Prevalence, risk, and outcomes of venous thromboembolic events in kidney transplant recipients: a nested case-control study.

INTRODUCTION: Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. METHODS: A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. RESULTS: Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. CONCLUSION: This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.

Vascular deficiencies in renal organoids and ex vivo kidney organogenesis.

Chronic kidney disease (CKD) and end stage renal disease (ESRD) are increasingly frequent and devastating conditions that have driven a surge in the need for kidney transplantation. A stark shortage of organs has fueled interest in generating viable replacement tissues ex vivo for transplantation. One promising approach has been self-organizing organoids, which mimic developmental processes and yield multicellular, organ-specific tissues. However, a recognized roadblock to this approach is that many organoid cell types fail to acquire full maturity and function. Here, we comprehensively assess the vasculature in two distinct kidney organoid models as well as in explanted embryonic kidneys. Using a variety of methods, we show that while organoids can develop a wide range of kidney cell types, as previously shown, endothelial cells (ECs) initially arise but then rapidly regress over time in culture. Vasculature of cultured embryonic kidneys exhibit similar regression. By contrast, engraftment of kidney organoids under the kidney capsule results in the formation of a stable, perfused vasculature that integrates into the organoid. This work demonstrates that kidney organoids offer a promising model system to define the complexities of vascular-nephron interactions, but the establishment and maintenance of a vascular network present unique challenges when grown ex vivo.

Short- and long-term outcomes of early initiation of peritoneal dialysis following catheter insertion.

INTRODUCTION: Early-start peritoneal dialysis (PD) (use of PD catheter within 48 hours of insertion) is an innovative approach for prompt initiation of PD. AIM: This study was conducted to analyze the outcomes of early-start PD. MATERIALS AND METHODS: A total of 100 patients on PD were retrospectively analyzed. Patients were grouped according to the "break-in period": < 48 hours (PD1) and ≥ 14 days (PD2). PD was initiated with low dwell volumes (500 mL) in a recumbent position within 48 hours of surgery. PD prescription was gradually incremented over 10 days to minimize any complications. RESULTS: In our study, there were 48 patients in the PD1 group and 52 in the PD2 group. The most common cause of end-stage kidney disease (ESKD) was diabetes mellitus in both groups. Incidence of early mechanical complications (within 30 days of catheter insertion), such as catheter obstruction, early catheter leakage, catheter malposition, tip migration, and infectious complications, were not found to be higher in the PD1 group. 1- and 4-year catheter patency rates were 97.0% and 96.2% in the PD1 group, respectively. These rates were comparable with those in the PD2 group. Early-start PD was not associated with an increased incidence of catheter failure (HR = 1.0, 95% CI 0.28 - 3.47). CONCLUSION: An early break-in period of < 48 hours is a feasible option for ESKD patients without any significantly increased risk of mechanical or infectious complications. It offers a safe and efficacious option for renal replacement therapy.

A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids.

BACKGROUND: There is an urgent need for approaches to prevent and treat SARS-CoV-2 infection. Administration of soluble ACE2 protein acting as a decoy to bind to SARS-CoV-2 should limit viral uptake mediated by binding to membrane-bound full-length ACE2, and further therapeutic benefit should result from ensuring enzymatic ACE2 activity to affected organs in patients with COVID-19. METHODS: A short variant of human soluble ACE2 protein consisting of 618 amino acids (hACE2 1-618) was generated and fused with an albumin binding domain (ABD) using an artificial gene encoding ABDCon, with improved albumin binding affinity. Human kidney organoids were used for infectivity studies of SARS-CoV-2 in a BSL-3 facility to examine the neutralizing effect of these novel ACE2 variants. RESULTS: Whereas plasma ACE2 activity of the naked ACE2 1-618 and ACE2 1-740 lasted about 8 hours, the ACE2 1-618-ABD resulted in substantial activity at 96 hours, and it was still biologically active 3 days after injection. Human kidney organoids express ACE2 and TMPRSS2, and when infected with SARS-CoV-2, our modified long-acting ACE2 variant neutralized infection. CONCLUSIONS: This novel ACE2 1-618-ABD can neutralize SARS-CoV-2 infectivity in human kidney organoids, and its prolonged duration of action should ensure improved efficacy to prevent viral escape and dosing convenience.

CMV presenting as a skin growth in renal transplant patient.

