Glomerular Hyperfiltration in Obese African American Hypertensive Patients Is Associated with Elevated Urinary Mitochondrial-DNA Copy Number

Alfonso Eirin, Ahmed Saad, John R. Woollard, Luis A. Juncos, David A. Calhoun, Hui Tang, Amir Lerman, Stephen C Textor, Lilach O Lerman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients. METHODS We prospectively measured systemic, renal vein (RV), inferior vena cava (IVC), and urinary copy number of the mtDNA genes COX3 and ND1 by quantitative-PCR in CEH and ObAAEH patients during constant sodium intake and antihypertensive regimens, and compared them with healthy volunteers (HV) (n = 23 each). RESULTS Blood pressure was similarly elevated in CEH and ObAAEH, while glomerular filtration rate (GFR) was higher and age lower in ObAAEH. Urinary (but not plasma) COX3 and ND1 were higher in CEH compared to HV, and further elevated in ObAAEH patients. COX3 and ND1 renal gradients (RV-IVC) were higher in ObAAEH vs. CEH, and their urinary levels directly correlated with GFR. In multivariate analysis, GFR remained the only predictor of elevated urinary COX3 and ND1 levels. CONCLUSIONS Urinary fragments of the mitochondrial genome are elevated in ObAAEH patients and correlate with glomerular hyperfiltration. A positive gradient across the kidney in ObAAEH suggests selective renal release. These results are consistent with mitochondrial injury that may aggravate renal damage and accelerate hypertension-related morbidity/ mortality rates in ObAAEH.

Original languageEnglish (US)
Pages (from-to)1112-1119
Number of pages8
JournalAmerican Journal of Hypertension
Volume30
Issue number11
DOIs
StatePublished - Nov 1 2017

Fingerprint

Mitochondrial DNA
African Americans
Kidney
Glomerular Filtration Rate
Renal Veins
Wounds and Injuries
Inferior Vena Cava
Healthy Volunteers
Urine
Hypertension
Mitochondrial Genome
Mitochondrial Genes
Antihypertensive Agents
Mitochondria
Multivariate Analysis
Sodium
Blood Pressure
Morbidity
Polymerase Chain Reaction
Mortality

Keywords

  • African American
  • blood pressure
  • hyperfiltration
  • hypertension
  • mitochondria
  • obesity

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Glomerular Hyperfiltration in Obese African American Hypertensive Patients Is Associated with Elevated Urinary Mitochondrial-DNA Copy Number. / Eirin, Alfonso; Saad, Ahmed; Woollard, John R.; Juncos, Luis A.; Calhoun, David A.; Tang, Hui; Lerman, Amir; Textor, Stephen C; Lerman, Lilach O.

In: American Journal of Hypertension, Vol. 30, No. 11, 01.11.2017, p. 1112-1119.

Research output: Contribution to journalArticle

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title = "Glomerular Hyperfiltration in Obese African American Hypertensive Patients Is Associated with Elevated Urinary Mitochondrial-DNA Copy Number",
abstract = "BACKGROUND Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients. METHODS We prospectively measured systemic, renal vein (RV), inferior vena cava (IVC), and urinary copy number of the mtDNA genes COX3 and ND1 by quantitative-PCR in CEH and ObAAEH patients during constant sodium intake and antihypertensive regimens, and compared them with healthy volunteers (HV) (n = 23 each). RESULTS Blood pressure was similarly elevated in CEH and ObAAEH, while glomerular filtration rate (GFR) was higher and age lower in ObAAEH. Urinary (but not plasma) COX3 and ND1 were higher in CEH compared to HV, and further elevated in ObAAEH patients. COX3 and ND1 renal gradients (RV-IVC) were higher in ObAAEH vs. CEH, and their urinary levels directly correlated with GFR. In multivariate analysis, GFR remained the only predictor of elevated urinary COX3 and ND1 levels. CONCLUSIONS Urinary fragments of the mitochondrial genome are elevated in ObAAEH patients and correlate with glomerular hyperfiltration. A positive gradient across the kidney in ObAAEH suggests selective renal release. These results are consistent with mitochondrial injury that may aggravate renal damage and accelerate hypertension-related morbidity/ mortality rates in ObAAEH.",
keywords = "African American, blood pressure, hyperfiltration, hypertension, mitochondria, obesity",
author = "Alfonso Eirin and Ahmed Saad and Woollard, {John R.} and Juncos, {Luis A.} and Calhoun, {David A.} and Hui Tang and Amir Lerman and Textor, {Stephen C} and Lerman, {Lilach O}",
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T1 - Glomerular Hyperfiltration in Obese African American Hypertensive Patients Is Associated with Elevated Urinary Mitochondrial-DNA Copy Number

