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Abstract Background Sunitinib is a standard treatment for metastatic renal cell carcinoma (RCC). Currently, the data available on the effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular (CV) risk factors are limited, and we aimed to evaluate these aspects in patients with RCC after a short period of treatment. Methods Patients affected by metastatic RCC were enrolled and evaluated before starting sunitinib (T0) and after 40 days of treatment (T1) by the flow‐mediated dilation (FMD), carotid intima media thickness (IMT), ankle‐brachial pressure index (ABI), and 24‐hour proteinuria. We also assessed serum metabolic and nutritional parameters at T0 and T1. Results Twenty patients (7 female), with a mean age of 61.4 ± 12.0 years, were studied. Overtime, we observed a reduction in estimated glomerular filtration rate (P = .002), FMD (P = .001) and in fasting plasma glucose levels (P = .04), as well as an increase in plasma insulin (P

Background Whether a very low-protein diet supplemented with ketoanalogues (sVLPD), compared with a standard low-protein diet (LPD), improves outcomes in patients with chronic kidney disease (CKD) under stable nephrology care is undefined. Objectives To compare the effectiveness of sVLPD compared with LPD in patients regularly seen in tertiary nephrology care. Methods Participants were patients with CKD stages 4–5, followed for at least 6 mo, randomly allocated to receive sVLPD or LPD [0.35 or 0.60 g/kg ideal body weight (IBW)/d, respectively], stratified by center and CKD stage. The primary outcome was time to renal death, defined as the first event between end-stage renal disease (ESRD) and all-cause mortality; secondary outcomes were the single components of the primary outcome, cardiovascular outcome, and nutritional status. Results We analyzed 223 patients (sVLPD, n  = 107; LPD, n  = 116). Mean age was 64 y, 61% were male, and 35% had diabetes. Median protein intake (PI), which was 0.8 g/kg IBW/d at baseline in both groups, was 0.83 and 0.60 g/kg IBW/d in LPD and sVLPD, respectively, during the trial with a large decrease only in sVLPD (P = 0.011). During a median of 74.2 mo, we recorded 180 renal deaths (141 dialysis and 39 deaths before dialysis). Risk of renal death did not differ in sVLPD compared with LPD (HR: 1.17; 95% CI: 0.88, 1.57; P = 0.28). No difference was observed for ESRD (HR: 1.12; 95% CI: 0.81, 1.56; P = 0.51), mortality (HR: 0.95; 95% CI: 0.62, 1.45; P = 0.82), or time to fatal/nonfatal cardiovascular events (P  = 0.2, log-rank test). After 36 mo, still active patients were 45 in sVLPD and 56 in LPD. No change of nutritional status emerged during the study in any arm. Conclusions This long-term pragmatic trial found that in patients with CKD under stable nephrology care, adherence to protein restriction is low. Prescribing sVLPD compared with standard LPD is safe but does not provide additional advantage to the kidney or patient survival. [ABSTRACT FROM AUTHOR]

Aims: This joint document of the Italian Society of Nephrology and the Italian Diabetes Society reviews the main indications to perform a renal biopsy in diabetic patients, according to the recommendations of a panel of experts based on all available scientific evidence.Data Synthesis: Renal biopsy has a pivotal role in assessing the nature and severity of renal injury in patients with diabetic kidney disease (DKD). The procedure is mandatory in the presence of one of more of the following features: rapid onset or progression of albuminuria or sudden onset of nephrotic syndrome, rapid GFR decline with or without albuminuria, hematuria, active urine sediment, clinical and/or laboratory suspicion of other systemic diseases, and, in patients with type 1 diabetes, short diabetes duration and absence of retinopathy. Indeed, ~40% of diabetic individuals with kidney injury undergoing renal biopsy are affected by a non-diabetic renal disease (NDRD). Furthermore, the histological evaluation of patients with suspected classical diabetic nephropathy allows to define the extent of glomerular, tubulo-interstitial and vascular lesions, thus providing important prognostic (and potentially therapeutic) data. In the future, the indications for renal biopsy might be extended to the definition of the histological lesions underlying the "nonalbuminuric" DKD phenotypes, as well as to the evaluation of the response to treatment with the new anti-hyperglycemic drugs that provide cardiorenal protection.Conclusions: In view of the heterogeneous clinical presentation and course of DKD and of the related heterogeneous histopathological patterns, a more extensive use of renal biopsy may be crucial to provide valuable information with important pathogenic, diagnostic, prognostic, and therapeutic implications. [ABSTRACT FROM AUTHOR]

