A case of TAFRO syndrome after vaccination, successfully treated with cyclosporine.

BACKGROUND: TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. CASE PRESENTATION: An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. CONCLUSIONS: Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

Association Between Bone Mineral Density of the Distal Third of the Radius and Mortality in Patients on Hemodialysis, a Retrospective Cohort Study.

INTRODUCTION: Although several investigators have reported the relationship between bone mineral density (BMD) and mortality in patients on hemodialysis, it is unclear BMD of which site is most strongly associated with mortality. METHODS: We examined the factors related to fractures in patients on hemodialysis in 2009. Based on these data, we investigated the influence of BMD of different sites on mortality in this cohort of 81 patients on hemodialysis. BMD was measured at the distal third of the radius (1/3 Rad), lumbar spine, and total hip. Fifteen patients had prevalent vertebral fractures and seven had prevalent hip fractures. The influences of age, body mass index (BMI), serum creatinine (Cr), serum albumin (Alb), dialysis vintage, and parathyroid hormone (PTH, measured as whole PTH) on mortality were also studied. RESULTS: Fifty-two patients died by August 31, 2018. BMD was significantly higher in the survival group than in the deceased group only for the 1/3 Rad group (P < .001). Although patients with prevalent hip or vertebral fractures showed a higher mortality rate than those without fractures, no significant difference was observed. In the deceased group, age was significantly higher, and BMI and Cr levels were significantly lower than those in the survival group (P < .001, P < .05, and P < .01; respectively). After adjustment for these parameters, BMD of the 1/3 Rad remained a significant prognostic factor. CONCLUSION: Although this was a study with a limited number of patients, BMD of the 1/3 Rad appears to be associated with mortality in patients on hemodialysis.

Saccharated ferric oxide attenuates haematopoietic response induced by epoetin beta pegol in patients undergoing haemodialysis.

BACKGROUND: Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis. Recently, erythroferrone (ERFE) has been identified as a factor that regulates hepcidin. In addition, fibroblast growth factor 23 (FGF23), which has been recognized as a phosphorus-regulating hormone, appears to be involved in haematopoietic regulation. Clarification of the detailed mechanism of haematopoiesis could lead to the improvement of renal anaemia treatment. METHODS: Epoetin beta pegol (CERA) was administered to patients undergoing haemodialysis at week 0, and the same amount of CERA with saccharated ferric oxide (SFO) was administered at week 4. The changes in haematopoiesis-related biomarkers, including ERFE, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), and inflammatory markers, were examined. RESULTS: Administration of CERA increased ERFE levels, decreased hepcidin levels, and stimulated iron usage for haematopoiesis, leading to an increase in reticulocytes (Ret) and haemoglobin (Hb). Simultaneous administration of SFO with CERA (CERA + SFO) significantly attenuated the responses of ERFE, Ret, and Hb compared with CERA alone. Although iFGF23 levels were not affected by either CERA or CERA + SFO, cFGF23 was significantly elevated from baseline after CERA. Since cFGF23 levels were not affected by CERA + SFO, cFGF23 levels after CERA + SFO were significantly lower than those after CERA alone. The ratio of iFGF23 to cFGF23 (i/cFGF23 ratio) was significantly higher after CERA + SFO than that after CERA alone. In addition, high-sensitivity C-reactive protein (hsCRP) levels were significantly higher after CERA + SFO than after CERA alone. CONCLUSION: Administration of SFO suppressed haematopoietic responses induced by CERA. Elevation of i/cFGF23 ratio and hsCRP could account for the inhibitory effects of SFO on haematopoiesis. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (ID UMIN000016552 ).

Twice-monthly administration of a lower dose of epoetin beta pegol can maintain adequate hemoglobin levels in hemodialysis patients.

Epoetin beta pegol is a continuous erythropoietin receptor activator (CERA) with a long half-life. Although CERA has been shown to maintain adequate hemoglobin (Hb) levels at prolonged dosing intervals, the optimal dosing schedule remains unclear. We therefore compared the efficacy of maintaining hemoglobin levels with administration of twice-monthly CERA (TWICE) versus once-monthly CERA (ONCE). Twenty hemodialysis patients receiving epoetin beta (EPO) were enrolled in this crossover study. Patients were assigned to either the TWICE or the ONCE group based on matching Hb levels and EPO doses. After 6 months of treatment, the CERA dosage was interchanged between the groups and the study was continued for an additional 6 months. The effect of the different regimens on iron metabolism was also assessed during the first 6 months of the study. Hb levels significantly increased in the TWICE group, allowing for a reduction in CERA dosage, while the dose of CERA required to maintain Hb levels in the ONCE group remained unchanged. After the interchange, a decrease in Hb levels with incremental increase in CERA dosage was observed in the TWICE→ONCE group, with the opposite effect observed in the ONCE→TWICE group. Although increases in ferritin and hepcidin-25 levels in the ONCE group were noted at one month, they disappeared at 6 months. Although Hb levels were maintained in both the ONCE and TWICE groups, a twice-monthly administration was advantageous, as it required a lower dose of CERA.

Comparison of 2-week versus 4-week dosing intervals of epoetin beta pegol on erythropoiesis and iron metabolism in hemodialysis patients.

