[Quantitative imaging in nephrology: limits and potentials of elastosonography].

Chronic kidney disease is characterized by increasingly amplified fibrotic processes regardless of etiology. The severity of renal fibrosis seems to correlate with an increased risk of end-stage renal disease; therefore, monitoring of renal fibrosis over time may play an important role in the follow-up of both focal and diffuse renal diseases and in evaluating the response to treatments. Renal biopsy is the only method capable of providing objective and comparable information on the extent of fibrosis, but it is not suitable for outpatient monitoring of chronic kidney disease due to its invasiveness. Elastosonography is an innovative and non-invasive ultrasound method that allows the measurement of tissue elasticity through the transmission of mechanical waves and the measurement of their propagation speed. Although some authors have demonstrated the usefulness of elastosonographic techniques for the quantification of liver fibrosis, few studies have investigated the applications of elastosonography in renal pathology. Furthermore, the depth of native kidneys, the high anisotropy of the renal tissue, and the possibility of examining only a small region of interest currently limit its spread in clinical practice. The aim of this review is to examine the physical principles of elastosonography and to review the latest evidence about the possible applications of the ARFI (acoustic radiation force impulse) technique in the study of kidney diseases.

GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are highly effective in improving glycaemic control either as monotherapy or in combination with other hypoglycaemic drugs, and have low incidence of side effects, such as hypoglycaemia, nausea and weight gain, thus increasing patients' adherence to therapy. Methods: In this review we report the most recent studies demonstrating the beneficial effects of GLP-1RAs on renal outcomes, and also discuss the direct and indirect mechanisms through which they confer kidney protection. Finally, we discuss the metabolic and anti-inflammatory effects of GLP-1RAs in diabetic patients with COVID-19 disease. Results: GLP-1RAs have a nephroprotective action, which is expressed through both indirect (improvement of blood pressure and glycaemic control, weight loss) and direct (restoration of normal intrarenal haemodynamics, prevention of ischaemic and oxidative damage) effects. They have shown also metabolic and anti-inflammation beneficial effects in patients with COVID-19 disease. Conclusions: GLP-1RAs prevent albuminuria and slow the decline of renal function towards end stage renal disease in patients with diabetic kidney disease. They might be an opportunity to break the typical inflammation processes of COVID-19 disease.

[Urinary tract infections in nephrology: antibiotic therapy in the era of antibiotic resistance].

Urinary tract infections (UTIs) are an emerging health problem. Kidney patients with UTI are at increased risk of antimicrobials resistance (AMR) and bad prognosis. In the nephrological setting, optimizing the management of UTIs is certainly a challenge, but it is indispensable for a favorable clinical outcome and in fighting AMR. When UTIs caused by multidrug-resistant germs are suspected, it is necessary to initiate empirical antibiotic therapy timely, pending microbiological study and bacterial sensitivity. The empirical choice of antibiotic must be based on: guidelines, resistance rates recorded in the region, and knowledge of pharmacokinetic and pharmacodynamic characteristics of the drug, in order to maximize efficacy, reduce adverse effects and minimize AMR development. Recently, the clinical use of old drugs such as colistin has increased, due to the limited circulation of resistant bacterial strains. On the other hand, ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, imipenem/cilastatin/relebactam and meropenem-vaborbactam are very promising new antibiotics. Ongoing clinical studies will be able to determine the place for these interesting molecules in the treatment of infections and in fighting AMR.

[GLP-1 receptor agonists in the treatment of diabetes mellitus type 2: cardioprotection, and more!]

Optimal glycemic control in diabetic patients remains a difficult goal to achieve. Hypoglycemia, nausea and weight gain can compromise the patients' adherence to antidiabetic therapy over time. GLP-1 receptor agonists have been shown to improve glycemic control and reduce the incidence of side effects both when used in monotherapy and in combination with other hypoglycemic drugs. The growing interest of nephrologists in GLP-1 receptor agonists derives from numerous studies showing that not only they positively affect traditional cardiovascular risk factors, but also exert a protective effect on renal function regardless of their hypoglycemic effects, thus delaying the development and progression of diabetic nephropathy. The aim of this paper is to review the latest evidence on pharmacokinetics and pharmacodynamics and the direct and indirect mechanisms through which GLP-1 receptor agonists confer nephroprotection, improving the renal outcomes of diabetic patients.

Feasibility of routine ultrasound-guided percutaneous transluminal angioplasty in the treatment of native arteriovenous fistula dysfunction.

