Serum Renin Concentration Research Articles

RENIN AND ANGIOTENSIN (1-7) OFFER PREDICTIVE VALUE IN PEDIATRIC SEPSIS: FINDINGS FROM PROSPECTIVE OBSERVATIONAL COHORTS.

Background: Pediatric sepsis is a common and complex syndrome characterized by a dysregulated immune response to infection. Aberrations in the renin-angiotensin system (RAS) are factors in several infections of adults. However, the precise impact of RAS dysregulation in pediatric sepsis remains unclear. Methods: Serum samples were collected from a derivation cohort (58 patients with sepsis, 14 critically ill control subjects, and 37 healthy controls) and validation cohort (50 patients with sepsis, 37 critically ill control subjects, and 46 healthy controls). Serum RAS levels on day of pediatric intensive care unit admission were determined and compared with survival status and organ dysfunction. Results: In the derivation cohort, the serum renin concentration was significantly higher in patients with sepsis (3,678 ± 4,746) than that in healthy controls (635.6 ± 199.8) ( P < 0.0001). Meanwhile, the serum angiotensin (1-7) was significantly lower in patients with sepsis (89.7 ± 59.7) compared to that in healthy controls (131.4 ± 66.4) ( P < 0.01). These trends were confirmed in a validation cohort. Nonsurvivors had higher levels of renin (8,207 ± 7,903) compared to survivors (2,433 ± 3,193) ( P = 0.0001) and lower levels of angiotensin (1-7) (60.9 ± 51.1) compared to survivors (104.0 ± 85.1) ( P < 0.05). A combination of renin, angiotensin (1-7) and procalcitonin achieved a model for diagnosis with an area under the receiver operating curve of 0.87 (95% CI: 0.81-0.92). Conclusion: Circulating renin and angiotensin (1-7) have predictive value in pediatric sepsis.

Renin as a Biomarker of Acute Kidney Injury and Mortality in Children With Severe Malaria or Sickle Cell Disease.

Globally, a very high percentage of acute kidney injury (AKI) occurs in low- and middle-income countries (LMICs) where late recognition contributes to increased mortality. There are challenges with using existing biomarkers of AKI in LMICs. Emerging evidence suggests renin may serve as a biomarker of kidney injury that can overcome limitations in creatinine-based diagnostics. Two study populations in Uganda were assessed. Cohort #1 was a two-site, prospective cohort study enrolling 600 children with severe malaria (SM). Cohort #2 was a prospective cohort study enrolling 185 children with sickle cell disease (SCD) hospitalized with a vaso-occlusive crisis. Plasma or serum renin concentrations were measured in both cohorts of children at the time of hospital admission using Luminex® (Luminex Corporation,Austin, Texas, United States) or enzyme-linked immunosorbent assay (ELISA), respectively. We assessed the ability of renin to discriminate between children with or without AKI and between children who survived and children who died using receiver operating characteristic curves. In both cohorts, renin concentrations were strongly associated with AKI and mortality. Renin was able to discriminate between children with or without AKI with an area under the curve (AUC) of 0.70 (95%CI, 0.65-0.74) in children with SM and 0.72 (95%CI, 0.6co3-0.81) in children with SCD. Renin was able to discriminate between children who survived and children who died with an AUC of 0.73 (95%CI, 0.63-0.83) in children with SM and 0.94 (95%CI, 0.89-0.99) in children with SCD. In Cohort #2, we compared renin against urine neutrophil gelatinase-associated lipocalin (NGAL) as the leading biomarker of AKI, and it had comparable performance in discriminating AKI and predicting mortality. In two independent populations of children at risk of AKI with key differences in the etiology of kidney injury, renin was strongly associated with AKI and mortality and had moderate to good diagnostic performance to predict mortality.

