Methodologic Issues in the Measurement of Urinary Renin

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.

Conclusions

The 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.     

Accuracy of preoperative workup in a prospective series of surgically resected cystic pancreatic lesions

Abstract Background. Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are considered useful techniques in the evaluation of pancreatic cysts. Aim of this study was to prospectively compare the diagnostic value of these techniques. Methods. This study included consecutive patients who underwent MRI, EUS, and EUS-FNA for a pancreatic cyst that was eventually resected surgically. Observers scored for cyst characteristics, a distinction between mucinous and non-mucinous cysts and a suspicion of malignancy. The interobserver agreement between MRI and EUS was calculated. Results. A total of 32 patients were included. Sensitivity for diagnosing a mucinous cyst was 78% for EUS versus 91% for MRI. Sensitivity for detecting malignancy was 25% (1/4) and 50% (2/4) for EUS and MRI respectively. Sensitivity of EUS-FNA for diagnosing a mucinous cyst (positive cytology and/or CEA >192 ng/ml) was 61%. Sensitivity for detecting malignancy (positive cytology) was 1/4 (25%). Interobserver agreement between MRI and EUS for the features was poor to fair. Conclusion. MRI and EUS are comparable techniques for the morphological characterization of pancreatic cysts. Combined sensitivity of EUS and MRI was higher than the sensitivity of one of the techniques alone. For diagnosing a mucinous cyst, FNA findings showed a low sensitivity, but a high specificity.     

Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure

Aims Biochemical marker testing has improved the evaluation and management of patients with cardiovascular diseases over the past decade. Natriuretic peptides (NPs), used in clinical practice to assess cardiac dysfunction, exhibit many limitations, however. We used an unbiased proteomics approach for the discovery of novel diagnostic plasma biomarkers of heart failure (HF). Methods and results A proteomics pipeline adapted for very low-abundant plasma proteins was applied to clinical samples from patients admitted with acute decompensated HF (ADHF). Quiescin Q6 (QSOX1), a protein involved in the formation of disulfide bridges, emerged as the best performing marker for ADHF (with an area under the receiver operator characteristic curve of 0.86, 95% confidence interval: 0.79-0.92), and novel isoforms of NPs were also identified. Diagnostic performance of QSOX1 for ADHF was confirmed in 267 prospectively collected subjects of whom 76 had ADHF. Combining QSOX1 to B-type NP (BNP) significantly improved diagnostic accuracy for ADHF by particularly improving specificity. Using thoracic aortic constriction in rats, QSOX1 was specifically induced within both left atria and ventricles at the time of HF onset. Conclusion The novel biomarker QSOX1 accurately identifies ADHF, particularly when combined with BNP. Through both clinical and experimental studies we provide lines of evidence for a link between ADHF and cardiovascular production of QSOX1.     

Bilateral Lobar Lung Transplantation — the First Two Cases in Belgium

In the last twenty years lung transplantation has become an established treatment for end-stage lung failure refractory to medical management. Over this time, better short and long-term results have been achieved due to improvements in organ procurement, perfusion and preservation strategies, newer immunosuppressant regimes and better post-transplant care. The limiting factor for the number of lung transplantation procedures performed is the shortage of available donor organs. This results in longer waiting times for listed patients, with a substantially increased risk of dying prior to transplantation, especially in the paediatric population.

Several surgical strategies have evolved to overcome the donor shortage, with lobar transplantation becoming a viable alternative. We describe our initial experience with two young patients with end-stage cystic fibrosis (CF) who required lung transplantation. Given their small size it was not possible to transplant an entire lung from an adult donor in each hemithorax. We describe lobar transplantation as a technique used to overcome this, in the first such operation in Belgium.     

Stimulation of the intra-cardiac vagal nerves innervating the AV-node to control ventricular rate during AF: specificity, parameter optimization and chronic use up to 3?months

Background  

Stimulation of the intra-cardiac vagal nerves innervating the AV-node (AVNS) is a promising approach to slow down ventricular rate (VR) during atrial fibrillation (AF). Our purpose was to demonstrate that effects on R-R-interval during stable AF can be maintained for several months once optimized and that AVNS affects specifically the nerves innervating the AV-node.