Antonietta Gigante

In systemic sclerosis macrovascular damage of hands digital arteries correlates with microvascular damage

OBJECTIVE To assess morphology and blood flow of the proper palmar digital arteries (PPDA) by color Doppler ultrasonography (CDUS) and its relationship with nailfold videocapillaroscopy (NVC), skin blood perfusion and digital arteries pulsatility of hands in SSc patients and healthy controls. METHODS CDUS, NVC, laser Doppler perfusion imaging (LDPI) and photoplethysmography (PPG) were performed in 36 systemic sclerosis (SSc) patients and 20 healthy controls. RESULTS CDUS was pathologic in 69% of patients with SSc and in none of healthy controls (p<0.0001). SSc patients with low vascular damage (early capillaroscopic pattern) have a normal morphology of PPDA, but the blood flow, evaluated by peak systolic velocity (PSV) and end diastolic velocity (EDV), is reduced and vascular resistance, measured by resistive index (RI) and pulsatility index (PI), increased. At this stage the LDPI mean perfusion and digital artery pulsatility, evaluated by PPG, were reduced. The US changes appear with microvascular damage progression (active and late capillaroscopic patterns), while the PPDA blood flow progressively decreases (PSV and EDV decreased, RI and PI increased). The macrovascular damage correlates with disease duration. Anti-topoisomerase I represents an independent predictive factor for macrovascular damage. We not observed any association between digital ulcer history, pulmonary fibrosis and US findings. CONCLUSION PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy.

Antiphospholipid Antibodies and Renal Involvement

Antiphospholipid antibodies are a heterogeneous group of autoantibodies associated with the hypercoagulable state affecting all vascular districts with thrombosis named antiphospholipid syndrome (APS). APS is an autoimmune disease with multifactorial etiology that includes cellular, molecular, genetic and pathogenic mechanisms. The APS clinical features are a combination of arterial and/or venous thrombosis, hematological events, recurrent fetal losses, neurological disorders and intra-abdominal manifestations. The renal involvement is associated with both primary and secondary APS. Clinical features include hypertension, renal artery stenosis, thrombotic microangiopathy and other histological manifestations of the nephropathy (APSN), venous renal thrombosis, APSN in the course of systemic lupus erythematosus and renal failure. APSN is an independent risk factor that should be included in the classification criteria for definite APS with characteristic clinical and histological features.

Thrombosis in Nephrotic Syndrome

Nephrotic syndrome (NS) is characterized by heavy proteinuria, edema, hypoalbuminemia, and hyperlipidemia and the most frequent causes are glomerular diseases. An uncommon presentation is iatrogenic NS, an adverse effect of some drugs administration. In the clinical course of NS, a typical feature is dysregulated coagulation state, promoted by the breakdown of permselectivity barrier of the glomerular capillary wall, resulting in the leakage of high-molecular-mass proteins, at least the size of albumin. This hypercoagulable condition is supported by several factors, such as abnormalities in platelet activation and an imbalance between anticoagulation/antithrombosis and procoagulant/prothrombotic mechanisms. Thus, NS and the risk of developing thromboses are strictly related. Thrombotic events affect the venous system rather than arterial vessels with different features and frequencies. Deep venous system of the lower extremities and renal veins are the most frequent source of pulmonary embolism, the most dangerous NS complication. Prophylactic anticoagulation and thrombosis treatment are not clearly established because large randomized trials and guidelines are lacking. The management of NS and the decision of when and how to anticoagulate the patient represent a teamwork challenge for physicians.

N-acetylcysteine infusion reduces the resistance index of renal artery in the early stage of systemic sclerosis

Aim:To evaluate resistance index (RI) changes in renal artery after N-acetylcysteine infusion in patients with systemic sclerosis.Methods:In an open-label study 40 patients with systemic sclerosis (SSc) were treated with N-acetylcysteine (NAC) iv infusion over 5 consecutive hours, at a dose of 0.015 g·kg−1·h−1. Renal haemodynamic effects were evaluated by color Doppler examination before and after NAC infusion.Results:NAC infusion significantly reduced RI in a group of sclerodermic patients with early/active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS) <14 and mild-moderate score to the vascular domain of Medsger Scleroderma Disease Severity Scale (DSS). RI increased after NAC infusion in patients with late capillaroscopic pattern, mTRSS>14 and severe-end stage score to the vascular domain of DSS. In patients with reduction of RI after NAC infusion, diffusion capacity for carbon monoxide mean value was significantly higher than in those patients with an increase of RI. No significant differences in renal blood flow were found between patients with different subsets of SSc.Conclusion:In patients with low disease severity NAC ameliorates vascular renal function.

