Publications by authors named "Vivekanand Jha"

374 Publications

Chronic Kidney Disease of Unknown Etiology in India: What Do We Know and Where We Need to Go.

Kidney Int Rep 2021 Nov 9;6(11):2743-2751. Epub 2021 Aug 9.

George Institute for Global Health India, UNSW, New Delhi, India.

Chronic kidney disease (CKD) not associated with known risk factors has been reported from parts of India and is presumed to be similar to CKD of unknown etiology (CKDu) that has been described from Central America. The reports from India have been fragmented without clear description of the disease phenotype or its determinants. This paper summarizes the current state of knowledge around CKDu in India based on a review of literature, multi-stakeholder consultation, and a survey of Indian nephrologists. We also contacted individual research groups to solicit data. Our findings suggest that that CKDu is reported from most regions in India; however, it is interpreted differently from the phenotype described from Central America and Sri Lanka. The differences include lack of a clear demographic or occupation group, older age of affected participants, and presence of mild hypertension and low-grade proteinuria. Well-designed prospective field studies with appropriate diagnostic workup are needed to establish the disease burden and identify etiologies, along with socioeconomic and health consequences, the intersection with the environment, and the public health response. Community-based research should phenotype the entire CKD population rather than be restricted to cases with presumed CKDu based on predefined criteria. Guidelines are needed for clinical evaluation, referral, management, and harmonization of clinical documentation and health records. More data are needed to support the existence of a unique CKDu phenotype in India.
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http://dx.doi.org/10.1016/j.ekir.2021.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589686PMC
November 2021

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

BMC Infect Dis 2021 Nov 20;21(1):1170. Epub 2021 Nov 20.

Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, UK.

Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ).

Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.

Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.

Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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http://dx.doi.org/10.1186/s12879-021-06829-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605464PMC
November 2021

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

Intensive Care Med 2021 Nov 10. Epub 2021 Nov 10.

Department of Anaesthesia and Critical Care Medicine, Odense University Hospital, Odense C, Denmark.

Purpose: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation.

Methods: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone.

Results: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses.

Conclusion: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
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http://dx.doi.org/10.1007/s00134-021-06573-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579417PMC
November 2021

Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis.

N Engl J Med 2021 Nov 5. Epub 2021 Nov 5.

From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), and Boston University School of Medicine and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.), the School of Public Health, Imperial College London (V.J.), King's College Hospital (I.C.M.), and the Department of Renal Medicine, University College London (D.C.W.), London, and GlaxoSmithKline, Brentford (L.K.) - all in the United Kingdom; George Institute for Global Health, New Delhi, and Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal - both in India (V.J.); Hennepin Healthcare, University of Minnesota, Minneapolis (K.L.J.); Duke University Medical Center, Duke Clinical Research Institute, Durham, NC (R.D.L.); Universidad Panamericana School of Medicine, Mexico City (G.T.O.); the University of Würzburg, Würzburg, Germany (C.W.); the Medical University of Silesia, Katowice, Poland (A.W.); GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., T.L.D., A.M.M., L.T.); and the University of New South Wales, Sydney (V.P.).

Background: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown.

Methods: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke).

Results: Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups.

Conclusions: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).
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http://dx.doi.org/10.1056/NEJMoa2113380DOI Listing
November 2021

Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.

N Engl J Med 2021 Nov 5. Epub 2021 Nov 5.

From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), School of Public Health, Imperial College London (V.J.), King's College Hospital (I.C.M.), and the Department of Renal Medicine, University College London (D.C.W.), London, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; Hennepin Healthcare, University of Minnesota, Minneapolis (K.L.J.); Duke University Medical Center, Duke Clinical Research Institute, Durham, NC (R.D.L.); Universidad Panamericana School of Medicine, Mexico City (G.T.O); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).

Background: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels.

Methods: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25.

Results: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups.

Conclusions: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).
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http://dx.doi.org/10.1056/NEJMoa2113379DOI Listing
November 2021

The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics.

