Renovascular Hypertension with Low-to-Normal Plasma Renin: Clinical and Angiographic Features

Rossi, Gianpaolo; Pavan, Edoardo; Chiesura-Corona, M; Bäder, Michael; Paganini, Greta; Cesari, Maurizio; Toni, Renzo De; Feltrin, Giampietro; Ganten, Detlev; Pessina, Achille C.

doi:10.1042/cs0930435

Cited by 24 publications

(18 citation statements)

References 37 publications

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“…However, some limitations of this study should be recognized. Previous clinical studies reported normal plasma renin activity (PRA) levels in 25%-37% of patients with RVD 35,36 (suggesting PRA as an unreliable index of RVD 37 ), whereas the swine model show an early but transient increase that goes back to baseline levels after 4-6 weeks of RVD. 10,38 Because of the growth pattern and size limitations, the animals used in the study are relatively young and consequently, lack some common comorbid diseases often observed associated with human CKD, such as obesity 39,40 or diabetes, 41 that may compromise renal outcomes.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

Chade¹,

Tullos²,

Stewart³

et al. 2015

Journal of the American Society of Nephrology

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Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. Chronic renovascular disease (RVD) increases the risk of cardiovascular morbidity and mortality and may progressively induce renal injury, leading to ESRD. 1 Percutaneous transluminal renal angioplasty/stenting (PTRAS) is a frequently used therapeutic strategy to treat patients with chronic RVD. Targeting the renal stenosis is a logical choice for treating RVD, because the resolution of the vascular obstruction followed by restoration of blood flow to the site of injured tissues should play an important role to initiate successful repairing responses. The use of PTRAS in RVD grew significantly during the past 20 years, 2 with tremendous progress in successfully resolving renal stenosis and restoring blood flow (.95% of the cases). 3 However, despite the high technical success of PTRAS, improvement in renal function is still observed in a relatively small portion of the cases. 4 The reasons for the persistent poor outcomes after PTRAS in RVD are still unclear. Furthermore, the dissociation between the technical success of PTRAS and renal outcomes underscores a pressing need to identify more effective therapeutic strategies in RVD.Endothelin-1 (ET-1) is a powerful renal vasoconstrictor and mitogenic peptide that plays important roles in controlling BP and renal function.

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Section: Discussionmentioning

confidence: 99%

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

Chade¹,

Tullos²,

Stewart³

et al. 2015

Journal of the American Society of Nephrology

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“…Plasma renin activity was measured by a commercially available kit (Ares Serono, Milan, Italy, supine normal values with a daily sodium intake of 100 to 200 mmol: 0.51 to 2.64 ng Ang I ⅐ mL Ϫ1 ⅐ h Ϫ1 ) as reported. 17 PAI-1:Ag levels were assayed by an ELISA method (TintElize PAI-1, Biopool, Umeå, Sweden) following the manufacturer's protocols 18 (normal range 4 to 30 ng/mL). The within and between assay coefficients of variation of this assay were 1.9% and 2.4%, respectively.…”

Section: Blood Sampling and Biochemical Measurementsmentioning

confidence: 99%

Determinants of Plasma Levels of Plasminogen Activator Inhibitor-1

Cesari

Sartori

Patrassi

et al. 1999

ATVB

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Abstract-We investigated whether plasma levels of the plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) are genetically determined in monozygotic (MZ) and dizygotic (DZ) twins. Twenty-five pairs of healthy twins underwent measurements of PAI-1:Ag and other variables, including body mass index, mean blood pressure, plasma renin activity, insulin, and glucose. To ascertain the zygosity of twins, highly discriminating micro-and minisatellite systems with variable numbers of tandem repeats were analyzed by PCR amplification followed by polyacrylamide gel electrophoresis. Subjects were also genotyped for the 4G/5G polymorphism by PCR. Estimates of genetic variance and heritability were obtained for PAI-1:Ag, and for body mass index, mean blood pressure, plasma renin activity, glucose, and insulin by jointly examining data in a path analysis with TWINAN90. Results showed that 12 pairs of twins were MZ and 13 were DZ. Key Words: plasminogen activator inhibitor type 1 Ⅲ fibrinolysis Ⅲ gene polymorphism Ⅲ twins Ⅲ humans P lasminogen activator inhibitor type 1 (PAI-1) is the key regulator 1 of the activity of the fibrinolytic system, an important protective mechanism against thrombosis. Reduced fibrinolytic activity, mainly caused by increased plasma levels of PAI-1, is a common finding in many cross-sectional studies of patients with coronary artery disease (CAD) 2 and recurrent myocardial infarction (MI), 3-5 deep vein thrombosis, 6,7 and stroke. 8 Although extensive investigations have led to identification of the environmental factors regulating PAI-1:Ag and PAI-1 activity (PAI-1:act) levels in plasma (see for review 7,9 ), only limited information exists on their genetic determinants. To our knowledge the following 8 polymorphisms of the PAI-1 gene have been identified 10 : two (CA) n repeat polymorphisms, a HindIII restriction fragment length polymorphism, an insertion (5G)/deletion (4G) polymorphism on the promoter, ie, Ϫ675 bp upstream from the start of transcription of the PAI-1 gene, and 4 polymorphisms in the PAI-1 gene by use of the single-strand conformational polymorphism (SSCP) method. 10 A major effect of the 4G/5G polymorphism on PAI-1:act was reported, but conflicting results are also available. 9 -13 In fact, a relationship between both PAI-1 antigen and activity levels and the 4G/5G polymorphism (the 4G homozygous having the highest mean plasma PAI-1 levels) has been shown in patients with CAD, non-insulin-dependent diabetes mellitus (NIDDM), and healthy control subjects. 9,11,12,14,15 However, in contrast with these findings no significant association was found between both PAI-1 antigen and activity levels and the 4G/5G polymorphism or the HindIII RFLP in 189 patients with NIDDM, and between PAI-1:act levels and the 4G/5G polymorphism and four polymorphisms identified in the PAI-1 gene by use of the SSCP method, in healthy men aged 50 to 59 years. 10,13 Thus, the issue of whether plasma PAI-1:act and/or plasma PAI-1:Ag are under the effect of a major gene is still under debate.Studies of twi...

