Viberti G C, Messent J
Department of Medicine, Guy's Hospital, London, UK.
Cardiology. 1991;79 Suppl 1:55-61. doi: 10.1159/000174907.
Diabetic patients who develop proteinuria show a marked increase in cardiovascular morbidity and mortality. The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain, in part, obscure. However, there is now evidence that renal disease clusters in families and that genetic factors may be of central importance in determining susceptibility. Predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. Interestingly, fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first clinical signs of renal involvement are the appearance of microalbuminuria and a small elevation in arterial pressure. Mesangial expansion accompanies these changes. Microalbuminuria is associated with abnormalities of lipoprotein profiles and higher Na+/Li+ countertransport rates. The environmental changes brought about by diabetes could lead in susceptible individuals to increased systemic and intraglomerular pressures on the one hand and to mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered, involving reduction in renal function, further hypertension, proteinuria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or premature cardiovascular death.
出现蛋白尿的糖尿病患者心血管发病率和死亡率显著增加。人类糖尿病肾病的确切发病机制以及导致易感性的因素部分仍不明确。然而，现在有证据表明肾脏疾病在家族中聚集，并且遗传因素在决定易感性方面可能至关重要。动脉高血压的易感性被认为在肾脏疾病的发展中起促成作用。肥大过程可能与糖尿病患者动脉壁损伤和肾小球损伤的易感性有关。有趣的是，糖尿病肾病患者的成纤维细胞比无肾病的糖尿病患者的成纤维细胞表现出更高的Na+/H+反向转运活性和更高的3H-胸腺嘧啶核苷掺入DNA的能力。肾脏受累的最初临床迹象是微量白蛋白尿的出现和动脉压的轻微升高。这些变化伴有系膜扩张。微量白蛋白尿与脂蛋白谱异常和更高的Na+/Li+逆向转运率有关。糖尿病引起的环境变化一方面可能导致易感个体全身和肾小球内压力增加，另一方面导致系膜扩张。这两个过程将导致蛋白尿和肾小球硬化。脂质异常可能会进一步加重肾脏组织学损伤，并与高血压一起，导致糖尿病肾病患者典型的加速动脉粥样硬化。这样就会引发一个恶性循环，包括肾功能下降、进一步高血压、蛋白尿、肾小球荒废和高脂血症，最终导致终末期肾衰竭或过早心血管死亡。
