Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease: a nested case-control study.
BACKGROUND
Semaphorins are guidance proteins implicated in several processes such as angiogenesis, organogenesis, cell migration, and cytokine release. Experimental studies showed that semaphorin-3a (SEMA3A) administration induces transient massive proteinuria, podocyte foot process effacement and endothelial cell damage in healthy animals. While SEMA3A signaling has been demonstrated to be mechanistically involved in experimental diabetic glomerulopathy and in acute kidney injury, to date its role in human chronic kidney disease (CKD) has not been investigated.


METHODS
To test the hypothesis that SEMA3A may play a role in human CKD, we performed a cross-sectional, nested, case-control study on 151 matched hypertensive patients with and without CKD. SEMA3A was quantified in the urine (USEMA) by ELISA. Glomerular filtration rate was estimated (eGFR) by the CKD-EPI formula and albuminuria was measured as albumin-to-creatinine ratio (ACR).


RESULTS
USEMA levels were positively correlated with urine ACR (p = 0.001) and serum creatinine (p < 0.001). USEMA was higher in patients with both components of renal damage as compared to those with only one and those with normal renal function (p < 0.007 and <0.001, respectively). The presence of increased USEMA levels (i.e. top quartile) entailed a fourfold higher risk of combined renal damage (p < 0.001) and an almost twofold higher risk of macroalbuminuria (p = 0.005) or of reduced eGFR, even adjusting for confounding factors (p = 0.002).


CONCLUSIONS
USEMA is independently associated with CKD in both diabetic and non diabetic hypertensive patients. Further studies may help clarify the mechanisms underlying this association and possibly the pathogenic changes leading to the development of CKD.
Department of Internal Medicine, University of Genoa and IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Viale Benedetto XV, 6 CAP 16132, Genoa, Italy, francesca.viazzi@unige.it.
Francesca
F
Viazzi
Ganesan
G
Ramesh
Calpurnia
C
Jayakumar
Giovanna
G
Leoncini
Debora
D
Garneri
Roberto
R
Pontremoli
D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000503:physiopathology / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000503:physiopathology / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000175:diagnosis; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D012307:Risk Factors; D040121:Semaphorin-3A / Q000652:urine*; D015854:Up-Regulation; D016482:Urinalysis
D015415:Biomarkers; C108639:SEMA3A protein, human; D040121:Semaphorin-3A