SavedAdd your journal

Journals / Uludağ Üniversitesi Tıp Fakültesi Dergisi / 2026 / Cilt: 52

Investigation of Uric Acid/HDL-Cholesterol Ratio as an Independent Risk Factor for Diabetic Nephropathy: A Cross-Sectional Study

Diyabetik Nefropati için Bağımsız Bir Risk Faktörü Olarak Ürik Asit/HDL Kolesterol Oranının İncelenmesi: Kesitsel Bir Çalışma

Zekeriya Keskin(Sivas Cumhuriyet University, Department of Internal Medicine, Sivas, Türkiye.)0000-0003-3623-9892
Onur Büyüktekeli(Sivas Cumhuriyet University, Department of Nephrology, Sivas, Türkiye.)0000-0003-2321-7651
Muhammed Faruk Aşkın(Sivas Cumhuriyet University, Department of Nephrology, Sivas, Türkiye.)0000-0003-0115-1567
Pages
—
Publication Date
2026-07-22
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

These findings require validation in prospective studies.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Diabetic nephropathy (DN) is a major microvascular complication requiring early markers for risk stratification.
📊
Key Findings & Data:In this retrospective cross-sectional study, records of 934 patients with diabetes mellitus (DM) were analyzed.
💡
Conclusion & Impact:These findings require validation in prospective studies.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Diyabetik nefropati · Ürik asit/HDL oranı · Enflamasyon

Abstract

Diabetic nephropathy (DN) is a major microvascular complication requiring early markers for risk stratification. We investigated the clinical utility of the uric acid (UA) to high density lipoprotein cholesterol (HDL-C) ratio (UHR) as a practical proinflammatory-prooxidative marker for DN. In this retrospective cross-sectional study, records of 934 patients with diabetes mellitus (DM) were analyzed. UHR was calculated as [UA/HDL] x 100. DN was defined based on the albumin-to-creatinine ratio (ACR) and/or estimated glomerular filtration rate (eGFR) criteria. Patients were evaluated according to the presence of nephropathy, stage of nephropathy, and albuminuria categories. ROC analysis was performed for UHR, UA and HDL-C. Factors associated with DN were evaluated using logistic regression analysis. UHR was significantly higher in patients with DN compared to those without DN (p<0.001). UHR showed a significant increase across nephropathy stages and albuminuria categories (p<0.001). In the ROC analysis, UA demonstrated the highest performance in distinguishing DN (AUC=0.763; 95% CI: 0.733–0.794; p<0.001). The AUC value for UHR was 0.740 (95% CI: 0.709–0.771; p<0.001), and for HDL-C, it was 0.591 (95% CI:0.555–0.627; p<0.001). The optimal cutoff value for UHR was determined to be 13.07. In the multivariate logistic regression analysis, UHR was found to be independently associated with DN after adjusting for age, sex, systolic blood pressure, HbA1c, and triglycerides (OR=1.221; 95% CI: 1.179–1.265; p<0.001). In the component-based model, UA showed a strong positive association with DN (OR=1.971; 95% CI: 1.766–2.200; p<0.001), while HDL-C showed a significant inverse association (OR=0.983; 95% CI: 0.969–0.997; p=0.018). UHR was found to be significantly associated with the presence of DN, stage of nephropathy, and albuminuria categories. However, the fact that UA demonstrates slightly higher discriminatory performance compared to UHR suggests that UHR should be interpreted as an easily calculable complementary biomarker rather than a superior standalone marker in the assessment of DN. These findings require validation in prospective studies.

