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Background/aims: Several studies sought to identify new biomarkers for chronic kidney disease (CKD). As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR). We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria., Methods: We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC) curves, spearman correlation coefficients and linear regression models were calculated., Results: Urinary angiotensinogen [2,511 (196-31,909) vs. 18.6 (8.3-44.0) pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155) vs. 0.069 (0.045-0.148) pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01) and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01) were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results., Conclusion: Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may convey additional information beyond that provided by albuminuria., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

Background/aims: Acute tubular necrosis (ATN), a leading cause of acute kidney injury (AKI), is associated with decreased survival and increased progression of chronic kidney disease. A barrier to improving the clinical outcomes is the incomplete understanding of the pathogenesis of AKI. Our objective is to test the hypothesis that intrarenal renin-angiotensin system (RAS) is overexpressed in patients with ATN and could be an indicator of ATN severity., Methods: A transversal study was conducted in patients with biopsy-proven ATN. Intrarenal expression of angiotensinogen and angiotensin II, and urinary angiotensinogen were measured., Results: Patients with ATN demonstrated upregulation of intrarenal RAS, evidenced by upregulation of intrarenal angiotensinogen and angiotensin II. Patients with ATN also have elevated urinary angiotensinogen level that correlated with the overexpressed intrarenal RAS. Moreover, this increase in intrarenal RAS expression and urinary angiotensinogen was associated with the extent of acute tubular injury and urinary albumin excretion, respectively., Conclusions: We demonstrate that the intrarenal RAS is upregulated in patients with ATN and is associated with the severity of ATN. Urinary angiotensinogen reflects intrarenal RAS status, and is of value to assess the severity of ATN., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background/aims: Early onset of hypertension and its consequences account for the great majority of deaths in patients with autosomal dominant polycystic kidney disease (ADPKD). Renin-angiotensin system (RAS) components have been shown in ADPKD kidneys independent of systemic RAS. Thus, we examined the urinary angiotensinogen (UAGT) levels as a biomarker of intrarenal RAS status in ADPKD patients with/without hypertension and healthy subjects., Methods: Eighty-four ADPKD patients (43 with hypertension and 41 without hypertension) and 40 healthy controls were studied cross-sectionally. Patients with glomerular filtration rate <60 ml/min were excluded from the study. Hypertension was diagnosed with ambulatory blood pressure monitoring. Urinary and plasma concentration of angiotensinogen, spot urine microprotein and creatinine (UCre) levels were recorded for each participant., Results: UAGT/UCre levels were higher in hypertensive ADPKD patients (23.7 ± 8.4) compared with normotensive ADPKD patients (16.6 ± 5.2) and healthy controls (6.9 ± 3.3; p < 0.001). In univariate analysis, UAGT correlated with systolic blood pressure, diastolic blood pressure (DBP) and proteinuria. The independence of these correlations was analyzed in a regression model, and UAGT was shown to be significantly predicted by proteinuria and DBP., Conclusion: Intrarenal RAS activation which is monitored by UAGT levels clinically may be a harbinger of hypertension and kidney disease in ADPKD patients., (Copyright © 2013 S. Karger AG, Basel.)

Background: We recently reported that immunoreactivity of intrarenal angiotensinogen (AGT) is significantly increased in IgA nephropathy patients. Meanwhile, we have developed direct enzyme-linked immunosorbent assays to measure plasma and urinary AGT (UAGT) in humans. This study was performed to test the hypothesis that UAGT levels are increased in chronic glomerulonephritis patients., Methods: We analyzed 100 urine samples from 70 chronic glomerulonephritis patients (26 from IgA nephropathy, 24 from purpura nephritis, 8 from lupus nephritis, 7 from focal segmental glomerulosclerosis, and 5 from non-IgA mesangial proliferative glomerulonephritis) and 30 normal control subjects., Results: UAGT-creatinine ratio (UAGT/UCre) was correlated positively with diastolic blood pressure (p = 0.0326), urinary albumin-creatinine ratio (p < 0.0001), urinary protein-creatinine ratio (p < 0.0001) and urinary occult blood (p = 0.0094). UAGT/UCre was significantly increased in chronic glomerulonephritis patients not treated with renin-angiotensin system (RAS) blockers compared with control subjects (p < 0.0001). Importantly, glomerulonephritis patients treated with RAS blockers had a marked attenuation of this augmentation (p = 0.0021)., Conclusion: These data indicate that UAGT are increased in chronic glomerulonephritis patients and treatment with RAS blockers suppressed UAGT. The efficacy of RAS blockade to reduce the intrarenal RAS activity can be confirmed by measurement of UAGT in chronic glomerulonephritis patients., (2010 S. Karger AG, Basel.)

Background/aims: There are two major pathophysiologic processes involved in the development of hypertension: (1) expanded extracellular fluid volume and (2) vasoconstriction. We have developed a model of preeclampsia in the rat, in which excessive volume expansion (VE) plays a role. These animals excrete increased amounts of the bufodienolide, marinobufagenin (MBG), even before their hypertension and proteinuria become established. Furthermore, their hypertension is corrected by administration of resibufogenin (RBG), a compound structurally similar to MBG., Method: We studied two models of experimental hypertension in the nonpregnant animal, produced either by deoxycorticosterone acetate (DOCA)-salt administration or by angiotensin infusion., Results: RBG administered to the DOCA-salt rats lowered blood pressure and reduced proteinuria in the VE animals, but had no affect on the rats infused with angiotensin. Furthermore, although the production of superoxide anion in the aortas of both groups of hypertensive rats was increased over control, RBG reduced these levels to normal in the VE (DOCA-salt) animals only. RBG had no effect in the angiotensin-infused rats. The urinary excretion of angiotensinogen did not rise in VE-mediated hypertension, but did increase in the angiotensin-infused rats., Conclusions: MBG plays an important role in the causation of hypertension in the VE rats, but not in the vasoconstrictive model. RBG is effective only in VE-mediated hypertension., ((c) 2007 S. Karger AG, Basel.)

Puromycin aminonucleoside (PA)-nephrotic rats have a high plasma renin activity (PRA) and low angiotensinogen levels. We measured proteinuria, urine renin, and urine angiotensinogen daily, for 11 days after PA injection. Proteinuria and urine angiotensinogen were evident on day 5, and urine renin on day 6. Peak levels of urine renin and angiotensinogen were attained on day 8. These data suggest that angiotensinogen urine excretion may contribute to its low plasma levels, and urine renin loss may limit a further increase in PRA.