Papers by Banibrata Mukhopadhyay
Nephrology Dialysis Transplantation, 2017
Iron is well known to play a crucial role in oxygen transport as hemoglobin (Hb) component, but a... more Iron is well known to play a crucial role in oxygen transport as hemoglobin (Hb) component, but also in cardiac and skeletal muscle metabolism as component of oxidative enzymes. High prevalence of iron deficiency (ID) and cardiomyopathy were observed in patients with end-stage kidney disease (ESKD). The purpose of this study is to clarify the association between ID and cardiac remodeling at the start of maintenance dialysis. METHODS: We conducted a cross-sectional study of information obtained from the database of J-START. 1974 end-stage kidney disease patents were enrolled into this study. Levels of Hb, Fe, TIBC, ferritin, and cardiothoracic ratio (CTR), as a marker of cardiac enlargement, were measured immediately before the patients started their first HD session. The associations of circulatory ID defined as transferrin saturations (TSAT) <20% and stored ID defined as ferritin level <100 ng/dL with CTR were investigated. RESULTS: The mean age was 67.2 years, 67% males, and 42% diabetic kidney disease. Mean eGFR at the start of dialysys was 5.4mL/min/1.73 m 2 , and median CTR was 54 %. The prevalence of circulatory and stored ID were 38% and 34% respectively. 17.3% of patients met the both definitions of ID. CTR was higher in patients with TSAT<20% compared with those with TSAT20% (53.666.8 vs. 55.567.0, p<0.001). No significant deference of CTR was found between the patients with less ferritin 100ng/ dL and those of over (54.167.0 vs. 54.466.8, p<0.001). As shown in Figure, CTR is higher in anemia group of Hb <10 g/dL compared with non-anemia group of Hb 10
Kidney International Reports, 2021
Clinical Biochemistry, 2014
Biometals, 1997
Both in vitro and in vivo HgCl treatment demonstrated a remarkably high rate of progesterone synt... more Both in vitro and in vivo HgCl treatment demonstrated a remarkably high rate of progesterone synthesis accompanied by a low rate of conversion to 17ß-estradiol in the oocyte of Channa punctatus. On depuration, however, there was a reversal of the steroidogenic scenario with a low progesterone and high estradiol level. The accumulation of progesterone was positively correlated with the significant
Biometals, 1997
Specific binding of Hg to ouabain-sensitive Na-K-ATPase of rat liver plasma membrane was demonstr... more Specific binding of Hg to ouabain-sensitive Na-K-ATPase of rat liver plasma membrane was demonstrated with a K of 2.64¥10 and B of 1.6nmole mg protein. The binding of mercury to the enzyme also causes significant inhibition of the enzyme, which is greater than its ouabain sensitivity. In the cytosol Hg binding to reduced glutathione (GSH) is stimulated by GSH-S-transferase (GST),
Clinical Chemistry, 2010
INTRODUCTION Obesity precedes the development of many cardiovascular disease risk factors, includ... more INTRODUCTION Obesity precedes the development of many cardiovascular disease risk factors, including type 2 diabetes mellitus (DM), hypertension, and chronic kidney disease. Catalytic iron, which has been associated with these chronic diseases, may be one of the links between obesity and these multifactorial diverse disorders. OBJECTIVE We investigated whether urinary catalytic iron is increased in obese individuals without DM and overt kidney disease. STUDY DESIGN We measured urinary catalytic iron using established methods in 200 randomly selected individuals without DM [100 who were obese (body mass index ≥30 kg/m2) and 100 who were nonobese (body mass index ≤27)]. Participants were selected from an outpatient clinic and community setting and were part of an ongoing cross-sectional study of obesity in individuals between the ages of 18 and 70 years. RESULTS There was a significant difference in mean (95% CI) urinary catalytic iron excretion between the obese participants and the ...
