Plum J, Mirzaian Y, Grabensee B
Department of Nephrology, MNR Clinic, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Nephrol Dial Transplant. 1996 Jun;11(6):1034-42.
Oedema formation in the nephrotic syndrome is primarily due to tubular sodium retention. The pathogenetic role of alpha atrial natriuretic peptide (ANP), a hormonal promoter of natriuresis is unknown.
In 31 patients (aged 35+/-11 years) with nephrotic syndrome and histopathological evidence of primary glomerulonephritis, we investigated plasma ANP concentration and its influence on renal haemodynamics, natriuresis, and proteinuria (total protein, albumin, IgG excretion). Patients with a compensated treated form of nephrotic syndrome due to primary glomerulonephritis were included in the study. Serum creatinine levels were <=1.4 mg/dl. Diuretic medication was discontinued at least 24 h before the investigation was started. Patients were randomly assigned to ANP infusion (0.005 microg/kg*min; group II, n=15) or received placebo (group III, n=16). Ten healthy subjects (group I) served as normal controls.
In normal subjects (group I), ANP caused an increase in natriuresis from 14.5+/-4.2 mmol/h to 26.4+/-11.1 mmol/h (P<0.01). In patients with nephrotic syndrome (group II), baseline sodium excretion of 10.5+/-6.0 mmol/h was increased to 19.6+/-14.8 mmol/h with ANP infusion (P<0.01). No changes were seen in the placebo group III. The absolute increase in ANP induced natriuresis was not significantly different between group I and II. However, plasma ANP levels were significantly higher in patients with nephrotic syndrome (166+/-87 pg/ml vs. 74+/-21 pg/ml, P<0.05) and also reached higher levels after ANP infusion (P<0.01). Therefore, natriuresis was significantly reduced when circulating ANP levels were taken into account (P<0.05). ANP administration resulted in an increase of total protein excretion in patients with the nephrotic syndrome (group II, from 219+/-277 mg/h to 264+/-268 mg/h). Albumin elimination rose from 128+/-151 mg/h to 167+/-170 mg/h (P<0.05) and IgG excretion from 4.91+/-6.67 mg/h to 9.27+/-10.78 mg/h (P<0.05). Healthy subjects also showed a small but significant increase in albuminuria (48+/-38%, P<0.05). Low-dose ANP infusion did not, however, induce any significant alteration in GFR, ERPF and blood pressure.
ANP plasma concentrations in the steady state are elevated in patients with the nephrotic syndrome. The natriuretic effect of ANP is reduced when referring to circulating ANP plasma levels. Elevated ANP levels enhance urinary protein excretion in the nephrotic syndrome. This is not due to modulation of GFR or FF, but is most probably attributable to increased glomerular permeability.
肾病综合征中的水肿形成主要归因于肾小管钠潴留。利钠激素α心房利钠肽（ANP）的致病作用尚不清楚。
在31例（年龄35±11岁）患有肾病综合征且有原发性肾小球肾炎组织病理学证据的患者中，我们研究了血浆ANP浓度及其对肾脏血流动力学、利钠作用和蛋白尿（总蛋白、白蛋白、IgG排泄）的影响。研究纳入了因原发性肾小球肾炎导致的肾病综合征代偿性治疗形式的患者。血清肌酐水平≤1.4mg/dl。在开始研究前至少24小时停用利尿剂。患者被随机分配接受ANP输注（0.005μg/kg·min；第二组，n = 15）或接受安慰剂（第三组，n = 16）。10名健康受试者（第一组）作为正常对照。
在正常受试者（第一组）中，ANP使利钠作用从14.5±4.2mmol/h增加到26.4±11.1mmol/h（P<0.01）。在肾病综合征患者（第二组）中，基础钠排泄量为10.5±6.0mmol/h，输注ANP后增加到19.6±14.8mmol/h（P<0.01）。第三组安慰剂组未见变化。第一组和第二组中ANP诱导的利钠作用的绝对增加无显著差异。然而，肾病综合征患者的血浆ANP水平显著更高（166±87pg/ml对74±21pg/ml，P<0.05），并且在输注ANP后也达到更高水平（P<0.01）。因此，考虑循环ANP水平时，利钠作用显著降低（P<0.05）。给予ANP导致肾病综合征患者（第二组）总蛋白排泄增加（从219±277mg/h增加到264±268mg/h）。白蛋白清除率从128±151mg/h增加到167±170mg/h（P<0.05），IgG排泄从4.91±6.67mg/h增加到9.27±10.78mg/h（P<0.05）。健康受试者的蛋白尿也有小幅但显著的增加（48±38%，P<0.05）。然而，低剂量ANP输注未引起GFR、ERPF和血压的任何显著改变。
肾病综合征患者稳态下的ANP血浆浓度升高。参照循环ANP血浆水平，ANP的利钠作用降低。升高的ANP水平增加了肾病综合征患者的尿蛋白排泄。这不是由于GFR或滤过分数的调节，很可能归因于肾小球通透性增加。