Epoetin beta pegol (a continuous erythropoietin receptor activator; CERA) is usually administered once in 4 weeks or once monthly. However, the optimal dosing interval remains unknown. We, therefore, compared the effect of CERA administration between dosing intervals of 2 weeks (TWICE group) and 4 weeks (ONCE group) on erythropoiesis and iron metabolism in 20 hemodialysis patients. CERA was administered intravenously at weeks 0 and 2 for the TWICE group, and at week 0 for the ONCE group. Levels of hemoglobin (Hb), reticulocyte count, ferritin, transferrin saturation, content of Hb in reticulocytes and hepcidin-25 were monitored weekly for 4 weeks. Hemoglobin levels were significantly increased at weeks 3 and 4 in the TWICE group, while a gradual decrease after a significant increase at week 1 was observed in the ONCE group. Ferritin levels remained significantly low from week 1 to week 4 in the TWICE group. On the other hand, ferritin levels increased beyond baseline levels at week 4 in the ONCE group. Although hepcidin-25 did not significantly increase in the TWICE group, significant increases beyond baseline levels at weeks 3 and 4 were found in the ONCE group. These results indicate that continuous erythropoiesis was achieved with biweekly administration of CERA. Moreover, CERA at a 2-week interval led to a sustained suppression of ferritin and hepcidin-25 levels, suggesting a favorable influence on iron metabolism.

Calcification of the thoracic aorta determined by three-dimensional computed tomography predicts cardiovascular complications in patients undergoing hemodialysis.

PURPOSE: In patients on dialysis, the most common cause of death is cardiovascular disease. This is caused, at least in part, by excessive vascular calcification. Studies that have examined coronary calcification have been published, but these measurements require expensive equipment. Here, we used computed tomography to determine aortic calcification and evaluated these data as prognostic markers for cardiovascular disease. METHODS: Computed tomography with contrast medium was performed on 49 patients undergoing hemodialysis (29 males and 20 females; average age, 68.9 ± 11.0 years). A calcification score (CS) was defined as the ratio of the volume of vascular calcification to the volume of the thoracic aorta. All patients were monitored for cardiovascular end points, which included cerebral infarction or hemorrhage, myocardial infarction, electrocardiographic, or echocardiographic abnormalities that suggested myocardial ischemia, cardiac surgery, leg amputation, and hospitalization or death due to heart failure. RESULTS: Patients were followed for 3 years, with 12 patients reaching the end point. Both high CS (p = 0.007) and male gender (p = 0.009) were significantly associated with cardiovascular events. In contrast, events were not related to age, dialysis duration, diabetes mellitus, smoking status, low-density lipoprotein cholesterol level, pulse-wave velocity, maximum intima-media thickness of the carotid artery wall, systolic blood pressure, or left ventricular hypertrophy. Multiple logistic regression analysis revealed that a high baseline CS was a significant predictor for cardiovascular events (p < 0.05). CONCLUSIONS: Calcification of the thoracic aorta determined by three-dimensional computed tomography predicts cardiovascular complications in patients on hemodialysis.

Relationship between biochemical markers and radial cortical bone changes in hemodialysis patients.

BACKGROUND/AIM: Bone loss in patients with osteoporosis may be predicted by the elevation of biochemical markers of bone turnover. Therefore, we studied the relationship between biochemical markers, including parathyroid hormone (PTH), and the 2-year change in radial cortical bone in patients under chronic hemodialysis. METHODS: Tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, whole PTH, and total intact PTH were measured in 53 patients under maintenance hemodialysis. Additionally, radial cortical bone mineral density (BMD) and relative cortical area (RCA) were measured by peripheral quantitative computed tomography 2 years apart. RESULTS: In all patients, BMD decreased by 2.5% and RCA decreased by 5.8% during 2 years. TRACP-5b levels significantly correlated with decreased RCA in all and female patients, but not with decreased BMD. Bone-specific alkaline phosphatase correlated with decreased BMD in all patients and with decreased RCA in all and female patients. Whole PTH did not correlate with decreased RCA or BMD. Total intact PTH significantly correlated with decreased BMD in all and male patients and with decreased RCA in all and female patients. In stepwise multiple regression analysis, TRACP-5b and total intact PTH were selected as explanatory variables for decreased RCA and decreased BMD, respectively. CONCLUSION: These results suggest that TRACP-5b and total intact PTH are powerful markers to predict radial cortical bone loss in hemodialysis patients.

[Two cases of systemic lupus erythematosus accompanied by antiphospholipid syndrome nephropathy without immune complex nephritis].

We report here two interesting cases of systemic lupus erythematosus(SLE) accompanied by antiphospholipid syndrome nephropathy(APSN). These cases satisfied the criteria for SLE established by the American College of Rheumatology 1997 and also satisfied the criteria for antiphospholipid syndrome (APS) established by the Sapporo International Workshop of APS 1998. Both cases had high blood pressure with elevated plasma renin activity, proteinuria and renal dysfunction. Their biopsied renal specimens showed the characteristic findings for APSN, such as mesangial proliferation, double contours, thickening of the capillary loops, and intimal hyperplasia, but there was no evidence for immune complexes in the glomeruli, which were examined by the indirect immunofluorescence methods and the electron microscopy method. These results indicated that their renal dysfunction was caused by APSN, but not by immune complex nephritis. In addition to treatment with prednisolone, they were administered anticoagulants(warfarin, or aspirin, or heparin) for APSN and an angiotensin II receptor blocker, candesartan, for the hypertension. Subsequently, their conditions recovered with the improvement of renal function and hypertension. Our experiences suggest that anticoagulant therapy in addition to corticosteroids offers advantages in the treatment of patients with SLE accompanied by APSN and renal dysfunction.