Nature Communications, 2022
The most common cause of death in the intensive care unit (ICU) is the development of multiorgan ... more The most common cause of death in the intensive care unit (ICU) is the development of multiorgan dysfunction syndrome (MODS). Besides life-supporting treatments, no cure exists, and its mechanisms are still poorly understood. Catalytic iron is associated with ICU mortality and is known to cause free radical-mediated cellular toxicity. It is thought to induce excessive lipid peroxidation, the main characteristic of an iron-dependent type of cell death conceptualized as ferroptosis. Here we show that the severity of multiorgan dysfunction and the probability of death are indeed associated with plasma catalytic iron and lipid peroxidation. Transgenic approaches underscore the role of ferroptosis in iron-induced multiorgan dysfunction. Blocking lipid peroxidation with our highly soluble ferrostatin-analogue protects mice from injury and death in experimental non-septic multiorgan dysfunction, but not in sepsis-induced multiorgan dysfunction. The limitations of the experimental mice mode...
Journal of the American Society of Nephrology, 2019
BackgroundIron is a key mediator of AKI in animal models, but data on circulating iron parameters... more BackgroundIron is a key mediator of AKI in animal models, but data on circulating iron parameters in human AKI are limited.MethodsWe examined results from the ARF Trial Network study to assess the association of plasma catalytic iron, total iron, transferrin, ferritin, free hemoglobin, and hepcidin with 60-day mortality. Participants included critically ill patients with AKI requiring RRT who were enrolled in the study.ResultsOf the 807 study participants, 409 (51%) died by day 60. In both unadjusted and multivariable adjusted models, higher plasma concentrations of catalytic iron were associated with a significantly greater risk of death, as were lower concentrations of hepcidin. After adjusting for other factors, patients with catalytic iron levels in the highest quintile versus the lowest quintile had a 4.06-fold increased risk of death, and patients with hepcidin levels in the lowest quintile versus the highest quintile of hepcidin had a 3.87-fold increased risk of death. These ...
Indian Journal of Nephrology, 2007
Background: Radiographic contrast media (RCM) can cause a reduction in the renal function by mult... more Background: Radiographic contrast media (RCM) can cause a reduction in the renal function by multiple mechanisms; reactive oxygen species is one of them. Whether the reduction can be prevented by the administration of antioxidants is still debatable. N-acetylcysteine (NAC) has shown some beneÞ t in patients with renal dysfunction in the prevention of radiocontrast-induced nephropathy (RCIN). Materials and Methods: We prospectively studied 95 healthy kidney donors, who were undergoing intravenous urography (IVU) followed by digital subtraction renal angiography (DSRA) with ionic, high-osmolar contrast agent for pretransplant evaluation. Patients were randomly assigned either to receive the N-acetylcysteine 600 mg orally twice daily (acetylcysteine group) or placebo (control group) on the day before and that of RCM administration in addition to the intravenous 0.45% saline (1 ml/kg body weight per hour) on the day and following day of the procedure. Serum creatinine, urinary enzymes N-acetyl β glucosaminidase (NAG), γ glutamyl-1-transferase (GGT), alanine amino peptidase (AAP), fractional excretion of sodium (FeNa) and 24-h urinary creatinine clearance were performed before and 48 h after the procedure. The levels of urinary enzymes measured after 96 h of DSRA were available in only 57 donors. Radiocontrast-induced nephropathy was deÞ ned as an increase in the baseline serum creatinine of at least 0.5 mg/dl within 48 h after injection of radiocontrast media (RCM). Results: Increase in the urinary enzymes (NAG, GGT and AAP) and reduction in creatinine clearance was observed in both groups after receiving the contrast media. However, the number of patients with signiÞ cant increase in enzymuria (at least >50% increase above the baseline value) and mean drop in creatinine clearance was statistically not different between the acetylcysteine and control groups. Conclusion: Renal damage in the form of reduction in creatinine clearance and increase in urinary enzymes has been observed after administration of radiocontrast. However, clinically signiÞ cant RCM-induced acute kidney injury is uncommon in patients with normal renal function. Prophylactic oral administration of the antioxidant N-acetylcysteine at a dose of 600 mg twice daily before and on the day of contrast administration is probably not required in patients with normal renal function.
