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Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected patients with kidney disease, causing significant challenges in disease management, kidney research and trainee education. For patients, increased infection risk and disease severity, often complicated by acute kidney injury, have contributed to high mortality. Clinicians were faced with high clinical demands, resource shortages and novel ethical dilemmas in providing patient care. In this review, we address the impact of COVID-19 on the entire spectrum of kidney care, including acute kidney injury, chronic kidney disease, dialysis and transplantation, trainee education, disparities in health care, changes in health care policies, moral distress and the patient perspective. Based on current evidence, we provide a framework for the management and support of patients with kidney disease, infection mitigation strategies, resource allocation and support systems for the nephrology workforce.

Parasitic agents have been known to cause human disease since ancient times and are endemic in tropical and subtropical regions. Complications of parasitic diseases, including kidney involvement, are associated with worse outcomes. Chagas disease, filariasis, leishmaniasis, malaria and schistosomiasis are important parasitic diseases that can damage the kidney. These diseases affect millions of people worldwide, primarily in Africa, Asia and Latin America, and kidney involvement is associated with increased mortality. The most common kidney complications of parasitic diseases are acute kidney injury, glomerulonephritis and tubular dysfunction. The mechanisms that underlie parasitic disease-associated kidney injury include direct parasite damage; immunological phenomena, including immune complex deposition and inflammation; and systemic manifestations such as haemolysis, haemorrhage and rhabdomyolysis. In addition, use of nephrotoxic drugs to treat parasitic infections is associated with acute kidney injury. Early diagnosis of kidney involvement and adequate management is crucial to prevent progression of kidney disease and optimize patient recovery.

Peritoneal dialysis (PD) has several advantages compared to haemodialysis (HD), but there is evidence showing underutilization globally, especially in low-income and lower-middle-income countries (LLMICs) where kidney replacement therapies (KRT) are often unavailable, inaccessible, and unaffordable. Only 11% of all dialysis patients worldwide use PD, more than 50% of whom live in China, the United States of America, Mexico, or Thailand. Various barriers to increased PD utilization have been reported worldwide including patient preference, low levels of education, and lower provider reimbursement. However, unique but surmountable barriers are applicable to LLMICs including the excessively high cost of providing PD (related to PD fluids in particular), excessive cost of treatment borne by patients (relative to HD), lack of adequate PD training opportunities for doctors and nurses, low workforce availability for kidney care, and challenges related to some PD outcomes (catheter-related infections, hospitalizations, mortality, etc.). This review discusses some known barriers to PD use in LLMICs and leverages data that show a global trend in reducing rates of PD-related infections, reducing rates of modality switches from HD, and improving patient survival in PD to discuss how PD use can be increased in LLMICs. We therefore, challenge the idea that low PD use in LLMICs is unavoidable due to these barriers and instead present opportunities to improve PD utilization in LLMICs.

International audience; BACKGROUND AND OBJECTIVES: Nutrition intervention is an essential component of kidney disease management. This study aimed to understand current global availability and capacity of kidney nutrition care services, interdisciplinary communication, and availability of oral nutrition supplements. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The International Society of Renal Nutrition and Metabolism (ISRNM), working in partnership with the International Society of Nephrology (ISN) Global Kidney Health Atlas Committee, developed this Global Kidney Nutrition Care Atlas. An electronic survey was administered among key kidney care stakeholders through 182 ISN-affiliated countries between July and September 2018. RESULTS: Overall, 160 of 182 countries (88%) responded, of which 155 countries (97%) answered the survey items related to kidney nutrition care. Only 48% of the 155 countries have dietitians/renal dietitians to provide this specialized service. Dietary counseling, provided by a person trained in nutrition, was generally not available in 65% of low-/lower middle-income countries and "never" available in 23% of low-income countries. Forty-one percent of the countries did not provide formal assessment of nutrition status for kidney nutrition care. The availability of oral nutrition supplements varied globally and, mostly, were not freely available in low-/lower middle-income countries for both inpatient and outpatient settings. Dietitians and nephrologists only communicated "sometimes" on kidney nutrition care in ≥60% of countries globally. CONCLUSIONS: This survey reveals significant gaps in global kidney nutrition care service capacity, availability, cost coverage, and deficiencies in interdisciplinary communication on kidney nutrition care delivery, especially in lower-income countries.