Renin-angiotensin and endothelin systems in patients post takotsubo syndrome

Abstract Background We investigate if renin-angiotensin and endothelin-1 response pathways follow the same pattern of recovery as left ventricular ejection fraction in patients with takotsubo syndrome. Purpose To provide better insight into the pathophysiology underlying this condition. Methods Ninety takotsubo syndrome patients [n=30 in each of “acute”, “convalescent” (3–5 months) and “recovered” (&amp;gt;1 year) groups] who were on minimal or no medication and were free of any significant cardiac/metabolic co-morbidities, and 30 healthy controls were studied. Serum concentrations of renin, angiotensin converting enzyme, angiotensin II, big endothelin-1, endothelin-1 were measured using commercially available ELISA, and BNP was measured using an immunoassay. Results Left ventricular ejection fraction was 38±1.6% in acute, 63±2.0% in convalescent and 64±2.6% in recovered takotsubo syndrome patients. As shown in Figure 1, serum renin concentrations are persistently elevated after a takotsubo episode (p=0.03 vs controls). Angiotensin converting enzyme levels are significantly depressed during the acute phase compared to convalescent (p=0.004), recovered takotsubo (p=0.02) or controls (p=0.03). Angiotensin II is increased in takotsubo patients (p&amp;lt;0.001 vs controls) remaining persistently elevated long-term in the recovered group (p=0.03 vs controls). B-type natriuretic peptide concentrations remain elevated after a Takotsubo episode compared to controls (p=0.003). Big endothelin-1 levels are unchanged, but endothelin-1 is significantly lower after takotsubo syndrome compared to controls (p=0.03). Conclusions Despite “normalisation” of the left ventricular ejection fraction, there is long-term maladaptive activation of renin-angiotensin system in takotsubo syndrome patients. This suggests therapy aimed at modulating this pathway may be beneficial in the long-term. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): British Heart Foundation

Renin-Angiotensin and Endothelin Systems in Patients Post-Takotsubo Cardiomyopathy.

Background We investigate if renin-angiotensin and endothelin-1 response pathways follow the same pattern of recovery as left ventricular ejection fraction in patients with takotsubo cardiomyopathy. Methods and Results Ninety patients with takotsubo cardiomyopathy (n=30 in each of "acute," "convalescent" [3-5 months] and "recovered" [>1 year] groups) who were on minimal or no medication and were free of any significant cardiac/metabolic comorbidities, and 30 controls were studied. Serum concentrations of renin, angiotensin-converting enzyme, angiotensin II, big endothelin-1, endothelin-1 were measured using commercially available ELISA, and B-type natriuretic peptide was measured using an immunoassay. Mean left ventricular ejection fraction was <40% during the acute phase in all groups, but recovered to 63% in convalescent and 64% in the recovered groups, respectively. Serum renin concentrations remain persistently elevated after a episode of takotsubo cardiomyopathy (P=0.03 versus controls). Angiotensin converting enzyme levels are significantly depressed during the acute phase compared with convalescent (P=0.004), recovered takotsubo cardiomyopathy (P=0.02) or controls (P=0.03). Angiotensin II is increased in patients with takotsubo cardiomyopathy (P<0.001 versus controls) remaining persistently elevated in the chronically recovered group alone (P=0.03 versus controls). Big endothelin-1 levels are unchanged, but endothelin-1 is significantly lower after takotsubo cardiomyopathy compared with controls (P=0.03). Conclusions Despite "normalization" of the left ventricular ejection fraction, there is long-term maladaptive activation of renin-angiotensin system in patients with takotsubo cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02897739, NCT02989454.

Pregnane X Receptor Activator Rifampin Increases Blood Pressure and Stimulates Plasma Renin Activity.

We conducted a clinical trial with 22 healthy volunteers to investigate the effects of pregnane X receptor (PXR) agonist rifampin on blood pressure (BP). The study was randomized, crossover, single-blind, and placebo-controlled. Rifampin 600mg or placebo once daily was administered for a week and the 24-hour ambulatory BP was monitored at the end of each arm on the eighth day. Rifampin elevated the mean systolic and diastolic 24-hour BP (4.7mmHg, P<0.0001, and 3.0mmHg, P<0.001, respectively) as well as the mean heart rate (3.5bpm, P=0.038). The serum renin concentration and the plasma renin activity were increased. Although rifampin increased circulating 4β-hydroxycholesterol (4βHC) as expected, the plasma 4βHC concentration strongly negatively correlated with 24-hour BP, especially systolic, in both rifampin and placebo arms (rifampin systolic BP, r=-0.69, P<0.001; placebo systolic BP, r=-0.70, P<0.001). The 4βHC, an agonist for liver X receptor (LXR), induced renin expression modestly in LXR-α expressing Calu-6 cells but only at unphysiologically high 4βHC concentrations. In conclusion, rifampin stimulates renin activity and has a hypertensive effect. This finding should be considered when designing interaction studies involving rifampin or other PXR agonists. Furthermore, PXR may represent a putative therapeutic target for the treatment of hypertension.

