Complement in Renal Disease as a Potential Contributor to Arterial Hypertension

Abstract

<b><i>Objective:</i></b> Complement deposition is prevalent in kidney biopsies of patients with arterial hypertension and hypertensive nephropathy, but an association of hypertension and complement deposition or involvement of complement in the pathogenesis of hypertensive nephropathy has not been shown to date. <b><i>Methods:</i></b> In this study, we analyzed complement C1q and C3c deposition in a rat model of overload and hypertension by subtotal nephrectomy (SNX) and in archival human renal biopsies from 217 patients with known hypertension and 91 control patients with no history of hypertension using semiquantitative scoring of C1q and C3c immunohistochemistry and correlation with parameters of renal function. To address whether complement was only passively deposited or actively expressed by renal cells, C1q and C3 mRNA expression were additionally analyzed. <b><i>Results:</i></b> Glomerular C1q and C3c complement deposition were significantly higher in kidneys of hypertensive SNX rats and hypertensive compared to nonhypertensive patients. Mean arterial blood pressure (BP) in SNX rats correlated well with the amount of glomerular C1q and C3c deposition and with left ventricular weight, as an indirect parameter of high BP. Quantitative mRNA analysis showed that C3 was not only deposited but also actively produced by glomerular cells of hypertensive SNX rats and in human renal biopsies. Of note, in patients CKD-stage correlated significantly with the intensity of glomerular C3c staining, but not with that of C1q. <b><i>Conclusion:</i></b> Renal complement deposition correlated with experimental hypertension as well as the presence of hypertension in a variety of renal diseases. To answer the question, if and how exactly renal complement is causative for the pathogenesis of arterial hypertension in men, further studies are needed.

The Complement System in Metabolic-Associated Kidney Diseases

“…We have observed the deposition of complement components in renal biopsy from patients and animals with hypertensive kidney disease in both previous clinical practice and literature reports (67,68). And clinical trials have shown that serum C3 are paralleled with systolic blood pressure (69,70).…”

Recent Advances of Proteomics in Management of Acute Kidney Injury

“…In regard to the clinical utility of this biomarker, CD26 has been investigated towards ischemia-reperfusion injury in the kidneys and its potential role in suppression of apoptosis and inflammation. Moreover, CD26/DPP-4 inhibitors have been assessed and investigated for their nephroprotective role in glycemic management to reduce the incidence of micro- or macroalbuminuria in type 2 diabetes patients [ 115 , 116 , 117 ]. Lately, urinary exosomal CD26 has been investigated to see whether it can predict renal reversal and recovery from AKI.…”

Early Ultrastructural Changes in Biopsies From Patients With Symptomatic CKD of Uncertain Etiology

“…To determine the origin of tubular casts, formalin-fixed paraffin-embedded sections were stained for uromodulin using a mouse antihuman uromodulin (a gift from Professor J. Scherberich, LMU München, Germany) and a standard protocol for immunohistochemistry as described previously. 19 Histologic changes assessed explicitly for the quantification were glomerulosclerosis (GS), TA, IF, tubulitis, and interstitial mononuclear inflammation. Quantification of histologic changes was performed based on the percentage of total area affected by tubulointerstitial lesions and the percentage of sclerosed glomeruli.…”