Comparative outcomes of hemodialysis patients facing pre-Omicron and Omicron COVID-19 epidemics.

INTRODUCTION: This study elucidates factors affecting the severity and mortality in pre-Omicron and Omicron strains of SARS-CoV-2 and vaccination impact. METHODS: This single-center retrospective observational study included 1598 hospitalized COVID-19 patients. Patients were grouped into "pre-Omicron" and "Omicron" periods. The endpoint was severe COVID-19 (oxygen saturation [SpO2 ] < 94%). Logistic regression examined associations between clinical factors, including hemodialysis (HD), and the endpoint. RESULTS: The HD patient mortality rate dropped from 16% pre-Omicron to 4% during the Omicron epidemic. HD was significantly associated with the study endpoint in both epidemics. Unvaccinated patients had a greater risk of reaching the study endpoint among patients receiving HD. CONCLUSION: These findings suggest that the Omicron variant, alongside vaccination and healthcare innovations, led to improved prognoses for HD patients with COVID-19. However, HD patients remain at a greater risk for severe COVID-19. Increased vaccination rates and optimized healthcare resources can improve this vulnerable population's prognoses.

Serum chemokine CC-motif ligand 17 is a predictive marker of severe COVID-19 in haemodialysis patients: A retrospective observational study.

BACKGROUND: Maintenance haemodialysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown. METHODS: This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalization (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19. RESULTS: During hospitalization, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including lactate dehydrogenase and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/mL. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/mL) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017-0.227; p < .001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase significantly improved classification performance for severe COVID-19 using the net reclassification (1.16, 95% CI: 0.82-1.50, p < .001) and integrated discrimination (0.18, 95% CI: 0.09-0.26, p < .001) improvement. CONCLUSION: CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.

Efficacy and limitations of additional steroid pulse therapy in IgA nephropathy patients whose hematuria did not remit on tonsillectomy and protocol steroid pulse therapy.

BACKGROUND: Hematuria is the essential symptom of IgA nephropathy that has been suggested to be associated with long-term renal prognosis, Tonsillectomy and steroid pulse therapy (TSP), which is widely practiced in Japan, is effective for achieving hematuria remission. However, some cases are refractory to TSP, and additional steroid pulse therapy (SP) administered to these cases to achieve remission of hematuria. Nonetheless, the clinical significance of additional SP is unknown. METHODS: In this retrospective study, we enrolled 99 patients from Okubo Hospital whose hematuria persisted following TSP. Patients were divided into the hematuria remission and non-remission groups. A multivariate regression analysis was performed on the factors that contributed to hematuria remission. RESULTS: Following TSP, 103 of 403 patients (32.3%) did not achieve hematuria remission. Additional SP were performed in 99 of these patients, and remission of hematuria was achieved in 57 (57.6%). Patients with a greater degree of improvement in hematuria with TSP were significantly more likely to have remission of hematuria with additional SP (p = 0.0084*). Even in the hematuria non-remission group, both hematuria and proteinuria improved after additional SP. CONCLUSION: In IgA nephropathy, additional SP could induce hematuria remission and reduce proteinuria.

Hemodialysis patients with coronavirus disease 2019: reduced antibody response.

BACKGROUND: Because patients on maintenance hemodialysis (HD) have an impaired immune response to pathogens, they are at higher risk of severe coronavirus disease 2019 (COVID-19). However, data on antibody production among HD patients with COVID-19 is scarce. Thus, we performed a retrospective cohort study evaluating severe acute respiratory syndrome coronavirus two antibody (SARS-CoV-2) production within 1 month after COVID-19 onset in hospitalized patients on HD. METHODS: SARS-CoV-2-specific immunoglobulin (Ig) G levels were quantified using an iFlash 3000 Chemiluminescence Immunoassay analyzer (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for the S1 subunit of the spike protein (IgG-S1). Propensity score matching was used to balance covariate distribution in HD and non-HD patients. From April 2020 to February 2021, antibody testing was performed on 161 hospitalized patients with symptomatic COVID-19. Of them, 34 HD patients were matched to 68 non-HD patients. RESULTS: After propensity score matching, the median levels of IgG-S1 in the HD patients at 7-13 days after symptom onset were significantly lower than in non-HD patients, especially in those with severe disease. Among all patients, those with severe disease produced lower levels of IgG-S1 at 7-13 days compared with non-severe patients. CONCLUSION: COVID-19 patients with severe disease, especially those undergoing HD, had lower IgG-S1 production in the second week of the disease. Thus, the increased risk of severe COVID-19 in HD patients may be, in part, due to a slow and reduced antibody response.