Acknowledgements: The authors would like to thank the staff at UNION Therapeutics for their review of the niclosamide arm of the protocol, and ongoing engagement throughout the study, and to the staff at GlaxoSmithKline Plc and Vir Biotechnology Inc. for their review of the sotrovimab arm of the protocol, and ongoing engagement throughout the study., Funder: LifeArc; doi: http://dx.doi.org/10.13039/100012357, Funder: Kidney Research UK, Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; doi: http://dx.doi.org/10.13039/501100002927, Funder: Union Therapeutics, Funder: GlaxoSmithKline; doi: http://dx.doi.org/10.13039/100004330, BACKGROUND: Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to SARS-CoV-2 infection by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination. METHODS: PROTECT-V is a platform trial testing pre-exposure prophylactic interventions against SARS-CoV-2 infection in vulnerable patient populations (organ transplant recipients; individuals with oncological/haematological diagnoses, immune deficiency or autoimmune diseases requiring immunosuppression or on dialysis). Multiple agents can be evaluated across multiple vulnerable populations sharing placebo groups, with the option of adding additional treatments at later time points as these become available. The primary endpoint is symptomatic SARS-CoV-2 infection, and each agent will be independently evaluated in real time when the required number of events occurs. Presently, three agents are approved in the platform: intranasal niclosamide, nasal and inhaled ciclesonide and intravenous sotrovimab. DISCUSSION: Despite the introduction of vaccination, there remains a need for pre-exposure prophylactic agents against SARS-CoV-2. Several patient groups are more vulnerable to COVID-19 disease by virtue of underlying health conditions, treatments received or suboptimal responses to vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04870333. EudraCT 2020-004144-28.

Background Anaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important. Methods The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3–5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8–10 g/dL or receiving ESAs with screening Hb of 8–12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28–52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials. Results Overall, 3872 patients were randomized from 39 countries (median age 67 years, 56% female, 56% White, 27% Asian and 10% Black). The median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and estimated glomerular filtration rate was 18 mL/min/1.73 m2. Among randomized patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin–angiotensin system blockers, 55% were taking statins and 49% were taking oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials. Conclusion ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.

In earlier studies, blindfolded participants used a joystick to orient themselves to the direction of balance in the horizontal roll plane while in a device programmed to behave like an inverted pendulum. In this spaceflight analog situation, position relevant gravitational cues are absent. Most participants show minimal learning, positional drifting, and failure of path integration. However, individual differences are substantial, some participants show learning and others become progressively worse. In Experiment 1, our goal was to determine whether spatial acuity could explain these individual differences in active balancing. We exposed blindfolded participants to passive movement profiles, with different frequency components, in the vertical and horizontal roll planes. They pressed a joystick trigger to indicate every time they passed the start point. We found greater spatial acuity for higher frequencies but no relation between passive spatial accuracy and active balance control in the horizontal roll plane, suggesting that spatial acuity in the horizontal roll plane does not predict performance in a disorienting spaceflight condition. In Experiment 2, we found significant correlations between passive spatial acuity in the vertical roll plane, where participants have task relevant gravitational cues, and early active balancing in the horizontal roll plane. These correlations appeared after participants underwent brief provocative vestibular stimulation by making a pitch head movement during vertical yaw rotation. Our findings suggest that vestibular stimulation may be a valuable part of assessments of individual differences in performance during initial exposure to disorienting spaceflight conditions where there are no reliable gravity dependent positional cues.

Kidney international 100(4), 753-779 (2021). doi:10.1016/j.kint.2021.05.015, Published by Elsevier, New York, NY

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients—mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.

Objective To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. Design CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. Setting 17 hospital sites in India and Australia. Participants Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. Intervention Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. Main outcome measures The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. Results Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met. Conclusions In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. Trial registration ClinicalTrials.gov NCT04394117 .

Background. Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. Methods. We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. Results. We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. Conclusions. This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.