CMV infection is one of the most common opportunistic infection in kidney transplant patients. If not treated, it is associated with increased mortality and graft loss. It can present as viremia or CMV disease in the form of CMV syndrome or tissue invasive CMV disease. The cutaneous presentation of CMV disease is a rare finding. Its identification is vital as cutaneous CMV infection can signal systemic infection and poor prognosis. In our case, 46-year-old male who was a post renal allograft recipient (RAR) presented as a protuberant growth over the medial side of the left ankle. On skin biopsy, nucleomegaly and inclusion bodies were seen in the epithelial cells. Immunohistochemistry was positive for CMV infection. Patient was treated with Ganciclovir, however, he succumbed to death because of severe sepsis due to secondary bacterial infection. Thus, CMV disease should always be kept in mind in immunocompromised patients like post RAR patients who present with cutaneous features like ulcerative lesions or fungating growth.

Peritoneal dialysis: Status report in South and South East Asia.

BACKGROUND: Peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) is largely underutilized globally. We analyzed PD utilization, impact of economic status, projected growth and impact of state policy(s) on PD growth in South Asia and Southeast Asia (SA&SEA) region. METHODS: The National Nephrology Societies of the region responded to a questionnaire on KRT practices. The responses were based on the latest registry data, acceptable community-based studies and societal perceptions. The representative countries were divided into high income and higher-middle income (HI & HMI) and low income and lower-middle income (LI & LMI) groups. RESULTS: Data provided by 15 countries showed almost similar percentage of GDP as health expenditure (4%-7%). But there was a significant difference in per capita income (HI & HMI -US$ 28 129 vs. LI & LMI - US$ 1710.2) between the groups. Even after having no significant difference in monthly cost of haemodialysis (HD) and PD in LI & LMI countries, they have poorer PD utilization as compared to HI & HMI countries (3.4% vs. 10.1%); the reason being lack of formal training/incentives and time constraints for the nephrologist while lack of reimbursement and poor general awareness of modalities has been a snag for the patients. The region expects ≥10% PD growth in the near future. Hong Kong and Thailand with 'PD first' policy have the highest PD utilization. CONCLUSION: Important deterrents to PD underutilization were lack of PD centric policies, lackadaisical patient/physician's attitude, lack of structured patient awareness programs, formal training programs and affordability.

Aetiology, practice patterns and burden of end-stage kidney disease in South Asia and South-East Asia: A questionnaire-based survey.

AIM: There is paucity of data on the epidemiology of end-stage kidney disease (ESKD) from South Asia and South-East Asia. The objective of this study was to assess the aetiology, practice patterns and disease burden and growth of ESKD in the region comparing the economies. METHODS: The national nephrology societies of the region; responded to the questionnaire; based on latest registries, acceptable community-based studies and society perceptions. The countries in the region were classified into Group 1 (High|higher-middle-income) and Group 2 (lower|lowermiddle income). Student t-test, Mann-Whitney U test and Fisher's exact test were used for comparison. RESULTS: Fifteen countries provided the data. The average incidence of ESKD was estimated at 226.7 per million population (pmp), (Group 1 vs. Group 2, 305.8 vs. 167.8 pmp) and average prevalence at 940.8 pmp (Group 1 vs. Group 2, 1306 vs. 321 pmp). Group 1 countries had a higher incidence and prevalence of ESKD. Diabetes, hypertension and chronic glomerulonephritis were most common causes. The mean age in Group 2 was lower by a decade (Group 1 vs. Group 2-59.45 vs 47.7 years). CONCLUSION: Haemodialysis was the most common kidney replacement therapy in both groups and conservative management of ESKD was the second commonest available treatment option within Group 2. The disease burden was expected to grow >20% in 50% of Group 1 countries and 78% of Group 2 countries along with the parallel growth in haemodialysis and peritoneal dialysis.

Prevalence and Antibiogram of Urinary Tract Infections in Renal Transplant Recipients at a Tertiary Care Hospital in North India.

INTRODUCTION: Although, urinary tract infections (UTI) remain the most common cause of mortality and morbidity in renal allograft recipients, there is scarce data from India on the etiology and antibiogram of UTI post kidney transplantation. Therefore, the current study was undertaken to evaluate the prevalence, etiology and the antibiogram of pathogens causing UTI in this cohort. METHODS: Renal allograft recipients enrolled during the study period were screened for UTI by standard microscopy and routine culture on the day of admission and subsequently every 3rd day post-surgery till discharge. If UTI was present, the etiological agent and its antibiogram were recorded along with the demographic details of the patients. RESULTS: The prevalence of UTI post-transplantation at our centre was 30%. E.coli and Klebsiella pneumoniae were the most common organisms isolated in 42% and 39% cases, respectively. Majority of patients developed UTI on Day 6 (36.6%) and Day 9 (36.6%) post-transplant. Our study revealed a high percentage of resistance to commonly used 1st and 2nd line antibiotics like third generation cephalosporins (96.6%), fluoroquinolones (96.6%), and aminoglycosides (56.7%) and carbapenems (55.2%). CONCLUSION: Considering the high prevalence of UTI and antibiotic resistance rates in kidney transplant patients in our study, there is an urgent need for developing hospital based local antibiogram for appropriate management of UTI. Fosfomycin as an empirical therapy might be a useful choice for adequate coverage of potential pathogens at our centre. Further multi-centric studies on a larger sample size are recommended from India for formulating antibiotic policy.

