Research Highlights

Transplantation, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes Sablik M, Sannier A, Raynaud et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2408835 Recognition microvascular inflammation (MVI) in the absence antidonor HLA antibodies or complement deposition on kidney allograft biopsies1 has led to updates Banff classification system. The "2019 Classification Renal Allograft Pathology" was revised include 2 new diagnostic categories "2022 Pathology."2 These are (1) injury, donor-specific antibody (DSA)-negative, C4d-negative; (2) probable antibody-mediated rejection (probable AMR) C4d deposition, including DSA-positive cases with mild MVI but no deposition. Despite these advances, clinical significance newly recognized phenotypes question whether they require treatment remain unclear. In current study, al3 reclassified 16 293 transplant biopsies according 2022 assess implications for graft outcomes. were obtained from >30 centers Europe North America between 2004 2023, a mixture for-cause protocol (approximately half half) per standard practice each center. Among cases, 641 previously identified as "nonrejection" assigned phenotype 1 (N = 391) 250). Additionally, 76 classified only "T cell–mediated rejection" 48) 28). Similarly, 71 "borderline 64) 7). Importantly, grafts showed significantly worse survival compared those not (hazard ratio, 2.1 1.7, respectively). Interestingly, infrequently associated circulating DSAs at time transplantation almost never biopsy, suggesting non-DSA-mediated mechanism injury. However, both had higher cumulative incidence AMR during follow-up without MVI, although high bona fide diagnosis AMR. risk glomerulopathy development progress also than albeit still lower findings underscore importance recognizing refined stratification prognostication facilitated more nuanced understanding heterogenous phenotypes, highlighting their distinct profiles alloimmune-mediated disease progression reduced long-term survival. Dissecting pathological processes underlying may ultimately reveal targeted therapies future trials aiming halt revert phenotypes. MVIs biopsies, demonstrated by this will undoubtedly accelerate mechanistic studies define non-DSA, non-B-cell-mediated mechanisms roles innate immune cells T cells, impact conventional immunosuppressive MVI. natural clinically relevant contexts be critical designing interventions that enhance efforts, likely starting preclinical models, pave way therapeutic advances managing improving longevity. A Kidney-specific Fasting-mimicking Diet Induces Podocyte Reprogramming Restores Function Glomerulopathy Villani V, Frank C, Cravedi P, Sci Transl 2024;16:eadl5514Dietary periods fasting gaining interest across broad spectrum diseases.1 Fasting appear have broadly positive effects, inducing cellular adaptive responses organ systems reduce metabolic oxidative stress. Preclinical shown significant promise dietary incorporating elements al2 comprehensively renal-specific protection fasting-mimicking diet (FMD) rat model glomerular Animals treated low-salt FMD restricted caloric intake 5 consecutive days every fortnight exhibited temporary changes physiological parameters, body weight, heart rate, respiratory exchange ratios, normalized nonfasting periods. Treated animals resilient chemically induced injury using puromycin aminonucleoside, showing reductions proteinuria markers function short long term. Spatial transcriptomics revealed an increase mass transcriptional program consistent regeneration repair. At single nucleus resolution, observed podocytes, mesangial tubular indicating improved cell functionality. mouse lupus nephritis, similar approach slowed markers. Furthermore, pilot study 13 patients immune-mediated disease, modest improvements approximately 500 mg/d, estimated filtration enhanced total weight increased lean mass. Markers inflammation, insulin-like growth factor C-reactive protein, reduced. long-lived, differences persisted up year postintervention. Although protective investigated involve tissue rather directly modulating immunological processes, type nevertheless anti-inflammatory effects provided benefits forms extended well beyond intervention period. Dietary date predominantly focused reduction.3 research raises possibility could play role attenuating chronic potentially mitigating drug toxicity calcineurin mammalian target rapamycin inhibitors. If dietary-based prolong transplantation, it would represent breakthrough, particularly given challenges outcomes despite 1-y rates exceeding 90%.4 Given broader evidence induce systems, compelling investigate approaches effective other models. As low-risk intervention, certainly warrants further investigation human studies.

Язык: Английский

Gut microbiota-derived metabolites: Potential targets for cardiorenal syndrome

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107672 - 107672

Опубликована: Фев. 1, 2025

The characteristic of cardiorenal syndrome (CRS) is simultaneous damage to both the heart and kidneys. CRS has caused a heavy burden mortality incidence rates worldwide. regulation host microbiota metabolism that triggers kidney an emerging research field promotes new perspective on cardiovascular risk. We summarize current studies from bench bedside gut microbiota-derived metabolites better understand in context metabolites. focused involvement pathophysiology CRS, including lipid cholesterol disorders, coagulation abnormalities platelet aggregation, oxidative stress, endothelial dysfunction, inflammation, mitochondrial energy vascular calcification renal fibrosis, as well therapeutic approaches targeting which provides innovative treatment approach for improve patient prognosis overall quality life.

Язык: Английский