Related Experiment Video
Updated: Jan 11, 2026
10:31
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
593
Alternative pathway-mediated tubular complement activation in human proteinuric kidney diseases: a proof-of-concept
Firas F Alkaff1,2, Rosa G M Lammerts3, Gesa Tiller1
1Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Clinical Kidney Journal
|November 11, 2025
Summary
Proteinuria can cause kidney damage via tubular complement activation. This study shows the alternative pathway, initiated by properdin and syndecan-1, is key in proteinuric kidney diseases.
Area of Science:
- Nephrology
- Immunology
- Complement System Biology
Background:
- Proteinuria is a significant risk factor for progressive kidney injury.
- Tubular complement activation is a proposed mechanism contributing to kidney damage in proteinuria.
- The role of the alternative complement pathway in human proteinuric kidney diseases remains understudied.
Purpose of the Study:
- To investigate the specific complement pathways involved in apical tubular injury in human proteinuric kidney diseases.
- To determine the association between complement deposition, syndecan-1, and proteinuria levels.
- To explore the potential role of the alternative pathway in initiating tubular complement activation.
Main Methods:
- Analysis of 21 kidney biopsies from patients with proteinuric kidney diseases.
- Immunohistochemical staining for complement components (MASP-2, C1q, properdin, C3d, C5b-9) and syndecan-1.
- Semi-quantitative scoring of complement deposition and measurement of plasma and urinary soluble C5b-9.
Main Results:
- All biopsies exhibited apical proximal tubular C3d deposition, predominantly co-localizing with properdin.
- Tubular properdin deposition correlated significantly with C5b-9 deposition and was associated with syndecan-1.
- Higher proteinuria levels were observed in patients with tubular C5b-9 deposition and detectable urinary soluble C5b-9.
Conclusions:
- Apical tubular complement activation in proteinuric kidney diseases primarily involves the alternative pathway.
- Properdin binding to syndecan-1 is a likely initiator of this alternative pathway activation.
- Targeting the alternative complement pathway may offer a therapeutic strategy for proteinuric kidney diseases.
More Related Videos
09:40Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells
Published on: June 20, 2018
18.4K
07:06Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
Published on: May 9, 2025
644
Related Concept Videos
01:15Drug Elimination by Renal Route: Tubular Secretion
3.2K
Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
3.2K
01:29Acute Kidney Injury II: Pathophysiology
865
Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
865
01:28Renal Drug Excretion: Tubular Secretion
753
Active tubular secretion is a robust, energy-demanding process that utilizes carrier systems to transport drugs into renal tubules. The active renal secretion systems include the organic anion transporter (OAT) for weak acids and the organic cation transporter (OCT) for weak bases. Structurally similar drugs can compete for the same transporter, potentially leading to drug accumulation and toxicity. However, this principle can be exploited therapeutically. One example is probenecid (Probalan),...
753
01:20Renal Corpuscle
6.9K
The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
6.9K
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
254
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
254
01:25Chronic Kidney Disease I: Introduction
552
Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
552