Objective: This subgroup analysis aimed to evaluate the effect of comorbidities on infrapopliteal angioplasty outcomes in patients with chronic limb-threatening ischemia (CLTI). Methods: This was an observational study evaluating eligible CLTI patients aged >18 years who underwent infrapopliteal angioplasty between April 2014 and May 2017 at a tertiary care center. Subgroup analyses were based on (1) baseline glycated hemoglobin (HbA1c ≤6.5% vs >6.5%), (2) presence/absence of chronic kidney disease (CKD), and (3) control of lipid parameters. Results: A total of 231 patients with 332 infrapopliteal vessels were treated. While diabetes was prevalent in all participants, hypertension, coronary artery disease, and CKD were reported in 76.6%, 46.3%, and 25.5% of patients at baseline, respectively. The overall technical success rate was 84.4%, and the patency rate at 6 months was 82.04%. Patency at 6 months, wound healing, in-line flow, and complete plantar arch formation were numerically higher in patients with HbA1c ≤6.5% versus >6.5%, but all comparisons were nonsignificant. According to multivariable analysis, the odds of wounds not healing was 2.38 times higher (odds ratio [OR] = 2.4, 95% confidence interval [CI]: 1.2 to 4.5) and developing plantar arch was 5.88 times higher (OR = 5.9, 95% CI: 1.3 to 25) among patients with CKD compared with patients without CKD. Conclusions: The 6-month outcomes of infrapopliteal angioplasty may be better in patients with controlled versus uncontrolled glycemic levels. Control of lipid parameters may not have a significant influence on outcomes, especially in patients on statin therapy. The short-term outcomes may be similar in patients with and without CKD.

Background Maintenance hemodialysis (MHD) patients face disadvantages with higher risk of acquiring SARS‐CoV‐2 infection, atypical manifestations, and associated multiple comorbidities. We describe patients' outcomes with symptomatic COVID‐19 on MHD in a large cohort of patients from India. Methods Data were collected prospectively from hemodialysis units in 11 public and private hospitals between March 15, 2020, and July 31, 2020. The survival determinants were analyzed using stepwise backward elimination cox‐regression analysis. Results Of the 263 total patients (mean age 51.76 ± 13.63 years and males 173) on MHD with symptomatic COVID‐19, 35 (13.3%) died. Those who died were older (p = 0.01), had higher frequency of diabetic kidney disease (p = 0.001), comorbidities (p = 0.04), and severe COVID‐19 (p = 0.001). Mortality was higher among patients on twice‐weekly MHD than thrice‐weekly (p = 0.001) and dialysis through central venous catheter (CVC) as compared to arteriovenous fistula (p = 0.001). On multivariate analysis, CVC use (HR 2.53, 95% CI 1.26–5.07, p = 0.009), disease severity (HR = 3.54, 95% CI 1.52–8.26, p = 0.003), and noninvasive ventilatory support (HR 0.59, 95% CI 0.25–0.99, p = 0.049) had significant effect on mortality. Conclusion The adjusted mortality risk of COVID‐19 in MHD patients is high in patients associated with severe COVID‐19 and patients having CVC as vascular access.

Purpose: The purpose of this study is to describe the demographic profile, clinical features, visual outcomes, and follow-up patterns after successful cataract surgery in children from the tribal community in Odisha, India. Methods: We retrospectively reviewed records of tribal children aged 4 months–16 years, who underwent public health financed cataract surgery at our institute from January 1, 2015, to December 31, 2019. Collected data included demographic profile, clinical features, outcomes, and follow-up. Univariate and multivariate linear regression identified factors affecting the visual outcome at a 6-week follow-up. Results: During this period, a total of 352 children [536 eyes; mean age: 9.11 ± 4.4 years, 219 boys (62%)] underwent cataract surgery. The most common etiology and presenting complaints were idiopathic congenital cataract and decreased vision, respectively. In 304 children (86%), presenting best-corrected visual acuity (BCVA) was

Centers for Disease Control and Prevention published a case definition for the multisystem inflammatory syndrome in children in May 2020 when reports started pouring in about a clinical syndrome in children which was temporally associated with coronavirus disease 2019 infection. It has also been referred to as pediatric inflammatory multisystemic syndrome temporally associated with severe acute respiratory syndrome coronavirus 2. Most of these patients test positive for severe acute respiratory syndrome coronavirus 2 serology or reverse transcription-polymerase chain reaction, although a small number of patients could test negative which would require an epidemiological link to the coronavirus disease 2019 infection. The initial clinical presentation could overlap with Kawasaki disease, severe coronavirus disease 2019 infection, toxic shock syndrome, and macrophage activation syndrome. While multisystem inflammatory syndrome in children is characterized by multisystem involvement with hyper inflammation and severe clinical presentation initially, the prognosis is generally good. Since it was first described, there have been multiple studies describing the demographic characteristics, laboratory features, and treatment paradigm.