Ruptured renal artery in microscopic polyangiitis: a case report and literature review.

Medium-vessel hemorrhage is a rare occurrence in ANCA-associated vasculitis, and has been previously described in only a few patients with microscopic polyangiitis. We report a case of renal hemorrhage in a patient with microscopic polyangiitis that was successfully managed by transcatheter arterial embolization of the active bleeding sites. The early clinical findings included necrotizing arteritis, as indicated by skin biopsy; rapidly progressive glomerulonephritis; mononeuritis multiplex; positive screening for myeloperoxidase-specific antineutrophil cytoplasmic antibody. Corticosteroid therapy was initiated. The patient's health deteriorated at 1 week, with rapidly progressing anemia. Computerized tomography identified a large, right-sided, perirenal hematoma, with active bleeding. Bleeding was successfully managed via segmental embolization of the renal artery. The patient was treated with steroid therapy and MZR, and subsequently underwent maintenance hemodialysis treatment for end-stage renal disease. Spontaneous renal hemorrhage is a rare but fatal clinical condition. A ruptured renal artery should be considered in a patient with microscopic polyangiitis, even in the absence of previous trauma and renal biopsy, when unexplained anemia or signs of shock occur.

Renal biopsy findings and clinical indicators of patients with hematuria without overt proteinuria.

BACKGROUND: Whether to perform a renal biopsy for isolated hematuria remains a matter of controversy. We performed renal biopsy in hematuria without overt proteinuria patients and reported the proportion of glomerulonephritis, pathological activities, and statistical analysis of indicators associated with glomerulonephritis. METHODS: Among 203 patients who underwent renal biopsy in Okubo Hospital, Japan, between January 2008 and October 2013, we identified 56 patients who fulfilled the criteria: (1) urine dipstick examination shows equal to or greater than ± blood on three or more visits, (2) proteinuria <0.3 g/day (g/g Cr), (3) eGFR ≧60 ml/min/1.73 m(2), and (4) no current medication for renal disease. We investigated biopsy findings and compared the clinical indicators in the IgA nephropathy (IgAN) and non-IgAN group. RESULTS: The pathological diagnosis was IgAN in 35 cases (62 %), thin basement membrane disease (TBMD) in 7 (13 %), minor glomerular abnormality (MGA) in 6 (11 %), glomerular basement membrane (GBM) abnormality in 5 (9 %), and others in 3 (5 %). The histological grade of IgAN was I in 90 % and II in 10; 31 % of patients had some crescentic lesions. Comparisons between the IgAN and non-IgAN group revealed significant differences in age of onset (26 ± 13 vs. 34 ± 17 years, p = 0.04), serum IgA (340 ± 114 vs. 220 ± 101 mg/dl, p < 0.01), proteinuria (0.08 [0-0.25] vs. 0 [0-0.23] g/day [g/gCr], p < 0.01), and the presence of poikilocytes (40 vs. 10 %, p = 0.02). CONCLUSIONS: The proportion of IgAN in hematuria without overt proteinuria was high and the pathological activities were variable. Patients with hematuria without overt proteinuria should continue their medical follow-up and the best timing of biopsy may be controversial for these patients who have multiple risk factors of IgAN.

Axillary reverse mapping using fluorescence imaging is useful for identifying the risk group of postoperative lymphedema in breast cancer patients undergoing sentinel node biopsies.