Am J Nephrol 2021 Nov 3:1-10. Epub 2021 Nov 3.

The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.

Introduction: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants.

Methods: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment.

Results: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen.

Conclusions: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN.
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http://dx.doi.org/10.1159/000519812DOI Listing
November 2021

Preventing the Next Pandemic: The Case for Investing in Circulatory Health - A Global Coalition for Circulatory Health Position Paper.

Glob Heart 2021 12;16(1):66. Epub 2021 Oct 12.

World Stroke Organization, CH.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.
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http://dx.doi.org/10.5334/gh.1077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516006PMC
October 2021

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

JAMA 2021 11;326(18):1807-1817

Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease.

Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia.

Design, Setting, And Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021.

Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days.

Main Outcomes And Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days).

Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]).

Conclusions And Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.

Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.
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http://dx.doi.org/10.1001/jama.2021.18295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532039PMC
November 2021

Long-Term Follow-Up of Cyclical Cyclophosphamide and Steroids Versus Tacrolimus and Steroids in Primary Membranous Nephropathy.

Kidney Int Rep 2021 Oct 10;6(10):2653-2660. Epub 2021 Aug 10.

Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommends cyclical cyclophosphamide plus glucocorticoids (GC) (modified Ponticelli regimen) or calcineurin inhibitors (CNIs) such as tacrolimus (TAC) or cyclosporine as the first-line agents for the management of primary membranous nephropathy (PMN) that is resistant to antiproteinuric therapy with renin-angiotensin system blockers. However, the long-term outcome of patients treated with CNIs is not known.

Methods: We report the outcomes of 70 patients randomized 1:1 to receive modified Ponticelli regimen or TAC/GC for renin-angiotensin system-resistant PMN who were prospectively followed for 6 years. Patients were followed monthly for 12 months, then quarterly for 12 months, and then every 6 months through the end of 6 years.

Results: At the end of 6 years, 21 (61.76%) and 9 (28.12%) patients maintained relapse-free remission in modified Ponticelli regimen and TAC/GC groups, respectively (relative risk [RR]: 2.19, 95% confidence interval [CI]: 1.23 to 4.15), and 30 (88.23%) and 17 (53.12%) patients were in remission (including relapses) in modified Ponticelli regimen and TAC/GC groups (RR: 1.66; 95% CI: 1.21 to 2.45), respectively. There was no significant difference in the proportion of patients who had a 40% decline in the estimated glomerular filtration rate (eGFR), death, or end-stage kidney disease between the groups. None of the patients treated with modified Ponticelli regimen reported a solid organ or hematological malignancy.

Conclusions: To conclude, in the long-term, modified Ponticelli regimen is superior to TAC/GC as first-line therapy for the management of antiproteinuric-resistant PMN.
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http://dx.doi.org/10.1016/j.ekir.2021.07.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484506PMC
October 2021

Increased serum catalytic iron may mediate tissue injury and death in patients with COVID-19.

Sci Rep 2021 10 4;11(1):19618. Epub 2021 Oct 4.

The George Institute for Global Health, India, UNSW, New Delhi, India.

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.
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http://dx.doi.org/10.1038/s41598-021-99142-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490366PMC
October 2021

Membranous nephropathy.

Nat Rev Dis Primers 2021 09 30;7(1):69. Epub 2021 Sep 30.

Department of Nephrology, Radboud University Medical Center, Nijmegen, Netherlands.