To assess immediately loaded parallel conical connection (Nobel Biocare) implants with platform switch design in the maxillary esthetic zone for soft and hard tissue changes.A total of 20 patients (All patients showed uneventful healing. The difference in implant stability and density scores was significant (In the present study, immediate loading of Nobel parallel conical connection implant in the maxillary anterior region provided adequate primary stability, minimal marginal bone loss, and increased bone density indicating earlier osseointegration. Decreased probing depth, absence of bleeding on probing, and adequate tissue collar at the neck showed better soft tissue emergence in the esthetic zone. The platform switch design demonstrated promising results and therefore can be used as an alternative to the conventional method.The present study results suggest that parallel conical connection implants (Nobel Biocare) with TiUnite surface, built-in platform switch combined with conical connection interface, parallel walled body, tapered apex, and double threads from tip to platform are all designed to provide high primary stability and support immediate function protocol, hence can be used flexibly in different bone densities.

Peritoneal dialysis (PD) is an important home-based treatment for kidney failure and accounts for 11% of all dialysis and 9% of all kidney replacement therapy globally. Although PD is available in 81% of countries, this provision ranges from 96% in high-income countries to 32% in low-income countries. Compared with haemodialysis, PD has numerous potential advantages, including a simpler technique, greater feasibility of use in remote communities, generally lower cost, lesser need for trained staff, fewer management challenges during natural disasters, possibly better survival in the first few years, greater ability to travel, fewer dietary restrictions, better preservation of residual kidney function, greater treatment satisfaction, better quality of life, better outcomes following subsequent kidney transplantation, delayed need for vascular access (especially in small children), reduced need for erythropoiesis-stimulating agents, and lower risk of blood-borne virus infections and of SARS-CoV-2 infection. PD outcomes have been improving over time but with great variability, driven by individual and system-level inequities and by centre effects; this variation is exacerbated by a lack of standardized outcome definitions. Potential strategies for outcome improvement include enhanced standardization, monitoring and reporting of PD outcomes, and the implementation of continuous quality improvement programmes and of PD-specific interventions, such as incremental PD, the use of biocompatible PD solutions and remote PD monitoring.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected patients with kidney disease, causing significant challenges in disease management, kidney research and trainee education. For patients, increased infection risk and disease severity, often complicated by acute kidney injury, have contributed to high mortality. Clinicians were faced with high clinical demands, resource shortages and novel ethical dilemmas in providing patient care. In this review, we address the impact of COVID-19 on the entire spectrum of kidney care, including acute kidney injury, chronic kidney disease, dialysis and transplantation, trainee education, disparities in health care, changes in health care policies, moral distress and the patient perspective. Based on current evidence, we provide a framework for the management and support of patients with kidney disease, infection mitigation strategies, resource allocation and support systems for the nephrology workforce.

Consumption of poor quality water causes serious human health hazards. Therefore, it is very crucial to investigate factors influencing the quality of groundwater and its suitability for drinking purpose. In the present study, groundwater quality of the Dhenkanal district of Odisha, India was characterized and the spatial distribution of different water quality parameters were analyzed using the multivariate statistics, entropy theory, and geostatistics techniques. In the present study 112 number of groundwater tube well samples were collected from the study area. The entropy theory revealed that SO42-, Mg+2 and Cl- were the most influencing parameters. A similar observation was also observed based on the correlation coefficient analysis. Groundwater quality index (GWQI) and entropy-weighted water quality index (EWQI) classifications indicated that 78.57 and 43.75% of the collected groundwater samples were categorized under excellent water quality, whereas, the rest of the samples were varying from good to medium drinking water quality. In addition, the result of EWQI classification offers more realistic assessment than that of GWQIs owing to its high precision, simplicity and without application of artificial weight. The correlation coefficient between Ca+2 and HCO3-, Mg+2 and PO4- were significantly high which might be due the presence of CaHCO3 and MgPO4 in the groundwater samples. The GWQI revealed a weak spatial dependence of groundwater quality.

