INTRODUCTION:Kidney transplantation is the most effective treatment for end stage kidney disease. However, the long-term survival rate of graft kidney has not been significantly improved. It has been found that the expression and interaction of T cell immunoglobulin mucin 3 and high mobility group protein B1 play a crucial role in cellular immune regulation and inflammatory response in recent years. Further investigation is needed to explore the changes in T cell immunoglobulin mucin 3 and high mobility group protein B1 expression in kidney transplant recipients and their correlation with graft function. RESULTS:Vitamin D supplementation significantly increased serum 25(OH)D concentrations (85.66 ± 19.15 vs. 54.64 ± 24.97 nmol/L) and decreased iPTH levels (10.05 ± 11.53 vs. 31.14 ± 17.13 pmol/L) in the treated group compared with the untreated group at 12 months post-transplant. eGFR was also significantly higher in the treated group (66.75 ± 18.77 vs. 58.34 ± 25.13 mL/min per 1.73 m2) during the follow-up. Both sTim-3 (82.94 ± 16.93 vs. 110.36 ± 18.77 pg/mL) and HMGB1 (59.35 ± 17.78 vs. 79.69 ± 13.42 pg/mL) levels in the treated group showed a prominent and constant decreasing trend and were significantly lower compared to those in the untreated group. Multifactorial regression analysis indicated that vitamin D supplementation after transplantation was an independent predictor of sTim-3 and HMGB1 Levels at 12 months post-transplant. CONCLUSION:Post-transplant vitamin D supplementation was helpful in decreasing sTim-3 and HMGB1 levels, which might be associated with a better graft function at 12 months post-transplant.

Chronic kidney disease (CKD) and renal allograft failure represent escalating global health burdens characterized by progressive tissue remodeling. Although interstitial fibrosis and tubular atrophy (IF/TA) are the primary determinants of long-term prognosis, their assessment currently relies on invasive kidney biopsies, which are unsuitable for longitudinal monitoring. Here, we identify soluble T-cell immunoglobulin and mucin domain-containing protein 3 (sTIM-3) as a robust, non-invasive indicator of renal histopathology and clinical outcomes. In this multi-cohort study, we enrolled 256 kidney transplant recipients (KTRs) with allograft biopsies, 442 native CKD patients with biopsy-confirmed diagnoses, and 44 KTRs with longitudinal follow-up. Pre-biopsy plasma sTIM-3 levels were quantified by ELISA and analyzed for associations with renal function, histopathological parameters, and adverse outcomes. We found that elevated sTIM-3 levels consistently correlated with impaired renal function across diverse etiologies. Notably, post-transplantation sTIM-3 exhibited slower decline kinetics compared to estimated glomerular filtration rate (eGFR), suggesting that it may reflect active tissue remodeling rather than transient functional shifts. Histopathological analyses revealed that sTIM-3 levels increased progressively with IF/TA severity, demonstrating good discriminative capacity for moderate-to-severe fibrosis. Furthermore, in KTRs, elevated sTIM-3 predicted both allograft failure and rapid eGFR decline, with its prognostic value for the latter persisting after adjustment for eGFR and urine protein. Collectively, these findings establish sTIM-3 as a non-invasive biomarker reflecting tubulointerstitial fibrosis and adverse outcomes across diverse kidney disease settings, offering complementary information to conventional functional markers.

Renal fibrosis is the inevitable and irreversible consequence for chronic kidney disease (CKD). While organoid technology shows promise for modeling this process, statically cultured kidney organoid remains restricted, lacking the structural complexity or microenvironmental dynamics required to recapitulate CKD-associated fibrosis, thereby limiting its applications to anti-fibrotic research. To address such a bottleneck, we systematically leveraged microfluidic technology and developed a computer numerical control-fabricated kidney organoid chip (KOC). Comprised of a reservoir chamber and an organoid culture chamber, the KOC generates stable, high-flow shear stress in the culture chamber via connection to a peristaltic pump, enabling rapid production of a large number of kidney organoids. Morphology and gene expression evaluation of organoids in the KOC revealed that flow shear stress enhances renal tubular epithelial development and induces endogenous vascular endothelial formation. For practical application, the KOC was used to establish an in vitro renal fibrosis model by introducing the profibrotic inducer transforming growth factor-beta 1. Both protein and gene level analyses confirmed the presence of extracellular matrix deposition, epithelial-mesenchymal transition, and fibroblast-to-myofibroblast transition in this KOC-based fibrosis model, highlighting its potential as a valuable tool for anti-fibrotic drug development.

