Exogenous hydrogen sulfide prevents SOD2 degradation to safeguard renal function in diabetic kidney disease.

Diabetic kidney disease (DKD) is a major contributor to chronic kidney disease. Hydrogen sulfide (H2S) serves as an endogenous gaseous signaling molecule capable of safeguarding renal function within the context of DKD. However, the underlying mechanisms need to be elucidated. This study was undertaken to unveil the mechanisms by which H2S counteracts against DKD. Utilizing mice and human renal tubular epithelial (HK-2) cells, we demonstrated a reduction in cystathionine-γ-lyase/H2S levels within renal tissues of db/db mice and in HK-2 cells subjected to hyperglycemic and hyperlipidemic environments. Notably, we observed that sodium hydrosulfide (NaHS) supplementation could serve as an exogenous source of H2S. Exogenous H2S exhibited the capacity to mitigate the accumulation of reactive oxygen species and attenuate the degradation of superoxide dismutase 2 (SOD2) by Lon protease homolog 1 induced by hyperglycemia and hyperlipidemia, thus affording cellular protection against mitochondrial apoptosis. Consequently, NaHS treatment led to decreased serum levels of blood urea nitrogen and serum creatinine, reflecting alleviated renal damage and thereby preserving renal function in db/db mice. Based on these findings, we propose that exogenous H2S exerts a protective role against DKD by inhibiting SOD2 degradation.

Learning and depicting lobe-based radiomics feature for COPD Severity staging in low-dose CT images.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition that imposes a significant healthcare burden worldwide. Accurate staging of COPD severity is crucial for patient management and treatment planning. METHODS: The retrospective study included 530 hospital patients. A lobe-based radiomics method was proposed to classify COPD severity using computed tomography (CT) images. First, we segmented the lung lobes with a convolutional neural network model. Secondly, the radiomic features of each lung lobe are extracted from CT images, the features of the five lung lobes are merged, and the selection of features is accomplished through the utilization of a variance threshold, t-Test, least absolute shrinkage and selection operator (LASSO). Finally, the COPD severity was classified by a support vector machine (SVM) classifier. RESULTS: 104 features were selected for staging COPD according to the Global initiative for chronic Obstructive Lung Disease (GOLD). The SVM classifier showed remarkable performance with an accuracy of 0.63. Moreover, an additional set of 132 features were selected to distinguish between milder (GOLD I + GOLD II) and more severe instances (GOLD III + GOLD IV) of COPD. The accuracy for SVM stood at 0.87. CONCLUSIONS: The proposed method proved that the novel lobe-based radiomics method can significantly contribute to the refinement of COPD severity staging. By combining radiomic features from each lung lobe, it can obtain a more comprehensive and rich set of features and better capture the CT radiomic features of the lung than simply observing the lung as a whole.

Combating land degradation through human efforts: Ongoing challenges for sustainable development of global drylands.

Drylands, as highly vulnerable ecosystems, support environmental functions and human well-being. Nevertheless, widespread land degradation and desertification present significant global and regional environmental challenges, with limited consensus on their area and degree. This study used time-series vegetation productivity and meteorological data from 2000 to 2020 to quantify global land degradation trends and driving factors in drylands. The results show a notable restoration of land degradation in drylands worldwide, with the area of improved land exceeding the degraded area by 1.4 times, although the threat of degradation persists. India and China emerge as pioneers in effective land improvement strategies, offering valuable experiences for other regions. Combined effects, as quantitatively distinguished by our established model, dominate the degradation and improvement processes. Notably, human activities play a decisive role in influencing land degradation trends, with the potential for either exacerbation or reversal. This study provides new perspectives on environmental health and human activities from global and regional observations. Finally, our research provides scientific support for desertification control and contributes to the overall advancement of the SDGs globally.

Efficient removal of tetracycline hydrochloride through novel Fe/BiOBr/Bi2WO6 photocatalyst prepared by dual-strategy under visible-light irradiation.

