The primary cilia in diabetic kidney disease: A tubulocentric view?

ABSTRACT

Diabetic kidney disease is growing exponentially. This review aims to discuss alternate therapeutic approaches beyond the glomerulocentric view and to consider a novel tubulocentric approach with focus on the primary cilia. Renin-angiotensin-aldosterone system blockade to decrease glomerular capillary pressure and prevent albuminuria has been the mainstay of treatment for diabetic and non-diabetic proteinuric kidney disease. Landmark clinical trials have also shown cardiorenal benefit with sodium-glucose linked co-transporter 2 inhibitors and glucagon-like peptide 1 receptor analogues in patients with type 2 diabetes. Effective renoprotective drugs seem to have a common mechanistic mode of reducing glomerular hyperfiltration/hypertension. In the tubules, primary cilia act as "antennae" to detect mechanosensory changes such as glomerular hyperfiltration and trgger intracellular signalling pathways. They are also implicated in obesity and metabolic disorders linked to diabetes. To conclude, primary cilia of the kidney tubules offer a novel therapeutic target and may complement the current glomerulocentric approaches.