Nephrology Dialysis Transplantation, 2021
Background The non-transferrin-bound catalytic iron moiety catalyses production of toxic reactive... more 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 (ICKD) Study participants with at least one follow-up visit were tested for total iron, iron-binding capacity, transferrin saturation (TSAT), 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 [major adverse kidney event (MAKE), a composite of kidney death, kidney failure or >40% loss of estimated glomerular filtration rate (eGFR)] was examined using Cox proportional hazards model adjusted for sex and age. Results A total of 2002 subjects (mean ± standard deviation age 49.9 ± 11.6 years, 68.1% males, baseline eGFR 41.01 mL/min/1...
Scientific Reports, 2021
The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, w... more 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 need...
Journal of Minimal Access Surgery, 2017
Although the technical feasibility of laparoscopic donor nephrectomy (LDN) has been established, ... more Although the technical feasibility of laparoscopic donor nephrectomy (LDN) has been established, concerns have been raised about the impaired renal function resulting from pneumoperitoneum and its short- and long-term effects. We used urinary biomarkers of acute kidney injury including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary N-acetyl-beta-D-glucosaminidase (uNAG) to study the injury caused to the donor&amp;amp;#39;s retained kidney by pneumoperitoneum. This was a prospective cohort study of thirty consecutive patients who underwent LDN at our hospital. We measured urinary creatinine, uNAG and uNGAL at the time of induction of anaesthesia, at 1 h after starting surgery, at 5 min after clamping the ureter, at the time of skin closure and then at 4, 8 and 24 h after the surgery. The uNAG level showed a gradual increase from the start of the surgery and reached the peak at the time of the closure. Thereafter, there was a gradual fall in the level and reached to pre-operative level at 24 h post-surgery. Similarly, the uNGAL also showed a similar trend although it did not reach pre-operative value by 24 h. We objectively confirm that although there is acute injury to the retained kidney in the donor after LDN due to the CO2pneumoperitoneum, the renal function improves and reaches close to the pre-operative level within 24 h after surgery.
Clinical Journal of the American Society of Nephrology, 2014
Background and objectives Catalytic iron has been hypothesized to be a key mediator of AKI. Howev... more Background and objectives Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans. Design, settings, participants, & measurements A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria. Results ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 mmol/l [interquartile range, 0.31-3.65] versus 0.29 mmol/l [0.22-0.46]; P,0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (r s =0.29; P,0.001) and plasma free hemoglobin levels on ICU day 1 (r s =0.32; P,0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality. Conclusions Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.
Indian Journal of Clinical Biochemistry, 2004
Serum creatinine does not distinguish between various causes of graft dysfunction. Serial assay o... more Serum creatinine does not distinguish between various causes of graft dysfunction. Serial assay of proximal tubular enzymes N-Acetyl-D-glucosaminidase (NAG), Alanine aminopeptidase (AAP) and Gamma glutamyl transferase (GGT) in urine was done to assess their usefulness in distinguishing various causes of graft dysfunction. Daily serum creatinine and enzymuria were measured in 32 consecutive renal allograft recipients for first 15 postoperative days. Graft dysfunction was defined as >20% increase in serum creatinine and >100% increase in enzymuria over the baseline. The diagnosis of graft dysfunction was based upon clinical criteria, ultrasonography, cyclosporin trough level, allograft biopsy, response to anti-rejection therapy and alteration of cyclosporin dosage. Fifteen episodes of graft dysfunction were identified in 15 patients. The sensitivity and specificity of the enzymes (NAG, AAP and GGT) for predicting graft dysfunction were 87.5%,86.9%,88.5% and 98.2%,98.2%,97.9% respectively. There was a significant increase in enzymuria during acute tubular necrosis (ATN) and acute rejection episode compared to cyclosporin nephrotoxicity (p< 0.01). Enzymuria assay provides a simple, reliable and noninvasive method to distinguish cyclosporin nephrotoxicity from acute tubular necrosis and acute rejection in renal allograft recipients.
