PMID- 31194090
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 4
IP  - 6
DP  - 2019 Jun
TI  - Clinical Value of Complement Activation Biomarkers in Overt Diabetic Nephropathy.
PG  - 797-805
LID - 10.1016/j.ekir.2019.03.004 [doi]
AB  - BACKGROUND: Experimental studies support a role of complement activation in 
      diabetic nephropathy (DN), yet few clinical correlates exist. We evaluated 
      urinary levels of sC5b-9 membrane attack complex (MAC) in patients with overt DN, 
      and examined its association with the glomerular filtration rate (GFR) decline, 
      proteinuria, and inflammatory biomarkers. We explored different complement 
      pathways and compared our findings to autoimmune glomerulonephritis. METHODS: We 
      prospectively followed 83 patients with DN and obtained repeated measurements of 
      proteinuria, complement fragments (sC5b-9, C4a, C1q, mannose-binding 
      lectin-associated serine protease [MASP]-1, and factor Bb), monocyte 
      chemoattractant protein-1 (MCP-1), and transforming growth factor (TGF)-beta1. We 
      assessed independence and interactions using general linear models and repeated 
      measures analyses and compared levels with subjects with active focal and 
      segmental glomerulosclerosis, ANCA-associated vasculitis, and membranous and IgA 
      nephropathies (n = 63). RESULTS: The diabetic cohort had an initial GFR of 25 +/- 9 
      ml/min per 1.73 m(2) and a renal function decline of 2.9 +/- 3.0 ml/min per 1.73 
      m(2) per year. All complement biomarkers were strongly intercorrelated and 
      associated with biomarker inflammation and fibrosis, proteinuria, and the rate of 
      renal function decline. There was a significant interaction (P = 0.03) between 
      the level of proteinuria and urinary sC5b-9: in individuals with higher levels of 
      urinary MAC, the relationship between proteinuria and the rate of renal function 
      decline was more pronounced than in those with low urinary MAC. Finally, patients 
      with DN had levels of urinary sC5b-9 comparable to autoimmune glomerulonephritis, 
      when stratified by the level of proteinuria. CONCLUSION: Urinary MAC is present 
      in patients with overt DN at levels comparable to autoimmune glomerulonephritis 
      and correlates with the GFR decline, supporting that complement activation and 
      its measurement are clinically relevant in DN.
FAU - Pelletier, Karyne
AU  - Pelletier K
AD  - Nephrology Division, Hopital du Sacre-Coeur de Montreal, Quebec, Canada.
FAU - Bonnefoy, Arnaud
AU  - Bonnefoy A
AD  - Hematology Division, Centre Hospitalier Universitaire Ste-Justine, Montreal, 
      Quebec, Canada.
FAU - Chapdelaine, Hugo
AU  - Chapdelaine H
AD  - Immunology Division, Institut de Recherche Clinique de Montreal, Quebec, Canada.
FAU - Pichette, Vincent
AU  - Pichette V
AD  - Nephrology Division, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
FAU - Lejars, Matthieu
AU  - Lejars M
AD  - Hematology Division, Centre Hospitalier Universitaire Ste-Justine, Montreal, 
      Quebec, Canada.
FAU - Madore, Francois
AU  - Madore F
AD  - Nephrology Division, Hopital du Sacre-Coeur de Montreal, Quebec, Canada.
FAU - Brachemi, Soumeya
AU  - Brachemi S
AD  - Nephrology Division. Centre Hospitalier de l'Universite de Montreal, Quebec, 
      Canada.
FAU - Troyanov, Stephan
AU  - Troyanov S
AD  - Nephrology Division, Hopital du Sacre-Coeur de Montreal, Quebec, Canada.
LA  - eng
PT  - Journal Article
DEP - 20190320
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC6551506
OTO - NOTNLM
OT  - complement activation
OT  - diabetic nephropathy
OT  - fibrosis
OT  - glomerulonephritis
OT  - inflammation
OT  - proteinuria
EDAT- 2019/06/14 06:00
MHDA- 2019/06/14 06:01
PMCR- 2019/03/20
CRDT- 2019/06/14 06:00
PHST- 2019/01/03 00:00 [received]
PHST- 2019/02/14 00:00 [revised]
PHST- 2019/03/04 00:00 [accepted]
PHST- 2019/06/14 06:00 [entrez]
PHST- 2019/06/14 06:00 [pubmed]
PHST- 2019/06/14 06:01 [medline]
PHST- 2019/03/20 00:00 [pmc-release]
AID - S2468-0249(19)30089-0 [pii]
AID - 10.1016/j.ekir.2019.03.004 [doi]
PST - epublish
SO  - Kidney Int Rep. 2019 Mar 20;4(6):797-805. doi: 10.1016/j.ekir.2019.03.004. 
      eCollection 2019 Jun.