Hypereosinophilia-associated acute intradialytic hypotension: a report of three cases and literature review.

Occasionally, patients undergoing dialysis develop acute severe hypotension that requires interruption of dialysis within minutes of initiating every dialysis session. Although the underlying causes of recurrent intradialytic hypotension are evaluated extensively, including dialysis-associated allergic reactions or other possible causes, the definitive cause is sometimes missed. Dialysis is a life-sustaining procedure; therefore, prompt identification and management of the underlying cause of dialysis intolerance are crucial. Herein, we report three cases of patients undergoing dialysis who presented with hypereosinophilia-associated acute intradialytic hypotension. All three patients developed acute severe hypotension within minutes after the start of every dialysis session. The prescriptions for dialysis were changed, but episodes of intradialytic hypotension persisted. Pretreatment with methylprednisolone given intravenously before the dialysis session was also ineffective. All patients had hypereosinophilia (> 1500/µL) of different etiology. Eosinophil-lowering therapy with 0.5 mg/kg of prednisolone given orally daily was initiated, and all of them could restart dialysis without any hypotensive episodes within a few days. Our case report and literature review indicated that hypereosinophilia, regardless of its etiology, could result in severe acute hypotension shortly after the start of dialysis session. The oral administration of prednisolone daily was highly effective on hypereosinophilia-associated intradialytic hypotension, while pretreatment with intravenous corticosteroid therapy just before dialysis had no effect. Hypereosinophilia-associated acute intradialytic hypotension is an under-recognized condition; therefore, clinicians need to be aware of this clinical entity and initiate effective treatment strategies. We also provide a brief summary of previously published cases.

Relapse of minimal change disease following the third mRNA COVID-19 vaccination: a case report and literature review.

Mass vaccination is the most important strategy to terminate the coronavirus disease 2019 (COVID-19) pandemic. Reports suggest the potential risk of the development of new-onset or relapse of minimal change disease (MCD) following COVID-19 vaccination; however, details on vaccine-associated MCD remain unclear. A 43-year-old man with MCD, who had been in remission for 29 years, developed nephrotic syndrome 4 days after receiving the third dose of the Pfizer-BioNTech vaccine. His kidney biopsy revealed relapsing MCD. Intravenous methylprednisolone pulse therapy followed by oral prednisolone therapy was administered, and his proteinuria resolved within 3 weeks. This report highlights the importance of careful monitoring of proteinuria after COVID-19 vaccination in patients with MCD, even if the disease is stable and no adverse events occurred during previous vaccinations. Our case report and literature review of COVID-19 vaccine-associated MCD indicated that MCD relapse tends to occur later after vaccination and slightly more often following the second and subsequent vaccine doses than new-onset MCD.

PRDM9 activity depends on HELLS and promotes local 5-hydroxymethylcytosine enrichment.

Meiotic recombination starts with the formation of DNA double-strand breaks (DSBs) at specific genomic locations that correspond to PRDM9-binding sites. The molecular steps occurring from PRDM9 binding to DSB formation are unknown. Using proteomic approaches to find PRDM9 partners, we identified HELLS, a member of the SNF2-like family of chromatin remodelers. Upon functional analyses during mouse male meiosis, we demonstrated that HELLS is required for PRDM9 binding and DSB activity at PRDM9 sites. However, HELLS is not required for DSB activity at PRDM9-independent sites. HELLS is also essential for 5-hydroxymethylcytosine (5hmC) enrichment at PRDM9 sites. Analyses of 5hmC in mice deficient for SPO11, which catalyzes DSB formation, and in PRDM9 methyltransferase deficient mice reveal that 5hmC is triggered at DSB-prone sites upon PRDM9 binding and histone modification, but independent of DSB activity. These findings highlight the complex regulation of the chromatin and epigenetic environments at PRDM9-specified hotspots.