood flow in systemic sclerosis women is reduced not only for macro- and microvascular damage but also for impaired angiogenesis.

6.
Clin Exp Rheumatol ; 36 Suppl 113(4): 24-27, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29787366

RESUMEN

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.


Asunto(s)
Dedos/irrigación sanguínea , Corazón/inervación , Microvasos/fisiopatología , Sistema Nervioso Parasimpático/fisiopatología , Enfermedad de Raynaud/etiología , Esclerodermia Sistémica/complicaciones , Úlcera Cutánea/etiología , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Progresión de la Enfermedad , Femenino , Frecuencia Cardíaca , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Raynaud/sangre , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/fisiopatología , Flujo Sanguíneo Regional , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/fisiopatología , Úlcera Cutánea/sangre , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/fisiopatología
7.
Kidney Blood Press Res ; 43(3): 682-689, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29763902

RESUMEN

BACKGROUND/AIMS: Renal involvement is common in systemic sclerosis (SSc), including asymptomatic reduction of glomerular filtration rate (GFR), increased renal resistance indices, scleroderma renal crisis (SRC) and ANCA-associated vasculitis. The aim was to evaluate type and evolution of renal involvement for a period of five years. METHODS: 121 SSc patients (100 F, 21 M) with mean age of 54.9 ± 13.8, disease duration of 9 ± 6 years, of which 62 had a diffused form and 59 limited form were enrolled. All patients were screened annually for renal function by laboratory examination, ultrasound and color Doppler ultrasound of renal arteries. RESULTS: Over the five-year observation period, 6 SRC (3 M, 3 F) occurred, four of which required dialysis. One patient developed ANCA-related proliferative glomerulonephritis and the other one acute tubular necrosis. The remaining 113 patients had a preserved renal function (serum creatinine 0.75 ± 0.24 mg/dl, GFR 93.8 ± 20 ml/min, 24h proteinuria 0.20 ± 0.15 g). Doppler indices of intrarenal arterial stiffness increased with progression of capillaroscopic damage and with presence of digital ulcers. A negative correlation was observed between estimated GFR and pulsatile index (p< 0,05, r=-0.198), resistive index(p< 0,01, r=0.267), S/D ratio (p< 0,01, r=-0.237). CONCLUSION: In SSc patients, renal function was normal for 4.1 years despite the presence of increased intrarenal arterial stiffness. SRC was observed in 4.9% of SSc patients. In SSc patients, a periodic follow-up based on clinical and laboratory evaluation, colorDoppler ultrasound and, in some cases, renal biopsy is required to evaluate renal involvement.


Asunto(s)
Enfermedades Renales/fisiopatología , Riñón/fisiopatología , Esclerodermia Sistémica/complicaciones , Adulto , Biopsia , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Esclerodermia Sistémica/diagnóstico , Ultrasonografía Doppler , Rigidez Vascular
9.
Int Wound J ; 15(3): 424-428, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29600562

RESUMEN

Patients with systemic sclerosis (SSc) are at a high risk of the development of ischaemic digital ulcers (DUs) that can be complicated with infections, gangrene, and osteomyelitis. The aim of this study is to evaluate the role of endostatin in scleroderma DUs.In total, 90 SSc patients were enrolled in this study. Serum endostatin levels and DU assessment were determined in all SSc patients. The serum levels of endostatin significantly increased with progression of capillaroscopic damage (P < .01). The serum levels of endostatin are significantly (P < .05) higher in SSc patients with new DUs than in SSc patients without new DUs (127 ± 31.1 ng/mL vs 116.3 ± 39.7 ng/mL). The Receiver Operating Characteristic (ROC) curves demonstrated good accuracy of new DU prediction for the serum level of endostatin (0.70, P < .01 [95% confidence interval (CI) 0.59-0.81]). Using a cut-off value of 116 ng/mL, the odds ratio was 2.609 (CI 1.075-6.330, P < .05). The serum levels of endostatin are significantly (P < .01) higher in SSc patients with infected DUs than in SSc patients without infected DUs (139.2 [114.6-340.91] ng/mL vs 117.5 [64.3-163.9] ng/mL). Serum levels of endostatin are higher in patients with DUs, especially in those with infected DUs.