PROTECTIVE EFFECT OF SOME RENIN INHIBITORS IN ACUTE NEPHROTOXICITY INDUCED BY SOME ANTICARCINOGENIC DRUGS IN RATS

Investigation was carried out to study protective effect of some renin inhibitors in acute nephrotoxicity on forty male Sprague Dawely rats weighting 200g to 250g which divided into four equal groups each group included 10 rats GroupI (Control group): was fed on normal ration for one month. While GroupII (cisplatin group) was injected i.p. by 7.5 mg kg B.W of cisplatin for one month. GroupIII (captopril group) was injected i.p. by 60 mg kgB.W of captopril for one month.GroupIV (captopril plus cisplatin group) there is injection of cisplatin (7.5mg/kg b .wt) i.p and within one hour it is proceeded by i.p injection of captopril (60 mg/kg b. wt) daily for one month. At the end of experiment the obtained results revealed that, administration of cisplatin and captopril caused a highly significant decrease in serum and kidney MDA ,serum creatinine concentration , serum blood urea nitrogen concentration, serum angiotensin II concentration and serum aldosterone level. whole blood and kidney p53 concentration compared to cisplatin treated rats .Also there was highly significant increase in whole blood GSH concentration, serum Glutathione peroxidase, serum catalase activity, serum superoxide dismutase activity and serum renin concentration compared to cisplatin treated group. Administration of cisplatin only revealed in increase in serum and kidney MDA ,serum creatinine concentration , serum blood urea nitrogen concentration, serum angiotensin II concentration serum aldosterone level, whole blood and kidney p53 concentration as compared to control group . There was a highly significant decrease in whole blood GSH concentration, serum Glutathione peroxidase, serum catalase activity, serum superoxide dismutase activity and serum renin concentration compared with control group. Administration of captopril only result in decrease in serum and kidney MDA ,serum creatinine concentration , serum blood urea nitrogen concentration, serum angiotensin II concentration serum aldosterone concentration, whole blood and kidney p53 concentration compared to control group also there was highly significant increase in whole blood GSH concentration, serum Glutathione peroxidase, serum catalase activity, serum superoxide dismutase activity and serum renin concentration when compared to control group. These results were supported by histopathological examination which revealed some alterations represented by that the tubule was dilated and shrinked or atrophied , the tubular cells was removed and lost and there is asignificant destruction of glomerular with penetration of leuococyte and intratubular bleeding. While administration of cisplatin and captopril result in regenerating glomeruli and tubules of kidney tissues produce by cisplatin administration.

Renin and angiotensin-converting enzyme (ACE) as active components of the local synovial renin-angiotensin system in rheumatoid arthritis

Local functional renin-angiotensin systems (RAS) have been demonstrated in many organ and tissue systems. Angiotensins, the effector growth factors of the RAS, are essentially cytokines and growth factors which actively contribute to many inflammatory reactions. Among the components of RAS, angiotensin-converting enzyme (ACE) and renin have been previously investigated separately in RA. In this study, ACE levels and renin concentrations were measured in the sera of 16 patients with RA (median age: 45 (26-69), male/female: 3/13), 13 patients with osteoarthritis (OA) (median age: 55 (28-72), male/female: 5/8), and 11 healthy adults (median age: 44 (35-70), male/female: 6/5). Synovial ACE levels and renin concentrations were also measured concurrently in patients with RA and OA. Serum ACE levels were comparable between the groups. However, synovial fluid ACE levels were significantly higher in the patients with RA than in patients with OA. Likewise, synovial fluid renin concentrations were higher in RA patients than in OA patients, while serum renin concentrations were similar in patients with RA and OA and in healthy controls. Moreover, there was a significant negative correlation between the duration of the disease and synovial renin concentrations in RA patients. In conclusion, locally-generated active renin and ACE could contribute to joint destruction in rheumatoid arthritis.

Acute and chronic effects of isosorbide-5-mononitrate administration on effective renal plasma flow and the renin-aldosterone system in cirrhotic patients.

