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1.
BMC Nephrol ; 24(1): 286, 2023 09 29.
Article in English | MEDLINE | ID: mdl-37773103

ABSTRACT

BACKGROUND: Endothelial dysfunction is common in patients undergoing chronic haemodialysis, and is a major cause of posterior reversible encephalopathy syndrome (PRES). Recently, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to cause endothelial dysfunction by infecting vascular endothelial cells. Several cases of neurological complications in patients without kidney dysfunction, and only a few cases in patients with chronic kidney disease, have been reported in the literature. However, no previous report has yet described PRES associated with SARS-CoV-2 infection among patients undergoing maintenance dialysis. CASE PRESENTATION: A 54-year-old woman undergoing maintenance haemodialysis was admitted to our hospital for status epilepticus. She had developed end-stage kidney disease (ESKD) secondary to diabetic nephropathy. Seven days prior to admission, she had developed fever and was diagnosed with COVID-19. Subsequently her blood pressure increased from 160/90 mmHg to 190/100 mmHg. On admission, she presented with severe hypertension (> 220/150 mmHg), unconsciousness, and epilepticus. CT tomography revealed no signs of brain haemorrhage. Cranio-spinal fluid (CSF) examination revealed no signs of encephalitis, and CSF polymerase chain reaction (PCR) for SARS-CoV-2 was negative. MRI findings revealed focal T2/FLAIR hyperintensity in the bilateral parietooccipital regions, leading to the diagnosis of PRES. Deep sedation and strict blood pressure control resulted in a rapid improvement of her symptoms, and she was discharged without sequelae. CONCLUSIONS: We report the first case of PRES associated with SARS-CoV-2 infection in a patient undergoing maintenance haemodialysis. Patients undergoing maintenance haemodialysis are at high risk of PRES because of several risk factors. SARS-CoV-2 infection causes direct invasion of endothelial cells by binding to angiotensin-converting enzyme 2 (ACE2), initiating cytokine release, and hypercoagulation, leading to vascular endothelial cell injury and increased vascular leakage. In the present case, SARS-CoV-2 infection possibly be associated with the development of PRES.


Subject(s)
COVID-19 , Posterior Leukoencephalopathy Syndrome , Vascular Diseases , Humans , Female , Middle Aged , Posterior Leukoencephalopathy Syndrome/etiology , Posterior Leukoencephalopathy Syndrome/complications , COVID-19/complications , Endothelial Cells , SARS-CoV-2 , Renal Dialysis/adverse effects , Vascular Diseases/complications
2.
CEN Case Rep ; 12(1): 32-38, 2023 02.
Article in English | MEDLINE | ID: mdl-35749014

ABSTRACT

We report on an 80-year-old man diagnosed with Fanconi syndrome induced by mizoribine after 4 weeks of administration to treat membranous nephropathy. Mizoribine is an oral immunosuppressant that inhibits inosine monophosphate dehydrogenase and is widely used in Japan for the treatment of autoimmune diseases and nephrotic syndrome, as well as after renal transplantation. Acquired Fanconi syndrome is often caused by drugs (antibacterial, antiviral, anticancer, and anticonvulsant drugs) and is sometimes caused by autoimmune diseases, monoclonal light chain-associated diseases, or heavy metal poisoning. In our patient, hypokalemia, hypophosphatemia, glucosuria, hypouricemia, and severe proteinuria resolved gradually after discontinuation of mizoribine administration, despite oral administration of prednisolone followed by a single intravenous injection of rituximab. The patient was ultimately diagnosed with Fanconi syndrome induced by mizoribine based on his clinical course and his typical laboratory data with the absence of proximal tubular acidosis. To our knowledge, this is the first report of Fanconi syndrome possibly induced by mizoribine. Although the precise mechanism by which mizoribine induces proximal tubular dysfunction is unknown, we suggest that nephrologists should be aware of the onset of Fanconi syndrome, a rare complication during mizoribine treatment.


