Serum level of endostatin and digital ulcers in systemic sclerosis patients.

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.

Cardiovascular Risk and Quality of Life in Autosomal Dominant Polycystic Kidney Disease Patients on Therapy With Tolvaptan: A Pilot Study.

INTRODUCTION: Cardiovascular (CV) complications are the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients. In 2017, the Italian Medicines Agency authorised tolvaptan, a vasopressin V2 receptor antagonist, for the treatment of ADPKD, based on the Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO 3: 4), TEMPO 4: 4 and Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) studies. AIM OF THE STUDY: The aim of the study was to assess the impact of tolvaptan on CV risk and quality of life, evaluated by nutritional, inflammatory, metabolic, instrumental parameters and psychocognitive tests on ADPKD patients. METHODS AND MATERIALS: We evaluated 36 patients with ADPKD; 10 patients (7 males, mean age 42.5±7.0 years) treated with tolvaptan and 26 controls (11 males, mean age 36.7±9.1 years). They underwent, at T0, monthly, and at T1 (1 year) clinical, laboratory and instrumental evaluation, in addition to psychocognitive tests. RESULTS: In ADPKD patients treated with tolvaptan, we found at T1, a decrease in carotid intima-- media thickness (p=0.048), epicardial adipose tissue thickness (p=0.002), C-reactive protein (p=0.026), sympathovagal balance during night (p=0.045) and increased flow-mediated dilation (p=0.023) with a reduction in depression (Hamilton and Beck tests, p=0.008 and p=0.002, respectively) compared with controls. CONCLUSION: These preliminary results suggest that treatment with tolvaptan could improve early atherosclerosis and endothelial dysfunction markers and improve mood in ADPKD patients (probably by acting on endothelial cell and adipocyte V2 receptors).

Atrial natriuretic peptide predicts disease progression and digital ulcers development in systemic sclerosis patients.

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 ±â€Š14 years) with a disease duration of 11.1 ±â€Š8.3 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.

Drugs and Rhabdomyolysis: From Liver to Kidney.

Rhabdomyolysis is a syndrome due to a damage of skeletal muscle and the leakage of intracellular contents into the extracellular fluid and the circulation. Several causes may induce rhabdomyolysis and the major one is the crush syndrome. Most cases of non-traumatic rhabdomyolysis are related to drugs. Many molecules are subject to hepatic metabolism and the concomitant use of drugs, as statins, with other medications acting as substrates of the same isoenzymes can interact and increase the risk of myopathy. Subclinical rise of creatine kinase may be the expression of rhabdomyolysis that can present as a medical emergency such as acute kidney injury (AKI), compartment syndrome, cardiac dysrhythmias and disseminated intravascular coagulopathy. The main pathophysiological mechanisms of myoglobinuric-related AKI are renal vasoconstriction, formation of intraluminal casts and direct cytotoxicity promoted by heme-protein. The aim of this review is to analyze the pathophysiology of myolysis, the causes of rhabdomyolysis and especially the link between the liver and the kidney, which can represent the connecting element for the development of the syndrome.

Hypercoagulability and nephrotic syndrome.

Patients with nephrotic syndrome are at increased risk for thromboembolic events such as deep venous and arterial thrombosis, renal vein thrombosis and pulmonary embolism. This thrombophilic phenomenon has been attributed to a "hypercoagulable" state in which an imbalance between naturally occurring pro-coagulant/pro-thrombotic factors and anti-coagulant/antithrombotic factors promotes in situ thrombosis in deep veins or arteries. Management of thromboembolic events may be divided in prophylactic and therapeutic strategies. Hypoalbuminemia is the most significant independent predictor factor of thrombotic risk, especially for values <2 g/dL. However, the most important question in these patients is whether to anticoagulate prophylactically or not. The decision depends on type of glomerulonephritis, proteinuria severity, other predisposing factors and prior history of thrombosis. Reviewing the recent literature, we suggest the best therapeutic management of anticoagulation for patients with nephrotic syndrome, focusing on prophylactic strategies.