The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft nephropathy. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients. In particular, mTOR-I may induce systemic nonnephrological side effects including pulmonary toxicity, hematological disorders, dysmetabolism, lymphedema, stomatitis, cutaneous adverse effects, and fertility/gonadic toxicity. Although most of the adverse effects are dose related, it is extremely important for clinicians to early recognize them in order to reduce dosage or discontinue mTOR-I treatment avoiding the onset and development of severe clinical complications.
Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy.
Guidelines for vascular access recommend that the distal autogenous arteriovenous fistula (AVF) should be the first choice-access procedure for patients starting dialysis. Arteriosclerosis of radial artery may cause early failure, as well as failure of maturation of distal arteriovenous fistulas. To increase the incidence of distal AVFs, our team, specialized in vascular access surgery from 2004 onwards, has introduced Intraoperative Transluminal Angioplasty (ITA) under ultrasound (UG) or fluoroscopic guidance, to recruit inadequate arterials for creating distal fistulas. Intravascular lithotripsy (IL) is a novel approach to treat luminal and medial calcifications in patients with peripheral arterial disease and coronary disease. We believe that intraoperative IL may be an opportunity to recruit calcified radial arteries for creating distal radio-cephalic fistulas. Purpose of this study is to describe the intraoperative IL technical applied in our clinical experience. A 37-year-old diabetic patient with distal radio-cephalic fistula was recruited for the first IL experience. One year ago, a wrist radio-cephalic fistula was created in the right upper limb, with intraoperative UG radial artery angioplasty for extensive calcifications. The fistula was functioning but showed a delay in maturation. An angioplasty was unsuccessfully attempted to facilitate the maturation. Subsequently, a surgical revision of the fistula was performed, creating a new anastomosis immediately upstream of the previous one by performing an intraoperative IL UG of the radial artery. The fistula was immediately well functioning, and was cannulated with two needles after 1 month. It is currently being used with intradialytic adequate blood flow. The positive outcome of the case described in this paper, even if only anecdotal, could act as a trigger for further experiences with IL.
Introduction: The first-choice vascular access to starting dialysis in patients with End Stage Renal Disease (ESRD) is autogenous distal arteriovenous-fistula (AVF) to spare vascular district avoiding proximal fistula complications. One of most significant exclusion criteria to create distal AVF is still now the presence of huge calcification of the feeding artery due to large numbers of early failure (EF) and failure in maturation (FTM). In recent years the possibility to use new devices able to deliver intravascular lithotripsy (IVL) to treat high calcified stenosis could be a possibility to recruit these marginal arteries to create distal AVF. Methods: ESRD patients with totally calcified radial artery wall were enrolled to participate to this prospective, single arm, multicentric study. The selected patients were treated with intraoperative IVL at surgical time, during anastomosis creation to soften calcified radial artery. Patients were followed 1 month after surgery with eco-doppler, for flow and vessels maturation assessment. At 3 month was investigated how many patients have started dialysis treatment with two needle cannulation and good efficiency. Results: Nineteen distal forearm radio-cephalic fistula were built in 19 patients. One-month doppler assessment showed mean AVF flow of 743 ml/min and efferent vein caliper of 6.46 mm. At 3 months 14 patient have started stable 2 needles dialysis (other three patients were not yet dialysis dependent CKD). Were observed one immediate failure, one failure in maturation, and two late failures at 4 and 16 months respectively. Sixteen months primary and secondary patency was 78.9% and 89.5% respectively. Conclusion: These results showed how intraoperative IVL could help to recruit huge calcified marginal artery to create autogenous distal forearm AVF, avoiding proximal AVF, risking distal ischemia syndrome, and sparing vascular district to eventually rebuilt more proximal AVF in future.
Maturation failure remains a major clinical problem of distal arteriovenous fistula (AVF). Early failure (EF) is associated with the small size of the veins. For about 10 years we have used in more than 1000 fistulas, the Vessels Pre-Dilatation (VPD) to increase the recruitment of small veins for creating distal AVFs. The purpose of this study is to highlight if the VPD can reduce the incidence of EF or failure to mature (FTM) in AVFs created with small veins. Data of all the consecutive patients directly admitted to our Department for their first distal AVF from January to December 2019 were collected. The patients were divided in two groups, one with a vein diameter after the tourniquet ⩽2.0 mm (G1) and one >2 mm (G2). Both in G1 then in G2 the vessels had undergone VPD. Immediate failure (IF), EF, FTM, delayed or arrested maturation rate (DAM), unassisted AVFs and matured AFVs were evaluated. The patients recruited totalled 104, 37 in G1, and 67 in G2. The two groups were homogeneous in age, incidence of diabetes, obesity, heart disease, peripheral vasculopathy, and race. Female were more numerous in G1 (51% vs 12%, p < 0.001). In G1 and G2 occurred respectively 3 IF versus zero (p < 0.05), 10 EF (29%) versus 6 (9%) (p < 0.05), 6 DAM (16%) versus 6 (9%), 21 unassisted AVFs (57%) versus 57 (85%) (p < 0.01). Dividing the patients into groups of unassisted and assisted AVFs, female and low vein diameter are more represented in the assisted group. There were 32 matured AVFs (86%) in G1 and 65 (97%) in G2. In order to increase the incidence of the distal AVF, the PDV allows to include small veins. However, more patients require further interventions to achieve maturation of the fistula.