Membranous nephropathy (MN) is a glomerular disease that can occur at all ages. In adults, it is the most frequent cause of nephrotic syndrome. In ~80% of patients, there is no underlying cause of MN (primary MN) and the remaining cases are associated with medications or other diseases such as systemic lupus erythematosus, hepatitis virus infection or malignancies. MN is an autoimmune disease characterized by a thickening of the glomerular capillary walls due to immune complex deposition. Identification of the phospholipase A2 receptor (PLA2R) as the major antigen in adults in 2009 induced a paradigm shift in disease diagnosis and monitoring and several other antigens have since been characterized. Disease outcome is difficult to predict and around one-third of patients will undergo spontaneous remission. In those at high risk of progression, immunosuppressive therapy with cyclophosphamide plus corticosteroids has substantially reduced the need for kidney replacement therapy. Owing to carcinogenic risk, other treatments (calcineurin inhibitors and CD20-targeted B cell depletion therapy (rituximab)) have been developed. However, disease relapses are frequent when calcineurin inhibitors are stopped and the remission rate with rituximab is lower than with cyclophosphamide, particularly in patients with high PLA2R antibody titres. Other new drugs are already available and antigen-specific immunotherapies are being developed.
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http://dx.doi.org/10.1038/s41572-021-00303-zDOI Listing
September 2021

Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases.

Kidney Int 2021 10;100(4):753-779

Cochrane Kidney and Transplant, Sydney, New South Wales, Australia; Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.
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http://dx.doi.org/10.1016/j.kint.2021.05.015DOI Listing
October 2021

Humoral Response to One and Two Doses of ChAdOx1-S Vaccine in Patients on Hemodialysis.

Clin J Am Soc Nephrol 2021 Sep 20. Epub 2021 Sep 20.

George Institute for Global Health, UNSW, New Delhi, India

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http://dx.doi.org/10.2215/CJN.10170721DOI Listing
September 2021

Serum catalytic iron and progression of chronic kidney disease: findings from the ICKD study.

Nephrol Dial Transplant 2021 09 17. Epub 2021 Sep 17.

George Institute for Global Health India, New Delhi.

Background: The non-transferrin bound catalytic iron moiety catalyses production of toxic reactive oxygen species and is associated with adverse outcomes. We hypothesized that serum catalytic iron (SCI) is associated with progression of chronic kidney disease (CKD).

Methods: Baseline samples of the Indian Chronic Kidney Disease participants with at least one follow up visit were tested for total iron, iron binding capacity, transferrin saturation, SCI, ferritin and hepcidin. SCI was measured using the bleomycin-detectable iron assay that detects biologically active iron. Association with the incidence of major kidney endpoints, (MAKE, a composite of kidney death, kidney failure or > 40% loss of eGFR) was examined using Cox proportional hazards model adjusted for sex and age.

Results: 2002 subjects (49.9 ± 11.6 years, 68.1% males, baseline eGFR 41.01 ml/min/1.73m2) were enrolled. After a median follow up of 12.6 (12.2, 16.7) months, the composite MAKE occurred in 280 (14%). After adjusting for age and sex, increase from 25th to 75th percentile in SCI, transferrin saturation, ferritin and hepcidin were associated with 78% (43-122%), 34% (10-62%), 57% (24-100%) and 74% (35-124%) increase in hazard of MAKE, respectively. SCI was associated with MAKE and kidney failure after adjustment for occupational exposure, hypertension, diabetes, tobacco, alcohol use, history of AKI, baseline eGFR, uACR, and allowing baseline hazard to vary by centre.

Conclusions: SCI is strongly and independently associated with composite MAKE in patients with mild to moderate CKD. Confirmation in other studies will allow consideration of SCI as a risk marker and treatment target.
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http://dx.doi.org/10.1093/ndt/gfab271DOI Listing
September 2021

Prescription Practices in Patients With Mild to Moderate CKD in India.

Kidney Int Rep 2021 Sep 26;6(9):2455-2462. Epub 2021 Jun 26.

George Institute for Global Health India, New Delhi, India.

Introduction: Patients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD.

Methods: The ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use.

Results: Complete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively.

Conclusion: This study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD.
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http://dx.doi.org/10.1016/j.ekir.2021.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418981PMC
September 2021

Global Estimates of Capacity for Kidney Transplantation in World Countries and Regions.

Transplantation 2021 Sep 7. Epub 2021 Sep 7.

