Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Human Papillomavirus Infection of the Oropharyngeal and Laryngeal Squamous Papilloma: Disparities in Prevalence and Characteristics.

Human papillomavirus (HPV) infection has emerged as an etiologic factor of squamous papilloma (SP). The oropharynx and larynx are common sites of SP, but studies on the prevalence of HPV infection in these sites are lacking. This study aimed to evaluate and compare the prevalence and characteristics of HPV infection in oropharyngeal SP (OPSP) and laryngeal SP (LSP). HPV detection and genotyping data of patients with pathologically confirmed OPSP and LSP were retrospectively analyzed. A total of 119 patients were enrolled, consisting of 93 patients with OPSP and 26 patients with LSP. Of those patients, 13 patients with OPSP and 14 patients with LSP were positive for HPV infection, accounting for a prevalence of 14.0% and 53.8%, respectively (p < 0.001). The most prevalent genotype was HPV16 in OPSP and HPV6 in LSP. Over two-thirds (69.2%) of HPV(+)-OPSP infections were high-risk types compared with 14.3% of HPV(+)-LSP infections (p = 0.004). The prevalence of HPV infection in patients with OPSP and LSP demonstrated no differences in terms of age, sex, and smoking status. These results could provide a better understanding of HPV infection in OPSP and LSP and serve as a background for the epidemiology of HPV-related tumorigenesis of the oropharynx and larynx.

Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma via miR-876-3p.

Rationale: Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. Methods: The secretion profile was examined by utilizing an antibody microarray with conditioned medium obtained from the co-culture of OSCC cells and two types of primary CAFs. The effect of CAF-dependent factors on cisplatin resistance was investigated by utilizing conditioned media (CM) and extracellular vesicle (EVs) derived from CAFs. The impacts of candidate genes were confirmed using gain- and loss-of-function analyses in spheroids and organoids, and a mouse xenograft. Lastly, we compared the expression pattern of the candidate genes in tissues from OSCC patients exhibiting different responses to cisplatin. Results: When OSCC cells were cultured with conditioned media (CM) from the two different CAF groups, cisplatin resistance increased only under CAF-P CM. OSCC cells specifically expressed insulin-like growth factor binding protein 3 (IGFBP3) after co-culture with CAF-D. Meanwhile, IGFBP3-knockdown OSCC cells acquired cisplatin resistance in CAF-D CM. IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. Treatment with CAF-P EV carrying miR-876-3p antagomir decreased cisplatin resistance compared to control miRNA-carrying CAF-P EV. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients. Conclusion: These results provide insights for overcoming cisplatin resistance, especially concerning EVs within the tumor microenvironment. Furthermore, it is anticipated that the expression levels of GATA1 and miR-876-3p, along with IGFBP3, could aid in the prediction of cisplatin resistance.

Severe Acute Kidney Injury Associated with Transformation of Chronic Myelomonocytic Leukemia into Acute Myeloid Leukemia: A Case Report.

Chronic myelomonocytic leukemia (CMML) is a rare hematologic disorder that infrequently causes acute kidney injury (AKI). CMML can transform into acute myeloid leukemia (AML), which can be accompanied by a deterioration in kidney function. However, severe AKI due to extramedullary manifestations of AML is rare. Herein, we present the case of a 67-year-old male patient with CMML that transformed into AML with severe AKI necessitating hemodialysis. The cause of the AKI was the AML transformation. The patient, with stable kidney function after chemotherapy for CMML, presented with a sudden decline in kidney function. Hemodialysis was initiated because of severe AKI, and histopathologic evaluation of the kidney biopsy specimen revealed severe, diffuse mixed inflammatory cell infiltrates in the interstitium and c-kit-immunopositive myeloblast-like cells. A bone marrow biopsy was performed because of the kidney biopsy findings suggesting that leukemic infiltration led to the diagnosis of AML. The patient received chemotherapy for AML, and his kidney function recovered. As illustrated in this case, severe AKI can develop as an early extramedullary manifestation during transformation from CMML to AML. Therefore, in patients with CMML and rapidly declining renal function, transformation into AML should be considered and histopathologically confirmed by kidney biopsy.