BACKGROUND: Stenosis is the main cause of arteriovenous fistula failure and is due to neointimal hyperplasia. Percutaneous transluminal angioplasty is the gold standard for patients with vascular access stenosis. The aim of the study was to evaluate the efficacy and safety of ultrasound-guided percutaneous transluminal angioplasty in the treatment of native arteriovenous fistula venous stenosis. METHODS: The need for intervention was determined by physical examination and duplex ultrasound in 162 patients. All patients with failing or not maturing arteriovenous fistula were treated in the outpatient setting under ultrasound guidance. Procedural success was assessed with repeated post-procedural ultrasound examinations. All procedures were performed under local anesthesia by a single nephrologist and were performed in a single vascular laboratory, while follow-up ultrasound was performed in the dialysis unit of destination. RESULTS: Early technical success was obtained in 95.6% of cases (154 of 162). Complications occurred in 22 patients (13.5%) with no major complication requiring surgical or fluoroscopic endovascular intervention. Primary patency at 6 and 12 months was 84% and 69.8%, respectively. Risk factors for arteriovenous fistula failure/secondary percutaneous transluminal angioplasty were vascular access low blood flow rate and vintage, as well as the need for thrombolysis during the first percutaneous transluminal angioplasty. CONCLUSION: Ultrasound-guided percutaneous transluminal angioplasty is a valuable tool to treat vascular access stenosis.

New strategies for prevention and early diagnosis of iodinated contrast-induced nephropathy: a systematic review / Nuove strategie per la prevenzione e la diagnosi precoce della nefropatia da mezzo di contrasto iodato: revisione sistematica della letteratura

Iodinated contrast-induced nephropathy is one of the most feared complications of percutaneous coronary interventions and is associated with increased cardio-vascular mortality and a faster progression towards end stage renal disease. The effects of the iodinated contrast medium on intra-renal hemodynamics and its direct cytotoxic action on proximal tubular cells contribute synergistically to the pathophysiology of renal damage. Since the therapeutic options are extremely limited, the rapid identification of risk factors and the timely implementation of preventive strategies are mandatory to reduce the incidence of iodinated contrast-induced nephropathy. To date, the criteria for defining and staging contrast medium nephropathy are still based on the increase of serum creatinine and/or contraction of diuresis, which are lacking in specificity and therefore do not allow early diagnosis. The aim of this review is to report the latest evidence on the pathophysiological mechanisms that contribute to renal damage by iodinated contrast medium, on the risk stratification tools and on the new early biomarkers of contrast-induced nephropathy, while also focusing on the most validated prevention strategies.

Ultrasonography for diagnosis and management of nephrolithiasis: state of the art and new perspectives / L'ultrasonografia nella diagnosi e nel management della nefrolitiasi: stato dell'arte e prospettive future

The correct management of patients with kidney stones is a crucial issue for nephrologists. In recent years, the incidence and prevalence rates of nephrolithiasis have maintained a growing trend worldwide, showing a strong correlation with other systemic disease such as diabetes mellitus, hypertension, obesity, metabolic syndrome and chronic kidney disease. International guidelines indicate computed tomography as the first choice for all adult patients with suspected acute symptoms for obstructive nephrolithiasis. Intravenous pyelogram is more useful in the follow-up of patients with relapsing nephrolithiasis and known stone composition, while the high costs and the long image acquisition times limit the routine use of magnetic resonance. Recent innovative tools have improved the accuracy of kidney stone localization and measuring with B-Mode and color Doppler imaging, thereby reducing the gap between ultrasonography and computer tomography. The aim of this review is to report the latest evidence on risk factors and on the pathophysiology of nephrolithiasis, and to compare the utility of the available imaging techniques in the management of patients with kidney stones, focusing on the role of ultrasonography and the present and future strategies to improve its accuracy.

[Antifibrotic renal role of mineralcorticoid receptor antagonists].

Cardiovascular and renal diseases are one of the main health problems in all industrialized countries. Their incidence is constantly increasing due to the aging of the population and the greater prevalence of obesity and type 2 diabetes. Clinical evidence suggests that aldosterone and the activation of mineralocorticoid receptors (MR) have a role in the pathophysiology of cardiovascular and renal diseases. Moreover, clinical studies demonstrate the benefits of mineralocorticoid receptor antagonists (MRAs) on mortality and progression of heart and kidney disease. In addition to renal effects on body fluid homeostasis, aldosterone has multiple extrarenal effects including the induction of inflammation, vascular rigidity, collagen formation and stimulation of fibrosis. Given the fundamental role of MR activation in renal and cardiac fibrosis, effective and selective blocking of the signal with MRAs can be used in the clinical practice to prevent or slow down the progression of heart and kidney diseases. The aim of the present work is to review the role of MRAs in light of the new evidence as well as its potential use as an antifibrotic in chronic kidney disease (CKD). The initial clinical results suggest that MRAs are potentially useful in treating patients with chronic kidney disease, particularly in cases of diabetic nephropathy. We don't yet have efficacy and safety data on the progression of kidney disease up to the end stage (ESRD) and filling this gap represents an important target for future trials.