Özet

Diyabetik nefropati (DN), risk sınıflandırması için erken belirteçlere ihtiyaç duyulan önemli bir mikrovasküler komplikasyondur. Bu çalışmada, DN için pratik bir proinflamatuar-prooksidatif belirteç olarak ürik asit/HDL kolesterol oranının (UHR) klinik yararını araştırdık. Bu retrospektif kesitsel çalışmada, 934 diyabetik (DM) hastanın kayıtları analiz edilmiştir. UHR, [UA/HDL] x 100 olarak hesaplanmıştır. DN, albümin-kreatinin oranı (ACR) ve/veya tahmini glomerüler filtrasyon hızı (eGFR) kriterlerine göre tanımlanmıştır. Hastalar nefropati varlığı, nefropati evresi ve albüminüri kategorilerine göre değerlendirildi. UHR, UA ve HDL-C için ROC analizi yapıldı. DN ile ilişkili faktörler lojistik regresyon analizi kullanılarak değerlendirildi. UHR, DN'si olmayan hastalara kıyasla DN'si olan hastalarda anlamlı olarak daha yüksekti (p<0,001). UHR, nefropati evreleri ve albüminüri kategorileri boyunca anlamlı bir artış gösterdi (p<0,001). ROC analizinde, UA, DN'yi ayırt etmede en yüksek performansı gösterdi (AUC=0,763; %95 CI: 0,733–0,794; p<0,001). UHR için AUC değeri 0,740 (95% CI: 0,709–0,771; p<0,001), HDL-C için ise 0,591 (95% CI: 0,555–0,627; p<0,001) idi. UHR için optimal kesme değeri 13,07 olarak belirlendi. Çok değişkenli lojistik regresyon analizinde, yaş, cinsiyet, sistolik kan basıncı, HbA1c ve trigliseridler için düzeltme yapıldıktan sonra UHR'nin DN ile bağımsız olarak ilişkili olduğu bulunmuştur (OR = 1,221; %95 CI: 1,179–1,265; p<0,001). Bileşen tabanlı modelde, UA, DN ile güçlü bir pozitif ilişki gösterirken (OR=1,971; %95 CI: 1,766–2,200; p<0,001), HDL-C ise anlamlı bir ters ilişki gösterdi (OR=0,983; %95 CI: 0,969–0,997; p=0,018). UHR'nin DN varlığı, nefropati evresi ve albüminüri kategorileriyle anlamlı bir ilişkisi olduğu bulunmuştur. Ancak, UA'nın UHR'ye kıyasla biraz daha yüksek ayırt edici performans sergilemesi, UHR'nin DN değerlendirmesinde üstün bir tek başına belirteçten ziyade, kolayca hesaplanabilir tamamlayıcı bir biyobelirteç olarak yorumlanması gerektiğini düşündürmektedir. Bu bulguların prospektif çalışmalarda doğrulanması gerekmektedir.

🔖

Cite This Article

Keskin, Z., Büyüktekeli, O., Aşkın, M. F., *, Z. K. (2026). Investigation of Uric Acid/HDL-Cholesterol Ratio as an Independent Risk Factor for Diabetic Nephropathy: A Cross-Sectional Study. Uludağ Üniversitesi Tıp Fakültesi Dergisi, Cilt: 52. https://doi.org/10.32708/uutfd.1918355

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (34)

