A Case of TAFRO Syndrome Developed after COVID-19 Vaccination.

TAFRO syndrome is a systemic inflammatory disorder, which is characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. It often presents with progressive clinical symptoms and can be fatal. COVID-19 vaccination is important to reduce the number of COVID-19-infected populations and lower the risk of becoming severe. However, serious adverse events have been reported. TAFRO syndrome that progresses after the COVID-19 mRNA vaccination has not yet been reported. A 45-year-old man developed fever, gross hematuria, renal dysfunction, pleural effusions, and ascites immediately after vaccination. This case fulfilled three major categories (thrombocytopenia, anasarca, and systemic inflammation) and two minor categories (renal insufficiency and myelofibrosis) and was diagnosed with TAFRO syndrome. High-dose steroid treatment was initiated, followed by prednisolone administration. After treatment, renal dysfunction and fluid retention were resolved. Universal vaccination against COVID-19 is important for lowering the risk of spreading COVID-19 infection. Several complications, such as renal, hematological, and heart diseases, have been reported; however, its pathogenesis is unclear. The possibility of various complications after the COVID-19 vaccination, including TAFRO syndrome, should be considered.

Efficacy and safety of pemafibrate in patients with chronic kidney disease: A retrospective study.

Hypertriglyceridemia and chronic kidney disease (CKD) are known risk factors for cardiovascular disease. However, treatment with statins, which control low-density lipoprotein cholesterol levels, increases the risk of estimated glomerular filtration rate (eGFR) reduction. Although conventional fibrates, such as bezafibrate (Beza-F) and fenofibrate (Feno-F), are the mainstay for hypertriglyceridemia treatment, they may be associated with a risk of increased serum creatinine level and renal dysfunction. Pemafibrate (Pema) is pharmacologically defined as a selective peroxisomal proliferator-activated receptor α modulator which is excreted in bile and not likely to cause renal dysfunction. We evaluated the efficacy and safety of switching from Beza-F or Feno-F to Pema in CKD patients with hypertriglyceridemia. We recruited 47 CKD patients with hypertriglyceridemia who were receiving Beza-F, Feno-F, or eicosapentaenoic acid (EPA) but were switched to Pema from 2018 to 2021. A retrospective analysis of renal function and lipid profiles was performed before and 24 weeks after switching. CKD patients switching from EPA to Pema were used as study control. The effect of Pema on hypertriglyceridemia was equivalent to that of Beza-F or Feno-F. However, after switching to Pema, eGFR showed a marked average improvement of 10.2 mL/min/1.73 m2 (P < .001). Improvement in eGFR and levels of n-acetyl-ß-d-glucosaminidase and ß-2-microglobulin was observed only in cases of switching from Beza-F or Feno-F but not from EPA. Although Beza-F and Feno-F are useful medications for the treatment of hypertriglyceridemia, these are associated with a high risk of renal dysfunction. We also found that the deterioration in eGFR due to Beza-F or Feno-F is reversible with drug withdrawal and may not increase the risk for long-term renal dysfunction. We suggest that Pema may be an effective and safe treatment for hypertriglyceridemia in CKD patients.

March hemoglobinuria progressed to acute kidney injury after kendo practice: a case report.

BACKGROUND: March hemoglobinuria is caused by a hemolytic mechanism due to transient hematuria after physical exercise which, although rare, may lead to acute kidney injury. We report a case of a patient with march hemoglobinuria induced by kendo, which was diagnosed by the presence of Berlin blue iron staining in the proximal tubules through renal biopsy. CASE PRESENTATION: A 15-year-old male complained of fever (37 °C), general malaise, and nausea after hard kendo sessions. Laboratory findings revealed indirect bilirubin dominant hyperbilirubinemia (total bilirubin 3.8 mg/dL), high lactate dehydrogenase (LDH), and acute kidney injury (serum creatinine: 3.11 mg/dL and estimated glomerular filtration rate: 26 mL/min/1.73m2). Urine test was positive for occult blood but without hematuria. Renal biopsy was performed to clarify the cause of renal injury, which showed minor glomerular abnormalities. Meanwhile, hemosiderin deposition was identified in the proximal tubules by Berlin blue iron staining, and lysosomes were observed to contain granular iron. In addition to clinical background of strenuous kendo exercise, renal biopsy led to a definitive diagnosis of march hemoglobinuria. CONCLUSIONS: March hemoglobinuria is a hemolytic disease that can occur after intense exercise, especially kendo. Considering its rarity due to the lack of critical symptoms, it is important to note that occult blood-positive findings may be indicative of march hemoglobinuria if the patient underwent strenuous exercise. Therefore, clinicians should be aware of this possibility to provide timely and appropriate treatment.

