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Background Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. Method This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. Results RAS demonstrated a loss of medium-sized vessels (0.2–0.3 mm) compared with donor kidneys (P = 0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. Conclusions These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

Introduction Caregiver plays a vital role in taking good care of a cancer patient. But often, the caregiver’s quality of life (QOL) is overlooked. Objectives This study aimed to understand the Caregiver QOL Index—Cancer (CQOL-C) score of the primary caregivers and to find the significant predictors affecting CQOL-C. Materials and Methods A cross-sectional study was conducted among the caregivers attending a rural cancer center in western Maharashtra. The primary caregiver is an immediate relative who assists the patient in most routine activities and is not a professional caregiver. A pretested and predesigned questionnaire using the CQOL-C scale was used to interview the caregivers from December 2019 to June 2020. We analyzed the data using Statistical Package of Social Sciences (SPSS) software. Univariate analysis was done using Student’s t-test and a multivariate model was generated using linear regression analysis of the data. Results A total of 114 caregivers were interviewed. The mean total CQOL-C score was 44.15 ± 17.24 (confidence interval [CI]: 41–47.3). About 71% of the caregivers reported moderate-to-severe hampering of their QOL. The mean CQOL-C scores in caregivers of patients with and without recurrent cancer were 58.24 (CI: 51.66–64.81) and 40.58 (CI: 37.35–43.80), respectively (p < 0.001). The mean CQOL-C scores in caregivers of patients with and without metastatic cancer were 56.68 (CI: 51. 13–62.22) and 39.80 (CI: 36.45–43.14), respectively (p < 0.001). The mean CQOL-C score in caregivers of patients with hematological malignancies was 60.03 (CI: 58.88–61.17) which was significantly higher compared with other sites (p = 0.0257). Conclusion The majority of the caregivers in our study have moderate-to-severe detrimental QOL. Recurrence of cancer and metastatic cancer at presentation are the two significant factors affecting CQOL-C. There is an unmet need to cater to the primary caregiver’s concerns while we focus on treating cancer patients.

The eye and the kidney share structural and developmental similarities on a cellular and clinical level, and they are often affected by the same disease processes. Performing an eye exam to look for signs of conditions such as hypertension and diabetes can provide a helpful window into the health of the kidney. Patients with kidney transplants (KT) are a unique population that require close monitoring. These patients are maintained on a number of immunosuppressive medications and may face complications such as medication side effects, infections, and graft rejection. Patients with KT are at higher risk of both infectious and noninfectious eye conditions related to underlying systemic disease or use of immunosuppressive medications. Screening for eye conditions is important because preserving visual function is integral to quality of life, and also because the eye exam can help with early detection and treatment of systemic conditions. Here we describe some of the common eye findings and conditions in patients with KT. We recommend that patients with KT receive annual eye exams, and we hope that the information provided here can help nephrologists become more familiar with eye findings and identify situations where a referral to ophthalmology is warranted.

Background and Objectives There are two patient positions described for minimally invasive esophagectomy (MIE) for esophageal cancer, viz., left lateral and prone positions. To retain the benefits and overcome the disadvantages of these positions, a semi-prone position was developed by us. Our objective was to analyze the feasibility of performing MIE in this position. Materials and Methods A retrospective review of patients who underwent MIE at our center from January 2007 to December 2017 was done. A semi-prone position is a left lateral position with an anterior inclination of 45 degrees. Intraoperative parameters including conversion rate, immediate postoperative outcomes, and long-term oncological outcomes were analyzed. Statistical Analysis Statistical Package for the Social Sciences version 19 (IBM SPSS, IBM Corp., Armonk, New York, United States) was utilized for analysis. Survival analysis was done using Kaplan-Meier graph. Quantitative data were described as mean or median with standard deviation, and qualitative data were described as frequency distribution tables. Results Consecutive 224 patients with good performance status were included. After excluding those who required conversion (14 [6.6%]), 210 patients were further analyzed. Median age was 60 years (range: 27–80 years). Neoadjuvant treatment recipients were 160 (76%) patients. Most common presentation was squamous cell carcinoma (146 [70%]) of lower third esophagus (140 [67%]) of stage III (126 [60%]). Median blood loss for thoracoscopic dissection and for total operation was 101.5 mL (range: 30–180 mL) and 286 mL (range: 93–480 mL), respectively. Median operative time for thoracoscopic dissection alone was 67 minutes (range: 34–98 minutes) and for entire procedure was 215 minutes (range: 162–268 minutes). There was no intraoperative mortality. Median 16 lymph nodes were dissected (range: 5–32). Postoperative complication rate and mortality was 50% and 3.3%, respectively. Disease-free interval was 18 months (range: 3–108 months) and overall survival was 22 months (range: 6–108 months). Conclusion MIE with mediastinal lymphadenectomy in a semi-prone position is feasible, convenient, oncologically safe, which can combine the benefits of the two conventional approaches. Further prospective and comparative studies are required to support our findings.