Aims: This joint document of the Italian Diabetes Society and the Italian Society of Nephrology reviews the natural history of diabetic kidney disease (DKD) in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents.Data Synthesis: Recent epidemiological studies have disclosed a wide heterogeneity of DKD. In addition to the classical albuminuric phenotype, two new albuminuria-independent phenotypes have emerged, i.e., "nonalbuminuric renal impairment" and "progressive renal decline", suggesting that DKD progression toward end-stage kidney disease (ESKD) may occur through two distinct pathways, albuminuric and nonalbuminuric. Several biomarkers have been associated with decline of estimated glomerular filtration rate (eGFR) independent of albuminuria and other clinical variables, thus possibly improving ESKD prediction. However, the pathogenesis and anatomical correlates of these phenotypes are still unclear. Also the management of hyperglycemia in patients with type 2 diabetes and impaired renal function has profoundly changed during the last two decades. New anti-hyperglycemic drugs, which do not cause hypoglycemia and weight gain and, in some cases, seem to provide cardiorenal protection, have become available for treatment of these individuals. In addition, the lowest eGFR safety thresholds for some of the old agents, particularly metformin and insulin secretagogues, have been reconsidered.Conclusions: The heterogeneity in the clinical presentation and course of DKD has important implications for the diagnosis, prognosis, and possibly treatment of this complication. The therapeutic options for patients with type 2 diabetes and impaired renal function have substantially increased, thus allowing a better management of these individuals. [ABSTRACT FROM AUTHOR]

Highlights from the article: Chronic kidney disease (CKD) is a highly prevalent condition. The prevalence of urological unrecognized diseases in CKD patients by uroflowmetry. Not enrol patients who refused to give consent or patients with Outside the normal range; CKDth, patients with chronic kidney disease; CKD, CKD patients could contribute to identify potential urological.

Background. Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) has compiled a national census of Renal Units (RU) existing in the twenty Italian regions related to the year 2004. Methods. An on-line questionnaire including 158 items explored structural and human resources, organization aspects, activities and epidemiological data in SIN, 2004. Results. The census identified 363 public RU, 303 satellite Dialysis Centres (DC) and 295 private DC totalling 961 DC [16.4 per million population (pmp)]. The inpatient renal beds were 2742 (47 pmp). Renal and dialysis activity was performed by 3728 physicians (64 pmp), of whom 2964 (80%) were nephrologists. There was no permanent medical assistance in 41% of satellite DC. There were 1802 renal admissions pmp and 99 renal biopsies pmp. The management of acute renal failure (13 456 cases; 230 pmp) represented a relevant proportion of the activities conducted in public RU. In 2004 there were 9858 new cases of end-stage kidney disease requiring renal replacement therapy (RRT) (169 pmp). On 31 December 2004, 60 058 patients were on RRT (1027 pmp), 43 293 of which (740 pmp) were on dialysis and 16 765 (287 pmp) with renal graft. Conclusions. This census of the Italian RU and DC in 2004 provides decision makers and healthcare stakeholders with detailed data for benchmarking and has financial implications for the public health system. Similar analyses may be conducted in other countries permitting standardization of medical and cost-related aspects of renal care. [ABSTRACT FROM AUTHOR]