BACKGROUND: Axillary reverse mapping (ARM) is a novel technique for preserving the upper extremity lymphatic pathways during axillary lymph node surgery. However, there is no evidence of the usefulness of ARM for patients undergoing sentinel lymph node biopsy (SNB). METHODS: Between August 2009 and July 2012, 372 patients who underwent the SNB procedure for breast cancer were enrolled in this study. Using the indocyanine green fluorescence technique and indigocarmine blue dye method, we studied the relationship between the upper extremity lymphatic flow and breast sentinel node (SN). Our aim of this study was the probability of postoperative lymphedema with respect to whether the upper extremity lymphatics corresponded to the breast SN. RESULTS: Among the 327 patients who underwent the SNB procedure, the upper extremity lymphatics drainage into the breast SN in 76 (23.2%; corresponding group), and only 5 patients in this group developed lymphedema. In contrast, none of the patients in the noncorresponding group developed lymphedema. CONCLUSIONS: ARM during SN biopsy can identify the group of patients who are at high risk for developing lymphedema. More risk-focused guidance should be used for these patients.

A case of immunoglobulin A nephropathy treated successfully with tonsillectomy and steroid pulse therapy 20 years after onset.

A 46-year-old male was found to have proteinuria on a routine medical examination in 1985 at the age of 22 years and was diagnosed with immunoglobulin A (IgA) nephropathy by renal biopsy. He regularly visited a hospital, but 3 years later made the decision to stop. In 2000, his serum creatinine level was 1.3 mg/dl. His renal function then deteriorated, with persistent proteinuria and hematuria, following which he visited our hospital in December 2008. A further renal biopsy was performed. Active and chronic IgA nephropathy was confirmed histologically, with sclerosing lesions also being found. He was treated with three courses of steroid pulse therapy in February and tonsillectomy in April 2009. During the follow-up period at the outpatient clinic, results for proteinuria and hematuria were negative, suggesting that progression of renal impairment had been prevented. The efficacy of tonsillectomy plus steroid pulse therapy for early IgA nephropathy has been demonstrated, and this treatment was effective in our patient 20 years after the onset of the disease.

Five cases of tonsillectomy and steroid pulse therapy for recurrent immunoglobulin A nephropathy after kidney transplantation.

Five cases of recurrent immunoglobulin A nephropathy (IgAN) after kidney transplantation were successfully treated by tonsillectomy and steroid pulse therapy (SPT). The clinical background and pathology in the five cases were different, but good results were obtained in all of them. In cases 1 and 2, mild recurrent IgAN developed and failed to remit after tonsillectomy alone, but a remission was achieved in both cases after SPT. In case 3, highly active recurrent IgAN with crescent lesions developed 13 years after kidney transplantation, and a remission was achieved after SPT. In case 4, renal biopsy specimens showed pathological findings of recurrent IgAN with tubulitis, and hematuria and proteinuria resolved after SPT. In case 5, the biopsy findings indicated recurrent IgAN with chronic rejection. Tonsillectomy was followed by resolution of the proteinuria, and a remission was achieved after SPT. In conclusion, SPT is effective in inducing a remission of recurrent IgAN when tonsillectomy alone fails.

UV-dependent production of 25-hydroxyvitamin D2 in the recombinant yeast cells expressing human CYP2R1.

CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal its enzymatic properties. In this study, we examined production of 25-hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1. When vitamin D3 or vitamin D2 was added to the cell suspension of CYP2R1-expressing yeast cells in a buffer containing glucose and ß-cyclodextrin, the vitamins were converted into their 25-hydroxylated products. Next, we irradiated the cell suspension with UVB and incubated at 37 °C. Surprisingly, the 25-hydroxy vitamin D2 was produced without additional vitamin D2. Endogenous ergosterol was likely converted into vitamin D2 by UV irradiation and thermal isomerization, and then the resulting vitamin D2 was converted to 25-hydroxyvitamin D2 by CYP2R1. This novel method for producing 25-hydroxyvitamin D2 without a substrate could be useful for practical purposes.

[Three adult cases of severe acute glomerulonephritis with acute renal failure requiring hemodialysis].

Acute poststreptococcal glomerulonephritis (APSGN) typically recovers within 2 weeks with conservative therapy, but severe cases are known to develop acute renal failure and or nephrotic syndrome. We experienced 3 adult cases of APSGN with acute renal failure. All 3 cases required hemodialysis, 2 cases received double filtration plasmapheresis, and 2 cases received steroid therapy. In all cases, renal biopsy specimens showed endocapillary proliferative glomerulonephritis. One case had 25% cellular crescents and the others showed wide subendothelial deposits. There were no tubulointerstitial lesions. These 3 cases of severe APSGN with acute renal failure showed the benefits of combination therapy, hemodialysis, double filtration plasmapheresis and steroid therapy. Further clinical study is required to determine which therapy, double filtration plasmapheresis or steroid therapy, is useful.