Kidney international 100(4, Supplement) S1-S276 (2021). doi:10.1016/j.kint.2021.05.021 special issue: "KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases", Published by Elsevier, New York, NY

Background The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is noninferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: hemoglobin (Hb) efficacy and cardiovascular (CV) safety. Methods We report the trial design, key demographic, clinical and laboratory findings, and baseline therapies of 2964 patients randomized in the open-label (sponsor-blinded) active-controlled, parallel-group, randomized ASCEND-D clinical trial. We also compare baseline characteristics of ASCEND-D patients with patients who are on dialysis (CKD G5D) enrolled in other large CV outcome trials (CVOTs) and in the most relevant registries. Results The median age of patients was 58 years, 43% were female; 67% were White and 16% were Black. The median Hb at baseline was 10.4 g/dL. Among randomized patients, 89% were receiving hemodialysis and 11% peritoneal dialysis. Among key comorbidities, 42% reported a history of diabetes mellitus and 45% a history of CV disease. Median blood pressure was 134/74 mmHg. The median weekly dose of epoetin was 5751 units. Intravenous and oral iron uses were noted in 64 and 11% of patients, respectively. Baseline demographics were similar to patients with CKD G5D enrolled in other CVOTs and renal patient registries. Conclusions ASCEND-D will evaluate the efficacy and safety of daprodustat compared with epoetin alfa or darbepoetin alfa in the treatment of patients with anemia with CKD G5D. This trial is registered with ClinicalTrials.gov: NCT02879305. EudraCT Number: 2016-000541-31; Sponsor Protocol Number: 200807.

Background Early and accurate diagnosis followed by timely treatment are the key prerequisites to fight tuberculosis (TB) and reduce its global burden. Despite scientific advances, the rapid and correct diagnosis of both pulmonary and extrapulmonary tuberculosis remains a challenge because of traditional reliance on detection of the elusive bacilli. Mycobacterium tuberculosis (Mtb)-specific host immune activation and cytokine production have shown significant promise as alternative means of detecting and distinguishing active disease from latent infection. We queried the diagnostic ability of phenotypic markers on Mtb-specific cytokine-producing immune cell subsets for identifying active TB. Methods Subjects belonging to the following groups were recruited: pulmonary and extrapulmonary TB, latent TB, cured TB, sick controls, and healthy controls. Polychromatic flow cytometry was used to identify host immune biomarkers in an exploratory cohort comprising 56 subjects using peripheral blood mononuclear cells. Clinical performance of the identified biomarker was evaluated using whole blood in a blinded validation cohort comprising 165 individuals. Results Cytokine secreting frequencies of Mtb-specific cluster of differentiation 4-positive (CD4+) T cells with CD38+CD27– phenotype clearly distinguished infected individuals with active tuberculosis from those without disease. Tumor necrosis factor-α (TNF-α) secretion from CD38+CD27–CD4+ T cells upon stimulation with ESAT6/CFP10 peptides had the best diagnostic accuracy at a cutoff of 9.91% (exploratory: 96.67% specificity, 88.46% sensitivity; validation: 96.15% specificity, 90.16% sensitivity). Additionally, this subset differentiated treatment-naive patients with TB from individuals cured of TB following completion of anti-TB therapy. Conclusions Mtb-specific CD38+CD27–TNF-α +CD4+ T-cell subset is a robust biomarker both for diagnosing TB and assessing cure.

Phototherapy-induced hypocalcemia has been postulated to result from a decline in serum melatonin levels. The present observational study evaluated the effects of phototherapy on serum calcium and melatonin levels, and assessed their correlation, if any. Eighty-nine neonates with a total serum bilirubin levels of 14.1 ± 2.8 mg/dL were recruited at the mean age of 51.9 ± 21.7 h. After a median interquartile range (IQR) duration of phototherapy for 24.0 (24-25.5) h, serum calcium levels decreased significantly, from 9.6 ± 0.8 to 9.4 ± 0.6 mg/dL; p = 0.02, leading to asymptomatic hypocalcemia in 2.2% of the neonates. Median (IQR) serum melatonin levels also decreased from 187.8 (133.5-227.6) to 176.3 (145.6-202.5) pg/mL after phototherapy, the difference being statistically insignificant. No significant correlation was documented between the duration of phototherapy with calcium and melatonin levels. The authors conclude that phototherapy resulted in a small but significant reduction of serum calcium levels without any significant correlation with serum melatonin.