A high prevalence of vitamin D deficiency and insufficiency has been documented among individuals who have undergone kidney transplantation. The efficacy of post-transplantation vitamin D therapy remains inconclusive when examined through isolated studies. Therefore, a meta-analytic approach was employed to consolidate current literature and assess the influence of vitamin D supplementation on recipient outcomes following renal transplantation. Included were randomized controlled trials and prospective cohort studies related to kidney transplantation, as well as research examining the impact of regular vitamin D supplementation on outcomes following kidney transplantation. 8 studies ultimately satisfied selection criteria for this review. The temporal scope of included studies stretched from 2005 to 2025, encompassing patient populations between 79 and 536 recipients per investigation. Post-baseline surveillance periods diverged substantially, measuring 12 through 24 months. Vitamin D was administered at daily doses between 800 IU and 7000 IU. Supplementation produced significant elevation in 25(OH)D concentrations. A downward trend in parathyroid hormone levels was observed following vitamin D supplementation, though this reduction did not reach statistical significance. Notably, this was achieved safely without provoking hypercalcemia. Post-operative femoral neck bone mineral density T-score additionally showed improvement with vitamin D intervention. Post-transplant nutritional vitamin D supplementation increased serum 25(OH)D levels and improved femoral neck bone mineral density t-score in kidney transplant recipients. A downward trend in parathyroid hormone was observed but did not reach statistical significance. Whether vitamin D supplementation improves post-transplant bone disease remains uncertain and requires further investigation. Registered at PROSPERO with identification number CRD420251009160.

INTRODUCTION:ABO-incompatible (ABOi) kidney transplantation (KT) is now an established form of renal replacement therapy. However, it is important to note that ABO antibody clearance affects the procedure's success. As demonstrated in prior studies, both double-filtration plasmapheresis (DFPP) and plasma exchange (PE) can eliminate IgM and IgG isoagglutinins. However, relatively few studies have examined the long-term prognosis in patients with both conditions. The present study aimed to compare the efficacy and long-term prognosis of DFPP with those of PE in patients with ABOi-KT. METHODS:From September 2014 to April 2024, 230 consecutive ABOi living-donor KTs were performed. The participants were divided into DFPP and PE groups. Following propensity score matching (PSM), the primary outcomes included acute rejection (AR), infection, graft loss, patient death, and the effects of the two modalities on isoagglutinin titers (IgG and IgM). RESULTS:After 1:4 PSM, a total of 24 patients in the PE group and 63 patients in the DFPP group were included in the final analysis. Compared with PE, DFPP was associated with a significantly lower incidence of 6-month AR (6.3% vs. 33.3%, p = 0.003) and 6-month patient mortality (0% vs. 12.5%, p = 0.019), along with shorter hospital stays (22 [18-29] vs. 42 [36-48] days, p < 0.001). Multifactorial analysis revealed that the risk of AR in ABOi-KTs with antibody rebound was 6.43 times greater than that in ABOi-KTs without antibody rebound (OR = 6.43, 95% CI: 1.21-34.1, p = 0.029), whereas the risk of AR in ABOi-KTs pretreated with DFPP was 85.8% lower than that in ABOi-KTs pretreated with PE (OR = 0.142, 95% CI: 0.04-0.57, p = 0.006). However, no statistically significant differences were observed between the two groups in 6-month creatinine levels or 6-month graft loss. No significant differences were observed between the two groups in the reduction of IgG and IgM isoagglutinins. A single PE session led to a reduction in the IgM isoagglutinin titer by approximately 3-fold, in comparison with a 2-fold reduction that was observed with a single session of DFPP. Similarly, a single PE session led to a 2-fold reduction in IgG isoagglutinin titer. DFPP sessions resulted in a reduction that was marginally less than 2-fold. It is noteworthy that DFPP exhibited a more pronounced depletion of albumin (10.6 ± 6.7 vs. 4.8 ± 5.5 g/L, p < 0.001), globulin (10.4 ± 6.5 vs. 5.5 ± 5.7 g/L, p = 0.002), and fibrinogen (1.5 [1.2-2.2] vs. 1.1 [0.1-1.9] g/L, p = 0.024). CONCLUSIONS:Compared with PE, DFPP might be more advantageous in the ABOi-KT preconditioning regimen, but close monitoring of fibrinogen, albumin, and globulin is needed.