It is important to investigate whether combining two modification strategies has a synergistic effect on the activity of photocatalysts. In this manuscript, Fe-doped BiOBr/Bi2WO6 heterojunctions were synthesized by a one-pot solvothermal method, and excellent photocatalytic performance was obtained for the degradation of tetracycline hydrochloride (TCH) in water without the addition of surfactant. Combining experiments and characterization, the synergistic effect between Fe ion doping and the BiOBr/Bi2WO6 heterojunction was elucidated. The Fe/BiOBr/Bi2WO6 composite photocatalyst had a beneficial void structure, enhanced visible light response, and could inhibit the recombination of photogenerated support well, which improved the photocatalytic activity. The presented experiments demonstrate that Fe/BiOBr/Bi2WO6 removes 97% of TCH from aqueous solution, while pure BiOBr and Bi2WO6 only remove 56% and 65% of TCH, respectively. Finally, the separation and transfer mechanisms of photoexcited carriers were determined in conjunction with the experimental results. This study provides a new direction for the design of efficient photocatalysts through the use of a dual co-modification strategy.

Development of Adjustable High- to Low-Adhesive Superhydrophobicity Using Aligned Electrospun Fibers.

Superhydrophobic surfaces based on electrospun fibrous structures exhibit advantages of additive manufacturing and enable the passage of gases. Compared to randomly deposited fibers, directionally aligned fibers improve the control of surface wetting by a specified fiber orientation and predictable liquid-fiber contact interface. In this article, we create superhydrophobicity with adjustable adhesion based on the understanding of droplet wetting behavior on directionally aligned fibers. Directionally aligned polystyrene fibers with different diameters and interfiber distances (l) are produced using electrospinning with a rotating fin collector. The wetting behavior of droplets on the surfaces dressed by aligned fibers is characterized, and a thermodynamic model of wetting behavior is established to guide the experimental studies. As a result, high-adhesive superhydrophobicity is achieved on weak hydrophobic substrate surfaces dressed by aligned polystyrene fibers with a diameter of 1.8 µm and l between 5 and 130 µm. Water droplets (2 µL) exhibit a maximum contact angle of 156° and adhere to the fiber-dressed surfaces by tilting upside down. Low-adhesive superhydrophobicity is achieved by introducing an additional layer of aligned fibers to increase the transition energy barrier. On the dual-layer structure with an upper-layer l of 9 µm, droplets show a contact angle of 155° and can readily roll off the surface. Moreover, increasing the upper-layer l to 15 µm reserves the surface to high-adhesive superhydrophobicity.

Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway.

BACKGROUND: Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1ß in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1ß and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. METHODS: Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1ß, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1ß and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. RESULTS: The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1ß in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1ß, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. CONCLUSIONS: Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

Selective sulfidation-vacuum volatilization processes for tellurium and bismuth recovery from bismuth telluride waste thermoelectric material.

Bismuth telluride-based alloy materials are currently the best performing thermoelectric materials at near room temperature; however, their production and use generate waste (e.g., cutting waste and failed grains). There is also lack of efficient recycling strategies for the generated waste. In this study, a selective sulfidation-vacuum volatilization method is proposed for recovering bismuth telluride waste. The Gibbs free energies of the sulfidation reaction of bismuth telluride are calculated, the saturated vapor pressure of each substance is analyzed, and the composition of the products is predicted. Based on the differences among the sulfidation and volatile properties of bismuth and tellurium, by adding sulfur to bismuth telluride waste, the composition of the substances was regulated, and efficient separation of tellurium and bismuth was achieved. We combined theoretical calculations and experimental studies to investigate the effect of process conditions on the separation and recovery of tellurium and bismuth. The results show that bismuth was thoroughly sulfereted and tellurium was a pure metal when the mass ratio of sulfur to bismuth telluride was 0.168, the sulfidation temperature was 573 K, and the holding time was 60 min. After sulfidation of the bismuth telluride waste, the sulfides were telluride and bismuthous sulfide. The sulfides, that resulted from sulfureted bismuth telluride production, were treated via vacuum volatilization. The optimal vacuum volatilization condition was 873 K for 120 min. The purities of tellurium and bismuth sulfide obtained by the selective sulfidation-vacuum volatilization experiment were >99%. The distribution ratios of tellurium and bismuth were 98.46% and 99.59%, respectively. The method thoroughly separated tellurium and bismuth from bismuth telluride waste, considerably reducing the environmental and economic costs compared with those of the conventional processes.