  1. American Diabetes Association Professional Practice Committee. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):239-251.
  2. Doria A, Galecki AT, Spino C, et al. Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes. N Engl J Med. 2020;382(26):2493-2503.
  3. Zhu L, Wang X, Sun J, Qian Q, Yu J. Hyperuricemia Predicts the Progression of Type 2 Diabetic Kidney Disease in Chinese Patients. Diabetes Ther. 2023;14(3):581-591.
  4. Qin C, Li G, Yuan Y, Zou Y. Association between uric acid to high-density lipoprotein cholesterol ratio and diabetic kidney disease in US adults. Sci Rep. 2025;15(1):24353.
  5. Che Y, Zhao L, Xu H, et al. Serum uric acid to high‑density lipoprotein cholesterol ratio as a novel predictor of diabetic nephropathy: a cross‑sectional analysis of NHANES 2011–2018. Clin Exp Med. 2025;25(1):359.
  6. Zhao H, Wang Y, Liu Y, Du Z, Tian L. Uric acid to high-density lipoprotein cholesterol ratio is associated with the prevalence of diabetic kidney disease in euthyroid patients with type 1 diabetes mellitus in China: A multicenter cross-sectional study. J Diabetes Investig. 2025;16(9):1683-1691.
  7. Stevens PE, Ahmed SB, Carrero JJ, et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Vol. 105, Kidney International. 2024;105(4S):117-314.
  8. Uzeli U, Doğan AG. The Relationship Between Diabetic Neuropathy and Uric Acid/High-Density Lipoprotein Ratio in Patients With Type-2 Diabetes Mellitus. Cureus. 2023;15(9):e45151.
  9. Zhou Y, Fang L, Jiang L, et al. Uric acid induces renal inflammation via activating tubular NF-κB signaling pathway. PLoS One. 2012;7(6):e39738.
  10. Zhang Y, He F, Yu X, et al. Hyperuricemia-induced kidney injury: a narrative review of mechanisms and therapeutic advances. BMC Nephrol. 2025;26(1):629.
  11. Ji P, Zhu J, Feng J, et al. Serum uric acid levels and diabetic kidney disease in patients with type 2 diabetes mellitus: A dose-response meta-analysis. Prim Care Diabetes. 2022;16(3):457-465.
  12. Lai YJ, Chen YY, Ku PW, Chen LJ, Yen YF. Association between uric acid level and incidence of albuminuria in patients with type 2 diabetes mellitus A 4.5-year cohort study. Med (United States). 2021;100(41):e27496.
  13. Gao RH, Liu B, Yang Y, et al. Serum Lipoprotein(a) and High-Density Lipoprotein Cholesterol Associate with Diabetic Nephropathy: Evidence from Machine Learning Perspectives. Diabetes, Metab Syndr Obes. 2023;16:1847–1858.
  14. Wang H, Wu J, Lin M, et al. High levels of high-density lipoprotein cholesterol may increase the risk of diabetic kidney disease in patients with type 2 diabetes. Sci Rep. 2024;14(1):15362.
  15. Nakada K, Tanaka K, Kimura H, et al. High-density lipoprotein cholesterol and kidney disease progression in patients with type 2 diabetes mellitus: The Fukushima Cohort Study. BMJ Open Diabetes Res Care. 2025;13(6):e005581.
  16. Morton J, Zoungas S, Li Q, et al. Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: Results of the advance study. Diabetes Care. 2012;35(11):2201-2206.
  17. Liu K, Cooper ME, Chai Z, Liu F. High-Density Lipoprotein in Patients with Diabetic Kidney Disease: Friend or Foe? Int J Mol Sci. 2025;26(4):1683.
  18. Qian F, Hong Z, Wei J, et al. Association between the serum uric acid-to-high-density lipoprotein cholesterol ratio and microalbuminuria in individuals with type 2 diabetes mellitus. Eur J Med Res. 2025;30(1):1210.
  19. Liu P, Li J, Yang L, et al. Association between cumulative uric acid to high-density lipoprotein cholesterol ratio and the incidence and progression of chronic kidney disease. Front Endocrinol (Lausanne). 2023;14:1269580.
  20. Aktas G, Yilmaz S, Kantarci DB, et al. Is serum uric acid-to-HDL cholesterol ratio elevation associated with diabetic kidney injury? Postgrad Med. 2023;135(5):519-523.
  21. Xuan Y, Zhang W, Wang Y, et al. Association Between Uric Acid to HDL Cholesterol Ratio and Diabetic Complications in Men and Postmenopausal Women. Diabetes, Metab Syndr Obes. 2023;16:167-177.
  22. Wang L, Liu L, Luo H, Wu Y, Zhu L. Correlation Between the Ratio of Uric Acid to High-Density Lipoprotein Cholesterol (UHR) and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus:A Cross-Sectional Study. Diabetes, Metab Syndr Obes. 2025;18:173–183.
  23. Özkara Yılmaz B, Özenç B, Bayrak D, Yenilmez Yeşildaş P, Altunışık E. Comparison of HbA1c, Uric Acid/HDL-C ratio, and Electroneuromyography (ENMG) results in patients with Type 2 Diabetes Mellitus. Heal Sci Q. 2025; 5(4), 527–534.
  24. 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;15:1407348.
  25. Assar M El, Angulo J, Rodríguez-Mañas L. Diabetes and ageing-induced vascular inflammation. J Physiol.2016;594(8):2125-2146.
  26. Chen X, Dong H, Shi F, Qin F, Zhao Y. Association of uricacid to high-density cholesterol ratio (UHR) with biological age acceleration: evidence from NHANES 2009–2018. Sci Rep.2025;15(1):41847.
  27. Turner R, Holman R, Stratton I, et al. Tight blood pressurecontrol and risk of macrovascular and microvascularcomplications in type 2 diabetes: UKPDS 38. Br Med J.1998;317(7160):703-713.
  28. George LB, Matthew RW, Shahnaz S, et al. Effects of BloodPressure Level on Progression of Diabetic Nephropathy. ArchIntern Med. 2003;163(13):1555-1565.
  29. Choukem SP, Dzudie A, Dehayem M, et al. Comparison ofdifferent blood pressure indices for the prediction of prevalentdiabetic nephropathy in a sub-Saharan African population withtype 2 diabetes. Pan Afr Med J. 2012;11:67.
  30. Anderson RJ, Bahn GD, Emanuele N V., Marks JB, DuckworthWC. Blood pressure and pulse pressure effects on renaloutcomes in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2014;37(10):2782-2788.
  31. de Boer I, Sun W, Gao X, et al. Effect of intensive diabetestreatment on albuminuria in type 1 diabetes: Long-term follow-up of the diabetes control and complications trial andepidemiology of diabetes interventions and complicationsstudy. Lancet Diabetes Endocrinol. 2014;2(10):793-800.
  32. Kirkman MS, Mahmud H, Korytkowski MT. Intensive BloodGlucose Control and Vascular Outcomes in Patients with Type2 Diabetes Mellitus. Endocrinol Metab Clin North Am.2018;47(1):81-96.
  33. Dušejovská M, Vecka M, Rychlík I, Žák A. Dyslipidemia inpatients with chronic kidney disease: Etiology andmanagement. Vnitr Lek. 2020;66(5):275-281.
  34. Pontremoli R, Bellizzi V, Bianchi S, et al. Management ofdyslipidaemia in patients with chronic kidney disease: aposition paper endorsed by the Italian Society of Nephrology. JNephrol. 2020;33(3):417-430.