Vitamin D deficiency or insufficiency is prevalent among kidney transplant recipients. Reliable conclusions regarding post-transplant vitamin D supplementation in this population are lacking from any single trial. We conducted a meta-analysis to aggregate the available evidence and analyze the impact of vitamin D supplementation on the outcomes of kidney transplant recipients. We conducted a systematic literature search in the PubMed, Web of Science, and Cochrane databases. The included articles compared the clinical efficacy of vitamin D supplementation in kidney transplant recipients by evaluating various parameters. A total of 9 studies were included. The studies reviewed spanned the period from 2005 to 2023, with the number of recipients ranging from 79 to 536. The mean age of KTRs varied from 39 to 54 years, and the percentage of male participants ranged from 49% to 58%. The total follow-up duration across the studies varied from 12 to 27.7 months. Dose of vitamin D ranged from 800 to 7000 IU daily. There was a significant improvement in 25(OH)D levels (WMD 11.63 ng/ml, 95% CI 5.71–17.55). Post-transplant vitamin D supplementation was linked to lower levels of parathyroid hormone without increasing the risk of hypercalcemia (P = 0.049). Additionally, vitamin D supplementation was associated with higher post-transplant femoral neck bone mineral density scores (P = 0.036). No correlation was found between vitamin D supplementation and serum creatinine levels. Sensitivity analyses showed good stability of the pooled results. Post-transplant vitamin D supplementation in kidney transplant recipients significantly improves hyperparathyroidism, increases femoral neck bone mineral density, and alleviates post-transplant bone disease.

Epigallocatechin gallate (EGCG), a major catechin in tea, has been linked to various health outcomes; however, its association with kidney function remains unclear. This cross-sectional study included 5001 participants from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). Daily EGCG intake was estimated from two 24-h dietary recalls. Kidney function outcomes included chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). Multivariable logistic and linear regression models were used to assess associations, and restricted cubic spline (RCS) models were applied to examine potential nonlinear relationships. Per 100 mg/day higher EGCG, CKD odds did not change meaningfully: crude OR 1.03 (95% CI 0.93-1.15; p = 0.59) and adjusted OR 1.09 (0.97-1.23; p = 0.14). By contrast, EGCG was inversely related to eGFR: crude β -1.01 mL/min/1.73 m2 (95% CI -1.59 to -0.43; p = 0.0006) and adjusted β -0.86 (-1.23 to -0.49; p < 0.001). UACR showed no significant associations: crude β -13.09 (95% CI -89.26 to 63.08; p = 0.736) and adjusted β -22.49 (-103.87 to 58.90; p = 0.588). RCS indicated a nonlinear association for CKD (p-overall = 0.021; p-nonlinear = 0.010) with an inflection near 48.750 mg/day; for eGFR, the overall association was significant (p-overall < 0.001) with a visually N-shaped curve and a turning point near 52.707 mg/day, though nonlinearity was not significant (p-nonlinear = 0.063). No overall or nonlinear relationships were observed for UACR (p-overall = 0.764; p-nonlinear = 0.752). Higher EGCG intake was consistently associated with lower eGFR, and a significant nonlinear association with CKD risk was identified, suggesting that the relationship between EGCG and kidney function may vary across intake levels. No association was observed with UACR.