Subject(s)
Acidosis, Renal Tubular , Fanconi Syndrome , Glomerulonephritis, Membranous , Ribonucleosides , Male , Humans , Aged , Aged, 80 and over , Immunosuppressive Agents/adverse effects , Fanconi Syndrome/chemically induced , Fanconi Syndrome/diagnosis , Fanconi Syndrome/drug therapy , Glomerulonephritis, Membranous/drug therapy , Glomerulonephritis, Membranous/complications , Ribonucleosides/adverse effects , Acidosis, Renal Tubular/complications
3.
Transplant Proc ; 52(9): 2750-2753, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32951864

ABSTRACT

Common management of renal transplant recipients includes episodic renal biopsy based on clinical findings such as an increase in proteinuria or serum creatinine. When antibody-related rejection is suspected from the renal biopsy, subsequent testing for donor-specific antibodies (DSAs) is performed. We instead performed preemptive screening of asymptomatic post-renal transplant recipients for DSAs prior to renal biopsy. In this case, a 30-year-old woman with a secondary transplant was positive for 61 anti-HLA antibodies of class I and class II, among which DQ2 was a DSA with a mean fluorescence index of 2039. The patient had a living kidney transplant 9 years earlier. She had never been diagnosed with rejection, her serum creatinine was around 1.0 mg/dL, and her proteinuria was negative. Following the positive DSA result, a renal biopsy was performed, and she was diagnosed as C4d-negative chronic-active antibody-mediated rejection (CAABMR) with a Banff score of cg1b, (g + ptc) ≥ 2, and C4d 0. Intravenous steroid pulse, deoxyspagarin, antithymocyte globulin, rituximab, and oral everolimus were administrated. The treatment resulted in a gradual decrease in the DSA, which became negative 1 year later. The patient's serum creatinine remains around 1.0 mg/dL, and proteinuria remains negative. Treatments for advanced CAABMR are often expensive and ineffective. Our present case suggests that early detection and treatment through preemptive HLA antibody screening could improve the prognosis of renal transplants.


Subject(s)
Antibodies/blood , Graft Rejection/diagnosis , Graft Rejection/immunology , HLA Antigens/immunology , Kidney Transplantation , Adult , Biopsy , Early Diagnosis , Female , Humans , Tissue Donors , Transplant Recipients , Transplants/immunology
4.
Clin Chim Acta ; 507: 271-279, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32348784

ABSTRACT

BACKGROUND: Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress. METHODS: A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically. RESULTS: Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria

Subject(s)
Acute Kidney Injury/urine , Luminescence , Thioredoxins/urine , Acute Kidney Injury/diagnosis , Adult , Aged , Biomarkers/urine , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Oxidative Stress
5.
Nephron ; 141(3): 177-187, 2019.
Article in English | MEDLINE | ID: mdl-30540988

ABSTRACT

BACKGROUND/AIMS: Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury. METHODS: To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays. RESULTS: Deemed to be mainly exosomes based on their size distribution, the EVs in urine contained FSP1, and a portion of the FSP1-positive vesicles was also positive for podocalyxin. FSP1 levels in urinary EVs were (1) positively correlated with rates of biopsy-proven cellular crescent formation (r = 0.562, p < 0.001) and total crescent formation (r = 0.448, p = 0.005) among total glomeruli; (2) significantly higher in patients with cellular crescents affecting 20% or more of their glomeruli than in those with fewer affected glomeruli (p = 0.003); and (3) significantly decreased after glucocorticoid and immunosuppressant therapy (p < 0.05). A positive correlation between FSP1 levels in urinary EVs and urinary soluble CD163 levels was confirmed (r = 0.367, p < 0.05). CONCLUSION: These data suggest that a portion of urinary FSP1 is secreted as EVs originating from podocytes, and that FSP1 levels reflect active and ongoing glomerular injury and disease activity, such as cellular crescent formation.