Division of Nephrology and Immunology, Department of Medicine, University of Alberta, Edmonton, AB, Canada. Division of Nephrology and Hypertension, University of Cape Town, Cape Town, South Africa. Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada. Section of Nephrology, Department of Medicine, Regina General Hospital, Regina, SK, Canada. Department of Renal Medicine, Singapore General Hospital, Singapore. UK Renal Registry, Learning and Research, Southmead Hospital, Bristol, United Kingdom. Population Health Sciences, University of Bristol, Bristol, United Kingdom. The Richard Bright Renal Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom. George Institute for Global Health, UNSW, New Delhi, India. School of Public Health, Imperial College London, London, United Kingdom. Department of Medicine, Manipal Academy of Higher Education, Manipal, India. Intensive Care Nephrology and Transplantation Department, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. Faculty of Medicine, Sorbonne Université, Paris, France. Division of Nephrology, Bezmialem Vakif University, Istanbul, Turkey. Section of Nephrology and Hemodialysis, Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran. ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, Netherlands. Department of Medicine, University of Tennessee Health Science Center, Memphis, TN. Renal Unit, Westmead Clinical School, University of Sydney at Westmead Hospital, Sydney, Australia; The Westmead Institute for Medical Research, Westmead, Australia. Division of Nephrology and Hypertension, University of Cape Town, Cape Town, South Africa. Department of Medicine, University of Ilorin, Ilorin, Nigeria. Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Department of Medicine, University of Calgary, Calgary, AB, Canada. Pan-American Health Organization/World Health Organization's Collaborating Centre in Prevention and Control of Chronic Kidney Disease, University of Calgary, Calgary, AB, Canada. Centre for Transplantation and Renal Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia. Department of Nephrology, Metro South and Integrated Nephrology and Transplant Services (MINTS), Princess Alexandra Hospital, Brisbane, Australia. Centre for Kidney Disease Research, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia. Translational Research Institute, Brisbane, Australia.

Background: Kidney transplantation (KT) is the optimal treatment for kidney failure and is associated with better quality of life and survival relative to dialysis. However, knowledge of the current capacity of countries to deliver KT is limited. This study reports on findings from the 2018 International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) survey, specifically addressing the availability, accessibility, and quality of KT across countries and regions.

Methods: Data were collected from published online sources and a survey was administered online to key stakeholders. All country-level data were analyzed by ISN region and World Bank income classification.

Results: Data were collected via a survey in 182 countries of which 155 answered questions pertaining to KT. Of these, 74% stated that KT was available, with a median incidence of 14 pmp (range: 0.04 to 70) and median prevalence of 255 pmp (range: 3 to 693). Accessibility of KT varied widely; even within high income countries, it was disproportionately lower for ethnic minorities. Universal health coverage of all KT treatment costs was available in 31% and 57% had a KT registry.

Conclusions: There are substantial variations in KT incidence, prevalence, availability, accessibility, and quality worldwide, with the lowest rates evident in low- and lower-middle income countries. Understanding these disparities will inform efforts to increase awareness and the adoption of practices that will ensure high quality KT care is provided around the world.Supplemental Visual Abstract; http://links.lww.com/TP/C288.
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http://dx.doi.org/10.1097/TP.0000000000003943DOI Listing
September 2021

Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial.

Trials 2021 Aug 28;22(1):573. Epub 2021 Aug 28.

The George Institute for Global Health, University of New South Wales, Sydney, Australia.

Background: SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes.

Methods And Discussion: CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020.

Trial Registration: ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831).
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http://dx.doi.org/10.1186/s13063-021-05521-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397850PMC
August 2021

Expanding Utilization of Home Dialysis: An Action Agenda From the First International Home Dialysis Roundtable.

Kidney Med 2021 Jul-Aug;3(4):635-643. Epub 2021 May 25.

Venn Strategies, Washington, DC.