Intrarenal Hemodynamic Parameters Correlate with Glomerular Filtration Rate and Digital Microvascular Damage in Patients with Systemic Sclerosis

OBJECTIVES To evaluate intrarenal arterial stiffness by Doppler ultrasound and examine the correlation between renal Doppler indices, glomerular filtration rate, and digital microvascular damage in systemic sclerosis patients. METHODS Thirty systemic sclerosis patients and 30 healthy controls were enrolled in this study. Doppler indices of intrarenal arterial stiffness, peak systolic flow velocity, end diastolic flow velocity, resistive index, pulsative index, and systolic/diastolic (S/D) ratio were measured on the interlobar artery of both kidneys. Glomerular filtration rate was measured using Tc(99m) diethylenetriamine pentaacetic acid (DTPA). Equation 7 from the Modification of Diet in Renal Disease was used to estimate glomerular filtration rate. Nailfold videocapillaroscopy findings were classified as early, active, and late patterns. RESULTS The intrarenal arterial stiffness, evaluated by Doppler indices, was higher in systemic sclerosis patients than healthy controls. In systemic sclerosis patients pulsative index (r = -0.69), resistive index (r = -0.75), and S/D ratio (r = -0.74) showed a negative correlation with measured glomerular filtration rate (P < 0001). High correlation (P = 0008) was observed between measured and estimated glomerular filtration rate (r = 0.55). Pulsative index, resistive index, and S/D ratio significantly increased with progression of capillaroscopic damage. Conversely, measured glomerular filtration rate significantly decreased with capillaroscopic damage progression. CONCLUSIONS Doppler indices of intrarenal arterial stiffness are noninvasive diagnostic tests to evaluate renal damage in SSc patients. Intrarenal arterial stiffness and glomerular filtration rate correlate with capillaroscopic microvascular damage.

Revascularization versus medical therapy for renal artery stenosis: antihypertensive drugs and renal outcome.

Endovascular procedures may play a role in renal artery stenosis (RAS) treatment in attempt to preserve renal function and improve hypertension control. We determined renal outcome and the incidence of restenosis in patients with RAS treated with renal percutaneous transluminal angioplasty and stenting (RPTAs) and medical therapy versus patients with RAS treated only with medical therapy. We performed an observational study based on 93 patients with RAS. In all, 53 patients underwent RPTAs in association with medical therapy and 40 patients were only treated pharmacologically. In patients receiving RPTAs, a better renal outcome, a decrease of restenosis rate, and systolic—diastolic blood pressure were associated with angiotensin receptor blockers (ARBs) + angiotensin-converting enzyme inhibitors (ACE-is) therapy. In patients treated with medical therapy alone, renal improvement was related to ARBs in association with BBs (β-blockers; P < .0001). This study suggests that medical therapy may exert beneficial effects in patients with RAS.

Pathophysiology, Diagnosis and Clinical Management of Hepatorenal Syndrome: From Classic to New Drugs

Advanced cirrhosis is frequently associated with renal dysfunction. Hepatorenal syndrome (HRS) is characterized by the occurrence of kidney injury in cirrhotic patients in the absence of other identifiable causes. HRS is classified in 2 different types. Type 1 is characterized by acute renal failure and rapid functional deterioration of other organs, usually related to a precipitating event. Type 2 is characterized by slowly progressive renal failure and refractory ascites. Advanced liver disease induces the progression of hemodynamic alterations such as arterial vasodilation of splanchnic circulation and impairment of cardiac function. The resulting ineffective circulating blood volume promotes the activation of both the renin-angiotensin-aldosterone and sympathetic nervous system, by an increase of antidiuretic hormone activity, in an attempt to restore volemia. Despite fluid retention, ascites and dilutional hyponatremia, renal function is often initially preserved by renal production of vasodilators. However, further insults can lead to an imbalance between systemic vasoconstriction and local renal vasodilation, resulting in progressive renal failure. Over the last decade, clinical strategies to prevent HRS have been improved by a better understanding of the natural history of renal failure in cirrhosis, resulting in a reduction of HRS prevalence in cirrhotic patients. Vasoconstrictor drugs may improve renal function, but the effect on mortality has not yet been established. Vaptans, nonpeptide vasopressin receptor antagonists, may also reduce hyponatraemia and ascites, even if the clinical effects in HRS remain unknown. This review updates the pathophysiology, diagnosis and management of HRS.

