Complement in Renal Disease as a Potential Contributor to Arterial Hypertension

Area of Science:

• Nephrology
• Immunology
• Cardiovascular Research

Background:

• Complement deposition is frequently observed in kidney biopsies of patients with arterial hypertension.
• The direct association between hypertension and complement deposition, or complement's role in hypertensive nephropathy pathogenesis, remains unestablished.

Purpose of the Study:

• To investigate the presence and significance of complement C1q and C3c deposition in a rat model of hypertension and in human renal biopsies from hypertensive patients.
• To determine if complement components are actively expressed by renal cells in hypertensive conditions.

Main Methods:

• Analyzed C1q and C3c deposition via immunohistochemistry in rat kidneys after subtotal nephrectomy (SNX) and in human renal biopsies (217 hypertensive, 91 controls).
• Correlated complement deposition with renal function parameters and mean arterial blood pressure (BP) in rats.
• Assessed C1q and C3 mRNA expression in rat and human kidney samples to evaluate active complement production.

Main Results:

• Significantly higher glomerular C1q and C3c deposition in hypertensive SNX rats and hypertensive patients compared to controls.
• Glomerular deposition correlated with mean arterial BP and left ventricular weight in hypertensive rats.
• C3 mRNA expression confirmed active production by glomerular cells in hypertensive rats and humans; C3c staining intensity correlated with CKD stage in patients.

Conclusions:

• Renal complement deposition is associated with experimental hypertension and hypertension in various renal diseases.
• Further research is required to elucidate the causative role of renal complement in the pathogenesis of arterial hypertension in humans.