image: Aberrant Glycosylation Drives Kidney Disease Pathogenesis. This schematic illustrates how abnormal glycosylation contributes to diverse kidney diseases: (A) galactose-deficient IgA1 in Henoch–Schönlein purpura nephritis, (B) IgG4 glycosylation defects in primary membranous nephropathy, (C) N-glycosylation changes in anti-GBM disease, (D) altered IgG glycosylation in lupus nephritis, and (E) polycystin glycosylation defects in autosomal dominant polycystic kidney disease. These molecular changes disrupt immune regulation, protein stability, and signaling pathways, driving renal inflammation, fibrosis, and structural injury.
Credit: Precision Clinical Medicine
Glycosylation, the process of attaching sugar chains to proteins, is emerging as a key regulator in kidney health and disease. This modification controls protein folding, stability, and cellular communication, yet when disrupted it contributes to major renal disorders, from immunoglobulin A nephropathy (IgAN) to diabetic kidney disease (DKD), autosomal dominant polycystic kidney disease (ADPKD), renal cancer, and acute injury (AKI). Recent advances in glycoproteomic technologies now allow researchers to map these complex sugar structures with high precision, linking aberrant patterns to disease progression and prognosis. Understanding how glycosylation influences renal physiology not only uncovers hidden disease mechanisms but also points to promising biomarkers and therapeutic strategies for better kidney care.
Kidney diseases affect nearly 700 million people worldwide and are a growing cause of mortality and health care costs. Chronic kidney disease (CKD) alone contributes to over 1.2 million deaths annually, with AKI as a critical precursor. Despite this burden, effective treatments remain limited. A major challenge lies in understanding the molecular modifications that reshape proteins and disrupt cellular balance. Among more than 300 known post-translational modifications, glycosylation is particularly significant, influencing over half of human proteins. Aberrant glycosylation alters immunity, metabolism, and signaling, making it central to the pathology of renal disease. Due to these challenges, deeper investigation of glycosylation in kidney health and disease is urgently needed.
A research team from Sichuan University and collaborators published a comprehensive review (DOI: 10.1093/pcmedi/pbaf017) on July 11, 2025, in Precision Clinical Medicine, highlighting how protein glycosylation shapes kidney disease. The study integrates molecular biology, glycoproteomics, and clinical evidence to show how changes in glycosylation drive immunological, metabolic, and oncogenic pathways in the kidney. By compiling evidence across multiple disorders, the authors emphasize glycosylation as both a mechanistic driver and a potential diagnostic and therapeutic target in renal medicine.
The review outlines how distinct glycosylation patterns underpin a spectrum of kidney diseases. In IgAN, defective O-glycosylation of immunoglobulin A1 (IgA1) creates galactose-deficient molecules that trigger immune complex deposition and renal inflammation. In DKD, hyperglycemia fuels excessive O-GlcNAcylation, disrupting mesangial cells, podocytes, and tubular structures, driving fibrosis and proteinuria. In ADPKD, abnormal glycosylation of polycystin-1 and polycystin-2 impairs calcium signaling and accelerates cyst formation. Renal cell carcinoma progression is tied to N-glycan biosynthesis pathways that enhance tumor invasion. Beyond disease mechanisms, the review emphasizes analytical innovations—such as mass spectrometry, lectin microarrays, and liquid chromatography—that enable precise mapping of glycans and identification of disease-specific biomarkers. Despite advances, major barriers persist: high analytical costs, lack of standardized protocols, incomplete databases, and limited integration with multi-omics. These challenges highlight why glycosylation remains both a frontier and a bottleneck in kidney research.
"Glycosylation acts as a hidden language of the kidney," said Prof. Yong Zhang, corresponding author of the review. "By decoding this glycan code, we can better understand how diseases initiate and progress at the molecular level. However, the complexity of glycan structures and the lack of standardized analytical tools mean that this field requires collaborative innovation. Bridging glycobiology with clinical nephrology will be essential for translating these discoveries into diagnostic biomarkers and therapeutic strategies that can directly benefit patients."
The findings underscore glycosylation as both a diagnostic and therapeutic frontier. Serum glycan signatures, such as galactose-deficient IgA1 in IgAN or altered IgG glycosylation in lupus nephritis, already show potential as biomarkers for disease activity. Therapeutically, modulating glycosylation enzymes or pathways could slow progression of DKD or prevent cyst growth in ADPKD. Looking ahead, integrating glycoproteomics with genomics, transcriptomics, and metabolomics may provide a systems-level view of renal disease. Ultimately, precision diagnostics and glycosylation-targeted therapies could transform kidney medicine, shifting from symptom management to molecularly guided interventions that improve patient outcomes.
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References
DOI
Original Source URL
https://doi.org/10.1093/pcmedi/pbaf017
Funding information
This study was supported by the National Key Research and Development Program of China (grant Nos. 2022YFF0608401, 2022YFF0608404, 2021YFF0702003-02) and the National Natural Science Foundation of China (grant No. 92478101).
About Precision Clinical Medicine
Precision Clinical Medicine (PCM) commits itself to the combination of precision medical research and clinical application. PCM is an international, peer-reviewed, open-access journal that publishes original research articles, reviews, clinical trials, methodologies, perspectives in the field of precision medicine in a timely manner. By doing so, the journal aims to provide new theories, methods, and evidence for disease diagnosis, treatment, prevention and prognosis, so as to establish a communication platform for clinicians and researchers that will impact practice of medicine. The journal covers all aspects of precision medicine, which uses novel means of diagnosis, treatment and prevention tailored to the needs of a patient or a sub-group of patients based on the specific genetic, phenotypic, or psychosocial characteristics. Clinical conditions include cancer, infectious disease, inherited diseases, complex diseases, rare diseases, etc. The journal is now indexed in ESCI, Scopus, PubMed Central, etc., with an impact factor of 5.0 (JCR2024, Q1). For further information, please refer to the journal homepage: https://academic.oup.com/pcm
Journal
Precision Clinical Medicine
Subject of Research
Not applicable
Article Title
Glycosylation in kidney diseases
Article Publication Date
11-Jul-2025
COI Statement
The authors declare that they have no competing interests.