Rafael Noal Moresco

IgA nephropathy (IgAN) is a primary glomerular disease with various clinical features, disease progression, and therapeutic responses that affects people worldwide. Currently, risk stratification depends primarily on clinical variables, together with the Oxford MEST-C classification, which indicates structural damage. However, these approaches only provide a limited explanation of the molecular mechanisms responsible for the disease. Recent proteomic discoveries have enabled researchers to characterize proteins not only in blood plasma and urine but also in kidney tissues, opening new avenues for understanding the underlying biology of IgAN. Our review addresses existing findings in plasma proteomic studies and, at the same time, brings into the picture developments in urinary and tissue proteomic profiling, thereby demonstrating that molecular profiling has been essential for further understanding of IgAN pathogenesis. Several research studies highlight complement system dysregulation, immune system overactivity, extracellular matrix remodeling, and metabolic disturbances as the leading factors linked to disease activity and progression. Even after many years in biomarker discovery, the development and clinical application of single plasma-based molecules as markers for disease detection remain challenging. Proteomic signatures based on the various processes involved in a single disease consistently outperform single protein identification in describing complexity and distinguishing molecular endotypes. We also present the current status of proteomic-based profiling methods, cross-linking proteomics with other data sources, and the remaining clinical application barriers. Through the development of this technology, proteomics has not only enabled the discovery of new biomarkers but also provided a framework for viewing IgAN as a heterogeneous disease comprising distinct molecular endotypes. Overall, current evidence indicates that proteomics is evolving from biomarker discovery toward molecular disease classification, with the potential to improve prognostication, guide mechanism-based therapeutic selection, and advance precision nephrology in IgAN.

Cavity effusions are common in cats, and differentiating between transudates and exudates is essential for management. This study aimed to evaluate biomarkers in cats’ effusions to support differentiation. A total of 44 cats were included, and effusions were classified as transudate (TG) and exudate (EG). The following biomarkers were analyzed: matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), total protein (TP), glutathione S-transferase (GST), lactate dehydrogenase (LDH), albumin and globulin. For further analysis, effusions were classified as protein-rich transudate (PRT) and EG, and as neoplastic (NEO) or non-neoplastic (nNEO) for MMP-9 and GST evaluation. Non-neoplastic effusions were subdivided into exudates (nnEG) and transudates (nnTG) to assess MPO. MMP-9 was higher in EG (p= 0.022), as were MPO (p= 0.002), LDH (p= 0.030), TP (p< 0.0001), albumin (p= 0.004), globulin (p= 0.015), and cellularity (p< 0.0001). GST was higher in TG (0.048). ROC showed discrimination for cellularity (area under the curve - AUC = 0.98, p< 0.0001), MPO (AUC = 0.86, p< 0.0001), MMP-9 (AUC = 0.73, p= 0.036), and LDH (AUC = 0.72, p= 0.030). In EG, correlations occurred between MPO and TP (r= 0.619, p= 0.002), MPO and LDH (r= 0.624, p= 0.012), and LDH and TP (r= 0.546, p= 0.037). MPO was higher in PRT (p= 0.0258). No differences were observed for MMP-9 and GST between NEO and nNEO, whereas MPO was higher in nnEG (p= 0.0317). In conclusion, MPO emerged as a promising biomarker for classifying cats’ effusions, particularly in challenging scenarios.

Advanced oxidation protein products (AOPP) are generated from oxidation that is mainly promoted by the action of hypochlorous acid (HOCl) on proteins, such as albumin. However, new pathways and targets associated with AOPP formation must be identified and thoroughly evaluated. Non‐enzymatic post‐translational modifications (NEPTMs), such as protein carbamylation, are relevant in chronic kidney disease and other inflammation‐related processes. Therefore, the aim of this study was to determine whether incubating HOCl with gamma globulins promotes AOPP formation and whether potassium cyanate (KOCN)‐induced carbamylation of albumin and gamma globulins is a new pathway for AOPP formation. Solutions comprising 451 and 86 μM of albumin and gamma globulins, respectively, were incubated with HOCl (2 and 4 mM) and KOCN (150 nM and 150 μM) for 30 min, and then AOPP formation and the concentrations of protein carbonyl and homocitrulline were monitored. Notably, HOCl‐induced oxidation of gamma globulins and albumin increased AOPP production. Gamma globulins also generated a higher amount of AOPP than albumin. Exposure of albumin and gamma globulins to HOCl resulted in a significant increase in protein carbonyl content, whereas exposure to KOCN led to a significant increase in homocitrulline. These findings suggest that gamma globulins are a new target of AOPP and KOCN participates in an alternate pathway of AOPP formation, thereby providing a new hypothesis regarding the pathways of AOPP formation during inflammation.