Background. Few data are available from large population-based studies on survival and renal outcome of patients with renal involvement and different types of systemic amyloidosis. Methods. Two hundred and ninety of over 373 patients affected from systemic amyloidosis with renal involvement diagnosed in Italy between January 1995 and December 2000 were followed from diagnosis to death or until the last available clinical control. Eighty-three patients were excluded from analysis either because the amyloid type remained undetermined or they were lost at follow-up. Clinical and laboratory information was collected according to the different types of amyloidosis using a specific form which included renal function with 24 h proteinuria at diagnosis and at the end of follow-up, the type and the date of onset of dialysis and the kind of treatment they underwent. Results. The median time of follow-up was 24 months in primary (AL) amyloidosis (range: 1–88 months), 16 months in AL with associated multiple myeloma (MM + AL: range 1–76 months), 30 months in reactive (AA) amyloidosis (range: 1–99 months) and 52 months in patients with familial forms (AF: range 14–82 months). Patients with AL showed a significantly shorter survival than AA. Despite no significant differences of renal outcome or survival on dialysis being observed between the two groups, a lower renal survival with a higher number of patients who progressed to end-stage renal disease (ESRD) was observed in patients with AA. Overall survival was markedly improved in patients with AL who underwent a specific therapy (conventional chemotherapy or autologous stem cell transplantation (ASCT)) even in the absence of a positive kidney response. Multivariate analysis showed cardiac involvement and specific therapy to significantly influence survival in AL whereas age, serum creatinine (sCr) and heart involvement significantly affected survival in AA. In both groups, sCr and heart involvement were the most relevant predictors for renal outcome, together with urinary protein excretion, in patients with AA. Conclusions. Our results show a worse survival in AL due to the higher prevalence of heart involvement in this group and emphasize that a specific therapy significantly prolongs survival and slows the progression of renal disease in patients with AL. We suggest that a late nephrological referral is likely the cause of the higher sCr found at presentation in patients with AA and probably accounts for the lower renal survival observed in the short term in these patients. At the time being, renal transplantation and ASCT are still rare therapeutic options for renal patients affected from systemic amyloidosis. [ABSTRACT FROM AUTHOR]

Background. Few data are available on epidemiology and clinical picture of renal involvement in different forms of systemic amyloidosis. Methods. Patients with biopsy-proven systemic amyloidosis diagnosed in Italy between January 1995 and December 2000 were selected from 49 Nephrology and Internal Medicine Units provided they showed signs characteristic of renal involvement. Clinical and laboratory information were collected by using a specific data form for diagnosis integrated by a questionnaire on diagnostic tools. Collected data were matched both with the Italian Registry of Renal Biopsies (IRRB) and the Registry of the Italian Society of Amyloidosis (SIA) in order to approximate the incidence of the disease. Results. Of all patients, 373 were finally selected throughout Italy with an estimated mean incidence of renal amyloidosis of 2.1 per million population (p.m.p.) per year. Of those, 237 were affected from AL (primary) amyloidosis, 104 from AA (secondary) amyloidosis and 6 from AF (heredofamilial) forms. In 26 cases the type of amyloidosis remained undetermined. Among patients with AL, 36 presented an associated multiple myeloma (MM). Rheumatoid arthritis (RA) was the commonest underlying disease in AA. Median age ranged between 63 and 65 years in all groups. Males were prevalent in AL and females in AA. The main clinical features of renal involvement were represented by nephrotic syndrome and renal failure observed in 59 and 54% of cases, respectively. The presence of a lambda light chain, either in serum or urine was significantly associated to a more elevated urinary protein loss and to a reduced renal function. Patients with AA showed a worse renal function at presentation than patients with AL, possibly due to a late diagnosis and/or referral to nephrology units. Diagnosis was obtained by renal biopsy in 315 cases, by abdominal fat tissue (AFT) aspiration/biopsy in 156 patients and by other organ biopsies in 47 patients. Characterization of deposits was extremely variable among referring centres. Conclusions. Our results point to an increased incidence of renal amyloidosis observed in Italy over the period 1996–2000 with AL as the prevalent type. Characterization of amyloid deposits still remains the major diagnostic challenge of the disease. The institution of networks dedicated to rare diseases is strongly recommended in order to effectively afford this challenge. [ABSTRACT FROM AUTHOR]

To define whether age modifies the prognosis of patients with chronic kidney disease (CKD) on nephrology care, we prospectively followed patients with CKD who have been receiving nephrology care in a clinic for 1 year or more. The incidence of end-stage renal disease (ESRD), defined by the occurrence of dialysis or transplant, or death without ESRD was estimated by a competing-risk approach, and interactions between age and risk factors tested in Cox models over a median follow-up period of 62.4 months. Of 1248 patients with stage III-V CKD, 481 were younger than 65, 410 were between 65 and 75, and 357 were over 75 years old. Within each age class, the mean estimated glomerular filtration rate(eGFR) was 31, 32, and 29 ml/min per 1.73 m2, respectively. There were 394 ESRD events and 353 deaths. The risk of ESRD was higher than the risk of death without ESRD for ages <60 years, and independent of eGFR. The ESRD risk diminished with aging but still prevailed for eGFRs of 25-35 in patients between 65 and 75 years and with an eGFR below 15 in those up to 85 years old. Proteinuria significantly increased the risk of ESRD with advancing age. Surprisingly, the unfavorable effects of cardiovascular disease on ESRD and of diabetes on survival significantly decreased with increasing age. Male gender, higher phosphate, lower body mass index, and hemoglobin were age-independent predictors for ESRD, while cardiovascular disease, lower hemoglobin, higher proteinuria and uric acid, and ESRD also predicted death. Thus, in older patients on nephrology care, the risk of ESRD prevailed overmortality even when eGFR was not severely impaired. Proteinuria increases ESRD risk, while the predictive role of other modifiable risk factors was unchanged compared with younger patients. [ABSTRACT FROM AUTHOR]

