Molecular Mapping of Urinary Complement Peptides in Kidney Diseases

TY - JOUR

T1 - Molecular Mapping of Urinary Complement Peptides in Kidney Diseases

AU - Wendt, Ralph

AU - Siwy, Justyna

AU - He, Tianlin

AU - Latosinska, Agnieszka

AU - Wiech, Thorsten

AU - Zipfel, Peter F

AU - Tserga, Aggeliki

AU - Vlahou, Antonia

AU - Rupprecht, Harald

AU - Catanese, Lorenzo

AU - Mischak, Harald

AU - Beige, Joachim

PY - 2021/12/13

Y1 - 2021/12/13

N2 - Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology in 16,027 subjects, using mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database. Twenty-three different urinary peptides originating from complement proteins C3, C4 and factor B (CFB) could be identified. Most C3-derived peptides showed inverse association with estimated glomerular filtration rate (eGFR), while the majority of peptides derived from CFB demonstrated positive association with eGFR. Several peptides derived from the complement proteins C3, C4 and CFB were found significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation and could serve as non-invasive biomarkers to support development of complement interventions through assessing complement activity for patients' stratification and monitoring of drug impact. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.

AB - Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology in 16,027 subjects, using mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database. Twenty-three different urinary peptides originating from complement proteins C3, C4 and factor B (CFB) could be identified. Most C3-derived peptides showed inverse association with estimated glomerular filtration rate (eGFR), while the majority of peptides derived from CFB demonstrated positive association with eGFR. Several peptides derived from the complement proteins C3, C4 and CFB were found significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation and could serve as non-invasive biomarkers to support development of complement interventions through assessing complement activity for patients' stratification and monitoring of drug impact. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.

U2 - 10.3390/proteomes9040049

DO - 10.3390/proteomes9040049

M3 - SCORING: Journal article

C2 - 34941814

VL - 9

JO - PROTEOMES

JF - PROTEOMES

SN - 2227-7382

IS - 4

M1 - 49

ER -