Background: Cystatin C (CysC) is a biomarker used to assess kidney function. Produced by all nucleated cells, it is freely filtered by the glomeruli, and its serum levels increase rapidly following kidney injury. Establishing reference intervals (RIs) is fundamental for the clinical application of CysC, as these parameters vary with geographic region and ethnic origin. This study aimed to determine RIs for CysC in healthy children aged 5–11 years from public schools in Santa Maria, southern Brazil. Methods: We enrolled 134 healthy children (aged 5–11 years, both sexes). Cystatin C levels were measured via immunoturbidimetry, and RIs were defined by the 2.5th and 97.5th percentiles. Results: The RI for serum CysC was 0.59 to 1.10 mg/L. Sex-specific analysis revealed CysC RIs of 0.53–1.10 mg/L for females and 0.61–1.10 mg/L for males. Conclusions: These findings provide valuable insights for paediatric clinical decision-making in a previously unstudied population and underscore the need for further research to validate and refine the clinical applications of CysC in paediatrics.

Introduction: Insulin resistance (IR) is associated with diabetic kidney disease (DKD), and normoalbuminuric patients may present with renal tubular damage associated with insulin resistance (RTDAIR). In this context, the kidney injury molecule-1 (KIM-1) emerges as a useful biomarker for assessing tubular damage. Objective: To investigate the role of KIM-1 in the detection of RTDAIR in normoalbuminuric patients, as well as its relationship with HOMA-IR. Methodology: This was a cross-sectional study involving 82 normoalbuminuric patients with T2DM, divided into two groups according to HOMA-IR. Laboratory tests were performed, and data were analyzed using Student's t-test. A p-value < 0.05 was considered significant. Results: Patients with higher IR (HOMA-IR ≥ 2.77) had increased urinary KIM-1 (uKIM-1) concentrations (113.3 ± 65.0 ng/g creatinine), which may indicate incipient DKD. Conclusion: Increased HOMA-IR may be related to elevated uKIM-1 levels, suggesting that IR contributes to the development of RTDAIR. Furthermore, uKIM-1 may serve as a useful biomarker for its detection.

Resumo Introdução: A resistência à insulina (RI) está associada à doença renal diabética (DRD) e pacientes normoalbuminúricos podem apresentar lesão tubular renal associada à resistência à insulina (RTDAIR). Nesse contexto, a molécula de lesão renal-1 (KIM-1) se apresenta como um marcador útil para a avaliação da lesão tubular. Objetivo: Investigar o papel do KIM-1 na detecção de RTDAIR em pacientes normoalbuminúricos, bem como sua relação com o HOMA-IR. Metodologia: Estudo transversal envolvendo 82 pacientes com DM2 normoalbuminúricos, divididos em dois grupos pelo HOMA-IR. Foram realizados exames laboratoriais e os dados foram analisados utilizando o teste t de Student. Um valor de p < 0,05 foi considerado significativo. Resultados: Pacientes com maior RI (HOMA-IR ≥ 2,77) apresentaram concentrações de KIM-1 urinário (uKIM-1) mais elevadas (113,3 ± 65,0 ng/g creatinina), o que pode indicar DRD incipiente. Conclusão: O aumento do HOMA-IR pode estar relacionado à elevação do uKIM-1, sugerindo que a RI contribui para o desenvolvimento da RTDAIR. Além disso, o uKIM-1 pode ser um marcador útil para sua detecção.