Asunto(s)
Endostatinas/sangre , Dedos , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/complicaciones , Úlcera Cutánea/sangre , Úlcera Cutánea/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Esclerodermia Sistémica/diagnóstico , Úlcera Cutánea/diagnóstico
10.
Microcirculation ; 25(4): e12449, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29537711

RESUMEN

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.


Asunto(s)
Arterias/lesiones , Endostatinas/sangre , Dedos/irrigación sanguínea , Microvasos/lesiones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica , Piel/irrigación sanguínea
12.
Nephrology (Carlton) ; 23(11): 991-996, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28817218

RESUMEN

AIM: Overweight has been related to renal arteriolosclerosis and is able to modify intrarenal haemodynamics. Increasing evidence suggests an association between weight in excess and primary glomerulonephritis (GN). The aim of this study was to evaluate the relationship between nutritional status and intrarenal arterial stiffness in primary GN associated to arteriolosclerosis. We have considered the glomerular diameter (GD) as morphological parameter in overweight and obese patients. METHODS: Clinical, laboratory, anthropometric data and renal Doppler ultrasound were performed immediately before kidney biopsy. RESULTS: Primary GN was diagnosed in 92 patients. Mild arteriolosclerosis was found in 19.6% of patients, moderate in the 20.6%, severe in the 10.9% while nephroangiosclerosis was diagnosed in 8.7% of patients. A positive correlation was found between body mass index (BMI) and renal resistive index (RRI) (P < 0.01, r = 0.34). RRI were significantly higher in patients with severe arteriolosclerosis at kidney biopsy (P < 0.05). Furthermore, higher BMI (P < 0.01) was found in patients with renal arteriolosclerosis than patients without renal arteriolosclerosis (26.1 ± 4.4 kg/m2 vs. 24.4 ± 4.5 kg/m2 ). Finally, in overweight and obesity patients we found a positive correlation between maximal GD and BMI (P < 0.01) and maximal GD and RRI (P < 0.01). CONCLUSION: In overweight and obese patients affected by primary GN, it might be found not only glomerular but also renal vascular lesions. Finally, we believe that nephroangiosclerosis, in combination with weight in excess, is able to modify intrarenal haemodynamic parameters. Moreover, in response to these changes, the renal tissue morphologically promotes a GD increase regardless of the underlying GN.


Asunto(s)
Arterioloesclerosis/etiología , Índice de Masa Corporal , Glomerulonefritis/etiología , Adulto , Anciano , Femenino , Hemodinámica , Humanos , Riñón/patología , Riñón/fisiopatología , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Sobrepeso/complicaciones
13.
Microvasc Res ; 114: 41-45, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28602918

RESUMEN

BACKGROUND: The angiogenesis in systemic sclerosis (SSc) is impaired. An imbalance of pro-angiogenic factors and angiogenesis inhibitors has been implicated in the progression of peripheral microvascular damage, defective vascular repair and fibrosis. Intrarenal resistance index are considered markers of renal vasculopathy. The aim of the study is to evaluate angiogenic and angiostatic factors (VEGF and endostatin) in SSc patients and to correlate with intrarenal hemodynamic parameters. METHODS: 91 SSc patients were enrolled in this study. Serum VEGF and endostatin levels were determined. All patients underwent a renal Doppler ultrasound RESULTS: A significant positive correlation was observed between endostatin and renal Doppler parameters (p<0.0001). A negative correlation was observed between serum levels of endostatin and eGFR (p<0.01). In SSc patients with high resistive index, serum levels of endostatin were significantly (p<0.01) higher than in SSc patients with normal resistive index. The serum levels of endostatin significantly increased with progression of nailfold videocapillaroscopy damage (p<0.01) and were significantly (p<0.05) higher in SSc patients with digital ulcers than in SSc patients without digital ulcers. CONCLUSION: This is the first study that assess in SSc patients intrarenal hemodynamic parameters and endostatin. In SSc patients, endostatin represents a marker of renal scleroderma-associated vasculopathy.