In a groundbreaking meeting, leading global kidney disease organizations came together in the fall of 2020 as an International Home Dialysis Roundtable (IHDR) to address strategies to increase access to and uptake of home dialysis, both peritoneal dialysis and home hemodialysis. This challenge has become urgent in the wake of the coronavirus disease 2019 (COVID-19) pandemic, during which patients with advanced kidney disease, who are more susceptible to viral infections and severe complications, must be able to safely physically distance at home. To boost access to home dialysis on a global scale, IHDR members committed to collaborate, through the COVID-19 public health emergency and beyond, to promote uptake of home dialysis on a broad scale. Their commitments included increasing the reach and influence of key stakeholders with policy makers, building a cooperative of advocates and champions for home dialysis, working together to increase patient engagement and empowerment, and sharing intelligence about policy, education, and other programs so that such efforts can be operationalized globally. In the spirit of international cooperation, IHDR members agreed to document, amplify, and replicate established efforts shown to improve access to home dialysis and support new policies that facilitate access through procedures, innovation, and reimbursement.
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http://dx.doi.org/10.1016/j.xkme.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350829PMC
May 2021

Treatment preferences for primary membranous nephropathy: Results of a multinational survey among nephrologists in the South Asia Pacific region.

Nephrology (Carlton) 2021 Aug 14. Epub 2021 Aug 14.

Department of Nephrology, Royal Adelaide Hospital and the University of Adelaide, Adelaide, Australia.

Aim: There is no clear consensus on how best to treat primary membranous nephropathy (PMN). This study aimed to ascertain prevailing views among nephrologists on their choice of immunosuppressive agents to treat this disease.

Methods: The Australasian Kidney Trials Network conducted a multinational online survey among nephrologists from the South Asia-Pacific region to identify prescribing practices to treat PMN. Survey questions focused on the types of immunosuppressive therapies used, preferred first-line and second-line therapies, indications for starting immunosuppressive therapy, the preferred mode of combining corticosteroid and cyclophosphamide, the use of serum phospholipase A2 receptor antibody testing in clinical practice, indications for anticoagulation, and interest in participating in future clinical trials in PMN.

Results: One hundered fifty-five nephrologists from eight countries responded to the online survey. The majority of them were senior nephrologists from Australia and India with significant experience managing patients with PMN. The combination of cyclophosphamide and corticosteroid was the preferred first-line therapy. Of those who used this combination, only 34.8% followed the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines by adding intravenous methylprednisolone. The combination of calcineurin inhibitor with corticosteroid was the most common second-line therapy. Most respondents considered prophylactic anticoagulation if serum albumin was less than 25 g/L. Most nephrologists were keen to participate in a clinical trial with a control arm consisting of cyclophosphamide and corticosteroids.

Conclusion: The combination of corticosteroid with cyclophosphamide (without intravenous methylprednisolone) is the most commonly reported first-line immunosuppressive therapy for the management of PMN.
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http://dx.doi.org/10.1111/nep.13953DOI Listing
August 2021

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

Nephrology (Carlton) 2021 Nov 6;26(11):898-906. Epub 2021 Aug 6.

Department of Nephrology, Meenakshi Mission Hospital and Research Centre, India.

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.
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http://dx.doi.org/10.1111/nep.13949DOI Listing
November 2021

Health System Building Blocks and Organ Transplantation in India.

Transplantation 2021 08;105(8):1631-1634

George Institute for Global Health, UNSW, New Delhi, India.

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http://dx.doi.org/10.1097/TP.0000000000003685DOI Listing
August 2021

Building optimal and sustainable kidney care in low resource settings: The role of healthcare systems.

Nephrology (Carlton) 2021 Dec 27;26(12):948-960. Epub 2021 Jul 27.

George Institute for Global Health, University of New South Wales (UNSW), New Delhi, India.