Subject(s)
Calcium-Binding Proteins/urine , Extracellular Vesicles/metabolism , Glomerulonephritis/urine , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/urine , Female , Humans , Male , Middle Aged , S100 Calcium-Binding Protein A4 , Young Adult
6.
J Am Soc Nephrol ; 28(12): 3688-3698, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28794148

ABSTRACT

Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected. We recently discovered a case of tubulointerstitial nephritis showing IgM-positive plasma cell accumulation within the interstitium. To further explore the morphologic and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven tubulointerstitial nephritis and high serum IgM levels. We identified 13 patients with tubulointerstitial nephritis and IgM-positive plasma cell infiltration confirmed with the immunoenzyme method. The clinical findings for these patients included a high prevalence of distal renal tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and colocalized IgM-positive plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3--Cl- anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cell-tubulointerstitial nephritis.


Subject(s)
Immunoglobulin M , Nephritis, Interstitial/blood , Nephritis, Interstitial/immunology , Plasma Cells/immunology , Adult , Aged , Female , Humans , Male , Middle Aged
7.
Exp Hematol ; 36(1): 37-50, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18037226

ABSTRACT

OBJECTIVE: Rho GTPase may be involved in human cancer invasion via the augmentation of cell motility and adhesion. We report on two point mutations of the D4-guanine diphosphate (GDP)-dissociation inhibitor (GDI) gene, one of the Rho-GDIs, which were found in a human leukemic cell line, Reh, and the mutated D4-GDI functions as an accelerator of leukemic cell invasion. MATERIAL AND METHODS: We investigated the altered activity of GDP dissociation by mutated (mt) D4-GDI and the functions of this mt and wild-type (wt) D4-GDI in invasion. The mice inoculated with wt or mt D4-GDI vector-transfected Raji cells were observed and examined pathologically. Adhesiveness and cell motility of wt or mt D4-GDI vector-transfected Raji cells were examined. Finally, it was examined whether Rho activation was changed by mutation of D4-GDI under the condition of Rho-GDI knockdown. RESULTS: Two point mutations of the D4-GDI gene were found in Reh cells. The region of mutations is conserved among members of the Rho-GDI family at the amino acid level. D4-GDI with two mutations (V68L and V69A) functioned in a dominant negative manner in the inhibition of GDP dissociation from Rho. Severe combined immune-deficient mice inoculated with Raji cells developed hemiparalysis. The Raji cells were present in bone marrow and peripheral blood, and hepatic invasion was observed in 20% of the mice. Mice inoculated with wt D4-GDI vector-transfected Raji cells (wt D4) showed later paralysis and none developed hepatic invasion. Mice inoculated with mt D4-GDI-transfected Raji cells (mt D4) showed a 5-day reduction in the time to paraplegia and death. In addition, hepatic invasion was evident in 80% of mice transplanted with mt D4 cells. There were no differences in growth rates and amounts of guanine triphosphate (GTP)-bound Rho, cdc42, or Rac among all clones, however, GTP-bound Rho in mt D4 clone with short hairpin RNA (shRNA) vector for Rho-GDI knockdown was increased compared with wt D4 clone with shRNA vector for Rho-GDI knockdown. The mt D4 cells showed an augmentation of adhesiveness and cell motility. On the other hand, wt D4 cells showed a decreased ability of cell motility. CONCLUSION: These results suggest the mutated D4-GDI functions as a dominant negative molecule against the wt D4-GDI and accelerates invasion via regulation of cytoskeletal machinery.


