Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease

a nested case–control study

Francesca Viazzi, Ganesan Ramesh, Calpurnia Jayakumar, Giovanna Leoncini, Debora Garneri, Roberto Pontremoli

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number97
Pages (from-to)315-320
Number of pages6
JournalJournal of Nephrology
Volume28
Issue number3
DOIs
StatePublished - Jun 26 2015

Fingerprint

Semaphorin-3A
Chronic Renal Insufficiency
Urine
Kidney
Creatinine
Albumins
Semaphorins
Podocytes
Albuminuria
Organogenesis
Glomerular Filtration Rate
Proteinuria
Acute Kidney Injury
Cell Movement
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Cytokines
Serum

Keywords

  • Albuminuria
  • Chronic kidney disease
  • Diabetes
  • Hypertension
  • Semaphorin-3A

ASJC Scopus subject areas

  • Nephrology

Cite this

Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease : a nested case–control study. / Viazzi, Francesca; Ramesh, Ganesan; Jayakumar, Calpurnia; Leoncini, Giovanna; Garneri, Debora; Pontremoli, Roberto.

In: Journal of Nephrology, Vol. 28, No. 3, 97, 26.06.2015, p. 315-320.

Research output: Contribution to journalArticle

Viazzi, Francesca ; Ramesh, Ganesan ; Jayakumar, Calpurnia ; Leoncini, Giovanna ; Garneri, Debora ; Pontremoli, Roberto. / Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease : a nested case–control study. In: Journal of Nephrology. 2015 ; Vol. 28, No. 3. pp. 315-320.
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T1 - Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease

T2 - a nested case–control study

AU - Viazzi, Francesca

AU - Ramesh, Ganesan

AU - Jayakumar, Calpurnia

AU - Leoncini, Giovanna

AU - Garneri, Debora

AU - Pontremoli, Roberto

PY - 2015/6/26

Y1 - 2015/6/26

N2 - 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.

AB - 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.

KW - Albuminuria

KW - Chronic kidney disease

KW - Diabetes

KW - Hypertension

KW - Semaphorin-3A

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