Many patients with atrial fibrillation (AF) who are in need of stroke prevention are not treated with oral anticoagulation or discontinue treatment shortly after its initiation. Despite the availability of direct oral anticoagulants (DOACs), such undertreatment has improved somewhat but is still evident. This is due to continued risks of bleeding events or ischemic strokes while on DOAC, poor treatment compliance, or aversion to anticoagulant therapy. Because of significant improvements in procedural safety over the years left atrial appendage closure (LAAC), using a catheter-based, device implantation approach, is increasingly favored for the prevention of thromboembolic events in AF patients who cannot have long-term oral anticoagulation. This article is an executive summary of a practical guide recently published by an international expert consensus group, which introduces the LAAC devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. This practical guide, aligned with published guideline/guidance, is aimed at those non-implanting physicians who may need to refer patients for consideration of LAAC., Competing Interests: R. B. received personal fees from Bayer, Bristol Myers Squibb, LEO-Pharma, Pfizer, VIATRIS. Research support by the Bavarian State Ministry of Health; CPC University of Colorado; FADOI, Italy. S.Be. received proctor and speaker fees Boston Scientific, Edwards, Abbott, fees go to the Department. L.B. received consultant for Medtronic, Boston Scientific, Adagio and ACUTUS fees go to the Department. G.B. received speaker fees from Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Janssen, and Sanofi. S.Bo. received consultant for Medtronic, Boston Scientific, Microport, and Zoll. A.J.C. received personal fees from Abbott, Boston Scientific, Medtronic, and Sanofi. W.D. received consulting and speaker fees from Ai Mediq, Bayer, Boehringer Ingelheim, Medtronic, Boston Scientific, Vifor Pharma, travel support from Pharmacosmos, research support from EU (Horizon2020), German Ministry of Education and Research, German Center for Cardiovascular Research, Vifor Pharma. S.G. received consulting and speaker fees from Boston Scientific. M.G. serve as an advisory Board Member for Boston Scientific; Proctor for Boston Scientific, Abbott; Fees for lectures and travel grants: from Boston Scientific, Abbott, Occlutech, Pfizer. K.G.H. received speaker's honoraria, consulting fees, lecture honoraria and/or study grants from Abbott, Amarin; Alexion, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, and W.L. Gore and Associates. J.E.N.K. received consultant to Boston Scientific, Medtronic, Edwards Lifesciences, Picardia, Venus Medtech, Speaker for Abbott. U.L. received research Grant to Institution from Abbott, Bayer, Speaker or Consulting Honorary from Abbott, Boston Scientific, Bayer; Pfizer, Daiichi Sankyo. G.Y.H.L. received consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, funded from the European Union's Horizon 2020 research and innovation program under grant agreement No. 899871. J.E.N.K. received research grants Abbott, Boston Scientific, Novo Nordic Foundation JENK: Research grants Abbott, Boston Scientific, Novo Nordic Foundation. E.M. received research grants from Abbott, Biotronik, Boston Scientific, Medtronic, MicroPort and Zoll. Consultant and speaker fees from Abbott, Abbott, Medtronic, and Zoll. J.E.N.K. received research grants Abbott, Boston Scientific, Novo Nordic Foundation. P.O. received speaking honoraria from Bayer, Abbott, Boston Scientific. B.S. received consultant and Speaker for Bostin Scientific, Abbott, Medtronic, Biosense Webster. R.B.S. received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program under the grant agreement No. 648131, from the European Union's Horizon 2020 research and innovation program under the grant agreement No. 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103 and 81Z0710114); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239). Wolfgang Seefried project funding German Heart Foundation, Lecture fees and advisory board fees from BMS/Pfizer and Novartis outside this work. C.T. serves as an advisory Board Member of Boston Scientific; Proctor for Boston Scientific and Abbott. Fees for lectures and travel grants from Boston Scientific and Abbott. A portion of the fees goes to the institute. A.T. received consultant and proctor for Abbott, Consultant for Boston Scientific and Pie Medical., (Thieme. All rights reserved.)