Subject(s)
Amino Acid Substitution , Guanine Nucleotide Dissociation Inhibitors/genetics , Guanosine Diphosphate/metabolism , Mutation, Missense , Neoplasm Invasiveness/physiopathology , Neoplasm Proteins/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Tumor Suppressor Proteins/genetics , rho GTP-Binding Proteins/metabolism , Amino Acid Sequence , Animals , Burkitt Lymphoma/pathology , Cell Adhesion , Cell Line, Tumor/metabolism , Cell Movement , Child , Conserved Sequence , Female , Genes, Dominant , Guanine Nucleotide Dissociation Inhibitors/physiology , Humans , Leukemia, T-Cell/pathology , Mice , Mice, SCID , Molecular Sequence Data , Neoplasm Proteins/physiology , Paresis/etiology , Sequence Alignment , Tumor Suppressor Proteins/physiology , rho Guanine Nucleotide Dissociation Inhibitor beta , rho-Specific Guanine Nucleotide Dissociation Inhibitors
8.
Article in English | MEDLINE | ID: mdl-15243465

ABSTRACT

OBJECTIVE: This investigation was conducted to quantitate the anxiety associated with third molar extraction in university students, and to compare the measured anxiety before and after extraction and between men and women, first and second extraction, and impacted versus nonimpacted tooth extraction. STUDY DESIGN: The Japanese version of The State-Trait Anxiety Inventory (STAI), a psychological test, was given to 108 students undergoing third molar extraction. The students completed the test on the first examination (day 1), immediately before the extraction (day 2), and the day after the extraction (day 3). RESULTS: The state anxiety (STAI-S) score showed no significant difference between days 1 and 2, but the score on day 3 was lower than that on day 1, with a decrease in cases with a stage IV or V. Women showed more anxiety state on day 2 than men. The anxiety score on days 2 and 3 for the second extraction were significantly lower than those for the first extraction in 43 students who underwent third molar extractions twice. The change in the trait anxiety (STAI-T) stage was unremarkable among days 1, 2, and 3. No statistical difference was found in the anxiety between students undergoing impacted and nonimpacted third molar extraction. CONCLUSIONS: The anxiety status of students undergoing third molar extraction could be quantitatively evaluated using the STAI. The results of this investigation may provide oral maxillofacial surgeons with useful information about patients' anxiety throughout the tooth removal process.


Subject(s)
Dental Anxiety/diagnosis , Molar, Third/surgery , Tooth Extraction/psychology , Adolescent , Adult , Analysis of Variance , Female , Humans , Male , Manifest Anxiety Scale , Sex Factors , Statistics, Nonparametric , Tooth, Impacted/surgery
9.
Clin Diagn Lab Immunol ; 9(2): 287-94, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11874865

ABSTRACT

This study of stress-related antinuclear antibody (ANA) reactivity was undertaken with the objective of improving clinical ANA testing. ANA was determined by parallel enzyme-linked immunosorbent assays of crude nuclear protein antigen extracted from HEp-2 cells either grown under optimal conditions (providing nonstress ANA antigen) or exposed to stress (providing stress ANA antigen). The stress stimuli used were gamma radiation (causing DNA damage) and a hypertonic environment (causing apoptosis). Signs of stress-related ANA reactivity were seen among connective tissue disease (CTD) patients (including patients with systemic lupus erythematosus; mixed CTD; calcinosis, Reynaud's phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia; scleroderma; and Sjögren's syndrome): 11% showed stress-positive ANA (i.e., a significantly stronger ANA reactivity with the extract from stressed cells), whereas 21% showed a markedly weaker reaction with the stress antigen. In contrast, among ANA screening patient sera, with no diagnosis of CTD, the fraction showing stress-positive ANA was higher (7 to 8%, depending on the type of stress) than among those showing a lower reactivity with stress antigen (1.5 to 2.5%). Only one serum among 89 (1%) tested sera from healthy individuals showed a stress-related ANA reaction. This demonstration of stress-related ANA suggests a means to improve the performance of clinical ANA testing.


Subject(s)
Antibodies, Antinuclear/analysis , Apoptosis/immunology , Epithelial Cells/immunology , Antibodies, Antinuclear/immunology , Antigen-Antibody Reactions , Autoimmune Diseases/diagnosis , Autoimmune Diseases/immunology , DNA Damage , Enzyme-Linked Immunosorbent Assay , Epithelial Cells/cytology , Epitopes , Humans , Hypertonic Solutions , Osmotic Pressure , Tumor Cells, Cultured
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