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In children with idiopathic nephrotic syndrome, rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin inhibitors. Long-term effects including the number of repeated infusions to maintain remission are unknown. To test this, we treated 46 consecutive children with idiopathic nephrotic syndrome lasting for at least 1 year (mean 6.3 years), maintained in remission with oral prednisone and calcineurin inhibitors. They received 1–5 rituximab courses during a median follow-up of 3 years. Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and 2-year-remission probabilities were, respectively, 20 and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months, respectively, following the first and subsequent courses. The time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20, or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Thus, rituximab can be safely and repeatedly used as a prednisone and calcineurin inhibitor–sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further study is needed to identify patients who will benefit most from rituximab therapy.

In children with idiopathic nephrotic syndrome rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin-inhibitors. Long-term effects including number of repeated infusions to maintain remission are unknown. We treated with rituximab 46 consecutive children with idiopathic nephrotic syndrome lasting for at least one year (6.3±4.1 years), who were maintained in remission with oral prednisone and calcineurin inhibitors. They received 1–5 rituximab courses during a median follow-up of three years (range 1–5). Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and two-year-remission probabilities were respectively 20% and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months respectively following the first and subsequent courses. Time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20 or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Rituximab can be safely and repeatedly used as prednisone and calcineurin-inhibitor-sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further research is needed to identify patients who will benefit most from rituximab therapy.

Ali Gharavi, Rick Lifton and colleagues report a genome-wide association study for IgA nephropathy, a major cause of kidney failure. They identify five susceptibility loci. We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance ( P values for association between 1.59 × 10 −26 and 4.84 × 10 −9 and minor allele odds ratios of 0.63–0.80). These five loci explain 4–7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures.

Coronary sinus (CS) Reducer implantation improves myocardial perfusion and symptoms in patients with debilitating refractory angina. Its impact on myocardial remodeling remain uncertain. Aim of the present study was to assess possible impact of CS Reducer on myocardial systolic-diastolic deformation and microstructural remodeling, as assessed through cardiac magnetic resonance (CMR) feature tracking and mapping analysis. Twenty-eight consecutive patients with refractory angina underwent multiparametric stress CMR before and 4 months after CS Reducer implantation. Eight patients were excluded (6 for absence of inducible ischemia, 2 for artifacts). Modifications in 3D systo-diastolic myocardial deformation were evaluated using feature tracking analysis on rest cine images. Myocardial microstructural remodeling was assessed by native T1 mapping, cellular and matrix volume and extracellular volume fraction (ECV). Collaterally, the percentage of ischemic myocardium (ischemic burden %) and the myocardial perfusion reserve index (MPRI) were measured. After CS Reducer implantation, myocardial contractility improved (ejection fraction rose from 61 to 67%; p = 0.0079), along with longitudinal (from − 16 to − 19%; p = 0.0192) and circumferential strain (from − 18 to − 21%; p = 0.0017). Peak diastolic radial, circumferential and longitudinal strain rate did not change (p > 0.05), and no changes in native T1, ECV, cellular and matrix volume were observed. Myocardial perfusion improved, with a reduction of ischemic burden (13–11%; p = 0.0135), and recovery of intramural perfusion balance in segments with baseline ischemia (MPRi endocardial/epicardial ratio from 0.67 to 0.96; p = 0.0107). CS Reducer improves myocardial longitudinal and circumferential strain, without microstructural remodeling and no impact on diastolic proprieties.

BackgroundCoronary access after transcatheter aortic valve implantation (TAVI) with supra-annular self-expandable valves may be challenging or un-feasible. There is little data concerning coronary access following transcatheter aortic valve-in-valve implantation (ViV-TAVI) for degenerated surgical bioprosthesis.AimsTo evaluate the feasibility and challenge of coronary access after ViV-TAVI with the supra-annular self-expandable ACURATE neo valve.Materials and methodsSixteen patients underwent ViV-TAVI with the ACURATE neo valve. Post-procedural computed tomography (CT) was used to create 3D-printed life-sized patient-specific models for bench-testing of coronary cannulation. Primary endpoint was feasibility of diagnostic angiography and PCI. Secondary endpoints included incidence of challenging cannulation for both diagnostic catheters (DC) and guiding catheters (GC). The association between challenging cannulations with aortic and transcatheter/surgical valve geometry was evaluated using pre and post-procedural CT scans.ResultsDiagnostic angiography and PCI were feasible for 97 and 95% of models respectively. All non-feasible procedures occurred in ostia that underwent prophylactic “chimney” stenting. DC cannulation was challenging in 17% of models and was associated with a narrower SoV width (30 vs. 35 mm, p < 0.01), STJ width (28 vs. 32 mm, p < 0.05) and shorter STJ height (15 vs. 17 mm, p < 0.05). GC cannulation was challenging in 23% of models and was associated with narrower STJ width (28 vs. 32 mm, p < 0.05), smaller transcatheter-to-coronary distance (5 vs. 9.2 mm, p < 0.05) and a worse coronary-commissural overlap angle (14.3° vs. 25.6 o , p < 0.01). Advanced techniques to achieve GC cannulation were required in 22/64 (34%) of cases.ConclusionIn this exploratory bench analysis, diagnostic angiography and PCI was feasible in almost all cases following ViV-TAVI with the ACURATE neo valve. Prophylactic coronary stenting, higher implantation, narrower aortic sinus dimensions and commissural misalignment were associated with an increased challenge of coronary cannulation.

Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions.

To the Editor: The uric acid hypothesis proposes that hyperuricemia or gout increases the risk of progression of chronic kidney disease and is based on studies showing exponentially increased risk when serum urate levels exceed 7 mg per deciliter. 1-3 Both the PERL (Preventing Early Renal Loss in Diabetes) trial conducted by Doria et al. and CKD-FIX (Controlled Trial of Slowing of Kidney Disease Progression from the Inhibition of Xanthine Oxidase) conducted by Badve et al. (June 25 issue) 4,5 included normouricemic participants and did not directly test this hypothesis. The PERL trial, which did not show a benefit with allopurinol, was . . .

Chyluria denotes the urinary excretion of chyle, which is a lymphatic fluid rich in chylomicrons. Chyle flows from the intestinal lacteals to the left subclavian vein through the thoracic duct. When an abnormal connection between these structures and the urinary tract develops, chyluria appears. The syndrome is often associated with a nephrotic-range proteinuria, and this could be a wrong indication to perform renal biopsy. Chyluria is classified as parasitic or nonparasitic, the former being induced by lymphatic filariasis, whereas the latter is caused by medical, traumatic or inherited diseases. The patient usually reports excretion of milky urines, monolateral flank pain, malnutrition, weight loss and weakness. Urinalysis demonstrates lymphocyturia associated with chylomicrons and triglycerides in the supernatant. The diagnostic approach is aimed to define the site of lymphourinary fistula. A selective ureteral catheterization allows to collect urine samples from each kidney, demonstrating a monolateral source of proteins and lipids and making renal biopsy superfluous. Other diagnostic tools include nuclear magnetic resonance urography and lymphoangiography. Many therapeutic options have been proposed. Sclerosing solution instillation into the renal pelvis and laparoscopic renal pedicle disconnection are the invasive procedures most commonly employed. Among the medical alternatives, a low-fat diet supplemented with medium-chain triglycerides is often followed by complete clinical and biochemical remission. Copyright © 2011 S. Karger AG, Basel [PUBLICATION ABSTRACT]

Abstract Introduction The BRING-UP 3 Heart Failure (HF) study was designed to evaluate the real-world implementation of guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), given the limited evidence on the uptake of the contemporary four-pillar treatment strategy. Methods BRING-UP 3 HF study is an observational, prospective, nationwide investigation encompassing 179 sites. This analysis includes HFrEF patients enrolled in the ambulatory and hospitalized cohorts with complete pharmacological data at 6-month follow-up. The objective was to describe the use of the four GDMT pillars after 6 months. Results Among 3201 HFrEF patients enrolled, 142 (4.4%) had died by 6 months, and treatment data were available for 2950 patients. Mean age was 69 ± 11 years (26.6% > 75 years), 18.0% were female. Prescription rates of GDMT were high at baseline and remained stable over 6-months, with a shift from ACE-I/ARBs to ARNIs, and a modest increase in SGLT2i use. A significant reduction in diuretic prescription was also observed. Quadruple therapy was prescribed in 64.3% of patients at 6 months versus 63.9% at baseline/discharge (P = NS), while quadruple therapy including ARNI went from 52.9% to 55.9%, P < .0001. Dose up-titration of GDMT remained suboptimal, with most agents prescribed at <50% of target doses. Discontinuation rates at follow-up were very low. Conclusion In this large nationwide cohort, guideline-directed therapies for HFrEF were widely implemented and maintained over 6 months with excellent treatment persistence. However, dose optimization remains a key unmet need in routine clinical practice. Graphical Abstract Graphical Abstract Six-month management of heart failure patients enrolled in the BRING-UP 3 HF study For image description, please refer to the figure legend and surrounding text.