Genomic Mismatch at LIMS1 Locus and Kidney Allograft Rejection.

BACKGROUND: In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection. METHODS: We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor-recipient pairs. We defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses. RESULTS: In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the LIMS1 locus represented by rs893403 (hazard ratio with the risk genotype vs. nonrisk genotypes, 1.84; 95% confidence interval [CI], 1.35 to 2.50; P = 9.8×10-5). This effect was replicated under the genomic-collision model in three independent cohorts involving a total of 2004 donor-recipient pairs (hazard ratio, 1.55; 95% CI, 1.25 to 1.93; P = 6.5×10-5). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI, 1.37 to 1.95; P = 4.7×10-8). We identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses. CONCLUSIONS: We found that the LIMS1 locus appeared to encode a minor histocompatibility antigen. Genomic collision at this locus was associated with rejection of the kidney allograft and with production of anti-LIMS1 IgG2 and IgG3. (Funded by the Columbia University Transplant Center and others.).

Diagnostic Utility of Exome Sequencing for Kidney Disease.

BACKGROUND: Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally. METHODS: We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings. RESULTS: In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management. CONCLUSIONS: Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases. (Funded by the National Institutes of Health and others.).

The antibacterial activity of a novel NK-lysin homolog and its molecular characterization and expression in the striped catfish, Pangasianodon hypophthalmus.

Aeromonas hydrophila was a common bacterial pathogen in aquaculture resulting in considerable losses to the striped catfish aquaculture industry. As an emergent antimicrobial peptide (AMP), NK-lysin (NKL) had activity against various microorganisms. However, the antibacterial activity of NKL from striped catfish (Pangasianodon hypophthalmus) both in vitro and vivo remains unclear. In this study, the cDNA sequence of P. hypophthalmus NK-lysin gene (PhNK-lysin) was cloned and characterized. The amino acid sequence of PhNK-lysin contains a signal peptide sequence of 17 amino acid (aa) residues and a mature peptide composed of 130 aa. The saposin B domain of mature peptide comprised six conserved cysteines forming three putative disulfide bonds. Phylogenetic analysis revealed that the PhNK-lysin was most closely related to that of the channel catfish (Ictalurus punctatus) NK-lysin. The transcriptional levels of the PhNK-lysin were significantly upregulated in response to A. hydrophila infection in various tissues including heart, liver, spleen, head kidney, trunk kidney and gill. The synthetic PhNK-lysin-derived peptide consisting of 38aa showed antibacterial activity against Vibrio harveii, Aeromonas hydrophila and Escherichia coli. The MIC for V. harveii, A. hydrophila and E. coli were 15.625 µM, 250 µM and 31.25 µM respectively. Besides, the synthetic PhNK-lysin decreased the bacterial load of liver and trunk kidney in vivo as well as increased the survival rate of A. hydrophila infected striped catfish. Hence, these data suggest that PhNK-lysin had antimicrobial effect and protects the host from pathogenic infection.

Structural, electronic and catalytic properties of AgnSnn (n = 2-14) clusters by density functional theory.

