Zoccali C
Divisione di Nefrologia, Azienda Ospedaliera di Reggio Calabria e Centro di Fisiologia Clinica CNR, Reggio Calabria.
G Ital Nefrol. 2002 Sep-Oct;19(5):517-22.
For about three decades glomerular diseases have been the most intensively investigated research area in nephrology. The increasing proportion of patients with end-stage renal disease (ESRD) secondary to hypertension has now revived interest in hypertension. Prospective studies have firmly established that high blood pressure is associated with an increased risk of renal failure independent of other risk factors. Hypertension-related renal injury might be interpreted in a general context taking into account genes, intrauterine growth and environmental factors. Disturbed intrauterine growth (due to malnutrition or other factors) has a negative influence on the development of the cardiovascular system and favours the occurrence of hypertension, insulin resistance, hypercholesterolaemia and hyperuricaemia in adult life (Barker's hypothesis). Altered intrauterine growth has also been associated with a reduced number of nephrons at birth. Damage attributable to glomerular hyperperfusion in kidneys with a reduced number of nephrons is aggravated by vascular lesions in middle and small arterial vessels (secondary to hypertension, hyperlipidaemia and environmental risk factors such as smoking). The observation that subjects homozygous for the D allele of the ACE gene are predisposed to both cardiovascular complications and nephrosclerosis, suggests that genetic factors may interact with altered intrauterine growth in determining the risk of cardiovascular and renal diseases.
大约三十年来，肾小球疾病一直是肾脏病学领域研究最为深入的领域。由高血压继发的终末期肾病（ESRD）患者比例的增加，如今又重新引发了人们对高血压的关注。前瞻性研究已确凿证实，高血压与肾衰竭风险增加相关，且独立于其他风险因素。考虑到基因、宫内生长及环境因素，可从总体角度对高血压相关的肾脏损伤进行解读。宫内生长受干扰（由于营养不良或其他因素）对心血管系统的发育有负面影响，并有利于成年期高血压、胰岛素抵抗、高胆固醇血症和高尿酸血症的发生（巴克假说）。宫内生长改变还与出生时肾单位数量减少有关。肾单位数量减少的肾脏中，肾小球高灌注所致的损伤会因中小动脉血管病变（继发于高血压、高脂血症和吸烟等环境风险因素）而加重。ACE基因D等位基因纯合子个体易患心血管并发症和肾硬化症这一观察结果表明，在确定心血管和肾脏疾病风险方面，遗传因素可能与宫内生长改变相互作用。