Purpose: To report clinical profile, diagnostic challenges, and outcomes in cases of subacute/chronic cerebral sinus venous thrombosis (CSVT) presenting to neuro-ophthalmologists/neurologists. Methods: This was a multicentric, retrospective, observational study. Records of patients with neuroimaging proven subacute/chronic CSVT seen the from January 1, 2016 to March 31, 2020 were analyzed. Data collected included duration of symptoms, diagnosing physician, ophthalmological vs. focal/generalized neurological symptoms, optic disc examination, perimetry, and neuroimaging findings. Statistical analysis was performed using STATA software. Results: Forty-three patients with subacute (30)/chronic (13) CSVT were identified (32 males, 11 females). Median age was 37 (IQR 27–47) years. The presenting complaints were blurred vision 34 (79%), headaches in 25 (58%), vomiting 12 (28%), and diplopia 11 (26%). Eleven patients had associated sixth cranial nerve palsy. All but two patients had either disc edema/optic atrophy; four had unilateral disc edema at presentation. Ophthalmologists and neurologists diagnosed/suspected CSVT correctly in 13/29 (45%) and 11/14 (78.5%) patients, respectively. Most common initial alternate diagnosis was idiopathic intracranial hypertension in 12 (28%). Female gender, age ≤36, unilateral papilledema, not obtaining venogram at initial workup increased chances of initial alternate diagnosis. Median follow-up duration was 21 days. Average visual function remained stable in majority of patients at last follow-up. In total, 47.6% of patients had best-corrected visual acuity ≥20/30 at the final follow-up. Conclusion: In our series, subacute or chronic CSVT presented presented primarily with symptoms of intracranial hypertension. Unilateral papilledema, middle-aged patients, female gender, lack of focal/generalized neurological symptoms created diagnostic dilemma. Visual function remained stable in majority of patients.

The accelerating environmental degradation as a result of modernisation and climate change is an urgent threat to human health. Environment change can impact kidney health in a variety of ways such as water scarcity, global heating and changing biodiversity. Ever increasing industrialization of health care has a large carbon footprint, with dialysis being a major contributor. There have been calls for all stakeholders to adopt a ‘one health approach’ and develop mitigation and adaptation strategies to combat this challenge. Because of its exquisite sensitivity to various elements of environment change, kidney health can be a risk marker and a therapeutic target for such interventions. In this narrative review, we discuss the various mechanisms through which environmental change is linked to kidney health and the ways that the global kidney health communities can respond to environmental change.

Acute kidney injury (AKI) increases the risk of morbidity, mortality, and progression to chronic kidney disease (CKD). There are few data on the risk of CKD following community-acquired AKI (CA-AKI) and its predictors from developing countries. We evaluated the association of a panel of serum and urine biomarkers at the time of hospital discharge with 4-month renal outcome in CA-AKI. Patients of either sex, aged between 18 and 70 years, with no underlying CKD, and with CA-AKI were recruited at the time of discharge from hospital in this prospective observational study. Levels of serum and urine biomarkers were analyzed and association between these markers and development of CKD, defined as eGFR 2 or dialysis dependence at 4 month after discharge, were analyzed using multivariate logistic regression analysis and penalized least absolute shrinkage and selection operator logistic regression. Out of a total 126 patients followed up for 4 months, 25 developed CKD. Those who developed CKD were older (p = 0.008), had higher serum creatinine (p

ObjectivesTo determine whether hydroxychloroquine when used with personal protective equipment reduces the proportion of laboratory-confirmed COVID-19 among healthcare workers in comparison to the use of personal protective equipment alone.DesignMulticentre, parallel-group, open-label randomised trial. Enrolment started on 29 June 2020 and stopped on 4 February 2021. Participants randomised in HydrOxychloroquine Prophylaxis Evaluation were followed for 6 months.Setting9 hospitals across India.ParticipantsHealthcare workers in an environment with exposure to COVID-19 were randomised in a 1:1 ratio to hydroxychloroquine plus use of personal protective equipment or personal protective equipment alone. 886 participants were screened and 416 randomised (213 hydroxychloroquine arm and 203 personal protective equipment).InterventionParticipants in intervention arm received 800 mg of hydroxychloroquine on day of randomisation and then 400 mg once a week for 12 weeks in addition to the use of personal protective equipment. In the control arm, participants continued to use personal protective equipment alone.Main outcomeProportion of laboratory-confirmed COVID-19 in the 6 months after randomisation.ResultsParticipants were young (mean age 32.1 years, SD 9.1 years) with low-comorbid burden. 47.4% were female. In the 6 months after randomisation (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary endpoint (5.2% vs 5.9%; OR 0.85, 95% CI 0.35 to 2.07, p=0.72). There was no heterogeneity of treatment effect in any prespecified subgroup. There were no significant differences in the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms, respectively. There were no serious adverse events in either group.Conclusions and relevanceHydroxychloroquine along with personal protective equipment was not superior to personal protective equipment alone on the proportion of laboratory-confirmed COVID-19. Definitive conclusions are precluded as the trial stopped early for futility, and hence was underpowered.Trial registration numberCTRI/2020/05/025067.

Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported.To evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients.This prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete.Randomized 1:1 to daprodustat or darbepoetin alfa.The primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability.A total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa.This randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population.ClinicalTrials.gov Identifier: NCT03029208.

Changes in absorptive capacity and first‐pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically‐based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn’s disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1–19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of CYP3A4 mRNA correlated significantly with villous length in the TI (P = 0.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (P

Context Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most important markers for clinical assessment of kidney function. Though hypothyroidism is associated with proteinuria in cross-sectional data, the impact of treatment on proteinuria is unknown. Objective This study explores the effect of thyroid hormone replacement therapy on eGFR and 24-hour urine protein excretion in patients with severe primary hypothyroidism. Design and Participants This study was a prospective, observational cohort study in adults with severe primary hypothyroidism (serum thyrotropin [TSH] > 50 µIU/mL). Individuals with preexisting or past kidney disease, kidney or urinary tract abnormalities, calculi or surgery, diabetes mellitus, or hypertension were excluded. The participants received thyroid hormone replacement therapy. Thyroid functions, eGFR, 24-hour urine protein excretion, and biochemical parameters were measured at baseline and 3 months. Setting This study took place at a single center, a tertiary care referral and teaching hospital. Results Of 44 enrolled participants, 43 completed 3 months of follow-up. At 3 months, serum TSH levels decreased and thyroxine levels increased (P Conclusions Thyroid hormone replacement therapy in patients with severe primary hypothyroidism improves eGFR and decreases 24-hour urine protein excretion, thereby suggesting reversible alterations.

Whole-body vibration (WBV) is one of the leading risk factors for development of musculoskeletal disorders (MSDs) that develop symptoms of lower back pain, pain in the neck and shoulders, digestive problems, blood pressure and diabetes among professional dumper operators. The present study specifically aimed at assessing the WBV exposure of 79 dumper operators engaged in two Indian opencast coal mines through vibration measurements followed by questionnaire survey. From the daily frequency-weighted root mean square exposure, dumper operators have experienced vibration levels higher than the Health Guidance Caution Zone (HGCZ) of Standard No. ISO 2631-1:1997. However, on the basis of daily vibration dose values, 60.8% of operators have experienced vibration levels above the HGCZ. Finally, an attempt was also made to explore the potential of a Bayesian network to predict the risk factors for WBV of dumper operators in development of MSDs to prioritize the factors for human health risk assessment.

There have been concerted efforts toward cataloging rare and deleterious variants in different world populations using high-throughput genotyping and sequencing-based methods. The Indian population is underrepresented or its information with respect to clinically relevant variants is sparse in public data sets. The aim of this study was to estimate the burden of monogenic disease-causing variants in Indian populations. Toward this, we have assessed the frequency profile of monogenic phenotype-associated ClinVar variants. The study utilized a genotype data set (global screening array, Illumina) from 2795 individuals (multiple in-house genomics cohorts) representing diverse ethnic and geographically distinct Indian populations. Of the analyzed variants from Global Screening Array, ~9% were found to be informative and were either not known earlier or underrepresented in public databases in terms of their frequencies. These variants were linked to disorders, namely inborn errors of metabolism, monogenic diabetes, hereditary cancers, and various other hereditary conditions. We have also shown that our study cohort is genetically a better representative of the Indian population than its representation in the 1000 Genome Project (South Asians). We have created a database, ClinIndb, linked to the Leiden Open Variation Database, to help clinicians and researchers in diagnosis, counseling, and development of appropriate genetic screening tools relevant to the Indian populations and Indians living abroad.