AU - Eirin, Alfonso

AU - Saad, Ahmed

AU - Woollard, John R.

AU - Juncos, Luis A.

AU - Calhoun, David A.

AU - Tang, Hui

AU - Lerman, Amir

AU - Textor, Stephen C

AU - Lerman, Lilach O

PY - 2017/11/1

Y1 - 2017/11/1

N2 - BACKGROUND Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients. METHODS We prospectively measured systemic, renal vein (RV), inferior vena cava (IVC), and urinary copy number of the mtDNA genes COX3 and ND1 by quantitative-PCR in CEH and ObAAEH patients during constant sodium intake and antihypertensive regimens, and compared them with healthy volunteers (HV) (n = 23 each). RESULTS Blood pressure was similarly elevated in CEH and ObAAEH, while glomerular filtration rate (GFR) was higher and age lower in ObAAEH. Urinary (but not plasma) COX3 and ND1 were higher in CEH compared to HV, and further elevated in ObAAEH patients. COX3 and ND1 renal gradients (RV-IVC) were higher in ObAAEH vs. CEH, and their urinary levels directly correlated with GFR. In multivariate analysis, GFR remained the only predictor of elevated urinary COX3 and ND1 levels. CONCLUSIONS Urinary fragments of the mitochondrial genome are elevated in ObAAEH patients and correlate with glomerular hyperfiltration. A positive gradient across the kidney in ObAAEH suggests selective renal release. These results are consistent with mitochondrial injury that may aggravate renal damage and accelerate hypertension-related morbidity/ mortality rates in ObAAEH.

AB - BACKGROUND Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients. METHODS We prospectively measured systemic, renal vein (RV), inferior vena cava (IVC), and urinary copy number of the mtDNA genes COX3 and ND1 by quantitative-PCR in CEH and ObAAEH patients during constant sodium intake and antihypertensive regimens, and compared them with healthy volunteers (HV) (n = 23 each). RESULTS Blood pressure was similarly elevated in CEH and ObAAEH, while glomerular filtration rate (GFR) was higher and age lower in ObAAEH. Urinary (but not plasma) COX3 and ND1 were higher in CEH compared to HV, and further elevated in ObAAEH patients. COX3 and ND1 renal gradients (RV-IVC) were higher in ObAAEH vs. CEH, and their urinary levels directly correlated with GFR. In multivariate analysis, GFR remained the only predictor of elevated urinary COX3 and ND1 levels. CONCLUSIONS Urinary fragments of the mitochondrial genome are elevated in ObAAEH patients and correlate with glomerular hyperfiltration. A positive gradient across the kidney in ObAAEH suggests selective renal release. These results are consistent with mitochondrial injury that may aggravate renal damage and accelerate hypertension-related morbidity/ mortality rates in ObAAEH.

KW - African American

KW - blood pressure

KW - hyperfiltration

KW - hypertension

KW - mitochondria

KW - obesity

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U2 - 10.1093/ajh/hpx103

DO - 10.1093/ajh/hpx103

M3 - Article

C2 - 28641368

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VL - 30

SP - 1112

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JO - American Journal of Hypertension

JF - American Journal of Hypertension

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