Isosorbide-5-mononitrate (ISMO) has been shown to be effective in reducing the risk of variceal bleeding in patients with cirrhosis. However, recent studies have suggested that this drug compromises renal function. The present study was conducted to assess the acute and chronic effects of ISMO on effective renal plasma flow (ERPF) and the renin-aldosterone profile in cirrhotic patients. Fifteen cirrhotic patients were included in the present study. The mean arterial pressure (MAP), heart rate (HR), serum renin concentration (SR), ERPF and plasma aldosterone concentration (PA) were checked before ISMO treatment (baseline study), after a single oral dose of 20 mg ISMO (acute effect study) and after 3 weeks of ISMO treatment (chronic effect study). Our data showed that the oral administration of a single dose (20 mg) of ISMO to cirrhotic patients was associated with significant decreases in ERPF (from 405.18 to 369.06 mL/min) and MAP (from 93.26 to 86.40 mmHg), and increases in HR (from 65.53 to 70.06 beats/min), SR (from 24.15 to 54.41 pg/mL), and PA (from 105.1 to 148.7 pg/mL). However, no significant changes were observed in HR, MAP, PA, SR, or ERPF after 3 weeks of ISMO treatment when compared with the baseline study. The administration of ISMO causes a decrease in ERPF in cirrhotic patients and its use in patients with renal impairment should be considered cautiously.

Evidence against a pressor role for vasopressin in spontaneous hypertension.

The hypothesis that the vasoconstrictor action of vasopressin may contribute to the development of hypertension in spontaneously hypertensive rats (SHR) was tested by chronic infusion of a specific antagonist of the vascular effects of vasopressin. From 4 to 13 weeks of age, SHR and Wistar-Kyoto rats (WKY) received subcutaneously either isotonic saline or the vasopressin pressor antagonist, d(CH2)5Tyr(Me)arginine vasopressin by osmopump. Systolic blood pressure was measured by tail cuff from 5 to 11 weeks of age. In SHR, the vasopressin analogue did not alter the rate or magnitude of increase in systolic blood pressure. In WKY, systolic blood pressure in the vasopressin analogue group was slightly reduced compared with the saline infusion values until 10 weeks of age (F1, 10 = 10.18, p = 0.008). At 12 to 14 weeks of age, all animals were prepared with indwelling arterial and venous catheters. Resting mean arterial pressure was not altered significantly by the vasopressin analogue infusion in either strain, but the response to an acute vasopressin infusion of 5, 15, or 50 ng/kg body weight was markedly attenuated by the analogue treatment, indicating that plasma levels of the vasopressin analogue were sufficient to block pressor effects of endogenous vasopressin. A bolus injection of the angiotensin II converting enzyme inhibitor teprotide (SQ 20881) resulted in a decrease in mean arterial pressure (p less than 0.05) that was comparable in all groups, and serum renin concentration was not elevated in the vasopressin analogue-treated rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin stimulation by isoproterenol and theophylline in the isolated perfused kidney

The intrarenal mechanisms of renin release were studied in the isolated perfused rabbit kidney during stimulation by isoproterenol, 0.01 mug/kg per min, and by theophylline, 0.87 mg/kg per min. In the absence of urinary flow during the early stages of perfusion, isoproterenol caused a 17% increase of renal vein serum renin concentration (RVSRC) (P less than 0.001) without changing renal blood flow, renal vascular resistance, or serum potassium. dl-Propranolol, 2.0 mg/kg per min. abolished this isoproterenol-induced renin release. A moderate reduction in perfusion pressure prior to the infusion of isoproterenol resulted in a marked additional stimulation of renin release. Studies during and following ureteral occlusion demonstrated that theophylline stimulates renin release by decreasing renal vascular resistance, whereas the concomitant increase in sodium transport to the macula densa exerted an opposite effect. dl-Propranolol did not affect theophylline-induced renin secretion. It is concluded that single exogenous stimuli may activate more than one intrarenal mechanism simultaneously. Isoproterenol has a direct renin-stimulatory effect on intrarenal beta-adrenergic receptors that may be reinforced by baroreceptor stimulation. Theophylline stimulates renin via a baroreceptor mechanism, with simultaneous renin suppression via a sodium-macula densa effect.

Stimulation of renin secretion by various methods: optional results with hydrochlorothiazide.

Serum renin concentration (SRC) was determined in 97 hypertensive patients under basal conditions and during stimulation of renin secretion. Renin secretion was stimulated by upright posture and by either of the following means: (a) diet containing 20 mEq Na/24 hours for 3 days; (b) 300 mg i.v. diazoxide injections; (c) oral ingestion of 80 mg furosemide; (d) oral hydrochlorothiazide (HCT), 25 mg twice daily for 3 days. HCT was used in 6 patients previously treated with daizoxide and in 8 patients previously treated with furosemide. Using pairs of basal and stimulated SRC determinations, the patients could be classified as high, normal, or low renin hypertensives. HCT proved to be the most convenient stimulus as far as efficacy, reliability and the patients' tolerance were concerned, and compared well with sodium restriction.

