Overlapping Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy with Mutation in CFI in a Japanese Patient: A Case Report.

A 34-year-old Japanese man presented with blurred vision, headache, nausea, anemia, thrombocytopenia, and severe renal dysfunction. Thrombotic microangiopathy was initially suspected to have been caused by malignant hypertension. Antihypertensive medications did not improve his thrombocytopenia or renal dysfunction, and other diseases causing thrombotic microangiopathy were ruled out. Therefore, the patient was diagnosed with atypical hemolytic uremic syndrome. A renal biopsy revealed an overlap of thrombotic microangiopathy and C3 glomerulopathy. Genetic testing revealed c.848A>G (p.Asp283Gly), a missense heterozygous variant in the gene encoding complement factor I. Overlapping atypical hemolytic uremic syndrome and C3 glomerulopathy with complement factor I mutation is very rare, especially in Japan.

Risk Factors for Therapeutic Intervention of Remdesivir in Mild to Moderate COVID-19-A Single-Center Retrospective Study of the COVID-19 Fourth Pandemic Period in Wakayama, Japan.

Background and Objectives: The incidence of coronavirus disease 2019 (COVID-19) has increased in Wakayama, Japan, due to the spread of the highly infectious B.1.1.7 variant. Before this event, the medical systems were almost unaffected. We aimed to assess the clinical characteristics of patients hospitalized with COVID-19 and the risk factors for therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. Materials and Methods: This single-center retrospective study enrolled 185 patients with mild to moderate COVID-19 hospitalized in our hospital without intensive care between 14 March and 31 May 2021. Results: In this period, 125 (67.6%) of the 185 patients had the B.1.1.7 variant. Sixty-three patients (34.1%) required remdesivir treatment. Age upon admission and length of hospitalization were significantly different between remdesivir treatment and careful observation groups (mean (standard deviation); 59.6 (14.7) versus 45.3 (20.6) years; p < 0.001 and median (interquartile range); 10 (9-12) versus 9 (8-10) years; p < 0.001). One patient was transferred to another hospital because of disease progression. At hospital admission, age ≥60 years (odds ratio (OR) 6.90, p < 0.001), a previous history of diabetes mellitus (OR 20.9, p = 0.002), B.1.1.7 variant (OR 5.30; p = 0.005), lower respiratory symptoms (OR 3.13, p = 0.011), headache (OR 3.82, p = 0.011), and fever ≥37.5 °C (OR 4.55, p = 0.001) were independent risk factors to require remdesivir treatment during the admission. Conclusions: Many patients with mild to moderate COVID-19 required the therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. From the clinical data obtained at admission, these risk factors could contribute to a prediction regarding the requirement of remdesivir treatment in cases of mild to moderate COVID-19.

Excessive ADAM17 activation occurs in uremic patients and may contribute to their immunocompromised status.

INTRODUCTION: We previously reported that fibroblast growth factor 23 (FGF23)-klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23-klotho signaling pathway in immune cells may occur in these patients. METHODS: We analyzed the number of klotho-positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme-linked immunosorbent assay. RESULTS: The number of klotho-positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients. CONCLUSIONS: We concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti-inflammatory and immunosuppressive factor.

Tuberculous Spondylitis Caused by Intravesical Bacillus Calmette-Guerin Therapy.

A 74-year-old man underwent intravesical bacillus Calmette-Guerin (BCG) therapy for bladder cancer and later presented with lower left back pain. Magnetic resonance imaging of the spine showed high signal intensity, diagnosed as a cystic lesion in the epidural and bilateral intestinal psoas muscle. A computed tomography-guided needle biopsy and histological examination revealed bacteria from the family Mycobacteriaceae, and Mycobacterium bovis was identified using multiplex polymerase chain reaction. If lower back pain appears in a patient who has undergone BCG therapy, it is necessary to test for tuberculous spondylitis. In addition, QuantiFERON is useful for the differential diagnosis of M. bovis BCG infection.

Preventive Strategies for Vascular Calcification in Patients with Chronic Kidney Disease.

BACKGROUND: Vascular calcification is significant because of the close association between the degree of vascular calcification and cardiovascular mortality in chronic kidney disease (CKD) patients. SUMMARY: There are 2 types of vascular calcification in CKD patients. One is endothelial vascular calcification, a common type of vascular calcification. Another is medial vascular calcification, a specific type that is common in CKD patients. The former is mainly associated with atherosclerosis due to hyperlipidemia, especially hypercholesterolemia. The latter CKD-specific type is called Moenckeberg's arteriosclerosis. A known risk factor for this type of vascular calcification is hyperphosphatemia. In this review article, we mainly discuss a preventive strategy for Moenckeberg type vascular calcification in CKD, primarily involving the treatment of hyperphosphatemia. Several possible modalities are considered. However, at present, dietary restriction of phosphate is not recommended so as to avoid malnutrition in CKD patients. The first consideration is the enhancement of phosphate removal by renal replacement therapy in dialysis patients. Various phosphate binder therapies can be beneficial and effective. Surgical and pharmacological parathyroidectomies are also useful for treating secondary hyperparathyroidism. Good quality bone provides a good pool of calcium and phosphate. Thus, bone protection is another option for preventing vascular calcification. Several therapeutic agents have been developed to manage osteoporosis. These trial agents may be reasonably effective in impeding the progression of vascular calcification in CKD patients. Key Messages: We should make full use of several modalities so as to completely prevent vascular calcification.