Molecular cloning and preliminary expression analysis of banded dogfish (Triakis scyllia) TNF decoy receptor 3 (TNFRSF6B).

Decoy receptor 3 (DcR3), a member of TNF receptor superfamily, is a soluble receptor without death domain and cytoplasmic domain, and secreted by cells and binds with FasL, LIGHT and TL1A. The principal function of DcR3 is the inhibition of apoptosis by the binding cytotoxic ligands. Expression of DcR3 has been reported in a wide array of normal human tissues as well as tumors and tumor cell lines. Recently, DcR3 was reported to modulate a variety of immune responses in mammals. TNFR or DcR3 has been identified in some teleost fishes. However, DcR3 is not reported in cartilaginous fish which is the lowest vertebrate possessing the adaptive immune system. Here we identified DcR3 cDNA in shark (Trsc-DcR3) from an SSH library prepared from peripheral white blood cells stimulated with PMA. Four cysteine-rich domains (CRDs) in common with TNF receptor family members are present in the Trsc-DcR3 sequence. The deduced amino acid sequence of Trsc-DcR3 showed highest identity with the chicken (50.4%), followed by human (46.8%) and rainbow trout (36.5%) DcR3. In a phylogenetic tree of known TNFRSF sequences, the Trsc-DcR3 grouped with the chicken and human DcR3. Trsc-DcR3 mRNA was detected strongly in the gill, moderately in the brain, and weakly in the kidney, thymus and leydig. These data strongly suggest that the gene encoding Trsc-DcR3 in banded dogfish is a homolog of the human gene. mRNA expression of Trsc-DcR3 in the thymus and leydig suggests that DcR3 may act as a modulator in the immune system even at the phylogenetic level of cartilaginous fish.

Molecular cloning and preliminary expression analysis of banded dogfish (Triakis scyllia) CC chemokine cDNAs by use of suppression subtractive hybridization.

Suppression subtractive hybridization was carried out by using cDNAs of peripheral white blood cells (PWBCs) of banded dogfish (Triakis scyllia) after phorbol 12-myristate 13-acetate (PMA) stimulation. The Trsc-SCYA107, MIP3alpha1 and MIP3alpha2 clones contained an open reading frame encoding 97, 99 and 97 amino acids, respectively. Comparison of the deduced amino acids showed that the banded dogfish MIP3alpha1 and MIP3alpha2 sequences shared 42.3% and 40.0% identity with human SCYA20, respectively, while the Trsc-SCYA107 sequence shared 50.6, 44.2 and 42.0% identity with the catshark (Scyliorhinus canicula) Scca-SCYA107, rainbow trout (Oncorhynchus mykiss) CK4A and CK4B, respectively. The genomic sequences of banded dogfish Trsc-SCYA107, MIP3alpha1 and MIP3alpha2 contain four exons and three introns, and MIP3alpha1 and MIP3alpha2 shared the same intron/exon organization with that of human. The MIP3alpha1 and MIP3alpha2 genes of lipopolysaccharide (LPS)-unstimulated banded dogfish were expressed in gill, kidney and liver, while Trsc-SCYA107 mRNA was detected in various tissues except for brain. However, the constitutive expression of MIP3alpha2 gene was much lower than the Trsc-SCYA107 and MIP3alpha1 genes. RT-PCR analysis of the Trsc-SCYA107 expression in tissues of LPS-stimulated fish showed enhanced expression at 24 h poststimulation in the gill, heart, leydig, spleen and testes, while the expression of MIP3alpha1 and MIP3alpha2 was not influenced by LPS-stimulation in vivo. Furthermore, a relative increase in the expression of the Trsc-SCYA107 and MIP3alpha2 genes in PWBCs was observed at 1-12 h poststimulation with PMA and LPS, with maximal expression observed at 3 h, while MIP3alpha1 expression was observed at 3-12 h poststimulation only with PMA.