Obesity promotes dysfunction and impairs the reparative capacity of mesenchymal stem/stromal cells (MSCs), and alters their transcription, protein content, and paracrine function. Whether these adverse effects are mediated by chromatin-modifying epigenetic changes remains unclear. We tested the hypothesis that obesity imposes global DNA hydroxymethylation and histone tri-methylation alterations in obese swine abdominal adipose tissue-derived MSCs compared to lean pig MSCs. MSCs from female lean (n = 7) and high-fat-diet fed obese (n = 7) domestic pigs were assessed using global epigenetic assays, before and after in-vitro co-incubation with the epigenetic modulator vitamin-C (VIT-C) (50 μg/ml). Dot blotting was used to measure across the whole genome 5-hydroxyemthycytosine (5hmC) residues, and Western blotting to quantify in genomic histone-3 protein tri-methylated lysine-4 (H3K4me3), lysine-9 (H3K9me3), and lysine-27 (H3K27me3) residues. MSC migration and proliferation were studied in-vitro. Obese MSCs displayed reduced global 5hmC and H3K4m3 levels, but comparable H3K9me3 and H3K27me3, compared to lean MSCs. Global 5hmC, H3K4me3, and HK9me3 marks correlated with MSC migration and reduced proliferation, as well as clinical and metabolic characteristics of obesity. Co-incubation of obese MSCs with VIT-C enhanced 5hmC marks, and reduced their global levels of H3K9me3 and H3K27me3. Contrarily, VIT-C did not affect 5hmC, and decreased H3K4me3 in lean MSCs. Obesity induces global genomic epigenetic alterations in swine MSCs, involving primarily genomic transcriptional repression, which are associated with MSC function and clinical features of obesity. Some of these alterations might be reversible using the epigenetic modulator VIT-C, suggesting epigenetic modifications as therapeutic targets in obesity.

Background Obesity is a major public health challenge, and recent literature sheds light on the concept of “normalization” of obesity. Objective We aimed to study the worldwide pattern of web-based information seeking by public on obesity and on its related terms and topics using Google Trends. Methods We compared the relative frequency of obesity-related search terms and topics between 2004 and 2019 on Google Trends. The mean relative interest scores for these terms over the 4-year quartiles were compared. Results The mean relative interest score of the search term “obesity” consistently decreased with time in all four quartiles (2004-2019), whereas the relative interest scores of the search topics “weight loss” and “abdominal obesity” increased. The topic “weight loss” was popular during the month of January, and its median relative interest score for January was higher than that for other months for the entire study period (P Conclusions Despite a worldwide increase in the prevalence of obesity, its popularity as an internet search term diminished over time. The reason for peaks in months should be explored and applied to the awareness campaigns for better effectiveness. These patterns suggest normalization of obesity in society and a rise of public curiosity about image-related obesity rather than its medical implications and harm.

BACKGROUND Obesity is a major public health challenge, and recent literature sheds light on the concept of “normalization” of obesity. OBJECTIVE We aimed to study the worldwide pattern of web-based information seeking by public on obesity and on its related terms and topics using Google Trends. METHODS We compared the relative frequency of obesity-related search terms and topics between 2004 and 2019 on Google Trends. The mean relative interest scores for these terms over the 4-year quartiles were compared. RESULTS The mean relative interest score of the search term “obesity” consistently decreased with time in all four quartiles (2004-2019), whereas the relative interest scores of the search topics “weight loss” and “abdominal obesity” increased. The topic “weight loss” was popular during the month of January, and its median relative interest score for January was higher than that for other months for the entire study period (P CONCLUSIONS Despite a worldwide increase in the prevalence of obesity, its popularity as an internet search term diminished over time. The reason for peaks in months should be explored and applied to the awareness campaigns for better effectiveness. These patterns suggest normalization of obesity in society and a rise of public curiosity about image-related obesity rather than its medical implications and harm.

