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