A rare case of alveolar hemorrhage with hypertensive emergency.

INTRODUCTION: Alveolar hemorrhage presents with severe respiratory failure, requiring prompt diagnosis and treatment. Alveolar hemorrhage is often caused by autoimmune diseases accompanied by progressive renal dysfunction. However, few cases without autoimmune diseases occur, making diagnosis difficult. Here, we report a case of alveolar hemorrhage with hypertensive emergency. PATIENT CONCERNS: A 28-year-old man presented with dyspnea and bloody sputum. His blood pressure was 200/120 mm Hg. DIAGNOSIS: The chest computed tomography showed suggestive of alveolar hemorrhage. Renal dysfunction and proteinuria were observed. However, autoantibodies were not detected. Echocardiogram revealed left ventricular function decrease. Ejection fraction was 20% to 30% with no ventricular asynergy or any valvular diseases. Brain magnetic resonance imaging showed hyperintense lesions on fluid-attenuated inversion recovery in the white matter of both cerebral and right cerebellar hemispheres, which were compatible with posterior reversible encephalopathy syndrome. Renal biopsy did not reveal any immune-mediated glomerulonephritis or vasculitis, but hypertensive nephropathy was diagnosed. INTERVENTIONS: Blood pressure was controlled with combination therapy using calcium channel blocker, angiotensin II receptor blocker, α1 blocker, and ß blocker. OUTCOMES: Alveolar hemorrhage and proteinuria improved with strict blood pressure control. CONCLUSION: This case indicates that severe hypertension can possibly cause alveolar hemorrhage. Accumulating these cases is important for general physicians to diagnose the alveolar hemorrhage with hypertensive emergency in its early stage and to avoid unnecessary treatment such as immunosuppressive therapy.

IgA Nephropathy with Gross Hematuria Following COVID-19 mRNA Vaccination.

A 28-year-old woman experienced gross hematuria after the administration of the second dose of an messenger ribonucleic acid (mRNA) vaccine (BNT162b2). She was diagnosed with Immunogloblin A nephropathy (IgAN) by a renal biopsy two weeks after vaccination, which revealed a mild increase in mesangial cells and a matrix with co-depositions of galactose-deficient IgA1 and C3 in the mesangial region. The gross hematuria and proteinuria gradually improved without any medication, suggesting that immune activation by the mRNA vaccine may not elicit continuous disease progression of IgAN. Thus, further studies investigating the relationship between mRNA vaccines against COVID-19 and the progression of IgAN should be conducted.

Atypical histological abnormalities in an adult patient with nephronophthisis harboring NPHP1 deletion: a case report.

BACKGROUND: Nephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13-14 years old), and adolescent type (approximately 19 years old). Here, we report a case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities. CASE PRESENTATION: A 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary ß2-microglobulin was high (805 µg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP. CONCLUSIONS: NPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.

Suffocation due to Acute Airway Edema in a Patient with Hereditary Angioedema Highlighted the Need for Urgent Improvements in Treatment Availability in Japan.

A 42-year-old Japanese man with hereditary angioedema suffered accidental trauma to his jaw in Shizuoka Prefecture, Japan, which gradually caused facial edema. Since plasma-derived human C1 inhibitor (pdh C1-INH) was unavailable, he had to be transferred to Juntendo University Hospital in Tokyo. Due to his severe edema, he suffered asphyxiation leading to cardiopulmonary arrest upon arrival. The patient was resuscitated and promptly treated with pdh C1-INH. In Japan, the self-administration of pdh C1-INH is not allowed, and every prefecture does not always possess stocks of pdh C1-INH. This case emphasizes the need for urgent improvements in treatment availability in Japan.

Dendrin location in podocytes is associated with disease progression in animal and human glomerulopathy.

BACKGROUND: Adriamycin (ADR) nephrosis in mice has been extensively studied and has enabled a greater understanding of the processes underlying the progression of renal injury. Dendrin is a novel component of the slit diaphragm with proapoptotic signaling properties, and it accumulates in the podocyte nucleus in response to glomerular injury in mice. The present study re-evaluated chronic progressive nephropathy in ADR mice and the localization of dendrin in mice and in human glomerulopathy. METHODS: To investigate the localization of dendrin, a mouse model of nephrosis and glomerulosclerosis was used, in which ADR was injected once. WT-1-positive cells and apoptotic cells were counted in vivo and in vitro. To check the expression of dendrin in ADR mice, immunostaining and Western blot were performed. A survey of dendrin staining was performed on human kidney biopsy specimens. RESULTS: The injection of ADR induced proteinuria, podocyte loss and glomerulosclerosis. It also caused the relocation of dendrin from the slit diaphragm to the podocyte nucleus. We demonstrated the location of dendrin to podocyte nuclei in several cases of human glomerulopathy. The mean occurrence of dendrin-positive nucleus per glomerulus increased in several cases of human glomerulopathy. CONCLUSIONS: These findings suggest that the relocation of dendrin to the podocyte nuclei is useful as a novel marker of podocyte injury in human glomerulopathy.

