PDGFD

Renal fibrosis is a critical pathological process driving chronic kidney disease (CKD) and end-stage renal disease (ESRD). Early diagnosis is essential for timely intervention, yet traditional methods like renal biopsy are invasive and present significant limitations. Consequently, noninvasive techniques are gaining attention for renal fibrosis assessment. Biomarkers such as transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor D (PDGF-D) have been explored for monitoring fibrosis progression, though their specificity and reliability challenges persist. Emerging imaging techniques, including molecular and functional imaging, offer valuable structural and functional insights but remain limited in detecting early-stage fibrosis. Artificial intelligence (AI) has emerged as a promising tool to enhance diagnostic accuracy by integrating imaging and biomarker data. Machine learning algorithms applied to ultrasound, computed tomography, and magnetic resonance imaging have demonstrated improved predictive capabilities for renal fibrosis detection. Furthermore, AI-driven multimodal approaches, combining clinical, imaging, and biomarker data, provide new opportunities for accurate, noninvasive diagnosis and monitoring. Despite these advancements, challenges such as small sample sizes, lack of standardization, and AI model interpretability must be addressed. Future research should focus on refining noninvasive biomarkers, improving imaging techniques, and developing AI-driven models to enhance diagnostic accuracy and clinical applicability in renal fibrosis assessment. This review provides a comprehensive overview of recent advancements in noninvasive approaches for detecting renal fibrosis, highlighting their potential to advance clinical decision-making and ultimately benefiting CKD management and patient outcomes.

Adenosine deaminase deficient-severe combined immunodeficiency (ADA-SCID) is an inborn error of immunity characterised by pan-lymphopenia, failure to thrive, severe infections, autoimmunity, and non-immunological organ dysfunction secondary to accumulated cytotoxic adenine metabolites (Kohn et al. 2019). ADA-SCID has been associated with an increased risk of tumour growth, including dermatofibrosarcoma protuberans (DFSP), a locally aggressive fibroblastic neoplasm associated with PDGFB or PDGFD fusions (Gardner et al. 2024). Here, we present a 6-year-old boy with ADA-SCID (treated with family-matched haematopoietic cell transplant (HCT) at age 5 months) with a six-month history of atrophic, roughened, hyperpigmented plaques over his abdomen, back, neck and right medial thigh. Post-transplant, he maintained high donor chimerism (94% donor myeloid and B-lymphocyte; 91% donor T-lymphocyte). Five excision biopsies were performed: all showed a spindle cell lesion in the dermis, with subcutaneous extension in four specimens. Immunohistochemistry revealed diffuse CD34 positivity of the spindle cells, consistent with multicentric DFSP. The tumours demonstrated reduced cellularity and more eosinophilic cytoplasm compared with typical DFSP, findings characteristic of DFSP arising in the context of ADA-SCID. This case highlights the increased incidence and distinct histological features of DFSP in ADA-SCID. Further reporting of cases of DFSP occurring in ADA-SCID is needed to raise clinical awareness and to better define any temporal relationship to enzyme-replacement therapy, HCT or gene therapy. Careful dermatological surveillance is warranted in this patient population. Any new or abnormal skin lesions should prompt early referral, histopathological assessment, and tailored surgical management, preferably with Mohs’ micrographic surgery or wide local excision.

Muscle larvae of the mammalian parasitic nematode Trichinella spp. live in a senescent nurse cell (NC). The NC is formed from a portion of the invaded myofiber and muscle satellite cells that fuse with it. In continuation of our previous research, which documented a senescent phenotype in a fully developed NC analyzed 7 months post-infection, we show in this current study that cellular senescence is a primary event during NC establishment, and occurs as early as 26 days post-infection. At both stages of the formation process, 26 days and 7 months post-infection, the NC was found to express angiogenic factors: angiopoietin 2, interleukin 1β, matrix metallopeptidase 2, platelet-derived growth factor D, and vascular endothelial growth factor C. We hypothesize that the nuclei of the degenerating myofiber transforms the senescent program to the fusing satellite cells. Hypersecretory activity of the senescent NC may facilitate the development of a circulatory rete, which has long been known to accompany the formation of the NC-larva complex.