Introduction: The horseshoe kidney (HSK) is the most common type of renal fusion anomaly. The incidence and characteristics of kidney stones in patients with HSK are not well studied. The aim of this meta-analysis was to evaluate the incidence and types of kidney stones in patients with HSK. Methods: A systematic literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases' inception through November 2016. Studies assessing the incidence and types of kidney stones in patients with HSK were included. We applied a random-effects model to estimate the incidence of kidney stones. The study protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016052037). Results: A total of 14 observational studies with 943 patients (522 adults and 421 pediatric) with HSK were enrolled. The estimated pooled incidence of kidney stones was 36% (95% confidence interval [CI], 15%–59%) in adults with the HSK. Kidney stones were less common in pediatric patients with HSK with an estimated pooled incidence of 3% (95% CI, 2%–5%). The mean age of adult stone formers with HSK was 44.9 ± 6.2 years, and 75% were males. Within reported studies, 89.2% of kidney stones were calcium-based stones (64.2% calcium oxalate [CaOx], 18.8% calcium phosphate [CaP], and 6.2% mixed CaOx/CaP), followed by struvite stones (4.2%), uric acid stones (3.8%), and others (2.8%). Conclusions: Kidney stones are very common in adult patients with HSK with an estimated incidence of 36%. Calcium-based stones are the most prevalent kidney stones in adults with HSKs. These findings may impact the prevention and clinical management of kidney stones in patients with HSK.

INTRODUCTION: Mesenchymal stem cells (MSCs) have endogenous reparative properties, and may constitute an exogenous therapeutic intervention in patients with chronic kidney disease. The microenvironment of metabolic syndrome (MetS) induces fat inflammation, with abundant expression of tumor necrosis factor (TNF)-α. MetS may also alter the content of adipose tissue-derived MSCs, and we hypothesized that the inflammatory profile of MetS manifests via upregulating MSC mRNAs and proteins of the TNF-α pathway. METHODS: Domestic pigs were fed a 16-week Lean or MetS diet (n=4 each). MSCs were harvested from abdominal subcutaneous fat, and their extracellular vesicles (EVs) isolated. Expression profiles of mRNAs and proteins in MSCs and EVs were obtained by high-throughput sequencing and proteomics. Nuclear translocation of the pro-inflammatory transcription factor (NF)-kB was evaluated in MSC and in pig renal tubular cells (TEC) co-incubated with EVs. RESULTS: We found 13 mRNAs and 4 proteins in the TNF-α pathway upregulated in MetS- vs. Lean-MSCs (fold-change>1.4, p

Objective To establish and characterize a novel domestic porcine model of obesity. Methods Fourteen domestic pigs were fed normal (lean, n = 7) or high-fat/high-fructose diet (obese, n = 7) for 16 weeks. Subcutaneous abdominal adipose tissue biopsies were obtained after 8, 12, and 16 weeks of diet, and pericardial adipose tissue after 16 weeks, for assessments of adipocyte size, fibrosis, and inflammation. Adipose tissue volume and cardiac function were studied with multidetector computed tomography, and oxygenation was studied with magnetic resonance imaging. Plasma lipids profile, insulin resistance, and markers of inflammation were evaluated. Results Compared with lean pigs, obese pigs had elevated cholesterol and triglyceride levels, blood pressure, and insulin resistance. Both abdominal and pericardial fat volume increased in obese pigs after 16 weeks. In abdominal subcutaneous adipose tissue, adipocyte size and both tumor necrosis factor (TNF)-α expression progressively increased. Macrophage infiltration showed in both abdominal and pericardial adipose tissues. Circulating TNF-α increased in obese pigs only at 16 weeks. Compared with lean pigs, obese pigs had similar global cardiac function, but myocardial perfusion and oxygenation were significantly impaired. Conclusions A high-fat/high-fructose diet induces in domestic pigs many characteristics of metabolic syndrome, which is useful for investigating the effects of the obesity.

Renovascular hypertension alters cardiac structure and function. Autophagy is activated during left ventricular hypertrophy and linked to adverse cardiac function. The Angiotensin II receptor blocker Valsartan lowers blood pressure and is cardioprotective, but whether it modulates autophagy in the myocardium is unclear. We hypothesized that Valsartan would alleviate autophagy and improve left ventricular myocardial mitochondrial turnover in swine renovascular hypertension. Domestic pigs were randomized to control, unilateral renovascular hypertension, and renovascular hypertension treated with Valsartan (320 mg/day) or conventional triple therapy (Reserpine+hydralazine+hydrochlorothiazide) for 4 weeks post 6-weeks of renovascular hypertension (n=7 each group). Left ventricular remodeling, function and myocardial oxygenation and microcirculation were assessed by multi-detector computer tomography, blood-oxygen-level-dependent magnetic resonance imaging and microcomputer tomography. Myocardial autophagy, markers for mitochondrial degradation and biogenesis, and mitochondrial respiratory-chain proteins were examined ex vivo. Renovascular hypertension induced left ventricular hypertrophy and myocardial hypoxia, enhanced cellular autophagy and mitochondrial degradation, and suppressed mitochondrial biogenesis. Valsartan and triple therapy similarly decreased blood pressure, but Valsartan solely alleviated left ventricular hypertrophy, ameliorated myocardial autophagy and mitophagy, and increased mitochondrial biogenesis. In contrast, triple therapy only slightly attenuated autophagy and preserved mitochondrial proteins, but elicited no improvement in mitophagy. These data suggest a novel potential role of Valsartan in modulating myocardial autophagy and mitochondrial turnover in renovascular hypertension-induced hypertensive heart disease, which may possibly bolster cardiac repair via a blood pressure-independent manner.