Density functional theory (DFT) calculations of clusters were carried out to investigate the structural and electronic properties of AgnSnn (n = 2-14) clusters. Their lowest energy structure, average binding energy, second-order differential energy, HOMO-LUMO energy gap and density of states were analyzed. The reactions of carbon monoxide and oxygen on the Ag8 cluster and Ag4Sn4 cluster were compared to measure the adsorption and catalytic properties of the Ag4Sn4 cluster. The results show that Ag atoms gather together and are encapsulated by peripheral Sn atoms. The Ag4Sn4 cluster has a magic size. The sp-hybridization plays a crucial role in AgnSnn clusters. For both CO and O2 adsorption, the effect of the Ag4Sn4 cluster is better than that of the Ag8 cluster. The addition of an equal proportion of Sn atoms enhanced the catalysis compared to the Ag8 cluster with the same number of atoms. Our results suggest that the addition of Sn atoms can be an efficient and attractive way of tuning the adsorption ability and reactivity of silver clusters and can provide constructive input for the design of efficient nanocatalysts.

Enhanced dewaterability of anaerobically fermented sludge through acid-driven indigenous enzymatic hydrolysis.

The poor dewaterability of fermented sludge is an important factor limiting the development of anaerobic fermentation applications. Herein we reported an efficient strategy, i.e., using acidic regulation to stimulate the release of indigenous enzymes, to enhance the hydrolysis and dewatering of fermented sludge. The results showed that after acidic regulation at pH 4.0 for 1 day, the activity of protease and α-glucosidase were improved by 131.4% and 146.0%, while the capillary suction time and specific resistance to filtration were decreased by 93.8% and 69.5%, respectively. Mechanism study revealed that the method firstly destroyed the slime and bound EPS and cells of fermented sludge, causing the release of indigenous enzymes (i.e., protease and α-glucosidase) contained in. Then, the released enzymes directly accelerated the hydrolysis and acidification of fragmentized extracellular polymeric substances, thereby benefited the release of bound water in sludge particles. Finally, such acidic condition decreased the electrostatic repulsive interactions between destroyed sludge particles, further improving their flocculation. The findings not only deepen the understanding of indigenous enzymes contained in fermented sludge affecting sludge dewatering, but also might guide engineers to develop promising strategies to facilitate fermented sludge dewatering and fermentation liquid recovery in the future.

Oxalate crystal-related acute renal injury caused by orlistat: A case report. / å¥¥åˆ©å¸ä»–è‡´è‰é ¸ç›ç»“æ™¶ç›¸å ³æ€¥æ€§è‚¾æŸä¼¤1例.

We reported a case of oxalate crystal-related acute kidney injury caused by orlistat. The patient was admitted for nephrotic syndrome and acute kidney injury. The pathomorphological assessment of renal biopsy showed intratubular oxalate crystals. The patient reported that she had taken orlistat regularly to loss weight for more than a year. This patient had a habit of drinking vegetable soup and strong herbal tea daily. Orlistat, an intestinal lipase inhibitor, may cause secondary hyperoxaluria, that is, intestinal hyperoxaluria. Dietary habits could be a common precipitating factor for orlistat-relevant hyperoxaluria. It was comprehensively considered to be oxalate crystal-related acute renal injury, and the patient's renal function recovered gradually after drug withdrawal. Clinicians should pay attention to screening drug-related acute kidney injury including orlistat when observing patients with unexplained acute kidney injury, and renal biopsy should be performed if necessary. It is also important to warn people who take the orlistat for weight loss about the side effects of this drug so as to adjust the eating habits.

A review of enrichment methods for circulating tumor cells: from single modality to hybrid modality.

Circulating tumor cell (CTC) analysis as a liquid biopsy can be used for early diagnosis of cancer, evaluating cancer progression, and assessing treatment efficacy. The enrichment of CTCs from patient blood is important for CTC analysis due to the extreme rarity of CTCs. This paper updates recent advances in CTC enrichment methods. We first review single-modality methods, including biophysical and biochemical methods. Hybrid-modality methods, combining at least two single-modality methods, are gaining increasing popularity for their improved performance. Then this paper reviews hybrid-modality methods, which are categorized into integrated and sequenced hybrid-modality methods. The state of the art indicates that the CTC capture efficiencies of integrated hybrid-modality methods can reach 85% or higher by taking advantage of the superimposed and enhanced capture effects from multiple single-modality methods. Moreover, a hybrid method integrating biophysical with biochemical methods is characterized by both high processing rate and high specificity.

