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Christina M Gant1,2, Gozewijn D Laverman3, Liffert Vogt4
1Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. C.Gant@zgt.nl.
Insights
In chronic kidney disease (CKD), reduced kidney function is linked to higher aldosterone levels, which contribute to hypertension. This can be managed with a combination of renin-angiotensin-aldosterone system inhibition, hydrochlorothiazide, and sodium restriction.
Area of Science:
- Nephrology
- Endocrinology
- Cardiovascular Medicine
Background:
- Aldosterone levels are frequently elevated in chronic kidney disease (CKD) patients.
- The precise determinants and role of plasma aldosterone concentration (PAC) in CKD-related hypertension remain incompletely understood.
- Investigating aldosterone's role is crucial, especially during renin-angiotensin-aldosterone system inhibition (RAASi), a common treatment for CKD with albuminuria.
Purpose of the Study:
- To investigate the determinants of plasma aldosterone concentration (PAC) in patients with chronic kidney disease (CKD).
- To examine the association between PAC and blood pressure in CKD patients.
- To evaluate these associations under various renin-angiotensin-aldosterone system inhibition (RAASi) regimens and dietary sodium intakes.
Main Methods:
- Post-hoc analysis of a randomized, double-blind, cross-over trial involving 33 non-diabetic CKD patients.
- Patients received losartan (ARB) or ARB + hydrochlorothiazide (HCT) during regular and low sodium intake periods.
- PAC, creatinine clearance (CrCl), and blood pressure were analyzed, including during ACE inhibition (ACEi) and dual RAASi.
Main Results:
- Lower CrCl significantly correlated with higher PAC, irrespective of RAASi.
- Higher PAC was consistently associated with elevated systolic blood pressure.
- The blood pressure difference between high and low PAC groups was abolished only with maximal treatment (ARB + HCT + sodium restriction).
Conclusions:
- Worse renal function in CKD patients is associated with elevated aldosterone levels, even during RAASi.
- Higher aldosterone levels are linked to increased blood pressure in CKD.
- A combination of RAASi, HCT, and dietary sodium restriction effectively manages blood pressure in these patients.
Background:
Aldosterone is elevated in chronic kidney disease (CKD) and may be involved in hypertension. Surprisingly, the determinants of the plasma aldosterone concentration (PAC) and its role in hypertension are not well studied in CKD. Therefore, we studied the determinants of aldosterone and its association with blood pressure in CKD patients. We also studied this during renin-angiotensin-aldosterone system inhibition (RAASi) to establish clinical relevance, as RAASi is the treatment of choice in CKD with albuminuria.
Methods:
We performed a post-hoc analysis on data from a randomized controlled double blind cross-over trial in non-diabetic CKD patients (n = 33, creatinine clearance (CrCl) 85 (75-95) ml/min, proteinuria 3.2 (2.5-4.0) g/day). Patients were treated with losartan 100 mg (ARB), and ARB + hydrochlorothiazide 25 mg (HCT), during both a regular (200 ± 10 mmol Na+/day) and low (89 ± 8 mmol Na+/day) dietary sodium intake, in 6-week study periods. PAC data at the end of each study period were analyzed. The association between PAC and blood pressure was analyzed continuously, and according to PAC above or below the median.
Results:
Lower CrCl was correlated with higher PAC during placebo as well as during ARB (β = -1.213, P = 0.008 and β = -1.090, P = 0.010). Higher PAC was not explained by high renin, illustrated by a comparable association between CrCl and the aldosterone-to-renin ratio. The association between lower CrCl and higher PAC was also found in a second study with single RAASi with ACE inhibition (ACEi; lisinopril 40 mg/day), and dual RAASi (lisinopril 40 mg/day + valsartan 320 mg/day). Higher PAC was associated with a higher systolic blood pressure (P = 0.010) during different study periods. Only during maximal treatment with ARB + HCT + dietary sodium restriction, blood pressure was no longer different in subjects with a PAC above and below the median.
Conclusions:
In CKD patients with a standardized regular sodium intake, worse renal function is associated with a higher aldosterone, untreated and during RAASi with either ARB, ACEi, or both. Furthermore, higher aldosterone is associated with higher blood pressure, which can be treated with the combination of RAASi, HCT and dietary sodium restriction. The first study was performed before it was standard to register trials and the study was not retrospectively registered. The second study was registered in the Netherlands Trial Register on the 5th of May 2006 (NTR675).
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