ArticlePLoS genetics2022
Genetics of osteopontin in patients with chronic kidney disease: The German Chronic Kidney Disease study.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan.Nature communications · 2024Pooled it
- SMOC2 promotes partial epithelial-mesenchymal transition and maladaptive repair in renal tubular epithelial cells.JCI insight · 2026Article
- TRAP5 Inhibition Targeting Scar-Associated Macrophages Ameliorates Acute Kidney Injury to Chronic Kidney Disease Transition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- INPP5D/SHIP1-mediated immunometabolic remodeling of renal monocytes in idiopathic membranous nephropathy.Frontiers in immunology · 2026Article
- The fat-heart entanglement and the role of 'osteopontin mechanics' in cardiometabolic senescence.European journal of clinical investigation · 2026Review
- Acute Kidney Injury Biomarkers in Perioperative Care: A Scoping Review of Clinical Implementation.Diagnostics (Basel, Switzerland) · 2025Review
- Hydronephrosis-Associated Renal Fibrosis: Clinical Validation of Spp1 as a Biomarker and Therapeutic Target.Kidney & blood pressure research · 2025Article
- Relationship between SPP1 (Osteopontin) and extracellular matrix dynamics: a comprehensive review.Frontiers in medicine · 2025Review
- Identification of common and specific fibrosis-related genes in three common chronic kidney diseases.Renal failure · 2024Article
- Plasma proteomics of acute tubular injury.Nature communications · 2024Article
- Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis.Cellular & molecular immunology · 2024Article
- Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages.PLoS genetics · 2024Article
- Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023Review
- Article
- Osteopontin (SPP1) expression on gallstone formation in rabbits fed with a lithogenic diet.Journal of advanced veterinary and animal research · 2023Article
- Will osteopontin bridge the gap towards clinical application in chronic kidney disease?Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Osteopontin as a Biomarker in Chronic Kidney Disease.Biomedicines · 2023Review
- Osteopontin in pancreatic cancer: A systematic review.Medicine internationalArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteopontin (OPN), encoded by SPP1, is a phosphorylated glycoprotein predominantly synthesized in kidney tissue. Increased OPN mRNA and protein expression correlates with proteinuria, reduced creatinine clearance, and kidney fibrosis in animal models of kidney disease. But its genetic underpinnings are incompletely understood. We therefore conducted a genome-wide association study (GWAS) of OPN in a European chronic kidney disease (CKD) population. Using data from participants of the German Chronic Kidney Disease (GCKD) study (N = 4,897), a GWAS (minor allele frequency [MAF]≥1%) and aggregated variant testing (AVT, MAF<1%) of ELISA-quantified serum OPN, adjusted for age, sex, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR) was conducted. In the project, GCKD participants had a mean age of 60 years (SD 12), median eGFR of 46 mL/min/1.73m2 (p25: 37, p75: 57) and median UACR of 50 mg/g (p25: 9, p75: 383). GWAS revealed 3 loci (p<5.0E-08), two of which replicated in the population-based Young Finns Study (YFS) cohort (p<1.67E-03): rs10011284, upstream of SPP1 encoding the OPN protein and related to OPN production, and rs4253311, mapping into KLKB1 encoding prekallikrein (PK), which is processed to kallikrein (KAL) implicated through the kinin-kallikrein system (KKS) in blood pressure control, inflammation, blood coagulation, cancer, and cardiovascular disease. The SPP1 gene was also identified by AVT (p = 2.5E-8), comprising 7 splice-site and missense variants. Among others, downstream analyses revealed colocalization of the OPN association signal at SPP1 with expression in pancreas tissue, and at KLKB1 with various plasma proteins in trans, and with phenotypes (bone disorder, deep venous thrombosis) in human tissue. In summary, this GWAS of OPN levels revealed two replicated associations. The KLKB1 locus connects the function of OPN with PK, suggestive of possible further post-translation processing of OPN. Further studies are needed to elucidate the complex role of OPN within human (patho)physiology.
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Registered trials
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