Title:The Mechanistic Role of Different Mediators in the Pathophysiology of
Nephropathy: A Review
Volume: 24
Issue: 2
Author(s): Jaspreet Singh, Akash Jain, Rashmi Bhamra, Vaibhav Rathi and Ashwani K. Dhingra*
Affiliation:
- Guru Gobind Singh College of Pharmacy, Yamuna Nagar-135001, Haryana, India
Keywords:
Nephropathy, renin-angiotensin, system, oxidative stress, dyslipidemia, growth factors.
Abstract: Nephropathy has become the most common reason for end-stage renal disease worldwide.
The progression of end-stage renal disease occurs caused by decreased glomerular filtration
rate, damage to capillaries in renal glomeruli or a higher risk of cardiovascular morbidity and mortality
in diabetic patients. The involvement of mechanism in the development of nephropathy via
generation of AGEs, the elevation of growth factors, altered hemodynamic and metabolic factors,
inflammatory mediators, oxidative stress and dyslipidaemia. The prevalence of chronic kidney disease
in India will rise from 3.7 million in 1990 to 7.63 million in 2020 becoming the main cause of
mortality and morbidity. The pathogenesis of nephropathy mediates by various molecules that cause
alterations in the structure and function of the kidney like growth factors, endothelins, transforming
growth factor (TGF-β), and Angiotensin-converting enzymes (ACE), fibronectin and proinflammatory
cytokines, mast cells and dyslipidemia. Growth factors like VEGF, IGFs, PDGF,
EGFR and TGF-β contribute to excessive extracellular matrix accumulation, together with thickening
of the glomerular and tubular basement membranes and an increase in the mesangial matrix,
leading to glomerulosclerosis and tubulointerstitial fibrosis. Oxidative stress and inflammation factors
like TNF-α, IL-1 and IL-6 are hypothesized to play a role in the development of pathological
changes in nephropathy like renal hyperfiltration and hypertrophy, thickening of the glomerular
basement membrane (GBM), glomerular lesion and tubulointerstitial fibrosis. Dyslipidemia is involved
in the progression of nephropathy by impaired action of lipoprotein lipase, lecithincholesterol
acyltransferase (LCAT) and cholesteryl ester transferase protein (CETP) resulting in the
increased level of LDL-C, Triglyceride level and decrease HDL-C that enhance macrophage infiltration,
excessive extracellular matrix production and accelerate inflammation with the development
of proteinuria. Interruption in the RAS, oxidative stress and dyslipidemia have yielded much better
results in terms of reno-protection and progression of nephropathy. In this review, we would focus
on various factors that have been shown to contribute to renal injury in many experimental models
of nephropathy.
