Research Projects

India is a major hub for diabetics and diabetic kidney disease (DKD), a major microvascular complication of diabetes that progresses to end-stage kidney disease (ESKD) and kidney failure. Polypharmacy practice is often used against DKD due to persistent hyperglycemia, which disrupts metabolic profiling and kidney hemodynamics. Chronic therapy with angiotensin-II type 1 receptor (AT1R) blockers and sodium-glucose cotransporter-2 (SGLT2) inhibitors can cause life-threatening adverse effects like angioedema, dry cough, hyperkalemia, hypotension, and ketoacidosis. These drugs are dose-dependent, symptomatic, and non-specific, making them ineffective in preventing DKD progression and cure. There is a need for novel pharmacological interventions, such as α-Klotho, which can be given as monotherapy or in combination to reduce their side effects and improve clinical efficacy. α-Klotho, a renoprotective protein, has shown promising renoprotective effects when given exogenously or restored endogenously. However, it has not been studied in combination with AT1R blockers and SGLT2i in preclinical and clinical settings against DKD. The objective of this proposal is to verify and corroborate the therapeutic potential of α-Klotho against DKD. α-Klotho will be given as monotherapy and combined with AT1R blockers telmisartan and SGLT2i- dapagliflozin for the assessment of its therapeutic benefits and synergy. This approach will help refine the clinical efficacy of these regimens and reveal the underlying molecular mechanisms of their renoprotective actions.