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Community-acquired acute kidney injury (CA-AKI) is the dominant form of AKI encountered in developing countries in Asia. Economic disparities, variations in access to health care services, geographic conditions, environmental risk factors, and sociocultural circumstances shape the causes and outcomes of CA-AKI. Infections, drugs, plant and chemical toxins, envenomations, and obstetric complications are common causes of CA-AKI. Previously healthy young individuals who often work outdoors in fields or farms are exposed to a wide variety of work-related or environmental risk factors for CA-AKI. Improving disease definitions, better data, and evolving host-pathogen interactions have changed disease descriptions and presentations over the past 20 years. Among infections, although the incidence of malaria has decreased, the number of cases with dengue and scrub typhus have increased sharply. The recognition of AKI in relation to Plasmodium knowlesi, Plasmodium vivax, scrub typhus, and leptospirosis in areas not traditionally considered at risk, association of infections with the future development of chronic kidney disease, and the role of complement dysregulation in infection-associated AKI are important new findings. Snake-bite-related toxic envenomation continues to be an important cause of AKI in some counties and is a neglected public health problem. On the other hand, significant decreases in the incidence of AKI related to acute diarrheal illness or obstetric causes are signs of hope. Coordinated efforts between administrative stakeholders, society, and health care delivery services at all levels have the potential to propel research and improve outcomes in CA-AKI.

Diabetic nephropathy is the most common diabetic complication culminating often into end-stage renal disease. Classically, it is defined by the presence of albuminuria which has limited ability to be detected at early stages but deterioration in kidney function generally precedes albuminuria. This necessitates the development of newer diagnostic assays for diabetic nephropathy to determine the progression of the disease. Kidney associated diseases with non-albuminuria further complicates a timely diagnosis and thus demands an early biomarker. Urinary exosomes, the nanovesicular entities are released by every epithelial cells of the nephron. Their protein or molecular cargo varies in the diseased state which may provide the pathophysiology of the kidney associated diseases. This drives them to be exploited as non-invasive biomarker. This review thus integrates the recent findings on the significance of the urinary exosomes as diagnostic biomarker in kidney-associated diseases, primarily in diabetic nephropathy.

Asia is the largest and most populated continent in the world, with a high burden of kidney failure. In this Policy Forum article, we explore dialysis care and dialysis funding in 17 countries in Asia, describing conditions in both developed and developing nations across the region. In 13 of the 17 countries surveyed, diabetes is the most common cause of kidney failure. Due to great variation in gross domestic product per capita across Asian countries, disparities in the provision of kidney replacement therapy (KRT) exist both within and between countries. A number of Asian nations have satisfactory access to KRT and have comprehensive KRT registries to help inform practices, but some do not, particularly among low- and low-to-middle-income countries. Given these differences, we describe the economic status, burden of kidney failure, and cost of KRT across the different modalities to both governments and patients and how changes in health policy over time affect outcomes. Emerging trends suggest that more affluent nations and those with universal health care or access to insurance have much higher prevalent dialysis and transplantation rates, while in less affluent nations, dialysis access may be limited and when available, provided less frequently than optimal. These trends are also reflected by an association between nephrologist prevalence and individual nations’ incomes and a disparity in the number of nephrologists per million population and per thousand KRT patients.

Background Nausea is a common symptom in youth with chronic abdominal pain. The aims of the current study were to assess: 1) the frequency of nausea in patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS), respectively, as defined by Rome IV criteria; and, 2) relationships between nausea and mucosal inflammation as defined by antral and duodenal eosinophil and mast cell densities. A secondary aim was to assess relationships between nausea and other gastrointestinal symptoms, non-gastrointestinal somatic symptoms, and psychological dysfunction. Methods Records from patients with pain associated functional gastrointestinal disorders were retrospectively reviewed for gastrointestinal and somatic symptoms and anxiety, depression, and somatizations scores as assessed by the Behavior Assessment System for Children (BASC-2). In addition, previous gastric and mucosal biopsies were assessed for mast cell and eosinophil densities, respectively. Results 250 patients, ages 8 to 17 years, were assessed. Nausea was reported by 78% and was equally prevalent in those with FD alone, those with IBS alone, and those with both FD and IBS. Nausea was associated with increased mean (21.4 vs. 17.5) and peak (26.2 vs. 22.9) duodenal mast cell densities as compared those without nausea. Nausea was also associated with a wide variety of individual gastrointestinal symptoms, as well as headaches, fatigue, and dizziness. Lastly, nausea was associated with elevated self-report scores for anxiety (55.2 vs. 50.0), depression (50.2 vs. 46.1), and somatization (70.3 vs. 61.8). Conclusions Nausea is common in children and adolescents with pain-associated FGIDs as defined by Rome IV and is not unique to either FD or IBS. Nausea is associated with increased mucosal mast cell density, non-gastrointestinal somatic symptoms, and psychologic dysfunction.