Planar photonic crystal based multifunctional sensors.

A planar photonic crystal (PPC) structure capable of simultaneous detection of multiple parameters is presented in this paper. We analytically and numerically demonstrate that the reflection spectrum of the PPC structure exhibits multiple high-Q resonant modes that could respond distinctively to different external perturbations, rendering the PPC sensor superior capabilities for multiparameter sensing. We further demonstrate simultaneous pressure and temperature sensing with a PPC sensor. Other advantages of this device include efficient free-space-to-multimode coupling, high sensitivity, on-chip integration, and wafer-scale fabrications.

Planar photonic crystal based multifunctional sensors: erratum.

Here, we acknowledge related papers that should have been cited in our recent work [Appl. Opt.56, 1775 (2017)APOPAI0003-693510.1364/AO.56.001775].

Planar photonic crystal based multifunctional sensors: publisher's note.

This note points out a missed correction to the math on p. 1779 of Appl. Opt.56, 1775 (2017)10.1364/AO.56.001775.

Isolated diplopia associated with calcineurin inhibitor therapy in a patient with idiopathic membranous nephropathy: a case report.

BACKGROUND: Neurotoxicity is a common side effect of treatment with calcineurin inhibitors. Tremors are frequently reported as the most common manifestation. Variable presentations can include headaches, seizures, visual hallucinations or blindness. Sixth nerve palsy has been reported in previous cases of bone marrow and cardiac transplant patients receiving calcineurin inhibitors. In many of these previously reported cases, the drug was administered intravenously and very high drug levels were found. CASE PRESENTATION: We report the first case of isolated diplopia in a patient being treated for idiopathic membranous glomerulonephritis. This is also the first report where the neurotoxicity induced by initial tacrolimus therapy persisted with subsequent cyclosporine therapy, two structurally different calcineurin inhibitors which share a common mechanism of action. In our case toxicity occurred after 3 months of therapy despite low serum concentrations and the symptoms resolved completely after discontinuation of the drugs. CONCLUSION: Our case provides further evidence that the neurotoxicity is a result of calcineurin inhibition. Monitoring of serum concentrations of these drugs has not been correlated with toxicity. The mean duration to onset of symptoms can be as much as 70 days suggesting accumulation of the drug in the central nervous system plays a role. Recognition of this condition is important for prompt diagnosis and appropriate management.

Mortality in African-Americans Following Cardiac Resynchronization Therapy: A Single Center Experience.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves clinical outcomes and reduces mortality in heart failure patients who remain symptomatic despite optimal medical therapy. CRT trials have reported significant hemodynamic benefits, improvement in functional status, and reduced mortality and heart failure hospitalizations. However, African-American patient representation in these studies is limited thus the results may not be applicable to them. We described baseline clinical characteristics of African-American patients undergoing CRT and determined their outcomes relative to those reported in clinical trials. METHODS: We evaluated 131 African-American patients with New York Heart Association functional class II-IV heart failure undergoing CRT and determined predictors of all-cause mortality. Kaplan-Meier survival estimates and a Cox proportional hazards model determined mortality and risk of death. RESULTS: The mean age was 65 ± 12 years. Over a 6-year period, total mortality in African-Americans was 23% as compared with 29% in the MADIT-CRT trial. Increased mortality was associated with older age (hazard rate (HR) 1.04, 95% confidence interval (CI) 1.01-1.07, P=.01), ischemic cardiomyopathy (HR 2.86, 95% CI 1.36-6.04, P=.006), and absence of treatment with either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (HR 2.75, 95% CI 1.30-5.80, P=.008), or beta-blocker (HR 2.56, 95% CI 0.98-6.69, P=.05). Hydralazine plus nitrate therapy was used in a small number of patients and did not influence mortality outcomes. CONCLUSION: African-Americans experience the same survival benefits from CRT as Caucasian patients reported in major clinical trials. Publication indices used to find publications listed in references: PubMed.

Are sodium and potassium results on arterial blood gas analyzer equivalent to those on electrolyte analyzer?