Introduction: Mesenchymal stem cells (MSCs) possess endogenous reparative properties and may serve as an exogenous therapeutic intervention in patients with chronic kidney disease. Cardiovascular risk factors clustering in the metabolic syndrome (MetS) might adversely affect cellular properties. To test the hypothesis that Mets interferes with MSC characteristics, we performed comprehensive comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs. Methods: Domestic pigs were fed a 16-week Lean or MetS diet (n = 4 each). Expression profiles of co-existing microRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and liquid chromatography-mass spectrometry. TargetScan and ComiR were used to predict target genes of differentially expressed microRNAs, and DAVID 6.7 for functional annotation analysis to rank primary gene ontology categories for the microRNA target genes, mRNAs, and proteins. Results: Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs compared to Lean-MSCs (fold change>1.4, p

Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that angiotensin-converting enzyme inhibitors/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with Valsartan, or triple therapy (seven pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood oxygen level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly; however, Valsartan did not change the GFR of the stenotic kidney compared with renal artery stenosis and was similar to triple therapy. Both Valsartan and triple therapy stimulated microvascular density and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, Valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function.

Obesity-metabolic disorders (ObM) often accompany renal artery stenosis (RAS). We hypothesized that the coexistence of ObM and RAS magnifies inflammation and microvascular remodeling in the stenotic kidney (STK) and aggravates renal scarring. Twenty-eight obesity-prone Ossabaw pigs were studied after 16 wk of a high-fat/high-fructose diet or standard chow including ObM-sham, ObM-RAS, Lean-RAS, or Lean-sham (normal control) groups. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by multidetector computed tomography (CT), renal oxygenation and tubular transport capability by blood-oxygen-level-dependent MRI, and microcirculation by micro-CT for vessel density, and Western blotting for protein expressions of angiogenic factors (VEGF/FLK-1). Renal vein and inferior vena cava levels of inflammatory cytokines were measured to evaluate systemic and kidney inflammation. Macrophage (MØ) infiltration and subpopulations, fat deposition in the kidney, and inflammation in perirenal and abdominal fat were also examined. GFR and RBF were decreased in Lean-STK but relatively preserved in ObM-STK. However, ObM-STK showed impaired tubular transport function, suppressed microcirculation, and stimulated glomerulosclerosis. ObM diet interacted with RAS to blunt angiogenesis in the STK, facilitated the release of inflammatory cytokines, and led to greater oxidative stress than Lean-STK. The ObM diet also induced fat deposition in the kidney and infiltration of proinflammatory M1-MØ, as also in perirenal and abdominal fat. Coexistence of ObM and RAS amplifies renal inflammation, aggravates microvascular remodeling, and accelerates glomerulosclerosis. Increased adiposity and MØ-accentuated inflammation induced by an ObM diet may contribute to structural injury in the post-STK kidney.

Lithium-Induced Nephropathy A 59-year-old man with a history of bipolar disorder was admitted to the hospital after a fall and was incidentally found to have numerous small renal cysts, a finding consistent with previous lithium treatment.

Obesity and hypertension are major risk factors for cardiovascular diseases, and their growing coexistence accounts for an increase in adverse cardiac events, but the mechanisms are yet to be determined. We hypothesized that obesity exacerbates mitochondrial dysregulation imposed by hypertension and augments left ventricular dysfunction. Obesity-prone Ossabaw pigs were randomized to lean (standard diet) and obese (high-fat diet), without (Lean-sham and Obese-sham) or with renovascular hypertension (Lean-hypertension and Obese-hypertension), induced after 12 weeks of diet (n=7 each). Cardiac function, myocardial perfusion and oxygenation, and microvascular remodeling were assessed 4 weeks later. Mitochondrial biogenesis signals and structural proteins, respiratory chain complex activities, and mitochondrial self-degradation were examined, as was fibrosis. Obesity alone exerted no apparent effect on mitochondrial dynamics, but aggravated in hypertensive hearts the reduction of mitochondrial proteins, deoxyribonucleic acid content, and respiratory chain complex IV subunits activity, and amplified mitochondrial self-degradation. Synergistic interaction of obesity with hypertension also exacerbated myocardial fibrosis and left ventricular diastolic dysfunction. Mitochondrial content, respiratory chain complex IV subunits activity, and mitophagy were correlated with myocardial fibrosis. These findings suggest that obesity aggravates in renovascular hypertension cardiac mitochondrial aberrations. Mitochondrial function may regulate the progression of cardiac injury and functional deterioration in hypertension concomitant with obesity.