Tensin is expressed in glomerular mesangial cells and is related to their attachment to surrounding extracellular matrix.

Glomerular expression of tensin was immunohistochemically studied in normal and diseased rat kidneys to determine whether tensin might be related to specific binding in individual glomerular cells. Normal rat kidneys displayed an intense immunofluorescence reaction for tensin along the basal aspects of proximal and distal tubule cells and parietal epithelial cells of Bowman's capsules. In glomeruli, a positive reaction for tensin was detected only in the mesangial areas. Immunoelectron microscopy revealed a positive reaction in the mesangial cell (MC) processes. RT-PCR and immunoprecipitation demonstrated mRNA and protein levels of tensin in cultured rat MCs. Mesangial tensin expression was decreased when the mesangium was injured by Habu snake venom. During the regenerative process after mesangiolysis, tensin expression was not detected in early-phase proliferating MCs that did not have extracellular matrix (ECM). The expression of tensin recovered in late-phase proliferating MCs, which became attached to regenerated ECM. It appears that tensin is related to MC attachment to surrounding ECM, which suggests that signal transduction regulated by tensin may be related to a specific mechanism of MC matrix regeneration. Furthermore, tensin can act as a marker for rat MCs because the expression of tensin was detected only in MCs in glomeruli.

Tensin is potentially involved in extracellular matrix production in mesangial cells.

Tensin, a focal adhesion protein, is expressed in renal tubular epithelial cells (TECs). Tensin-null mice develop multiple large cysts in the renal proximal tubules. However, the role of tensin in human glomeruli remains unclear. In this study, we assessed tensin localization in human kidney and interaction between tensin and other adhesion components. In human mesangial cells (MCs) and TECs, we confirmed mRNA and protein expressions of tensin by RT-PCR and immunoprecipitation. In normal kidney, immunohistochemistry revealed that tensin was localized in MCs and parietal epithelial cells as well as TECs. In biopsy specimens, the expression of tensin was significantly increased in areas of mesangial expansion in patients with IgA nephropathy and diabetic nephropathy. These results suggest that the expression of tensin is associated with extracellular matrix (ECM) production. In vitro, immunocytochemistry revealed that MCs express tensin mainly at the ends of actin stress fibers and apparently in the focal adhesion areas. Integrin alpha5, but not alpha1 and alpha3, colocalized with tensin. Vinculin and focal adhesion kinase (FAK) were coprecipitated by tensin, suggesting that tensin can mediate signal transduction between cell and ECM through these molecules. Tensin may play important roles in mesangial ECM production through an adhesion complex with integrin alpha5, FAK, and vinculin.

MAP-LC3, a promising autophagosomal marker, is processed during the differentiation and recovery of podocytes from PAN nephrosis.

Microtubule-associated protein 1 light chain 3 (LC3) is a unique modifier protein. LC3-I, the cytosolic form, is modified to LC3-II, the membrane-bound form, by a mechanism similar to ubiquitylation by E1- and E2-like enzymes, Apg7p and Apg3p, respectively. In the present study, we found that LC3-I is processed to LC3-II during the differentiation and recovery from puromycin aminonucleoside-induced nephrosis of podocytes. LC3 is especially expressed in the podocytes of rat kidney as the membrane-bound form LC3-II. Biochemical analysis using a conditionally immortalized mouse podocyte clone (MPC) revealed that LC3-I is processed to LC3-II during the differentiation of cells into mature podocytes and accumulates in the membrane-rich fraction of the cell lysate. LC3-II-localized vesicles, which differ from lysosomes and endosomes, in differentiated MPC cells are morphologically similar to autophagic vacuoles during starvation-induced autophagy. During starvation-induced autophagy, autophagosomes fuses with lysosome and LC3-II on autophagosomes is finally degraded by lysosomal proteases. However, in differentiated MPC cells, little LC3-II on the vesicles is degraded by lysosomal proteases, suggesting that little LC3-II-localized vesicles in differentiated MPC cells fuse with lysosome. Furthermore, the LC3-II level in differentiated MPC cells increases with recovery from damage caused by experimental puromycin aminonucleoside-induced nephrosis. These results suggest that LC3-II-localized vesicles play an important role in the physiological function of podocytes.