Functional Analysis of Solute Carrier Transporter Genes in the Pathogenesis of Diabetic Kidney Stones

Authors

  • Zahra Haq Department of Physiology, Shahida Islam Medical and Dental College, Lodhran
  • Tahir Maqbool Department of IMBB (Institute of Molecular Biology and Biotechnology), University of Lahore
  • Mahwish Arooj University College of Medicine and Dentistry, University of Lahore, Lahore, Pakistan
  • Asya Ovais Department of Physiology, Quaid-e-Azam Medical College, Bahawalpur
  • Sampana Fatima Department of Physiology, Shahida Islam Medical and Dental College, Lodhran
  • Awais Altaf Department of IMBB (Institute of Molecular Biology and Biotechnology), University of Lahore
  • Syed Usama Shayan Zaidi Department of Physiology, Queen Mary College, Lahore
  • Muzammal Mateen Azhar Department of IMBB (Institute of Molecular Biology and Biotechnology), University of Lahore
  • Sikander Hayat Department of IMBB (Institute of Molecular Biology and Biotechnology), University of Lahore
  • Shabana Akhtar Scholar School System, Bradford Campus

Keywords:

Type 2 Diabetes Mellitus, Nephrolithiasis, Solute Carrier Transporters, SLC26A1, SLC26A6, SLC22A4, Gene Expression, Oxalate Metabolism

Abstract

Background: Nephrolithiasis is an under-recognized yet clinically significant complication in patients with type 2 diabetes mellitus (T2DM). Increasing evidence suggests that dysfunction of renal solute carrier (SLC) transporters contributes to lithogenic urinary alterations. This study investigates the expression and functional relevance of key SLC transporters in diabetic nephrolithiasis. Objective: To evaluate the gene expression and protein levels of SLC26A1, SLC26A6, and SLC22A4 in T2DM patients with nephrolithiasis and determine their role in disease pathogenesis. Methods: A retrospective case–control study was conducted on 80 individuals, comprising 20 healthy controls, 20 patients with T2DM, 20 with nephrolithiasis, and 20 with diabetes and nephrolithiasis. Clinical, biochemical, and hematological parameters were recorded. Protein quantification was performed using ELISA, and gene expression of SLC26A1, SLC26A6, and SLC22A4 was assessed via RT-PCR. Statistical analysis was conducted using SPSS 26.0. Results: T2DM nephrolithiasis patients exhibited significantly elevated HbA1c levels (mean ~9%) and poor glycemic control, especially among females. Renal function tests showed elevated serum urea, creatinine, and uric acid. Expression of SLC26A1, SLC26A6, and SLC22A4 was markedly reduced in diseased patients compared to controls (p < 0.05). Protein quantification confirmed significantly lower transporter concentrations in affected individuals. These molecular alterations correlated with biochemical markers of renal impairment and systemic inflammation. Conclusion: Reduced expression and activity of SLC26A1, SLC26A6, and SLC22A4 contribute to the pathophysiology of nephrolithiasis in T2DM. These transporters may serve as potential biomarkers and therapeutic targets. Molecular profiling of transporter dysfunction offers promising avenues for early diagnosis and personalized treatment of diabetic stone formers.

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Published

2025-09-30

Issue

Vol. 61 No. 2 (2025)

Section

Article