Asunto(s)
Endostatinas/sangre , Hemodinámica , Enfermedades Renales/sangre , Riñón/irrigación sanguínea , Circulación Renal , Esclerodermia Difusa/sangre , Esclerodermia Limitada/sangre , Enfermedades Vasculares/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/fisiopatología , Masculino , Angioscopía Microscópica , Persona de Mediana Edad , Neovascularización Patológica , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/fisiopatología , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/fisiopatología , Ultrasonografía Doppler , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/fisiopatología
15.
Microvasc Res ; 110: 1-4, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27838313

RESUMEN

Systemic sclerosis (SSc) patients are at high risk for the development of ischemic digital ulcers (DUs). The aim of this study was to assess in SSc patients a correlation between skin perfusion evaluated by LDPI and DUs and to evaluate the prognostic value of skin perfusion to predict the new DUs occurrence. Fifty eight (47 female, 11 male) SSc patients were enrolled. Skin perfusion of hands and region of interest (ROIs) was measured by Laser Doppler perfusion Imager (LDPI). The proximal-distal gradient (PDG) was present when the perfusion mean difference between ROI1 and ROI2 was >30 pU. The skin perfusion of hands is lower in SSc patients than in healthy controls. The skin perfusion decreased with severity of capillaroscopic damage. Both mean perfusion of hand and PDG are significantly (p<0.01 and p<0.0001, respectively) lower in SSc patients with new DUs than in SSc patients without DUs. Only 2 of 11 SSc patients (18.2%) with PDG developed new digital ulcers, conversely 36 of 47 (76.6%) SSc patients without PDG developed new digital ulcers (p<0.001). The ROC curves demonstrated a good accuracy of new DUs prediction for PDG (0.78, p<0.0001). Using this cut-off value of 30 pU, RR for new DUs development in SSc patients without PDG is 4,2 (p<0.001). LDPI indices could be used in association to the capillaroscopic and clinical findings or serological tests in the identification of patients at high risk of developing DUs.


Asunto(s)
Isquemia/etiología , Flujometría por Láser-Doppler , Imagen de Perfusión/métodos , Esclerodermia Sistémica/diagnóstico , Úlcera Cutánea/etiología , Piel/irrigación sanguínea , Adulto , Área Bajo la Curva , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Femenino , Mano , Humanos , Isquemia/diagnóstico , Isquemia/fisiopatología , Masculino , Angioscopía Microscópica , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Flujo Sanguíneo Regional , Reproducibilidad de los Resultados , Factores de Riesgo , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/fisiopatología , Índice de Severidad de la Enfermedad , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/fisiopatología
18.
Int J Immunopathol Pharmacol ; 29(3): 469-74, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27091839

RESUMEN

Renal Doppler ultrasound is increasingly used in nephrology for the evaluation of renovascular disease, allograft dysfunction, and chronic nephropathies. We compared intrarenal hemodynamic parameters to biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, crescents, arteriolosclerosis, and clinical variables in 100 patients. A positive correlation exists between renal function and percentage of glomerular sclerosis (P <0.01, r = 0.26), conversely a negative correlation exists between glomerular filtrate rate and percentage of glomerular sclerosis(P <0.0001, r = -0.35). The percentage of glomerular sclerosis correlate positively with pulsatile index (PI) (P <0.05, r = 0.21) and renal resistive index (RI) (P <0.05, r = 0.20). The percentage of crescents correlates positively with PI(P <0.05, r = 0.21) and RI (P <0.05, r = 0.20). Classifying arteriolosclerosis in four groups according to a severity scale, from absence to severe, PI (P <0.05) and RI (P <0.01) were significantly different. In the post hoc analysis, the median values of PI and RI are significantly different in patients with severe arteriolosclerosis than others. Ultrasound examination is a non-invasive diagnostic technique used on patients with suspected or established renal disease. Our study shows a close correlation between kidney function, ultrasound parameters, and histological findings. Measurement of renal parenchymal resistance by ultrasound could be used in association with biopsy and glomerular function for the evaluation of renal damage in patients with glomerulonephritis.