Pulmonary hypertension in end-stage renal disease patients on dialysis and predialysis patients.

PURPOSE: Pulmonary hypertension (PH) is a frequent and serious cardiovascular complication in patients with end-stage renal disease (ESRD) on dialysis. The purpose of this study was to investigate the prevalence of PH and its associated factors in patients with ESRD on maintenance dialysis and predialysis patients. METHODS: The medical records of ESRD patients who underwent kidney transplantation between January 2011 and December 2017 were retrospectively reviewed. Demographic and clinical characteristics including echocardiographic findings before joining the waiting list for transplantation were evaluated and compared among groups divided according to dialysis or not and dialysis types. The results of transthoracic Doppler echocardiography were used to determine the pulmonary artery pressure. Pulmonary hypertension was defined as a systolic pulmonary artery pressure (sPAP) greater than 35 mmHg. Univariate and multivariate analyses were used to investigate factors associated with PH. RESULTS: Data from 35 pre-dialysis patients with ESRD, 72 maintenance hemodialysis (HD) and 34 peritoneal dialysis (PD) patients were analysed. Pulmonary hypertension was 20.69% in pre-dialysis patients, 16.7% in HD patients and 14.7% in PD patients (P=0.957). There were negative correlations between sPAP and calcium (r=-0.230, P=0.012), Ca×P(r=-0.210, P=0.021), hemoglobin (r=-0.243, P=0.008) and a positive correlation between sPAP and cardiac output (r=0.481, P=0.000). Cardiac output (CO) was an independent risk factor of sPAP (B=1.431, confidence interval [CI] 95%: 0.687 to 2.175, P=0.000). CONCLUSION: Incidence of PH was not statistically different in ESRD patients on dialysis and pre-dialysis patients. Uremia may play a major role in the pathogenesis of PH in patients.

GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway.

Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known. We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8). These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1. We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians. Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians. Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1. By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells. Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.

Exome-Based Rare-Variant Analyses in CKD.

BACKGROUND: Studies have identified many common genetic associations that influence renal function and all-cause CKD, but these explain only a small fraction of variance in these traits. The contribution of rare variants has not been systematically examined. METHODS: We performed exome sequencing of 3150 individuals, who collectively encompassed diverse CKD subtypes, and 9563 controls. To detect causal genes and evaluate the contribution of rare variants we used collapsing analysis, in which we compared the proportion of cases and controls carrying rare variants per gene. RESULTS: The analyses captured five established monogenic causes of CKD: variants in PKD1, PKD2, and COL4A5 achieved study-wide significance, and we observed suggestive case enrichment for COL4A4 and COL4A3. Beyond known disease-associated genes, collapsing analyses incorporating regional variant intolerance identified suggestive dominant signals in CPT2 and several other candidate genes. Biallelic mutations in CPT2 cause carnitine palmitoyltransferase II deficiency, sometimes associated with rhabdomyolysis and acute renal injury. Genetic modifier analysis among cases with APOL1 risk genotypes identified a suggestive signal in AHDC1, implicated in Xia-Gibbs syndrome, which involves intellectual disability and other features. On the basis of the observed distribution of rare variants, we estimate that a two- to three-fold larger cohort would provide 80% power to implicate new genes for all-cause CKD. CONCLUSIONS: This study demonstrates that rare-variant collapsing analyses can validate known genes and identify candidate genes and modifiers for kidney disease. In so doing, these findings provide a motivation for larger-scale investigation of rare-variant risk contributions across major clinical CKD categories.

Donor's APOL1 Risk Genotype and "Second Hits" Associated With De Novo Collapsing Glomerulopathy in Deceased Donor Kidney Transplant Recipients: A Report of 5 Cases.

