Advancements in Research on Genetic Kidney Diseases Using Human-Induced Pluripotent Stem Cell-Derived Kidney Organoids.

Genetic or hereditary kidney disease stands as a pivotal cause of chronic kidney disease (CKD). The proliferation and widespread utilization of DNA testing in clinical settings have notably eased the diagnosis of genetic kidney diseases, which were once elusive but are now increasingly identified in cases previously deemed CKD of unknown etiology. However, despite these diagnostic strides, research into disease pathogenesis and novel drug development faces significant hurdles, chiefly due to the dearth of appropriate animal models and the challenges posed by limited patient cohorts in clinical studies. Conversely, the advent and utilization of human-induced pluripotent stem cells (hiPSCs) offer a promising avenue for genetic kidney disease research. Particularly, the development of hiPSC-derived kidney organoid systems presents a novel platform for investigating various forms of genetic kidney diseases. Moreover, the integration of the CRISPR/Cas9 technique into this system holds immense potential for efficient research on genetic kidney diseases. This review aims to explore the applications of in vitro kidney organoids generated from hiPSCs in the study of diverse genetic kidney diseases. Additionally, it will delve into the limitations of this research platform and outline future perspectives for advancing research in this crucial area.

Usefulness of BK virus-specific interferon-γ enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients.

BACKGROUND/AIMS: To investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). METHODS: We included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller (< 3 months) and noncontroller (> 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). RESULTS: BKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). CONCLUSION: BKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

Generation of a human induced pluripotent stem cell line (CMCi001-A) from a patient with karyomegalic interstitial nephritis with homozygous frameshift deletion mutation c.1985_1994del10 of the FANCD2/FANCI-Associated Nuclease 1 gene.

The human-induced pluripotent stem cell (KIN-hiPSCs) line (CMCi001-A), derived from peripheral blood mononuclear cells (PBMCs) of a 42-year-old woman with karyomegalic interstitial nephritis (KIN) caused by the mutation of FANCD2/FANCI-Associated Nuclease 1 (FAN1) gene, was generated using Sendai virus. KIN-hiPSCs showed a typical human embryonic stem cell like morphology and expressed all pluripotency-associated markers, and directly differentiated into all three germ layers. Karyotyping of PBMCs of the patient and KIN-hiPSCs showed 47, XXX. In summary, we generated a novel patient-specific hiPSC line containing the mutation of FAN1 gene and it can be used to provide additional insights for KIN pathophysiology.

Performance enhancement with low stress and anxiety modulated by cognitive flexibility.

OBJECTIVE: The purpose of this study was to compare cognitive flexibility abilities, stress, and anxiety between starters and non-starter athletes. METHODS: A total of 30 male professional-soccer and 40 professional-baseball athletes were recruited. Wisconsin Card Sorting Test (WCST) and Trail Making Test A & B (TMT A & B) were administered to assess cognitive flexibility during competition. The Korean version of the STAI form Y (STAI-KY) and Visual analogue scale for anxiety and stress were used to assess the anxiety and stress. RESULTS: The starter group had better cognitive function (fewer perseverative errors and rapid TMTB times) (Z=3.32, p<0.01; Z=2.20, p=0.03, respectively) and lower stress and anxiety (F=4.34, p=0.01; F=6.61, p<0.01, respectively) during competition than the non-starter group. CONCLUSION: The better cognitive performances were negatively correlated with stress and anxiety. Current results suggested that cognitive flexibility would enhance human performance by modulation of the anxiety and stress during competition.