Kidney International, 2015
Catalytic iron, the chemical form of iron capable of participating in redox cycling, is a key med... more Catalytic iron, the chemical form of iron capable of participating in redox cycling, is a key mediator of acute kidney injury (AKI) in multiple animal models, but its role in human AKI has not been studied. Here we tested in a prospective cohort of 250 patients undergoing cardiac surgery whether plasma catalytic iron levels are elevated and associated with the composite outcome of AKI requiring renal replacement therapy or in-hospital mortality. Plasma catalytic iron, free hemoglobin, and other iron parameters were measured preoperatively, at the end of cardiopulmonary bypass, and on postoperative days 1 and 3. Plasma catalytic iron levels, but not other iron parameters, rose significantly at the end of cardiopulmonary bypass and were directly associated with bypass time and number of packed red blood cell transfusions. In multivariate analyses adjusting for age and preoperative eGFR, patients in the highest compared with the lowest quartile of catalytic iron on postoperative day 1 had a 6.71 greater odds of experiencing the primary outcome, and also had greater odds of AKI, hospital mortality, and postoperative myocardial injury. Thus, our data are consistent with and expand on findings from animal models demonstrating a pathologic role of catalytic iron in mediating adverse postoperative outcomes. Interventions aimed at reducing plasma catalytic iron levels as a strategy for preventing AKI in humans are warranted.
Clinical Cardiology, 2013
Background: The potential of iron to generate reactive oxygen species has motivated a long-standi... more Background: The potential of iron to generate reactive oxygen species has motivated a long-standing interest in whether excess iron is causally linked to atherosclerotic heart disease. Circulating catalytic iron (''free'' iron) is that which is not bound to transferrin or ferritin and is available to generate reactive oxygen species that may have deleterious vascular effects. Hypothesis: We hypothesized that increased levels of catalytic iron would be associated with increased cardiovascular events. Methods: We investigated the association of catalytic iron with clinical outcomes in 1701 patients with unstable angina, non-ST-segment elevation myocardial infarction (MI), or ST-segment elevation MI who were followed for a median of 10 months. All endpoints were adjudicated by a blinded Clinical End Points Committee. Results: The median catalytic iron level was significantly higher in those who died, 0.45 μmol/L (0.37, 0.57), compared with survivors, 0.37μmol/L (0.31, 0.46; P = 0.016). Catalytic iron was associated with a stepwise increased risk of death, with the highest quartile at an almost 4-fold risk compared with baseline (hazard ratio: 3.94, P = 0.035), which persisted after adjustment for age, diabetes, prior MI, prior congestive heart failure, ST-segment deviation, creatinine clearance, B-type natriuretic peptide, smoking, and Killip class (adjusted hazard ratio: 3.97, P = 0.036). There was no association between catalytic iron and risk of MI, recurrent ischemia, heart failure, or bleeding. Conclusions: Increasing catalytic iron levels were associated with increased all-cause mortality. Although our findings suggest that catalytic iron is not likely to add to available tools as a routine biomarker for risk stratification of recurrent ischemic events, its association with mortality is intriguing and leaves open the question of whether cardiovascular therapeutics aimed at catalytic iron may be useful.