Effect of aging on plasma renin and aldosterone in normal man

The influence of aging on the renin-angiotensin-aldosterone system was evaluated by comparing young (20 to 30 yr) with elderly (62 to 70 yr) healthy subjects. Despite comparable body sodium-fluid balance in the two age groups, serum renin concentration, plasma renin activity and aldosterone concentrations were lower in the elderly. The age-related decreases in circulating renin and aldosterone concentrations were slight while subjects were supine and receiving normal sodium intake; when upright and during sodium depletion, they were more pronounced. Inverse renin-blood pressure interrelations were noted during two of four study conditions involving normal sodium intake or mild sodium depletion (r = --0.44 and --0.47, respectively), but not during progressive sodium depletion. Plasma renin levels were decreased in the elderly regardless of the presence or absence of an inverse relationship with blood pressure. Aldosterone and cortisol responses to corticotropin infusion were unaltered in the elderly. It is concluded that aging may cause a decrease in circulating renin, with parallel lowering of plasma aldosterone concentrations.

Six year follow-up of a child with Bartter syndrome.

Renal and metabolic studies were performed on a 4-year-old Negro girl with dwarfism, polyuria, polydipsia, salt craving, hyposthenuria, and hypokalemic alkalosis. Hypertrophy and hyperplasia of the juxtaglomerular apparatus were seen on renal biopsy. The aldosterone secretion was elevated. The serum renin concentration was unusually high and an inadequate elevation of blood pressure occurred in response to infusions of angiotensin, vasopressin, and levarterenol. Treatment with potassium salts, spironolactone, and liberal salt intake for a period of six years improved the hypokalemia and dwarfism in this girl.

Renin, aldosterone, sodium and hypertension

Serum renin concentration and twenty-four hour urinary aldosterone excretion were determined in forty-nine normokalemic patients with uncomplicated essential hypertension. The serum renin values for the hypertensive patients on normal sodium intake were significantly lower than those in eleven normotensive subjects, but the urinary aldosterone values were not significantly elevated. Since the urinary sodium excretion in the hypertensive patients was significantly higher than in the normotensive subjects regardless of sodium intake, and since some of the hypertensive patients failed to achieve sodium balance on a low sodium intake regardless of normal clinical tests of kidney function, the hypertensive patients were subdivided into three groups according to the way in which they reacted to sodium restriction. Although there was a significant difference in the mean values for the excretion of sodium in two of the three groups, there was no significant difference in the mean values for serum renin concentration or urinary aldosterone excretion, suggesting that these two measurements were not directly related to sodium excretion. Our data failed to indicate a relationship between serum renin concentration or urinary aldosterone excretion and race in essential hypertension. Nor was a significant correlation found between serum renin and duration of hypertension, age or diastolic blood pressure. None of these patients was found to have normokalemic primary aldosteronism using the criteria of low fixed serum renin activity occurring with inappropriately increased aldosterone excretion.

The mechanism of estrogen hypertension.

The mechanism of estrogen hypertension was studied in rats. After the administration of 0.2 mg of estriol and 2 mg of stilbestrol disulfate for 14 days, three of 10 rats have developed hypertension. However, in the rats with the same amount of estrogen and salt loading (1% NaCl as drinking solution), only 1 of 10 has developed hypertension. Renin substrate increased significantly in both the groups, but serum renin activity, serum renin concentration and renal renin content in estrogen treated rats were significantly higher than those in the rats with the combination of estrogen and salt loading. In addition, the rats in which hypertension has developed showed higher values of renin activity, renin concentration and renal renin content compared to those in the rats which remained normotensive. Therefore it seems to be possible to think that renin release and the rate of angiotensin formation with the high level of renin substrate play an important role in the development of estrogen hypertension. Furthermore, this study suggested that it might be possible to prevent estrogen hypertension by suppressing renin release completely.

Relationship between serum renin concentration, renal renin content, and juxtaglomerular apparatus in hypertensive patients.

On a variety of 30 hypertensive patients and 3 controls, relationship between serum renin concentration, renal renin content, and juxtaglomerular apparatus (JGA) was studied. A highly significant correlation was found between serum renin concentration and renal renin content. The correlations between serum renin concentration and juxtaglomerular granulation index (JGI), and between renal renin content and JGI were also significant. The correlation coefficients, however, were significantly lower than that between serum renin and renal renin. Several factors including staining techniques may be related to this difference. From these results, it is concluded that renin levels are related to the changes in the JGA on a variety of hypertensive patients, although these relations are still problematic in a few cases.