Hilar lymphadenopathy, development of tubulointerstitial nephritis, and dense deposit disease following Pfizer-BioNTech COVID-19 vaccination.

Despite the reports on glomerulonephritis associated with COVID-19 mRNA vaccines, no study has reported about the dense deposit disease (DDD). Here, we present a case of hilar lymphadenopathy after the COVID-19 mRNA vaccination, following which the patient developed tubulointerstitial nephritis (TIN) and DDD. A 74-year-old man received his second dose of mRNA vaccine, and on the next day, he developed fever, urticaria, and dyspnea. On further examination, he had pleural effusion and right hilar lymphadenopathies, which were improved with conservative therapy. After 48 days of the second vaccination, he developed renal dysfunction and new-onset hematuria. Light microscopy findings by renal biopsy revealed apparent mesangial cell proliferation, increased mesangial matrix in the glomeruli, and diffuse inflammatory cell infiltration in the interstitium. Immunofluorescence analysis revealed 1 + positive results for IgG and IgM, negative results for IgA, and 2 + positive results for C3 with a garland pattern on the capillary walls. Electron microscopy revealed that severe cell proliferation in the capillary rumen, and continuous, thickened, and highly dark-stained spotty dense deposits in the glomerular basement membrane; and noncontinuous spotty dense deposits in the tubular basement membrane. Based on the decrease in C3 and pathological findings, TIN accompanied with DDD was diagnosed. The mRNA vaccine might have contributed to the development of lymphadenopathies, TIN, and DDD in this case. Moreover, TIN and DDD might be associated with the activated alternative pathway induced by the mRNA vaccine.

Short-term effects of roxadustat on serum copper and iron changes in a peritoneal dialysis patient.

Dysregulation in total body copper causes severe complications and excess copper can be toxic. Divalent metal transporter 1, duodenal cytochrome B, and copper transporter ATPase7A are included in the many intestinal genes transactivated by HlF-α. On July X, 2022 an 80-year-old female patient on peritoneal dialysis was prescribed roxadustat 100 mg, because darbepoetin was unable to increase hemoglobin level effectively. On the same day, icodextrin 1 L was initiated to mitigate edema. Laboratory data showed hemoglobin 9.1 g/dL, transferrin saturation 77%, copper 123 µg/dL, and iron 170 µg/dL before changing to roxadustat. The patient visited us 6 days after the change because of the appetite loss. Transferrin saturation and serum copper and iron levels increased to 90%, 170 and 203 µg/dL, respectively, which were decreased or normalized after discontinuing roxadustat and icodextrin, suggesting that even short-term roxadustat administration can influence copper levels as well as iron levels. Excess copper and iron levels during roxadustat treatment do not immediately equate with toxicity, but indicate a physiological compensation or transient imbalance of metabolism especially in patients treated with ferric citrate. Further investigation for the hypoxia-inducible factor-prolyl hydroxylase inhibitors effects on iron and copper metabolisms is needed. Determining the short-term effect of roxadustat on serum copper and iron in only this case is impossible. Therefore, further accumulation of similar cases is necessary to clarify the short-term effects of roxadustat on serum copper and iron.

Four Cases of Serum Copper Excess in Patients with Renal Anemia Receiving a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor: A Possible Safety Concern.

Copper is an indispensable trace metal element and is mainly absorbed in the stomach and small intestine and excreted into the bile. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a novel approach for renal anemia management. Many intestinal genes, including divalent metal transporter 1, duodenal cytochrome B, and copper transporter ATPase7A, related to iron absorption are transactivated by HlF-α, during iron deficiency. We first report 4 cases of patients with renal anemia who showed excess in serum copper level during roxadustat or daprodustat treatment, which were decreased to the normal level after discontinuing HIF-PHIs and changing the drug to darbepoetin alfa, suggesting that HIF-PHI is associated with serum copper excess. HIF-PHI modulates iron metabolism, such as iron absorption, sequestration, and mobilization, and may increase serum copper levels by increasing copper absorption and/or redistribution of copper in tissues. Therefore, it is urgent to examine the correlation between HIF-PHI use and serum copper levels because copper excess might be involved in several acute or chronic adverse events.

A case of a hemodialysis patient with secondary hyperparathyroidism who was resistant to etelcalcetide treatment but not to cinacalcet hydrochloride.

Although both cinacalcet and etelcalcetide are calcimimetics that directly inhibit parathyroid hormone (PTH) secretion by activating the calcium (Ca)-sensing receptor (CaSR), their binding sites are different. We report a first case of a hemodialysis (HD) patient with secondary hyperparathyroidism (SHPT), in whom cinacalcet, but not etelcalcetide, could reduce serum intact PTH (i-PTH) levels. A HD patient received total parathyroidectomy (PTx) with auto-transplantation 16 years earlier. Due to SHPT relapse, cinacalcet was started at 7 years after PTx. His i-PTH levels had been controlled with both 75-100 mg of cinacalcet and 4.5 µg/week of calcitriol for a year before switching from cinacalcet to etelcalcetide. At 1 month following the switch, his serum i-PTH level increased to 716 pg/mL. The dose of etelcalcetide was gradually increased and finally reached the maximal dose of 45 mg/week. Because even the maximal dose of etelcalcetide for > 4 months did not reduce his serum i-PTH levels to < 700 pg/mL, etelcalcetide was switched to 50 mg/day of cinacalcet, which reduced the levels to 208 pg/mL at 2 months after the switch. Genomic sequencing test using whole blood revealed no mutation in the portion including Cys 482 of CaSR gene. The patient was resistant to etelcalcetide treatment but not to cinacalcet, suggesting the possibility that the enlarged parathyroid gland has some change in the portion including Cys 482 in the CaSR gene. Therefore, considering the possibility of etelcalcetide resistance during SHPT treatment should be kept in mind.