Healthcare systems in low-income and lower-middle income countries (LLMICs) face significant challenges in the provision of health services, for example, kidney care to the population. Although this is linked to several high-level factors such as poor infrastructure, socio-demographic and political factors, healthcare funding has often been cited as the major reason for the wide gap in availability, accessibility and quality of care between LLMICs and rich countries. With the steady rising incidence and prevalence of kidney diseases globally, as well as cost of care, LLMICs are likely to suffer more consequences of these increases than rich countries and may be unable to meet targets of universal health coverage (UHC) for kidney diseases. As health systems in LLMICs continue to adapt in finding ways to provide access to affordable kidney care, various empirical and evidence-based strategies can be applied to assist them. This review uses a framework for healthcare strengthening developed by the World Health Organization (WHO) to assess various challenges that health systems in LLMICs confront in providing optimal kidney care to their population. We also suggest ways to overcome these barriers and strengthen health systems to improve kidney care in LLMICs.
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http://dx.doi.org/10.1111/nep.13935DOI Listing
December 2021

Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases.

Lancet Gastroenterol Hepatol 2021 09 12;6(9):743-753. Epub 2021 Jul 12.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.

With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases.
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http://dx.doi.org/10.1016/S2468-1253(21)00132-1DOI Listing
September 2021

Outcomes of symptomatic coronavirus disease 19 in maintenance hemodialysis patient in India.

Semin Dial 2021 09 14;34(5):360-367. Epub 2021 Jul 14.

George Institute India, University of New South Wales, Sydney, New South Wales, Australia.

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.
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http://dx.doi.org/10.1111/sdi.13000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447077PMC
September 2021

Current status of health systems financing and oversight for end-stage kidney disease care: a cross-sectional global survey.

BMJ Open 2021 07 9;11(7):e047245. Epub 2021 Jul 9.

Department of Medicine, King Chulalong Memorial Hospital, Bangkok, Thailand.

Objectives: The Global Kidney Health Atlas (GKHA) is a multinational, cross-sectional survey designed to assess the current capacity for kidney care across all world regions. The 2017 GKHA involved 125 countries and identified significant gaps in oversight, funding and infrastructure to support care for patients with kidney disease, especially in lower-middle-income countries. Here, we report results from the survey for the second iteration of the GKHA conducted in 2018, which included specific questions about health financing and oversight of end-stage kidney disease (ESKD) care worldwide.

Setting: A cross-sectional global survey.

Participants: Key stakeholders from 182 countries were invited to participate. Of those, stakeholders from 160 countries participated and were included.

Primary Outcomes: Primary outcomes included cost of kidney replacement therapy (KRT), funding for dialysis and transplantation, funding for conservative kidney management, extent of universal health coverage, out-of-pocket costs for KRT, within-country variability in ESKD care delivery and oversight systems for ESKD care. Outcomes were determined from a combination of desk research and input from key stakeholders in participating countries.

Results: 160 countries (covering 98% of the world's population) responded to the survey. Economic factors were identified as the top barrier to optimal ESKD care in 99 countries (64%). Full public funding for KRT was more common than for conservative kidney management (43% vs 28%). Among countries that provided at least some public coverage for KRT, 75% covered all citizens. Within-country variation in ESKD care delivery was reported in 40% of countries. Oversight of ESKD care was present in all high-income countries but was absent in 13% of low-income, 3% of lower-middle-income, and 10% of upper-middle-income countries.

Conclusion: Significant gaps and variability exist in the public funding and oversight of ESKD care in many countries, particularly for those in low-income and lower-middle-income countries.
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http://dx.doi.org/10.1136/bmjopen-2020-047245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273453PMC
July 2021

COVID-19 and care for patients with chronic kidney disease: Challenges and lessons.

FASEB Bioadv 2021 Apr 29. Epub 2021 Apr 29.

George Institute for Global Health, UNSW New Delhi India.

