Does physical exercise ameliorate CKD-related complications? The case of anaemia and CKD-MBD.

Background Physical exercise (PE) can regulate inflammation, cardiovascular health, sarcopenia, anaemia and bone health in the chronic kidney disease (CKD) population. Experimental and clinical studies both help us to better understand the mechanisms that underlie the beneficial effects of the exercise, especially in renal anaemia and CKD-Mineral Bone Disorders (CKD-MBD). Here, we summarize this evidence, exploring the biological pathways involved, locally released substances and crosstalk between tissues, but also the shortcomings of current knowledge. Main findings Anaemia- Both in healthy and CKD subjects PE may mimic hypoxia, inhibiting PHDs; so hydroxylate HIF-α subunits may be translocated into the nucleus, resulting in dimerization of HIF-1α and HIF1ß, recruitment of p300 and CBP, and ultimately, binding to HREs at target genes to cause activation. However, in CKD subjects acute PE causes higher levels of lactate, leading to iron restriction by upregulating hepatic hepcidin expression; while chronic PE allows an increased lactate clearance and HIF-α and VEGFα levels, stimulating both erythropoiesis and angiogenesis. CKD-MBD -PE may improve bone health decreasing bone resorption and increasing bone formation throughout at least three main pathways: A) increasing osteoprotegerin and decreasing RANKL system; B) decreasing cytokines levels; and C) stimulating production of miokines and adipokines. Conclusions Future research needs to be defined to develop evidence-based exercise guidance to provide optimal benefit for CKD using exercise interventions as adjuvant therapy for CKD-related complications such as anaemia and CKD-MBD.

[Clinical Thermography for the Management of Hemodialysis Vascular Access].

The arteriovenous fistula (AVF) represents the favorite vascular access in individuals with chronic kidney disease (CKD). Because AVF is a guarantee of survival for these patients, proper surgical packing and a timely follow-up program is crucial. Although a good objective examination of the limb site of FAV provides useful information both in planning the fistula surgery and in its surveillance and monitoring, it is now well established that the advent of instrumental diagnostics (ultrasonography, digital angiography, Angio-TC, MRI) has contributed significantly to improving primary and secondary patency of FAV and early diagnosis of vascular access complications. In this area, clinical thermography, a noninvasive and nondestructive diagnostic technique for assessing minute surface temperature differences, has shown good potential for the assessment of AVF. In fact, thermographic analysis of a limb site of AVF shows an increase in temperature at the site of the anastomosis and along the course of the arterialized vein. In this article we report our experience on the use of thermography in preoperative evaluation and postoperative surgical packing of an AVF. Further studies could validate the use of clinical thermography as a diagnostic technique to be used in the field of hemodialysis vascular accesses.

Prevalence, risk factors, and treatment of anemia in hospitalized older patients across geriatric and nephrological settings in Italy.

Anemia is a common but often underdiagnosed and undertreated geriatric syndrome in hospitalized older patients. In this retrospective multicenter study, we aimed at characterizing the prevalence, risk factors, diagnostic and treatment approach to anemia in older patients admitted to acute care hospitals, focusing on differences between nephrology and geriatrics units. Prevalence and risk factors for anemia, diagnostic inertia (lack of iron, vitamin B12, and folate status assessment), replacement inertia (omitted treatment with iron, vitamin B12 or folic acid), and erythropoiesis-stimulating agents (ESA) inertia were explored. 1963 patients aged 82.7 (6.8) years were included in the study; 66.7% of the study population had anemia; among anemic patients, diagnostic inertia and replacement inertia were common with rates of 22-31% and 50-87%, respectively; omitted treatment with ESA affected 67.2% of patients and was more prevalent in geriatric units. In most cases, patients with ESA inertia were not routinely screened for iron tests. COPD, cancer, eGFR 45-60 ml/min were associated with increased tendency to ESA inertia. In conclusion, anemia had a high prevalence in older patients discharged from acute care units, but it is often underdiagnosed and undertreated.

Effectiveness and tolerability of givosiran for the management of acute hepatic porphyria: A monocenter real-life evaluation.

Acute hepatic porphyrias (AHPs) are a family of rare, autosomal, dominantly inherited conditions characterized by abnormalities in the production of heme. Advances in molecular engineering have provided new therapeutic possibilities for modifying the heme synthetic pathway in patients with porphyria. In particular, the RNA interference therapeutic givosiran was approved for the treatment of adults and adolescents with AHP aged >12 years based on the positive results of the phase III trial ENVISION. Despite the extended characterization of the activity of givosiran in clinical trials, reports on the long-term effects and effectiveness of the treatment in clinical practice are still scant. To fill this gap, this case series describes a monocentric Italian cohort of AHP patients treated with givosiran. Overall, our real-life experience supports the clinical evidence that long-term treatment with givosiran is well tolerated and able to provide sustained and continuous benefit to patients with acute intermittent porphyria, as reflected by the reduction in the frequency of attacks. In our series, givosiran treatment was also associated with improvement in assessments of quality of life, pain and fatigue.

Appropriateness of direct oral anticoagulant prescribing in older subjects with atrial fibrillation discharged from acute medical wards.

AIMS: Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. METHODS: We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug-drug interactions (DDIs). RESULTS: At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin-K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage-17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00-1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02-1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91-0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19-3.13 for missed prescription). CONCLUSIONS: This study showed a suboptimal DOAC prescriptive practice in older in-patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real-life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting.

Intrahepatic Cholangiocarcinoma and Acute Intermittent Porphyria: A Case Report.

Patients suffering from different forms of acute hepatic porphyria present a high risk of primary liver cancer, specifically hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72-year-old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with a histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.