Kidney transplantation is the most effective treatment for end-stage renal disease (ESRD). Previous studies have shown that post-transplant proteinuria is strongly associated with reduced long-term survival and graft function loss. Although SGLT-2 inhibitors have demonstrated efficacy in CKD, their role in KTRs, particularly those without diabetes, remains underexplored due to the complexity of post-transplant physiology and immunosuppressive therapies, which may alter drug efficacy and safety profiles. This study aimed to assess the efficacy and safety of dapagliflozin in proteinuric KTRs, irrespective of diabetes status. This prospective, real-world study enrolled 103 KTRs treated with dapagliflozin (ChiCTR2400087630). Mixed-effects repeated-measures models were used to assess changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) over 12 months, with subgroup analysis based on diabetes status to assess the efficacy of proteinuria reduction. Secondary efficacy outcomes included changes in routine blood and urine biomarkers, and safety outcomes were also evaluated. Significant reductions in UACR were observed at all post-baseline time points (P < 0.001, Fig. 1), indicating a decrease in proteinuria over time. Although eGFR showed a slight decline at month 12 (from 63.43 ± 18.58 mL/min/1.73 m² at baseline to 61.28 ± 19.44 mL/min/1.73 m²), this change was not statistically significant (P > 0.05, Fig. 2). Regardless of diabetes status, dapagliflozin was similarly effective in reducing proteinuria among KTRs, with no significant differences observed between the two groups (P > 0.05, Fig. 3). Additionally, there were notable improvements from baseline in red blood cell count (P = 0.01), hemoglobin (P = 0.029), fasting blood glucose (P < 0.001), serum magnesium (P < 0.001), and serum phosphorus (P = 0.007). The use of dapagliflozin did not significantly affect the stability of immunosuppressive drug concentrations, which remained within the therapeutic range throughout the study period. A total of 15 patients (14.6%) reported adverse events. The most common adverse event was urinary tract infection (7.8%), followed by kidney-related adverse events (4.9%). No serious adverse events or deaths were reported during the study. Dapagliflozin significantly reduced proteinuria in kidney transplant recipients, irrespective of diabetes status, and helped correct hypophosphatemia and hypomagnesemia. The drug demonstrated a favorable safety profile, with no serious adverse events and no significant impact on eGFR or immunosuppressive drug concentrations. These findings provide evidence for the anti-proteinuric efficacy and safety of short-term dapagliflozin in KTRs.

There is no consensus on the strategy for therapeutic drug monitoring of the immunosuppressive drug mycophenolic acid (MPA) in organ transplant recipients. The present study proposes the utilization of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for determining the concentrations of MPA and its metabolites: 7-O-mycophenolic acid glucuronide (MPAG) and acyl mycophenolic acid glucoside (AcMPAG) in peripheral blood mononuclear cells (PBMCs). We aimed to assess the potential application of monitoring MPA and its metabolite concentrations in PBMCs in the infection after transplantation in Chinese kidney transplant recipients (KTRs). The UPLC-MS/MS method we developed demonstrated good linearity in the quantitative ranges of 0.05-50.00 ng/mL for MPA, 0.50-50.00 ng/mL for MPAG, and 0.10-20.00 ng/mL for AcMPAG. AcMPAG in PBMCs was unstable, degrading significantly after 48 h of storage at -80 degrees C or after 3 freeze-thaw cycles. MPA and MPAG concentrations in KTRs' PBMCs exhibited high inter-individual variability, and the MPA concentration in PBMCs was poorly correlated with that in plasma (rs = 0.206, p = 0.117). Compared with the stable group, the infected group had significantly higher MPA concentration in PBMCs at 2 and 4 h post-dosing and in plasma at 4 h post-dosing (p < 0.05). The receiver operating characteristic (ROC) analysis for post-transplantation infection revealed that PBMCs MPA-C4 and PBMCs-MPA-C2 possessed much better diagnostic efficiency than Plasma-MPA-C4. This method is easy-to-use and reliable, making it a promising clinical quantitative tool for MPA, MPAG, and AcMPAG in PBMCs. PBMC-MPA monitoring may be a potential biomarker for infection monitoring for KTRs.

This study represents 2 cases of kidney transplant recipients (KTRs) with invasive pulmonary Rhizopus infection, successfully treated with oral isavuconazole monotherapy without lobectomy. The rapid detection via mNGS of bronchoalveolar lavage fluid enabled early diagnosis and timely intervention, resulting in complete recovery and stable graft function. The literature review revealed a 16.7% mortality rate among 13 cases, with a higher mortality rate of 66.7% among patients receiving antifungal treatment without surgical intervention. Our findings underscore the efficacy of isavuconazole as a first-line monotherapy, characterized by lower nephrotoxicity and fewer interactions with immunosuppressants, and emphasize the crucial role of metagenome next-generation sequencing (mNGS) in early diagnosis of invasive mucormycosis in high-risk population.