The COVID-19 pandemic has blurred the traditional distinction between communicable diseases (CD) and noncommunicable diseases (NCDs). The manifestations of COVID-19 range from an asymptomatic carrier state to fatal multiorgan failure. While initial reports did not report significant effects on the kidneys, it is now well established that kidney involvement (acute kidney injury, urinary abnormalities, tubular function defects) in COVID-19 is common and it is also associated with poorer outcomes. At the same time, care for patients with existing chronic kidney disease (CKD) has suffered during this pandemic and those with CKD are considered to have higher risk for severity of COVID-19 symptoms. Widespread lockdowns have affected the delivery of health care to patients with CKD, including those on dialysis or on transplant wait-lists. The pandemic has reinforced the need for accessible home-based therapies and highlighted the value of teleconsultation and remote monitoring technologies. COVID-19 has revealed the poor emergency preparedness by health systems around the world. It has underscored glaring inequities in availability of diagnostic tests and essential medications, including that for dialysis. In response, there has been increasing recognition of the necessity of universal health coverage and in prioritizing vaccine distribution to serve the most vulnerable, including those with kidney failure. The COVID-19 pandemic has also reaffirmed the role of the environment and eco-systems contributing to both CDs and NCDs. Attention to universal health coverage through a One Health approach is needed to prevent global health crises and prevent further kidney dysfunction and failure.
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http://dx.doi.org/10.1096/fba.2021-00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250957PMC
April 2021

Developing Supportive Care Services for Patients with Kidney Failure: An Idea Whose Time Has Come.

Authors:
Vivekanand Jha

Indian J Palliat Care 2021 May 30;27(Suppl 1):S3-S5. Epub 2021 May 30.

George Institute for Global Health India, New Delhi, India.

The number of patients developing kidney failure is increasing globally including in India. Dialysis is not the most optimal treatment for a number of these patients such as the elderly, the frail and those with multiple comorbidities and limited life expectancy. Moreover, some patients may prefer not to undergo dialysis. Supportive care focused on symptom management and improving the quality of life is a legitimate treatment option in these situations. It can be delivered alongside dialysis or to patients who choose to receive only conservative care and is being increasingly recognised as an integral component of holistic kidney care. Kidney care provider ecosystem needs to become aware of the principles of the principles of shared decision making, advanced care planning, understanding how to provide emotional, spiritual and information support to the patient and their families and when needed bereavement care. Supportive care facilities are underdeveloped in most low resource settings including in India. There is a need to develop capacity in this area so that our patients can derive the benefit of the full range of treatment options for kidney disease.
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http://dx.doi.org/10.4103/ijpc.ijpc_105_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191744PMC
May 2021

Hydro-geochemical analysis based on entropy and geostatistics model for delineation of anthropogenic ground water pollution for health risks assessment of Dhenkanal district, India.

Ecotoxicology 2021 Jun 25. Epub 2021 Jun 25.

Department of Chemistry, ITER, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India.

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 SO, Mg 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 and HCO, Mg and PO were significantly high which might be due the presence of CaHCO and MgPO in the groundwater samples. The GWQI revealed a weak spatial dependence of groundwater quality.
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http://dx.doi.org/10.1007/s10646-021-02442-1DOI Listing
June 2021

Data Challenges in Addressing Chronic Kidney Disease in Low- and Lower-Middle-Income Countries.

Kidney Int Rep 2021 Jun 17;6(6):1503-1512. Epub 2021 Apr 17.

The George Institute for Global Health, University of New South Wales, Sydney, Australia.

The burden of chronic kidney disease (CKD) is growing globally, particularly in low- and lower-middle-income countries (LLMICs) where access to treatment is poor and the largest increases in disease burden will occur. The individual and societal costs of kidney disease are well recognized, especially in developed health care systems where treatments for the advanced stages of CKD are more readily available. The consequences of CKD are potentially more catastrophic in developing health care systems where such resources are often lacking. Central to addressing this challenge is the availability of data to understand disease burden and ensure that investments in treatments and health resources are effective at a local level. Use of routinely collected administrative data is helpful in this regard, however, the barriers to developing a more systematic focus on data collection should not be underestimated. This article reviews the current tools that have been used to measure the burden of CKD and considers limitations regarding their use in LLMICs. A review of the literature investigating the use of registries, disease specific databases and administrative data to identify populations with CKD in LLMICs, which indicate these to be underused resources, is included. Suggestions regarding the potential use of administrative data for measuring CKD burden in LLMICs are explored.
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http://dx.doi.org/10.1016/j.ekir.2021.03.901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207309PMC
June 2021
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