Under-recognized post-stroke acute kidney injury: risk factors and relevance for stroke outcome of a frequent comorbidity.

BACKGROUND: Acute kidney injury (AKI) is emerging as a predictor of poor stroke outcome, however, it is often not recognized. The aim of our study was to evaluate post-stroke AKI burden, AKI risk factors and their influence in post-stroke outcome. METHODS: From 2013 to 2016, 440 individuals with stroke diagnosis admitted in Stroke Unit, Foundation IRCCS Policlinico San Matteo (Pavia, Italy), were retrospectively enrolled. AKI cases identified by KDIGO criteria through the electronic database and hospital chart review were compared with the ones reported in discharge letters or in administrative hospital data base. Mortality data were provided by Agenzia Tutela della Salute of Pavia. RESULTS: We included 430 patients in the analysis. Median follow-up was 19.2 months. We identified 79 AKI cases (18% of the enrolled patients, 92% classified as AKI stage 1), a fivefold higher number of cases than the ones reported at discharge. 37 patients had AKI at the admission in the hospital, while 42 developed AKI during the hospitalization. Cardioembolic (p = 0.01) and hemorrhagic (p = 0.01) stroke types were associated with higher AKI risk. Admission National Institutes of Health Stroke Scale (NIHSS, p < 0.05) and Charlson Comorbidity Index (p < 0.01) were independently associated with overall AKI, while admission NIHSS (p < 0.05) and eGFR (p < 0.005) were independently associated with AKI developed during the hospitalization. AKI was associated to longer in-hospital stay (p = 0.01), worse Rankin Neurologic Disability Score at discharge (p < 0.0001) and discharge disposition other than home (p = 0.03). AKI was also independently associated to higher in-hospital mortality (OR 3.9 95% CI 1.2-12.9 p = 0.023) but not with long-term survival. CONCLUSIONS: Post-stroke AKI diagnosis needs to be improved by strictly monitoring individuals with cardioembolic or hemorrhagic stroke, reduced kidney function, higher Charlson Comorbidity Index and worse NIHSS at presentation.

[The new frontier in endovascular treatment of arteriovenous fistula stenosis: the role of ultrasound-guided percutaneous transluminal angioplasty].

Native arteriovenous fistula is the preferred vascular access because of it does not usually cause infections and seems to be closely related with prolonged patient survival, compared to prosthetic grafts and central venous catheters; it also is cost effective. Venous stenosis is one of the main causes of AVF failure. It is caused by a number of upstream and downstream events. The former group comprises hemodynamic and surgical stressors, inflammatory stimuli and uraemia, while downstream events involve the proliferation of smooth muscle cells and myofibroblasts and the development of neo-intimal hyperplasia. Percutaneous transluminal angioplasty is the gold standard for arteriovenous fistula stenosis. It allows the visualization of the whole vascular circuit and the immediate use of the vascular access for the next dialysis session. Ultrasound-guided percutaneous endovascular angioplasty is a feasible and safe alternative to conventional fluoroscopic technique: it is equally effective in treating arteriovenous fistula stenosis, but it presents the advantage of not using contrast media or ionizing radiation. The aim of this review is to report the latest evidence on cellular and molecular mechanisms that contribute to the development of neo-intimal hyperplasia, as well as the current and future therapeutic perspectives, especially concerning the use of anti-proliferative drugs, and the efficacy of the ultrasound-guided angioplasty in restoring and maintaining the vascular access patency over time.

RBP4: A Culprit for Insulin Resistance in End Stage Renal Disease That Can Be Cleared by Hemodiafiltration.

INTRODUCTION: Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). In our study, we evaluated the association between RBP4 and IR in hemodialysis subjects (HD). We also assessed how circulating RBP4 could be influenced by kidney transplant or different dialytic techniques. METHODS: RBP4 serum levels were evaluated in HD (n = 16) and matched healthy controls (C; n = 16). RBP4 and glucose transporter type 4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating RBP4 was evaluated after kidney transplant (n = 7) and in hemodialysis patients (n = 10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF). RESULTS: HOMA index (P < 0.05) and serum RBP4 (P < 0.005) were higher in HD compared to C. RBP4 levels positively correlated with fasting serum glucose (P < 0.05). RBP4 mRNA was lower in HD compared to C (P < 0.05) and positively correlated with kidney function (P < 0.05) and GLUT4 mRNA (P < 0.001). Transplant or HDF reduced circulating RBP4 (P < 0.01 and P < 0.05, resp.). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels.