Correlation analysis of serum CRK, CD138, and APL with the prognosis of patients with diabetic nephropathy

Serum CRK, CD138, and APL in diabetic nephropathy

  • Yibo Chen Nanjing University of Chinese Medicine
  • Li Li The First Affiliated Hospital of Anhui Medical University
  • Rui Xia Nanjing University of Chinese Medicine
Keywords: Diabetic nephropathy, CITRON kinase-related kinase, Multiligand proteoglycan-1, APJ receptor ligand, Renal function, Prognostic analysis

Abstract


Objective To explore the relationships between the levels of serum CITRON kinase-related kinase (CRK), syndecan-1 (CD138), and APJ receptor ligand (APL) and renal function and prognosis in patients with diabetic nephropathy.

Methods From November 2023 to November 2025, 306 patients with diabetic nephropathy admitted to the hospital were selected as the study group, while 306 patients with simple diabetes were selected as the simple diabetes group; another 306 healthy individuals who underwent physical examinations during the same period composed the healthy control group. The levels of serum CRK, CD138, and APL were determined via enzyme-linked immunosorbent assay. Pearson correlation analysis was used to investigate the correlation between the levels of serum CRK, CD138, and APL and the clinical data of patients with diabetic nephropathy. To examine the variables determining a poor prognosis in patients with diabetic nephropathy, univariate and multivariate logistic regression analyses were performed. The prognostic usefulness of serum CRK, CD138, and APL levels for the unfavorable prognosis of individuals with diabetic nephropathy was examined using receiver operating characteristic (ROC) curves.

Results Compared with those in the healthy control group, the levels of serum CRK and CD138 in patients in the simple diabetes group and the study group were increased, whereas the level of APL was decreased. The estimated glomerular filtration rate (eGFR) of patients in the study group decreased, and the ratio of urinary albumin to creatinine (UACR) increased. All these differences were statistically significant (P < 0.05). The levels of serum CRK, CD138, and APL and the UACR in the study group were greater than those in the simple diabetes group, whereas the eGFR was lower than that in the simple diabetes group. All these differences were statistically significant (P < 0.05). Pearson correlation analysis revealed that the levels of serum CRK, CD138, APL, and UACR in the study group were negatively correlated with the eGFR (P < 0.05) and positively correlated with the renal disease stage, creatinine, 24-hour proteinuria, and UACR indicators (P < 0.05). Serum CRK, CD138, and APL levels, as well as the UACR, were higher (P < 0.05) and the eGFR was lower (P < 0.05) in the bad prognosis group than in the good prognosis group. Univariate and multivariate logistic regression analysis showed that serum CRK, CD138, and APL levels all had an impact on patients' prognoses (P < 0.05). The results of the ROC curve analysis revealed that the combined area under the curve (AUC) of serum CRK, CD138, and APL for predicting poor prognosis was significantly greater than that of CRK (Z = 2.857, P = 0.007), CD138 (Z = 2.429, P = 0.018), and APL (Z = 2.175, P = 0.033).

Conclusion The levels of CRK, CD138 and APL in the serum of patients with DN increase, and these increases are related to renal function. The combination of these three indicators has greater predictive efficacy for the prognosis of patients.

References

1.Cao B, Guo Z, Li DT, Zhao LY, Wang Z, Gao YB, Wang YX. The association between stress-induced hyperglycemia ratio and cardiovascular events as well as all-cause mortality in patients with chronic kidney disease and diabetic nephropathy. Cardiovasc Diabetol. 2025 Feb 6;24(1):55. doi: 10.1186/s12933-025-02610-1. PMID: 39915833; PMCID: PMC11803992.
2.Wang Y, Liu Y, Gu W, Cai B, Lei M, Luo Y, Zhang N. Association of immune-inflammation indexes with incidence and prognosis of diabetic nephropathy: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2025 Aug 18;16:1532682. doi: 10.3389/fendo.2025.1532682. PMID: 40900898; PMCID: PMC12399399.
3.Xu W, Zhou Y, Jiang Q, Fang Y, Yang Q. Risk prediction models for diabetic nephropathy among type 2 diabetes patients in China: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024 Jul 3;15:1407348. doi: 10.3389/fendo.2024.1407348. PMID: 39022345; PMCID: PMC11251916.
4.Wang B, Xiong Y, Deng X, Wang Y, Gong S, Yang S, Yang B, Yang Y, Leng Y, Li W, Li W. The role of intercellular communication in diabetic nephropathy. Front Immunol. 2024 Aug 22;15:1423784. doi: 10.3389/fimmu.2024.1423784. PMID: 39238645; PMCID: PMC11374600.
5.Li ZH, Sun ZJ, Tang SCW, Zhao MH, Chen M, Chang DY. Finerenone Alleviates Over-Activation of Complement C5a-C5aR1 Axis of Macrophages by Regulating G Protein Subunit Alpha i2 to Improve Diabetic Nephropathy. Cells. 2025 Feb 26;14(5):337. doi: 10.3390/cells14050337. PMID: 40072066; PMCID: PMC11898422.
6.Zhuo Y, Weng M, Lin J, Wu X, Nie K, Yang L, Cui J, Wan J. Clinical and Pathological Characteristics and Prognosis of Diabetic Nephropathy Patients With Tertiary Lymphoid Structures. J Diabetes Res. 2025 Aug 13;2025:6916580. doi: 10.1155/jdr/6916580. PMID: 40843318; PMCID: PMC12367377.
7.Liu M, Yan Z, Zhang Y, Zhang S. Effects of NEAT1 levels on cardiovascular events and prognosis in diabetic nephropathy patients undergoing peritoneal dialysis. Cell Mol Biol (Noisy-le-grand). 2024 May 27;70(5):178-183. doi: 10.14715/cmb/2024.70.5.25. PMID: 38814218.
8.Zhang J, Zhu H, Tang Q, Wu J. Correlation Analysis of Vascular Endothelial Growth Factor Level with Clinicopathological Features and Prognosis in Patients with Diabetic Nephropathy: A Biopsy-based Study. Cell Mol Biol (Noisy-le-grand). 2023 Aug 31;69(8):192-197. doi: 10.14715/cmb/2023.69.8.29. PMID: 37715389.
9.Dahal K, Rawal L, Shah S, Bhattarai M, Bhattarai HB, Acharya A, Bhandari S, Paudel A, Sah S, Mehta R, Gupta A. Efficacy and outcomes of dapagliflozin in diabetic nephropathy: A systematic review and meta-analysis. Medicine (Baltimore). 2025 Jul 4;104(27):e43171. doi: 10.1097/MD.0000000000043171. PMID: 40629621; PMCID: PMC12237297.
10.Yang S, Liao H, Ding H, Xu X. Investigation on the relationship between renal NONO expression, fibrosis and prognosis in diabetic nephropathy. Front Endocrinol (Lausanne). 2025 Oct 14;16:1652391. doi: 10.3389/fendo.2025.1652391. PMID: 41163679; PMCID: PMC12558785.
11.Alli AA. Extracellular Vesicles: Investigating the Pathophysiology of Diabetes-Associated Hypertension and Diabetic Nephropathy. Biology (Basel). 2023 Aug 16;12(8):1138. doi: 10.3390/biology12081138. PMID: 37627022; PMCID: PMC10452642.
12.Demirelli B, Boztepe B, Şenol EG, Boynueğri B, Bildacı YD, Gümrükçü G, Canbakan M, Öğütmen MB. Nondiabetic nephropathy in diabetic patients: incidence, HbA1c variability and other predictive factors, and implications. Int Urol Nephrol. 2024 Sep;56(9):3091-3100. doi: 10.1007/s11255-024-04066-w. Epub 2024 Apr 25. PMID: 38662267.
13.Tian F, Yi X, Yang F, Chen Y, Zhu W, Liu P, Li S. Research progress on the treatment of diabetic nephropathy with leech and its active ingredients. Front Endocrinol (Lausanne). 2024 Jan 26;15:1296843. doi: 10.3389/fendo.2024.1296843. PMID: 38344666; PMCID: PMC10853373.
14.Abdel-Tawab MS, Mohamed MG, Doudar NA, Rateb EE, Reyad HR, Elazeem NAA. Circulating hsa-miR-221 as a possible diagnostic and prognostic biomarker of diabetic nephropathy. Mol Biol Rep. 2023 Dec;50(12):9793-9803. doi: 10.1007/s11033-023-08846-y. Epub 2023 Oct 13. Erratum in: Mol Biol Rep. 2023 Dec 20;51(1):24. doi: 10.1007/s11033-023-09085-x. PMID: 37831346; PMCID: PMC10676308.
15.Barr SI, Abd El-Azeem EM, Bessa SS, Mohamed TM. Role of exosomes in pathogenesis, diagnosis, and treatment of diabetic nephropathy. BMC Nephrol. 2025 May 8;26(1):230. doi: 10.1186/s12882-025-04120-4. PMID: 40340661; PMCID: PMC12063312.
16.Jia J, Tan R, Xu L, Wang H, Li J, Su H, Zhong X, Liu P, Wang L. Hederagenin improves renal fibrosis in diabetic nephropathy by regulating Smad3/NOX4/SLC7A11 signaling-mediated tubular cell ferroptosis. Int Immunopharmacol. 2024 Jun 30;135:112303. doi: 10.1016/j.intimp.2024.112303. Epub 2024 May 21. PMID: 38776855.
17.Li Y, Wu C, Song C, Liu S, Nan Z. Efficacy and safety of Huangkui capsule for diabetic nephropathy: A systematic review and meta-analysis. Medicine (Baltimore). 2024 May 31;103(22):e38417. doi: 10.1097/MD.0000000000038417. PMID: 39259064; PMCID: PMC11142806.
18.Mohammad HMF, Galal Gouda S, Eladl MA, Elkazaz AY, Elbayoumi KS, Farag NE, Elshormilisy A, Al-Ammash BB, Hegazy A, Abdelkhalig SM, Mohamed AS, El-Dosoky M, Zaitone SA. Metformin suppresses LRG1 and TGFβ1/ALK1-induced angiogenesis and protects against ultrastructural changes in rat diabetic nephropathy. Biomed Pharmacother. 2023 Feb;158:114128. doi: 10.1016/j.biopha.2022.114128. Epub 2022 Dec 14. PMID: 36525822.
19.Liu Y, Duan P, Yang Z, Liu J, Jiang S, Chen H. Establishing a Risk Model for Diabetic Nephropathy and Addressing the Therapeutic Effect of Combined Epalrestat- Dapagliflozin Regimen. Iran J Kidney Dis. 2024 Oct 18;18(5):286-293. doi: 10.52547/ax1vqh41. PMID: 39423107.
20.Kwak Y, Lee JY, Kim JS, Yang JW, Hwang KH, Cha SK, Eom M. Clinical and pathological significance of Orai1 channel expression in human diabetic nephropathy. Kidney Res Clin Pract. 2024 Sep;43(5):626-634. doi: 10.23876/j.krcp.23.342. Epub 2024 Aug 7. PMID: 39109399; PMCID: PMC11467362.
21.Lin YQ, Yu F, Chen HJ, Deng YR, Lin J, Xu Y, Zheng X, Zhang JW, Liu JF. Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis. Ren Fail. 2024 Dec;46(2):2359033. doi: 10.1080/0886022X.2024.2359033. Epub 2024 Jun 5. PMID: 38836372; PMCID: PMC11155431.
22.Roointan A, Shafieizadegan S, Ghaeidamini M, Gheisari Y, Hudkins KL, Gholaminejad A. The potential of cardiac biomarkers, NT-ProBNP and troponin T, in predicting the progression of nephropathy in diabetic patients: A meta-analysis of prospective cohort studies. Diabetes Res Clin Pract. 2023 Oct;204:110900. doi: 10.1016/j.diabres.2023.110900. Epub 2023 Sep 9. PMID: 37678725.
23.Han Q, Xu H, Li L, Lei S, Li Z, Zhao L, Liu F. Higher density of CD4+ T-cell infiltration predicts severe renal lesions and renal function decline in patients with diabetic nephropathy. Front Immunol. 2024 Nov 25;15:1474377. doi: 10.3389/fimmu.2024.1474377. PMID: 39654881; PMCID: PMC11625791.
Published
2026/05/11
Section
Original paper