Department of Internal Medicine, Baylor Scott and White Health, Temple, TX, USA Texas A&M Health Sciences Center College of Medicine, Temple, TX, USA.
Department of Biostatistics, Baylor Scott and White Health, Temple, TX, USA.
Nephrol Dial Transplant. 2015 May;30(5):762-70. doi: 10.1093/ndt/gfu388. Epub 2014 Dec 19.
Angiotensin II (AII) mediates glomerular filtration rate (GFR) decline in animals with subtotal nephrectomy (Nx), but the mechanisms for increased AII activity are unknown. Because reduced GFR of Nx is associated with acid (H(+)) retention that increases kidney AII, AII-mediated GFR decline might be induced by H(+) retention.
We measured GFR and kidney microdialyzate H(+) and AII content in Sham and 2/3 Nx rats in response to amelioration of H(+) retention with dietary NaHCO3, to AII receptor antagonism and to both.
GFR was lower in Nx than that in Sham. Nx but not Sham GFR was lower at Week 24 than that at Week 1. Despite no differences in plasma acid-base parameters or urine net acid excretion, kidney H(+) content was higher in Nx than that in Sham, consistent with H(+) retention. Plasma and kidney microdialyzate AII were higher in Nx than that in Sham and dietary NaHCO3 reduced each in Nx but not in Sham. AII receptor antagonism was associated with higher Week 24 GFR in Nx with H(+) retention but not in Sham or in Nx in which H(+) retention had been corrected with dietary NaHCO3. Week 24 GFR after dietary NaHCO3 was higher than after AII receptor antagonism. Week 24 GFR was not different after adding AII receptor antagonism to dietary NaHCO3.
AII-mediated GFR decline in 2/3 Nx was induced by H(+) retention and its amelioration with dietary HCO3 conserved GFR better than AII receptor antagonism in this CKD model. H(+) retention might induce AII-mediated GFR decline in patients with reduced GFR, even without metabolic acidosis.
血管紧张素 II（AII）介导部分肾切除（Nx）动物肾小球滤过率（GFR）下降，但增加 AII 活性的机制尚不清楚。由于 Nx 的低 GFR与增加肾脏 AII 的酸（H（+））保留有关，AII 介导的 GFR 下降可能是由 H（+）保留诱导的。
我们测量了 Sham 和 2/3 Nx 大鼠的 GFR 和肾微透析液 H（+）和 AII 含量，以响应饮食 NaHCO3 改善 H（+）保留、AII 受体拮抗作用及其联合作用。
Nx 的 GFR 低于 Sham。Nx 但不是 Sham 的 GFR 在第 24 周比第 1 周低。尽管血浆酸碱参数或尿净酸排泄没有差异，但 Nx 的肾 H（+）含量高于 Sham，这与 H（+）保留一致。血浆和肾微透析液中的 AII 在 Nx 中高于 Sham，并且饮食 NaHCO3 降低了 Nx 中的 AII，但没有降低 Sham 中的 AII。AII 受体拮抗作用与 Nx 中伴有 H（+）保留的较高第 24 周 GFR 相关，但与 Sham 或用饮食 NaHCO3 纠正 H（+）保留的 Nx 无关。饮食 NaHCO3 后的第 24 周 GFR 高于 AII 受体拮抗作用后的第 24 周 GFR。添加 AII 受体拮抗作用至饮食 NaHCO3 后，第 24 周 GFR 没有差异。
在 2/3 Nx 中，AII 介导的 GFR 下降是由 H（+）保留诱导的，与该 CKD 模型中的 AII 受体拮抗作用相比，用饮食 HCO3 改善 H（+）保留可以更好地保存 GFR。即使没有代谢性酸中毒，低 GFR 的患者中 H（+）保留也可能诱导 AII 介导的 GFR 下降。