The American Journal of Cardiology, 2012
The ability of iron to cycle reversibly between its ferrous and ferric oxidation states is essent... more The ability of iron to cycle reversibly between its ferrous and ferric oxidation states is essential for the biological functions of iron but may contribute to vascular injury through the generation of powerful oxidant species. We examined the association between chemical forms of iron that can participate in redox cycling, often referred to as "catalytic" or "labile" iron, and cardiovascular disease (CVD). In our cross-sectional study of 496 participants, 85 had CVD. Serum catalytic iron was measured using the bleomycin-detectable iron assay that detects biologically active iron. The odds of existing CVD for subjects in the upper third of catalytic iron were 10 times that of subjects with lower catalytic iron in unadjusted analyses. The association was decreased by 1/2 by age adjustment, but little additional attenuation occurred after adjusting for age, Framingham Risk Score, estimated glomerular filtration rate, hypertension status, highdensity lipoprotein cholesterol, and systolic blood pressure, with the association remaining strong and significant (odds ratio 3.8, 95% confidence interval 1.4 to 10.1). In conclusion, we provide preliminary evidence for a strong detrimental association between high serum catalytic iron and CVD even after adjusting for several co-morbid conditions; however, broader prospective studies are needed to confirm these findings, which would support therapeutic trials to assess the beneficial effects of iron chelators on CVD. Published by Elsevier Inc. (Am J Cardiol 2012;109:438-442) Cardiomyopathy is known to occur in several iron overload states 1 ; however, a role for iron in atherosclerotic cardiovascular disease (CVD) in the absence of iron overload is less clear. 2-5 Although several in vitro 6 and animal 7,8 studies have supported a role for iron in atherosclerosis, human observational studies have provided inconsistent results. 3-5,9-11 Several factors, including the fact that total body iron is not reliably related to the level of biologically active iron, 12,13 may have contributed to these inconsistencies. 13 In the present study we evaluated groups of patients with several long-term conditions to assess the association between serum catalytic iron and CVD after controlling for various co-morbidities. Methods This cross-sectional study was approved by the institutional ethics committees at the participating centers, and written informed consent was obtained from all study participants. The 568 subjects who agreed to participate included 349 participants from a survey of healthy govern
American Heart Journal, 2013
Catalytic iron (CI) mediates vascular injury by generating reactive oxygen species. We evaluated ... more Catalytic iron (CI) mediates vascular injury by generating reactive oxygen species. We evaluated role of CI in predicting mortality in patients with acute coronary syndrome (ACS) and studied association of contrast nephropathy with CI levels. We investigated 806 patients with ACS undergoing contrast exposure for a cardiac procedure who were followed up for 30 days. Overall mortality was 1.6% at 30 days. Catalytic iron at baseline predicted mortality with CI levels significantly higher in those who died, 0.45 μmol/L (0.37, 0.68) compared with survivors 0.31 μmol/L (0.21, 0.40); P = .004. Catalytic iron was associated with increased risk of death in the highest quartile compared with lower 3 quartiles (hazard ratio 7.88, P = .001) after adjustment for age, diabetes, ST deviation, Killip class, ejection fraction, baseline creatinine, hemoglobin level, and troponin. Fifty-five patients (6.8%) developed contrast nephropathy. Patients with contrast nephropathy had a 27% increase in median CI levels from baseline up to 48 hours compared with a marginal 2.9% increase in those without contrast nephropathy (0.37, 0.14 μmol/L to 0.47, 0.20 μmol/L versus 0.35, 0.12 μmol/L to 0.36, 0.14 μmol/L, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). Patients with contrast nephropathy had significantly higher mortality compared with those without contrast nephropathy (9.1% vs 1.1%, P = .001). High baseline CI levels predicted mortality in patients with ACS. Occurrence of contrast nephropathy was associated with rise in CI levels and higher mortality. Therapeutic options to buffer or chelate CI may have beneficial effects on mortality in this setting.
Indian Journal of Nephrology, 2013
Indian Journal of Nephrology renal disease on dialysis is 5-to 15-fold higher [2] and mortality 1... more Indian Journal of Nephrology renal disease on dialysis is 5-to 15-fold higher [2] and mortality 10-to 30-fold higher [3] than that seen in the general population. [4-6] Systemic inflammation [7] and oxidative stress [8] have been implicated both in atherosclerotic CVD and in CKD. Renal dysfunction has emerged as a potent independent risk factor for mortality in patients with acute coronary syndrome. A common vascular link between CVD and renal disease, aptly called the cardio-renal syndrome, has been the subject of intense research interest. Serum catalytic iron (SCI) or "free" iron is the circulating iron that is not bound to transferrin or ferritin and is available to generate reactive oxygen species that may have deleterious vascular effects. We have recently reported the role of SCI as a vascular biomarker in patients with acute coronary syndrome both in assisting early diagnosis and in predicting adverse outcomes. [9,10] High levels of circulating catalytic iron may accelerate atherosclerosis by a variety of mechanisms, including generation of oxidized low-density lipoprotein (LDL), [11] endothelial dysfunction, arterial smooth proliferation
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Papers by Banibrata Mukhopadhyay