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.
Delayed interferon secretion and cytokine dysregulation are responsible for the life-threatening acute respiratory distress syndrome (ARDS), multiorgan dysfunction and shock in COVID 19, which closely resembles secondary hemophagocytic lymphohistiocytosis (sHLH). IL-6, a marker of hypercytokinemia in patients with COVID-19 is positively correlated with disease severity, development and progression of ARDS, and mortality. Therapy to either reduce IL-6 or inhibit its action with either non-specific inhibitors of inflammation like dexamthasone or Toclizumab a specific inhibitor of IL-6 has produced decrease in mortality. We describe a novel method of treatment in a patient with multiorgan involvement in COVID 19, using the oXiris hemofilter which delivers renal replacement therapy while also reducing cytokines like IL-6.
As maintenance hemodialysis patients are exposed to large quantities of dialysis water, any contamination of it might be reflected in plasma levels. We present a series of cases due to such a contamination. Six maintenance hemodialysis patients dialyzing at the same peripheral hemodialysis facility presented to us over a short period of time with symptoms mimicking inadequate dialysis. Their blood urea and creatinine levels were not very high, but all the patients had hypermagnesemia [serum Mg levels = 1.8 (±0.3) mmol/L]. Except for one patient who had cardiac arrest at presentation, all patients improved after undergoing hemodialysis at our center [serum Mg at discharge = 0.86 (±0.01) mmol/L]. The origin of hypermagnesemia was traced to dialysis water contamination with magnesium due to inadequate maintenance of the water treatment system. Corrective measures improved the quality of water, and no further cases were reported from that center. Proper maintenance and periodic checks of the quality of water are central to the outcomes of maintenance hemodialysis patients.
Aim: Pregnancy-associated hemolytic uremic syndrome (P-aHUS) is an important cause of peripartum acute kidney injury. Studies from Europe have described mutations in complement regulator genes, and data in Indian patients is scarce. Hence this study used multiplex ligation-dependent probe amplification (MLPA) to identify variants in complement genes in P-aHUS patients.Methods: We present 17 patients of P-aHUS who were investigated for complement protein levels and genetic analysis with MLPA for complement genes. Plasma exchange therapy was offered to all patients presenting in acute phase.Results: Mean age 26.74 (3.36) years with 15/17 delivered by caesarean section.Eleven patients received early (within 7 days) plasma exchange, three were dialysisdependent at 3 months and seven were dialysis-free. Only one of the three patients receiving late (after 7 days) plasma exchange was dialysis-free. MLPA showed that 11 patients had heterozygous deletions of exons 3, 5, 6 of CFHR1 and upstream region of exons 1, 2, 3, 6 and intron 4 of CFHR3 gene while four patients had homozygous deletions at the same loci. Two patients had no MLPA-detectable variations. Conclusion:This study reports a high proportion of deletions of exons of CFHR1 & CFHR3 genes in Indian P-aHUS patients detectable by MLPA by copy number variations. This needs confirmation in large multicentre studies. Plasma exchange can be an effective therapy in the non-availability of Eculizumab.
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