Background: A series of interesting literature reports acknowledges the notable loss of essential and non-essential amino acids (EAAs and NEAAs) during hemodialysis sessions. These losses may exceed 800 g/year, thus contributing towards accelerating the onset of malnutrition in hemodialysis patients (HD)., Objective: A novel tailored amino acid formula for oral administration was developed to replace total amounts of each individual amino acid lost during dialysis diffusive/convective HD strategies, monitoring the effects produced on nutritional and hematological status., Methods: A three-month randomized double-blind study was conducted on 30 subjects over the age of 70 years extrapolated from a total population of 86 hemodialysis patients. The 30 patients were randomly assigned to two groups: a treatment group of 15 HD patients (TG) to whom a novel mixture containing 5.4 g of AAs was administered solely on interdialytic days, and a control group of 15 HD patients (CG) who received no amino acid supplementation. The AAs mixture was administered post-dialysis at an extended interval from the end of solute and compartmental rebound to replace AA losses and optimize their role in protein anabolism., Results: The results obtained highlighted a significant improvement in protein intake g/kg/day (Protein Catabolic Rate, p = 0.014), and increased IgG (p = 0.008) and C3 serum levels (p = 0.003) in the TG group alone. Fat mass losses were initially confirmed by means of bioelectrical impedance analysis (BIA) (p = 0.011) and plicometry (p < 0.001) in the CG group alone, although the main objective was to preserve nutritional status and, particularly, muscle mass. The study was extended to investigate the effects produced on anemia, yielding evidence of continued positive effects three months after the end of the study in the TG group alone based on an increase in Hb levels from 11.2 ± 0.6 to 12.1 ± 0.6 (p = 0.004) associated with a reduced demand for erythropoietin i.v. from 12928 ± 9033 to 9286 ± 5398 U.I/week (p = 0.012) and iron i.v. from 75.9 ± 55 to 71.4 ± 33.4 mg/week (p = 0.045)., Conclusions: The results obtained following oral administration of this novel tailored AA replacement mixture aimed at reinstating the high AA losses produced during hemodialysis suggest the mixture should be prescribed as a standard procedure to all HD patients., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dietary factors may be implicated in the formation of kidney stones and should be closely monitored. To achieve this aim, patients are routinely assessed by means of generic dietary recall, a tool widely used by authors in a range of extensive patient populations to record food intake; the findings obtained, however, may be skewed due to dietary variations and underestimation of the effect of food additives. Fifty Frequent Kidney Stone Formers (FKSFs, mean age: 54.3 ± 13.9 years) with normal kidney function, absence of comorbidities, and reliable compliance were selected from a total of 68 patients' resident in Sardinia, an Italian island where genetic admixtures have been relatively rare for generations. The study, conducted from 1 January 2020 to 31 December 2023, was aimed at assessing nutritional values based on the meticulous recording of food quantities, quality, and potential modifications related to food preparation. Patients were selected during an initial clinical check-up and all efforts made to ensure they were capable of reliably recording all food and drinks consumed. A seven-day food diary was provided in which food and drink intake and their impact on 24 h urine output was recorded. The following parameters were measured in both foods and urine output: citrates, oxalates, calcium, phosphorous, uric acid, proteins and nitrogen compounds, magnesium, sulfates, potassium, carbohydrates, free fatty acids. Study outcomes established the presence of hypocitraturia, hyperoxaluria, hypercalciuria, and moderately high levels of nitrogen compounds. Univariate analysis followed by multivariate analysis for further confirmation were performed and the following observations made. Citrate intake correlated with citraturia but did not promote oxaluria; calcium intake promoted onset of sulfaturia, azoturia, and ammoniuria, whilst magnesium correlated with magnesiuria but not with oxaluria, calciuria, phosphaturia, and azoturia; sulfate intake elicited onset of azoturia but not kaliuresis; potassium intake promoted oxaluria and protein intake resulted in onset of ammoniuria and azoturia. (A) The chemical composition of urine based on dietary intake is hard to predict without taking into account the presence of dietary and urinary interferents; (B) the geographic isolation of patients studied underlines the importance of epigenetics in maintaining a traditional dietary heritage. (C) Moreover, the widespread use of food additives should consistently be taken into account to ensure a correct diagnosis of FKSF and set up a valid treatment plan.