Determinants of interindividual variation of renin and prorenin concentrations

Danser, A.H. Jan; Derkx, F. H. M.; Schalekamp, M. A. D. H.; Hense, Hans‐Werner; Riegger, Günter A.J.; Schunkert, Heribert

doi:10.1097/00004872-199816060-00017

Cited by 212 publications

(149 citation statements)

References 30 publications

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“…Alge et al (4) recently reported that urinary renin, together with urinary angiotensinogen, associates with AKI after cardiac surgery. Their urinary renin levels were measured with the Quantikine Renin ELISA Kit and exceeded published plasma renin levels (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, the kit simultaneously detects both renin and prorenin, and thus, given that in most body fluids prorenin greatly exceeds renin (up to 100-fold), it provides information on prorenin (11,12,16). Remarkably for a renin kit, the ELISA uses recombinant prorenin as a standard, and even more concerning, this prorenin has not been calibrated against the International Reference Preparation of human renin.…”

Section: Discussionmentioning

confidence: 99%

“…The former two groups have been described previously (7,8), and the latter two groups are part of an ongoing study investigating the RAS in pregnancy and preeclampsia. The four patients groups were chosen on the basis of availability and their wide variety in renin and prorenin levels; diabetic patients and preeclamptic women have relatively low renin and high prorenin levels versus hypertensive patients, and pregnant women have relatively high renin and prorenin levels (12,13). The 10 representatives from each group were chosen in a random manner.…”

Section: Samplesmentioning

confidence: 99%

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Methodologic Issues in the Measurement of Urinary Renin

Roksnoer

Verdonk

Garrelds

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Alge et al. recently reported that urinary renin may be a prognostic biomarker for AKI after cardiac surgery. However, their urinary renin levels far exceeded published plasma renin levels, whereas normally, urinary renin is ,10% of plasma renin. This result raises questions about the specificity of the new Quantikine Renin ELISA Kit used in the work by Alge et al., which is claimed to detect total renin (i.e., renin and prorenin). Therefore, this study tested this assay.Design, setting, participants, & measurements Plasma and urine from 30 patients with hypertension, diabetes, or preeclampsia and 10 healthy pregnant women (randomly selected from sample sets obtained earlier to investigate urinary renin-angiotensin system components) were used to compare the ELISA with a validated renin immunoradiometric assay and an in-house enzyme kinetic assay. Measurements were performed before and after in vitro prorenin activation, representing renin and total renin, respectively.Results Total renin measurements by ELISA, immunoradiometric assay, and enzyme kinetic assay were highly correlated. However, ELISA results were consistently $10-fold higher. The ELISA standard yielded low to undetectable levels in the immunoradiometric assay and enzyme kinetic assay, except after prorenin activation, when the results were $10-fold lower than the ELISA results. In plasma, prorenin activation increased ELISA results by 10%-15%. Urine contained no detectable prorenin. ConclusionsThe ELISA renin kit standard is prorenin, and its immunoreactivity and enzymatic activity after conversion to renin do not match the International Reference Preparation of human renin that has been used to validate previous immunoradiometric assays and enzyme kinetic assays; in fact, they are at least 10-fold lower, and thus, any measurements obtained with this ELISA kit yield levels that are at least 10-fold too high. The ELISA antibodies detect both renin and prorenin, with a preference for the former. Given these inconsistencies, urinary renin levels should be measured by established renin assays.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Samplesmentioning

confidence: 99%

See 1 more Smart Citation

Methodologic Issues in the Measurement of Urinary Renin

Roksnoer

Verdonk

Garrelds

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…The ability of aliskiren to inhibit prorenin activation has additional relevance because circulating levels of prorenin are about 10-fold those of renin. 125 This represents high potential renin activity. In addition, plasma prorenin levels can be substantially elevated in diabetes 126 and are strongly associated with microvascular complications of this disease.…”

Section: Aliskiren Localizes In the Kidneymentioning

confidence: 98%

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

Feldman

2010

Hypertens Res

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The renin-angiotensin-aldosterone system (RAAS) has a central function in the regulation of blood pressure. Aliskiren, the first direct renin inhibitor to be approved for the treatment of hypertension, blocks the RAAS at its point of activation. As renin inhibition acts at the top of the RAAS cascade, this mechanism has been proposed to offer advantages over existing modes of RAAS blockade. The RAAS is also considered to be a major factor in the pathogenesis of many renal diseases, especially diabetic nephropathy (DN), the main cause of end-stage renal disease. Existing therapies to block the RAAS slow the progression of DN, but they do not halt the disease. Therefore, more effective modes of interventions are needed. Studies to determine the efficacy of aliskiren in human renal disease are in progress. This review summarizes in vivo studies in which the efficacy of aliskiren was tested in experimental models of renal disease, and presents in vitro studies that provide insights into the possible mechanisms by which aliskiren confers renoprotection in animals. These works are discussed in the framework of the intrarenal RAAS and suggest that aliskiren may act by unique renoprotective mechanisms. Keywords: aliskiren; kidney; mechanism; nephropathy; renin INTRODUCTIONThe renin-angiotensin-aldosterone system (RAAS) is an ancient pathway 1 that has evolved into a central mechanism by which mammalian blood pressure (BP) and fluid homeostasis are regulated. Research in this field started with the discovery in 1898 by Tigerstedt and Berman 2 that a renal extract when injected into rabbits induced a rapid increase in systemic BP. Subsequent work over many years established the RAAS as a pivotal contributor to cardiorenal diseases. Hence, inhibitors of the middle and distal portions of the RAAS pathway, angiotensin-converting enzyme (ACE) inhibitors (ACEI) and AT 1 receptor blockers, respectively, have become mainstay therapies for treating hypertension. In 2007, aliskiren, the first direct renin inhibitor (DRI), was approved for the treatment of hypertension. This heralded the therapeutic control of BP by inhibiting the RAAS at its first and rate-limiting step. However, RAAS blockade is also effective for treating renal disease 3-6 and the efficacy of aliskiren for this purpose is currently being investigated. Accordingly, the subject of this review is to summarize the preclinical evidence for renoprotection by aliskiren, and to discuss recently published information on the possible mechanism(s) for these benefits. As it is well recognized that there is a tissue as well as circulating RAAS, 7 the preclinical actions of aliskiren will be discussed in the context of the intrarenal RAAS and the potential for its inhibition by aliskiren.

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“…Renin may diffuse into the interstitial space (18,28) or bind to renin receptors and/or renin-binding proteins (8,46,53). Because renin in blood is predominantly present in the form of its inactive precursor prorenin (11), it is also conceivable that the heart sequesters prorenin instead of renin. This prorenin must then be activated locally.…”

mentioning

confidence: 99%