Tea consumption has garnered significant attention due to its rich polyphenolic compounds and associated health benefits. However, existing research primarily focuses on the quantity of tea intake, while studies examining tea consumption timing remain limited. Given the circadian rhythm of kidney function and its metabolic implications, this study investigated the association between tea consumption timing, estimated glomerular filtration rate (eGFR), and chronic kidney disease (CKD) risk. Based on NHANES data from 2005 to 2018, 40,496 participants were included. Participants were grouped into high, medium, low, and non-tea intake groups. Additionally, tea consumption timing was categorized into four periods: dawn to noon, noon to afternoon, afternoon to night, and night to dawn. Multivariate regression models and restricted cubic spline models were employed to evaluate the associations between tea consumption timing, intake levels, and eGFR. Tea consumption timing showed a significant time-dependent association with eGFR levels. After adjusting for confounders, dawn-to-noon tea consumption demonstrated the strongest positive association with higher eGFR (3.18 mL/min/1.73 m2, p < 0.001), followed by noon to afternoon (1.12, p < 0.001) and afternoon to night (0.71, p < 0.01). Stratified analyses revealed that daytime tea consumption was significantly associated with higher eGFR levels in middle-aged and older groups, whereas nighttime tea consumption in the younger group showed a slight adverse association. Analyses by tea type showed consistently positive associations for black tea, while green and other teas showed more variable results. This study underscores the significant association of tea consumption timing on kidney function, with the strongest associations observed during the dawn-to-noon period. Given the cross-sectional design of this study, only associations were identified; thus, future longitudinal studies are necessary to confirm these findings. Adjusting tea timing may be a potential dietary consideration for CKD prevention, but further studies are warranted.

Kidney transplantation (KT) is considered the most effective treatment for end-stage renal disease (ESRD), and it significantly contributes to enhancing the quality of life and extending the survival of patients with ESRD. After kidney transplantation, the early and heavy use of immunosuppressants and glucocorticoids can affect the recipients' immune status to varying degrees, increasing the risk of postoperative infections caused by a wide range of pathogens. Thus, the prevention and management of infectious diseases are major factors contributing to improved outcomes in kidney transplantation. Protein-energy wasting (PEW) is commonly observed in uremic patients, and it may persist even after they have undergone kidney transplantation (KT). And PEW is a significant factor in the progression of chronic kidney disease (CKD). Providing appropriate dietary guidance and intervention is essential for enhancing the immune status of recipients, promoting a positive nitrogen balance in the body, minimizing infections, and safeguarding graft function. This study aimed to investigate the relationship between daily protein intake (DPI) and postoperative infections at 3 months post-transplant, which may establish a foundation for the early postoperative protein intake regimen, reducing the incidence of postoperative infections, and improving the early prognosis of kidney transplantation. This is a retrospective observational study. 176 kidney transplant recipients (KTRs) who underwent kidney transplant in West China Hospital from December 2021 to June 2022 were included and followed up regularly. 24-hour urine urea data were collected at months 1 and 3 post-transplant to calculate their DPI. These KTRs were further divided into two groups according to the recommended DPI for KTRs by the 2021 Practice Guidelines for the Nutritional Management of Chronic Kidney Disease, namely high intake group (Group 1, with DPI ≥ 1.4g/kg·d, n = 66) and low intake group (Group 2, with DPI < 1.4g/kg·d, n = 110). Occurrence of hospitalization and postoperative infections within 3 months were recorded. Multiple logistic regression was utilized to analyze the association between DPI and early postoperative infections at 3 months post-transplant. Mean DPI levels at month 1 post-transplant were 1.58 ± 0.22 g/kg·d in Group 1 and 1.02 ± 0.31 g/kg·d in Group 2, respectively (P < 0.05), this huge difference in DPI between the two groups continued to month 3. There was no significant difference in age, gender, pre-transplant body mass index (BMI), dialysis type and time, donor type, or the ratio of delayed graft function (DGF) between the two groups. There was a statistically significant difference in the percentage of hospitalization between the two groups during the postoperative period of 3 months (P = 0.027). Pneumonia was the most common reason of hospitalization after transplantation, followed by urinary tract infection. The results of multiple logistic regression analysis showed that higher DPI in the early post-transplant period was a protective factor for infection after kidney transplantation. In the early post-transplant period, consuming higher levels of dietary protein may reduce the risk of infections and complications, and help preserve the function of the transplanted kidney.