OBJECTIVES: The present study was conducted with the aim to compare the sodium (Na) and  potassium (K) results on arterial blood gas (ABG) and electrolyte analyzers both of which use direct ion selective electrode technology. MATERIALS AND METHODS: This was a retrospective study in which data were collected for simultaneous ABG and serum electrolyte samples of a patient received in Biochemistry Laboratory during February to May 2015. The ABG samples received in heparinized syringes were processed on Radiometer ABL80 analyzer immediately. Electrolytes in serum sample were measured on ST-100 Sensa Core analyzer after centrifugation. Data were collected for 112 samples and analyzed with the help of Excel 2010 and  Statistical software for Microsoft excel XLSTAT 2015 software. RESULTS: The mean Na level in serum sample was 139.4 ± 8.2 mmol/L compared to 137.8 ± 10.5 mmol/L in ABG (P < 0.05). The mean difference between the results was 1.6 mmol/L. Mean K level in serum sample was 3.8 ± 0.9 mmol/L as compared to 3.7 ± 0.9 mmol/L in ABG sample (P < 0.05). The mean difference between the results was 0.14 mmol/L. Statistically significant difference was observed in results of two instruments in low Na (<135 mmol/L) and normal K (3.5-5.2 mmol/L) ranges. The 95% limit of agreement for Na and K on both instruments was 9.9 to -13.2 mmol/L and 0.79 to -1.07 mmol/L respectively. CONCLUSIONS: The clinicians should be cautious in using the electrolyte results of electrolyte and ABG analyzer in inter exchangeable manner.

On-fiber plasmonic interferometer for multi-parameter sensing.

We demonstrate a novel miniature multi-parameter sensing device based on a plasmonic interferometer fabricated on a fiber facet in the optical communication wavelength range. This device enables the coupling between surface plasmon resonance and plasmonic interference in the structure, which are the two essential mechanisms for multi-parameter sensing. We experimentally show that these two mechanisms have distinctive responses to temperature and refractive index, rendering the device the capability of simultaneous temperature and refractive index measurement on an ultra-miniature form factor. A high refractive index sensitivity of 220 nm per refractive index unit (RIU) and a high temperature sensitivity of -60 pm/ °C is achieved with our device.

A prospective, multi-centre, observational study to examine kidney disease progression in adults with chronic kidney disease - CKDOD - Study design and preliminary results.

BACKGROUND: The objective of this article is to describe the organisation of an international, clinical registry, the Chronic Kidney Disease Observational Database (CKDOD), the processes of enrolling patients and entering data and preliminary results to date. DESIGN: The Chronic Kidney Disease Observational Database (CKDOD) is designed to assess the association between different factors with a known influence on chronic kidney disease (CKD) progression as well as treatment strategies such as dietary modifications, blood pressure control and pharmacological interventions in Asian countries (India, China, Malaysia and Thailand). The only inclusion criterion is the presence of CKD stage 2 or higher as defined by the KDIGO guidelines. Demographic and clinical information are collected by a standardised electronic questionnaire, available in English and Chinese. The data are transferred to the CKDOD database either by e-mail or via web access. All data are checked for consistency and missing values. Collection of data started in September 2011 and by April 2015, data on 1323 individual patients had been submitted. The mean age at inclusion was 57 ± 14 years, 67 % were male and 36 % were diabetic. The baseline estimated glomerular filtration rate was 26 ml/min/1.73 m(2). Of all enrolled patients, 324 (24 %) received ketoanalogue supplementation during at least one recorded visit. DISCUSSION: The CKDOD is a very large and comprehensive data repository, currently focused in subjects recruited from Asia. The database is expected to provide important long-term information on CKD progression, nutritional and metabolic derangements that accompany CKD progression and treatment strategies to ameliorate progression and complications of CKD. TRIAL REGISTRATION: Clinical Trial Registry - India: CTRI/2012/06/002743 ; 25th July 2012.

Biventricular paced QRS predictors of left ventricular lead locations in relation to mortality in cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) lead location during cardiac resynchronization therapy (CRT) has influenced mortality and heart failure events; however the biventricular paced QRS morphology has not been established as a predictor of LV lead location or mortality. METHODS: We evaluated the biventricular paced QRS morphology in 306 patients undergoing CRT in relation to specific anatomic locations. A logistic regression model and Kaplan-Meier survival estimates were used to determine predictors of LV lead location and survival. RESULTS: The mean age was 68±13years. Predictors of LV lead location from anterior, lateral, and posterior segments were: absence of R in V1, QS in aVL; and R in aVL, respectively. Absence of an R in II, III, or aVF predicted an inferior site. A QS in V4-V6 differentiated apical from basal sites (p=0.01). LV pacing from sites along the middle cardiac vein revealed a higher mortality (34%), than lateral sites (20%, p=0.02). CONCLUSIONS: Biventricular paced QRS criteria were predictive of LV lead locations. The proposed algorithm enhanced the predictive accuracy of these criteria. LV pacing sites along the middle cardiac vein were associated with increased mortality.