[Immune thrombocytopenia after BNT162b2 mRNA COVID-19 vaccination].

A 95-year-old male developed general subcutaneous petechiae, tongue hematoma, and melena two days after receiving the second BNT162b2 mRNA COVID-19 vaccine. Two days later, his platelet count decreased to below 1,000/µl. Laboratory testing was positive for a slight increase in D-dimer, Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody, lupus anticoagulant, and anticardiolipin IgG antibody levels. There were no severe infections or symptomatic thrombosis. Platelet transfusions were transiently effective. He was diagnosed with newly developed immune thrombocytopenia (ITP). We administered prednisolone (PSL) at 0.5 mg/kg/day and intravenous immunoglobulin (IVIG) at 0.4 g/kg/day. From the following day, his platelet count rapidly increased, with an improvement in bleeding tendency. H. pylori was eradicated after platelet count recovery. Thrombocytopenia did not relapse although PSL was tapered three months later. Causes of thrombocytopenia after SARS-CoV-2 vaccination include ITP, vaccine-induced immune thrombotic thrombocytopenia, and thrombotic thrombocytopenic purpura. Differential diagnosis is important to determine the proper therapy. Case reports of newly diagnosed ITP after SARS-CoV-2 vaccination have been increasing recently. In these cases, including ours, the responses to steroids and IVIG were good. Further follow-up studies are needed to manage thrombocytopenia following SARS-CoV-2 vaccination.

Biochemical evaluation of processed ascites in patients undergoing cell-free and concentrated ascites reinfusion therapy.

The biochemical composition of processed ascites is not well researched and may differ among institutions. This prospective study was conducted to evaluate the biochemical characteristics of processed ascites of 11 patients with liver cirrhosis and carcinoma who underwent cell-free and concentrated ascites reinfusion therapy. The ascites due to carcinoma were more acidic and had higher lactate dehydrogenase activity than those due to liver cirrhosis. The ascites due to liver cirrhosis contained a higher amount of immunoglobulin than those due to carcinoma. Immunoglobulin preparations were approximately 2.95% IgG in liver cirrhosis ascites and 2.25% IgG in carcinoma ascites. Moreover, the concern about IgA infusion in the patient with IgA deficiency made it important to identify the source of the ascites. The present study provided fundamental information regarding the safety of cell-free and concentrated ascites reinfusion therapy.

Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation and IgA Nephropathy: A Case Report Successfully Treated with Eculizumab.

We present a rare case of IgA nephropathy in a patient who developed atypical hemolytic uremic syndrome (aHUS) associated with a complement factor H (CFH) gene mutation, and who was successfully treated with eculizmab. A 76-year-old man was admitted as the patients had thrombotic microangiopathies findings. The patient was treated with plasma exchange, hemodialysis and methylprednisolone. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 level was not decreased. Light microscopy findings were consistent with hemolytic uremic syndrome and immunofluorescence analysis revealed IgA and C3 were detected. Genetic analysis revealed that mutation of p.Arg1215Gln in CFH was identified. The diagnosis of aHUS was confirmed and eculizmab therapy was currently effective for 5 months.

Premature diagnosis of calciphylaxis without pathological indications finally diagnosed as cutaneous small-vessel vasculitis: a post-mortem case report.

A man in his fifties with diabetes had a past history of myocardial infarction and ventricular septal perforation. He underwent hemodialysis about a year ago and was taking amiodarone. He presented with sores and purpura on the lower limbs.-Skin biopsy showed immunofluorescence-negative leukocytoclastic vasculitis. Skin lesions were treated with ointments, which ameliorated the symptoms to some extent, but ulceration relapsed and deteriorated in both number and size. Calciphylaxis was suspected, and a second skin biopsy was performed. No calcium detection,on the arteries was observed, but leukocytoclastic vasculitis was seen. Antineutrophil cytoplasmic antibody-related vasculitis, cryoglobulin vasculitis, or anti-phospholipid syndrome were ruled out by negative findings for autoantibodies. Although he was treated with 30 mg prednisolone, his systemic condition deteriorated, and he died of disseminated intravascular coagulation. Autopsy findings showed no vasculitis in the lung, kidney or intestine, and perimyocardial patch infection was observed.Although calciphylaxis was clinically suspected, his condition was diagnosed finally as cutaneous small-vessel vasculitis.