The use of immunosuppressants and glucocorticoids after transplantation will affect the recipients’ metabolism and aggravate their malnutrition. Adequate daily protein intake in the early post-transplant period facilitates the rapid recovery of surgical wounds. This study aimed to explore the relationship between daily protein intake and graft function in the early post-transplant period, which may provide a basis for clinical nutritional management of kidney transplant recipients. This is a retrospective observational study. 176 kidney transplant recipients who underwent kidney transplant in West China Hospital from December 2021 to June 2022 were included. 24-hour urine urea nitrogen data were collected at 1 month and 3 months post-transplant to calculate daily protein intake. These KTRs were further divided into two groups according to the recommended daily protein intake for KTRs by KDOQI Clinical Practice Guideline for Nutrition in CKD, namely High group (with DPI ≥ 1.4 g/kg·d, n = 66) and Low group (with DPI < 1.4 g/kg·d, n = 110). Laboratory data and post-transplant adverse events within 3 months were recorded. Linear regressions were used to analyze the relationship between DPI and early post-transplant recovery as well as graft function. Recipients were divided into High and Low protein intake groups according to their daily protein intake 3 months after transplantation. The estimated glomerular filtration rate measured at three months post-transplant was significantly greater in the High protein intake group compared to the Low protein intake group (67.32 mL/min per 1.73 m2 vs. 58.88 mL/min per 1.73 m2, p = 0.044). Supporting this result, multiple regression analysis revealed that higher protein intake early after transplantation was a significant protective factor for graft function (p = 0.014). In the early post-transplant period, increased daily protein intake was linked to improved kidney graft function, lipid metabolism, and hemoglobin levels. Higher protein intake during this early post-transplant phase independently contributed to protecting graft function after kidney transplantation. Long-term protein intake regimens should be customized based on kidney function evaluated one year after the transplantation. ChiCTR2500099186. (Registration Date 2025.03.19) Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Numerous patients with rheumatoid arthritis (RA) manifest severe syndromes, including elevated synovial fluid volumes (SF) with abundant immune cells, which can be controlled by TNF/JAK inhibitors. Here, we apply single-cell RNA sequencing (scRNA-seq) and subsequent validations in SF from RA patients. These analyses of synovial tissue show reduced density of SF-derived pathogenic cells (e.g., SPP1+ macrophages and CXCL13+CD4+ T cells), altered gene expression (e.g., SPP1 and STAT1), molecular pathway changes (e.g., JAK/STAT), and cell-cell communications in drug-specific manners in samples from patients pre-/post-treated with adalimumab/tofacitinib. Particularly, SPP1+ macrophages exhibit pronounced communication with CXCL13+CD4+ T cells, which are abolished after treatment and correlate with treatment efficacy. These pathogenic cell types alone or in combination can augment inflammation of fibroblast-like synoviocytes in vitro, while conditional Spp1 knocking-out reduces RA-related cytokine expression in collagen-induced arthritis mice models. Our study shows the functional role of SF-derived pathogenic cells in progression and drug-specific treatment outcomes in RA.

Somatic retinoblastoma 1 (RB1) loss is prevalent across different cancer types and is enriched in treatment-refractory tumors, such as castration-resistant prostate cancer (CRPC) and small-cell lung cancer, but cannot be considered as a direct druggable target. In this study, we revealed that the close proximity of nudix hydrolase 15 (NUDT15) and RB1 may result in their common somatic codeletion or epigenomic cosilencing in different cancer types and subsequent significant positive correlations of their expressions at the bulk transcriptional and single-cell levels. With clinical CRPC samples, co-loss of RB1 and NUDT15 were commonly observed (14 out of 21). Due to the contribution of NUDT15 deficiency to thiopurine-induced toxicity, exploiting a vulnerability conferred by RB1-NUDT15 loss raised the possibility of repurposing thiopurine (e.g., mercaptopurine) for precise therapeutics. A positive relationship between RB1/NUDT15 ploidy score and mercaptopurine drug sensitivity was found in 543 cancer cell lines. Experimentally, knocking-down NUDT15 sensitizes the cancer cell lines to mercaptopurine treatment by inhibiting cell cycle progression and increasing apoptosis, but does not induce mercaptopurine-related leucopenia in xenograft model. Our study elucidates the molecular basis for precise mercaptopurine therapy in RB1-deficient tumors and demonstrates how leveraging collateral lethality alongside drug repurposing uncovers targetable vulnerabilities in stratified patient cohorts.

The HLA-DRB1*16:76 allele differs from HLA-DRB1*16:02:01 by one nucleotide substitution (A > G) at position 37 in exon 1.