Asunto(s)
Glomerulonefritis/patología , Riñón/patología , Arterioloesclerosis/patología , Biopsia , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Fallo Renal Crónico/patología , Masculino , Persona de Mediana Edad
19.
Clin Nephrol ; 85(6): 326-31, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27125627

RESUMEN

OBJECTIVES: The most important renal complication of systemic sclerosis (SSc) is scleroderma renal crisis (SRC). Many patients demonstrate less severe renal complications, most likely associated with reduced renal blood flow and a consequent reduction in glomerular filtration rate (GFR). The mechanism of this slowly progressive form of chronic renal disease is unclear. The aim of this study was to evaluate GFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the 7-variable Modification of Diet and Renal Disease (MDRD) equations in SSc patients and to correlate estimated GFR (eGFR) with clinical variables of the disease. METHODS: 105 unselected and consecutive patients with SSc were enrolled. Serum creatinine was measured in all patients and GFR was estimated by 7-variable MDRD and CKD-EPI equations. Nailfold videocapillaroscopy was performed in all patients. RESULTS: The mean value of eGFR evaluated by both 7-variable MDRD and CKD-EPI was significantly different (p < 0.0001) in the three capillaroscopic groups and correlated negatively with the severity of capillaroscopic damage (early: 95 ± 16 mL/min and 101 ± 12 mL/min, active: 86 ± 25 mL/min and 95 ± 17 mL/min, late: 76 ± 21 mL/min and 82 ± 21 mL/min). The mean value of eGFR evaluated by 7-variable MDRD (97 ± 23 mL/min vs. 74 ± 15 mL/min, p < 0.0001) and CKD-EPI< (0.83 ± 0.20 mL/min vs. 0.68 ± 0.10 mL/min, p < 0.0001) was significantly higher in SSc patients without history of digital ulcers than in those with. CONCLUSION: We can conclude that in SSc patients without renal involvement, eGFR decreases with the progression of digital vascular damage.


Asunto(s)
Tasa de Filtración Glomerular , Riñón/fisiopatología , Esclerodermia Sistémica/fisiopatología , Adulto , Anciano , Creatinina/sangre , Femenino , Humanos , Masculino , Angioscopía Microscópica , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
20.
Cardiorenal Med ; 6(2): 135-42, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27022332

RESUMEN

BACKGROUND: Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions characterized by a simultaneous involvement of the heart and kidney in the course of a systemic disease. Systemic sclerosis (SSc) is frequently involved in the etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc patients, left ventricular mass (LVM) can be used as a marker of nutritional status and fibrosis, while altered intrarenal hemodynamic parameters are suggestive of early kidney involvement. METHODS: Forty-two consecutive patients with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to assess whether cardiac muscle mass can be related to arterial stiffness. Thirty subjects matched for age and sex were also enrolled as healthy controls (HC). All patients performed echocardiography and renal ultrasound. RESULTS: Doppler indices of intrarenal stiffness and echocardiographic indices of LVM were significantly increased in SSc patients compared to HC. A positive correlation exists between LVM/body surface area and pulsatile index (p < 0.05, r = 0.36), resistive index (p < 0.05, r = 0.33) and systolic/diastolic ratio (p < 0.05, r = 0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly higher in SSc patients with digital ulcers than in SSc patients without a digital ulcer history. CONCLUSIONS: SSc is characterized by the presence of microvascular and multiorgan injury. An early cardiac and renal impairment is very common. LVM and intrarenal arterial stiffness can be considered as early markers of CRS onset. The clinical use of these markers permits a prompt identification of organ damage. An early diagnosis allows the appropriate setting of pharmacological management, by slowing disease progression. © 2016 S. Karger AG, Basel.

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