Direct Radioimmunoassay of Human Renin

Galen, F. X.; Guyenne, Than T.; Devaux, C; Auzan, Colette; Corvol, Pierre; Ménard, Joël

doi:10.1210/jcem-48-6-1041

Cited by 76 publications

(37 citation statements)

References 26 publications

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“…Their specificity was established previously (38). Rabbit polyclonal antibodies against ACE (Y4) (39) and human angiotensinogen (40) also were from P. Corvol.…”

Section: Antibodiesmentioning

confidence: 99%

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Lacoste

Cai

Guicharnaud

et al. 2006

Journal of the American Society of Nephrology

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Renal tubular dysgenesis is a clinical disorder that is observed in fetuses and characterized by the absence or poor development of proximal tubules, early onset and persistent oligohydramnios that leads to the Potter sequence, and skull ossification defects. It may be acquired during fetal development or inherited as an autosomal recessive disease. It was shown recently that autosomal recessive renal tubular dysgenesis is genetically heterogeneous and linked to mutations in the genes that encode components of the renin-angiotensin system. This study analyzed the clinical expression of the disease in 29 fetus/neonates from 18 unrelated families and evaluated changes in renal morphology and expression of the renin-angiotensin system. The disease was uniformly severe, with perinatal death in all cases as a result of persistent anuria and hypoxia related to pulmonary hypoplasia. Severe defects in proximal tubules were observed in all fetuses from 18 gestational weeks onward, and lesions also involved other tubular segments. They were associated with thickening of the renal arterial vasculature, from the arcuate to the afferent arteries. Renal renin expression was strikingly increased in 19 of 24 patients studied, from 13 families, whereas no renal renin was detected in four patients from three families. Angiotensinogen and angiotensinconverting enzyme were absent or present in only small amounts in the proximal tubule, in correlation with the severity of tubular abnormalities. No specific changes were detected in angiotensin II receptor expression. The severity and the early onset of the clinical and pathologic expression of the disease underline the major importance of this system in fetal kidney function and development in humans. The identification of the disease on the basis of precise histologic analysis and the research of the genetic defect now allow genetic counseling and early prenatal diagnosis. (1) in two stillborn siblings who had developed fetal anuria that resulted in oligohydramnios and the Potter phenotype. Fetal urine is the major constituent of amniotic fluid, especially after 18 to 20 gestational weeks, and estimation of its abundance is the best approach for evaluation of fetal kidney function. Oligohydramnios, whatever the cause, leads to fetal compression and decreased intrauterine motility, resulting in the Potter sequence that includes redundant skin, facial dysmorphia with large and flattened low-set ears, limb positioning

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“…Their specificity was established previously (38). Rabbit polyclonal antibodies against ACE (Y4) (39) and human angiotensinogen (40) also were from P. Corvol.…”

Section: Antibodiesmentioning

confidence: 99%

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Lacoste

Cai

Guicharnaud

et al. 2006

Journal of the American Society of Nephrology

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“…Its purification from a juxtaglomerular cell tumor (1) and from cadaver kidney (2,3) facilitated the characterization of the enzyme and the generation of polyclonal antibodies in the rabbit. Polyclonal antibodies against human renin were used to set up a direct radioimmunoassay (RIA)' (4), to localize renin by immunohistochemistry (5,6), and to block in vivo the renin enzymatic activity in an experimental model of hypertension in the monkey (7,8).…”

Section: Introductionmentioning

confidence: 99%

New monoclonal antibodies directed against human renin. Powerful tools for the investigation of the renin system.

Galen¹,

Devaux²,

Atlas³

et al. 1984

J. Clin. Invest.

134

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A bstract. Monoclonal antibodies directed against human renin were obtained by the fusing of myeloma cells with spleen cells from Balb/c or highresponder Biozzi mice injected with pure tumoral or highly purified renal renin. These procedures resulted in the production of seven stable monoclonal antibodies to human renin. Antibodies in the hybridoma culture medium were screened by binding to pure iodinated renin or insolubilized renin in a solid phase assay. The concentration of purified antibodies that provided a 50% binding to iodinated renin varied from 1 X 10-10 to 1 X 10-7 M. Two monoclonal antibodies were found to be potent inhibitors of renin enzymatic activity in vitro, behaving as noncompetitive inhibitors (Ki, 1 to 4 X 10`s M). They were specific for primate renin. Three monoclonal antibodies provided suitable immunoadsorbants for renin purification. One of these immunoadsorbants was used for large-scale purification of the renal enzyme, resulting in an 825-fold renin enrichment in a single step. Two antibodies were able to distinguish between active and inactive renin and enabled concomitant separation and purification of the two enzyme forms in various biological fluids. Monoclonal antibodies also stained human and monkey renal renin when indirect immunofluorescence and peroxidase-antiperoxidase techniques were used. A highly sensitive radioimDr. Atlas is with the

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“…However, it was difficult to get a sufficient amount of renin or to purify an active renin to develop a suitable antigen for making antibodies. Moreover, antirenin antibodies employed in the early stages of developing a direct assay for renin gave heterogenous immune responses because of its polyclonal nature (Galen et al 1979). With this polyclonal antibody it was impossible to distinguish the active form of renin from the inactive form which constitutes approximately 70% of total renin in human plasma (Tsunoda et al 1986).…”

Section: Discussionmentioning

confidence: 99%

Comparison of immunoreactive renin and plasma renin activity in human plasma.

Tsunoda

Abe

Yasujima

et al. 1989

Tohoku J. Exp. Med.

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Measurement of immunoreactive plasma renin concentration (PRC) using direct radioimmunoassay (RIA) was compared with the common procedure, measurement of plasma renin activity (PRA). The sensitivity of the PRC assay was 5 pg/ml. In 67 normal subjects aged 45.2+1.2 year, the mean PRC value was 17.0+0.9 pg/ml in the recumbent position and 38.0 + 5.4 pg/ml in the upright position. In patients with high renin essential hypertension and renovascular hypertension, discrepancies were observed between changes in PRA and PRC at 60 min after the administration of captopril. In a patient with Bartter's syndrome PRC was markedly elevated (393 pg/ml) and the chages in PRA and in PRC after captopril were very different (452% vs. 1249%). In all 10 cases of primary hyperaldosteronism PRC was less than 5 pg/ml. The correlation coefficient between PRC and PRA was 0.85 (n =227, p <0.01). The slope of the regression line between PRA and PRC decreased in proportion to PRC values. Direct RIA for PRC is likely to be useful for the determination of plasma active renin when renin levels are high or substrate concentrations are abnormal. Moreover, the combined use of PRA and PRC measurements might be useful in assessing abnormalities in renin substrate concentration as well as in PRO. active renin ; PRA ; monoclonal antibodiesThe plasma renin level is an important indicator of the state of reninangiotensin (R-A) system. The development of methods for measurement of plasma renin level has contributed greatly to our understanding of both clinical and pathophysiological aspects of the R-A system. Recently, Corvol and col-

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Direct Radioimmunoassay of Human Renin

Cited by 76 publications

References 26 publications

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

New monoclonal antibodies directed against human renin. Powerful tools for the investigation of the renin system.

Comparison of immunoreactive renin and plasma renin activity in human plasma.

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