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“…In the majority of studies concerning adults, a lack of sensitivity and specificity of RVR ratios in predicting cure following surgery has been reported [15,16], especially in the presence of low-to-normal plasma renin [17]. The correlation between the arteriographic appearance and functional significance of renal artery stenosis has been poor in adults, perhaps due to the non-linear relationship between the anatomical degree of stenosis and its functional effects on flow and pressure distal to the stenosis [18,19].…”

Section: Introductionmentioning

confidence: 91%

“…The correlation between the arteriographic appearance and functional significance of renal artery stenosis has been poor in adults, perhaps due to the non-linear relationship between the anatomical degree of stenosis and its functional effects on flow and pressure distal to the stenosis [18,19]. Low values of peripheral renin, technical errors, bilateral disease, segmental artery involvement, and coexisting functionally unimportant renal artery stenosis in angiograms of patients with mainly essential hypertension contribute to its poor specificity [3,17,20,21,22]. In this retrospective study, we have assessed 25 years of our experience and, in particular, the association between RVR ratios and the subsequent outcome, with or without surgery/angioplasty, in hypertensive children.…”

Section: Introductionmentioning

confidence: 98%

The usefulness of renal vein renin studies in hypertensive children: a 25-year experience

Goonasekera

Shah

Wade

et al. 2002

Pediatric Nephrology

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Lateralised renin secretion predicts improvement following surgery/angioplasty of the affected kidney in paediatric hypertension. We retrospectively analysed all our renal vein renin (RVR) studies undertaken in hypertensive children and their subsequent clinical outcomes over a 25-year period. The outcomes were categorised as cure, improvement or no change in hypertension. The proportions that benefited by 'following' or 'ignoring' the RVR results in relation to the aetiology of hypertension and subsequent therapy were compared. A ratio between the RVR value of the dominant kidney and that of the contralateral kidney (R/Rc ratio) above 1.5 was considered to show significant lateralisation. A ratio between RVR value of the contralateral kidney and that of the caudal inferior vena cava (Rc/P ratio) of less than 1.3 was considered to indicate contralateral renin suppression. Of 233 RVR records, 137 were suitable for analysis. Of these, 39 had reflux nephropathy (RN), 73 renovascular disease (RVD) and the others miscellaneous conditions. Of the 39 hypertensive children with RN, the R/Rc ratio was over 1.5 in 20 subjects, of whom 11 underwent surgery. Amongst the 19 with an R/Rc less than 1.5, 4 also had surgery. Of the 73 hypertensive children with RVD, the R/Rc ratio was over 1.5 in 38 subjects, of whom 20 underwent surgery/angioplasty. Amongst the 35 with an R/Rc less than 1.5, 7 also underwent surgery/angioplasty. In RN there was no significant difference in the proportion that improved with allocated treatment, as suggested by the 'test' when compared with those who were 'misallocated'. In RVD, however, the proportion improved (35.0%) by 'following the test' (i.e. R/Rc ratio) was significantly greater than the proportion improved (12.5%) in the group in whom the test was 'ignored'. This was true for both R/Rc and Rc/P ratios. Thus, RVR measurements are useful for identifying hypertensive children with RVD that may have a favourable outcome after surgery, but this does not apply to children with RN. Measurements, however, may have diagnostic value even if surgery or angioplasty is not anticipated.

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Renovascular Hypertension with Low-to-Normal Plasma Renin: Clinical and Angiographic Features

Cited by 24 publications

References 37 publications

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

Determinants of Plasma Levels of Plasminogen Activator Inhibitor-1

The usefulness of renal vein renin studies in hypertensive children: a 25-year experience

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