Renoprotective RAAS inhibition does not affect the association between worse renal function and higher plasma aldosterone levels

Abstract 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)

Associations of NAM-A1 alleles with the onset of senescence and nitrogen use efficiency under Western Australian conditions

© 2018, Springer Nature B.V. Wheat grain yield and protein content are significantly influenced by the onset of senescence and the duration of the grain filling phase. The onset of senescence also affects Nitrogen use efficiency (NUE) through interacting pathways involving N accumulation and translocation of N into the grains. The objective of this study was to relate variation in NUE and its components with two groups of the NAM-A1 gene alleles; (i) early onset of senescence in cultivars carrying the NAM-A1a allele, (ii) delayed onset of senescence in cultivars carrying the Non-NAM-A1a allele (b, c, d) in wheat cultivars grown under Western Australia conditions. A field trial was carried out over two seasons examining 19 cultivars under different N rates and time of N application. The Normalized Difference Vegetation Index was utilized to determine the onset of senescence after anthesis. The early onset of senescence results in high grain yield, harvest index, and NUE due to improvements in the N utilization ability. Accelerating the onset of senescence results in a short grain filling period leading to grain maturity before the onset of unfavourable summer conditions. The function of alleles of NAM-A1 gene in controlling senescence hence the NUE is highly regulated by environmental conditions. This study concluded that the function of NAM-A1a allele induces the onset of senescence with a positive effect on the NUE and its components under Western Australian conditions