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BACKGROUND The rehospitalization rate in a hypertensive emergency is high, indicating the necessity for optimizing its long-term management. The role of the renin–angiotensin system (RAS) blockade in this disorder remains uncertain. METHODS We conducted a retrospective analysis involving 20 admitted patients who received aliskiren, a direct renin inhibitor (DRI), for the management of hypertensive emergency associated with elevated plasma renin activity (PRA). We analyzed the changes in blood pressure (BP), kidney function, and RAS activity in the subacute and chronic phases. RESULTS The use of DRI was associated with a marked reduction in PRA (median, from 25.0 to 1.2 ng/ml/h) and serum aldosterone levels (from 404 to 130 pg/ml) during the index admission. BP also decreased from 226/143 to 142/80 mm Hg. A comparison of clinical characteristics according to the renal function indicated that dialysis-dependent patients had higher aldosterone levels than non-dialysis-dependent patients at admission, despite comparable BP levels. After a median follow-up of 567 days in non-dialysis-dependent patients with DRI, eGFR levels were significantly increased from 14.3 to 23.1 ml/min/1.73 m2. PRA levels were consistently suppressed at 0.8 ng/ml/h. We found a significant correlation between the degree of PRA suppression and changes in eGFR (r  = –0.58), indicating that the effective blockade of RAS is associated with the preservation of eGFR in the study subjects. CONCLUSIONS DRI can successfully suppress PRA in patients with high-renin hypertensive emergency in both subacute and chronic phases. An efficient RAS blockade is associated with preserved renal function in these patients. [ABSTRACT FROM AUTHOR]

Background and Objectives Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD. Design, setting, participants, and measurements This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33   048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects. Results There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23–1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32–2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81–1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84–2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15–13.67). Conclusion Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs. [ABSTRACT FROM AUTHOR]

This article is a response to a letter from A.H. Jan Danser and Ingrid M. Garrelds regarding the clinical impact of sample storage at -20 °C on renin reference intervals and aldosterone-renin ratio calculations. The authors of the response paper argue that cryoactivation of prorenin is a preanalytical risk for renin measurements in plasma samples stored at -20 °C. They cite experiments that show highly variable increases in renin concentration when samples are frozen at -20 °C, but no cryoactivation when samples are snap-frozen or defrosted at ambient temperature. Based on this evidence, the authors advise laboratories to store plasma samples for renin analyses in a -70 °C freezer or snap-freeze samples and store them in a -20 °C freezer. [Extracted from the article]

The article discusses the phenomenon of cryoactivation, which refers to a cold-induced change in prorenin, the inactive precursor of renin. The authors explain that storing plasma samples at low temperatures for a long time can lead to the inactivation of serine protease inhibitors, resulting in the generation of kallikrein, which can cleave the prosegment of prorenin. The authors argue that storing samples at -20 °C is sufficient and that there is no advantage to storing them at -70 °C. They also mention that renin inhibitors can bind to the active site of prorenin, leading to overestimation of renin levels in certain assays. [Extracted from the article]

Since an understanding of the pathogenesis of essential hypertension is unlikely to be imminent, there is little chance that antihypertensive therapy will become curative in the near future. What progress can be expected in symptomatic therapy? In the past, nearly all major mechanisms involved in the regulation of blood pressure have become targets of antihypertensive drugs; they include the sympathetic neuro-effector system, neuronal substrates of central cardiovascular regulation, the kidney, the renin angiotensin aldosterone system and the vascular smooth muscle cell.Among drugs that influence the function of the sympathetic nervous system, the clinical potential of one mechanism of action has not yet been explored: it is the inhibition of noradrenaline release through stimulation of inhibitory receptors located at the adrenergic nerve terminals of the cardiovascular system (inhibitory presynaptic receptors). Among the multiple presynaptic receptors, dopamine receptors appear to be a particularly interesting target.The not entirely expected activity of angiotensin converting enzyme (ACE) inhibitors in essential hypertension prompted the search for renin inhibitors. Whether interruption of the cascade of the renin angiotensin system at the first reaction step by renin inhibitors, as compared to the interference at the second step by ACE inhibitors, will yield relevant progress in antihypertensive drug therapy remains to be seen. [ABSTRACT FROM PUBLISHER]