Evaluation of Chronic Kidney Disease Epidemiology Collaboration equation to estimate glomerular filtration rate in scleroderma patients

OBJECTIVE Renal involvement in SSc is often subclinical and chronic kidney disease (CKD) develops, with slow worsening of glomerular filtration rate (GFR). The present investigation was undertaken in order to study how well the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) correlates with measured GFR (mGFR) in a group of SSc patients with serum creatinine (sCr) in the normal range. METHODS Forty-one scleroderma patients (37 females and 4 males) with a median age of 46 years were enrolled. GFR was measured using technetium-99 m DTPA (Tc-99 m DTPA). The modified Cockroft-Gault formula, 4- and 7-variable Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations were used for estimated GFR (eGFR). RESULTS mGFR showed a median value of 84 ml/min (range 32.8-121.2 ml/min). Seven patients had reduced GFR (<60 ml/min), 19 had GFR within 60-90 ml/min and 15 had GFR >90 ml/min. The results showed mild correlation between the BSA-modified Cockroft-Gault and mGFR (P > 0.05), mild statistically significant correlation with 4-variable MDRD (P < 0.05), high statistically significant correlation with 7-variable MDRD (P = 0.01), but the greatest correlation was obtained using CKD-EPI (P = 0.002). No correlation with age, disease duration or subset of disease was found. CONCLUSIONS In scleroderma patients with normal sCr value, CKD-EPI is a useful formula to assess GFR.

Ischemic nephropathy: proteinuria and renal resistance index could suggest if revascularization is recommended.

Background: The aim of endovascular therapy in renal artery stenosis (RAS) is to preserve renal function and have a better hypertension control. The purpose of our study was to determine which biochemical and instrumental parameters could predict a better renal outcome in patients with RAS treated with percutaneous transluminal angioplasty and stenting (RPTAS). Methods: We performed an observational study based on 40 patients with RAS who met the following criteria before revascularization: urinary protein excretion of over 250 mg/24 h, normal renal function, and/or mild–moderate renal insufficiency (I, II, and III levels of classification of chronic kidney disease, K-DOQI). Results: Assessment at 12 months after RPTAS showed in 20 patients (Group A) that proteinuria serum creatinine (Scr) and creatinine clearance (CrCl) significantly worsened from the baseline; whereas in 20 patients (Group B) proteinuria remained unchanged and the renal function improved after the procedure. Conclusions: In our study, the decline of renal function after RPTAS is associated with an elevated renal resistance index (RI) in both kidneys (0.83 ± 0.2) and preexisting proteinuria.

Erectile Dysfunction, Endothelium Dysfunction, and Microvascular Damage in Patients with Systemic Sclerosis

INTRODUCTION Erectile dysfunction (ED) prevalence in men with systemic sclerosis (SSc) is high and can be considered a manifestation of endothelium damage. AIM This study aims to correlate ED with endothelial dysfunction and digital vascular damage in SSc patients. MAIN OUTCOME MEASURES The main outcome measures were erectile function, Doppler indices of cavernous arteries, flow-mediated dilation (FMD), capillaroscopic damage, skin perfusion, and digital pulsatility. METHODS In 23 SSc patients, erectile function was investigated using the International Index of Erectile Function-5 (IIEF-5). Doppler indices of cavernous arteries, peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were measured at the penoscrotal junction before and after pharmacostimulation with 20 mg prostaglandin E1. FMD and nailfold videocapillaroscopy (NVC) were used to evaluate endothelial dysfunction and capillaroscopic damage. Skin perfusion and digital sphygmic waves were measured by laser Doppler perfusion imaging (LDPI) and digital photoplethysmography (PPG), respectively. RESULTS IIEF-5 score was reduced in 83% of patients. PSV was reduced in 96%, while EDV was increased in 48% of patients. A positive correlation was observed between IIEF-5 score and FMD (r = 0.71, P < 0.0001) and between the former and PSV (r = 0.76, P < 0.0001). A negative correlation was observed between EDV and FMD (r = -0.509, P < 0.01). FMD and Doppler indices were reduced with capillaroscopic damage progression. A positive correlation exists between LDPI perfusion and IIEF-5 score (r = 0.743, P < 0.0001) and between the former and PSV (r = 0.714, P < 0.0001), while a negative correlation is observed between LDPI perfusion and EDV (r = -0.677, P < 0.0001). A positive correlation exists between PPG pulsatility and IIEF-5 score (r = 0.752, P < 0.0001) and between the former and PSV (r = 0.747, P < 0.0001), while negative correlation is observed between PPG pulsatility and EDV (r = -0.689, P < 0.0001). CONCLUSION In SSc patients, ED correlates with endothelial dysfunction and digital microvascular damage.