The presence of 2 APOL1 risk variants (G1/G1, G1/G2, or G2/G2) is an important predictor of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease in individuals of African descent. Although recipient APOL1 genotype is not associated with allograft survival, kidneys from deceased African American donors with 2 APOL1 risk variants demonstrate shorter graft survival. We present a series of cases of presumed de novo collapsing FSGS in 5 transplanted kidneys from 3 deceased donors later identified as carrying 2 APOL1 risk alleles, including 2 recipients from the same donor whose kidneys were transplanted in 2 different institutions. Four of these recipients had viremia in the period preceding the diagnosis of collapsing FSGS. Cytomegalovirus and BK virus infection were present in 3 and 1 of our 5 cases, respectively, around the time that collapsing FSGS occurred. We discuss viral infections, including active cytomegalovirus infection, as possible "second hits" that may lead to glomerular injury and allograft failure in these recipients. Further studies to identify additional second hits are necessary to better understand the pathologic mechanisms of donor APOL1-associated kidney disease in the recipient.

Transvenous dual-chamber pacemaker implantation in patients with persistent left superior vena cava.

BACKGROUND: Persistent left superior vena cava (PLSVC) is a rare congenital vascular anomaly. Permanent pacemaker implantation (PPI) in patients with PLSVC can be challenging because of the venous anomalies. We reported a case series of patients with PLSVC who underwent PPI with double active fixation leads. METHODS: From January 2012 to July 2016, 9 patients (three male and six females, mean age 68 ± 11 years) with PLSVC who received a dual-chamber pacemaker with double active fixation leads were enrolled retrospectively in this observational study. The indications for pacemaker implantation were symptomatic third-degree atrioventricular block in one and sick sinus syndrome in eight patients. RESULTS: PPI were implanted successfully in all 9 patients. Successful positioning of the ventricular leads at the right ventricular outflow tract (RVOT) septum with a "C" shaped stylet was achieved in 7 patients (77.8%). In the remaining two cases, the ventricular leads were placed in the right ventricular apex and the inferior free wall of the sub-tricuspid annulus. The atrial leads were placed at the lateral wall of the right atrium in all patients. Procedure time and fluoroscopy time were 85.3 ± 11.3 min and 4.5 ± 1.1 min respectively. During a mean follow-up of 4 years, no complications were observed and pacing parameters did not change significantly. CONCLUSION: PPI through PLSVC may be technically feasible, safe, and effective. Double active fixation leads may be standard for patients with PLSVC and most of the ventricular leads could be placed at the RVOT septum.

Unique electrocardiographic pattern "w" wave in lead I of idiopathic ventricular arrhythmias arising from the distal great cardiac vein.

BACKGROUND: The ECG characteristics of the distal coronary venous system ventricular arrhythmias (VAs) share common features with VAs arising from the aortic cusps or the endocardial left ventricular outflow tract (LVOT) beneath the cusps. The purpose of this study was to identify specific electrocardiographic and electrophysiological characteristics of VAs originating from the distal great cardiac vein (GCV). METHODS: Based on the successful ablation site, patients with idiopathic VAs from the distal GCV, left coronary cusp (LCC) or the subvalvular left ventricular outflow tract (LVOT) area were included in the present study. RESULTS: The final population consisted of 39 patients (35 males, mean age 51 ± 23 years). All VAs displayed a right bundle branch block (RBBB) morphology with inferior axis. Among these patients, 15 were successfully ablated at the GCV, 15 at the LCC and 9 at the subvalvular region. A "w" pattern in lead I was present in 12 out of 15 (80%) VAs originating from the distal GCV compared to none of VAs arising from the other two sites (p < 0.01). VAs with a GCV origin exhibited more commonly increased intrinsicoid deflection time, higher maximum deflection index and wider QRS duration compared to LCC and subvalvular sites (p < 0.05). Acceptable pace mapping at the successful ablation site was achieved in 10 patients. After an average of 36 ± 24 months follow up, 14 (93.3%) patients were free from VAs recurrence. CONCLUSION: A "w" pattern in lead I may distinguish distal GCV VAs from VAs arising from the LCC or the subvalvular region.