High doses of iron sucrose (Venofer((R)) at a dose of 250 mg/month) was equally effective in maintaining haemoglobin and equally well tolerated as low doses of iron gluconate (Ferrlecit((R)) at a dose of 62.5 mg once per week) in stable, rHuEpo treated haemodialysis patients.
The important initiating process of diabetic nephropathy is the glomerular accumulation of proteins which has been proposed to be due to a synergistic interaction of the disturbed intrarenal hemodynamic and the altered chemical composition of glomerular components. This study was performed to investigate whether there might be a reduced activity of glomerular proteinases in streptozotocin diabetic rats. Three weeks after the induction of diabetes by means of streptozotocin, we found a decreased proteinase activity in ultrasonically destroyed isolated glomeruli obtained by a differential sieving technique in comparison to nondiabetic controls. This held true at acidic (16.59 ± 1.56 vs. 22.19 ± 1.94 U/min/mg protein) as well as at neutral pH (7.82 ± 0.55 vs. 10.67 ± 0.81 U/min/mg protein) and could be confirmed when proteinase activity was related to the single glomerulus or DNA instead of protein. Treatment with insulin was effective in improving the degradative capacity at both pH levels. We suggest that decreased proteinase activity in diabetic glomeruli may, at least partly, explain the glomerular protein accumulation in diabetic nephropathy.
The pathogenesis of cardiac hypertrophy in chronic uremia is poorly understood. In the present study, the long-term effects of chronic uremia on cardiac morphology and various cysteine proteinases of the heart were investigated in rats with and without antihypertensive therapy by the angiotensin converting enzyme inhibitor enalapril or by the calcium channel blocker verapamil. 16 weeks after subtotal nephrectomy considerable uremia had developed associated with arterial hypertension, rise in heart weight and heart weight/body weight ratio. Morphologically myocardial cells developed marked hypertrophy. Determination of various cysteine proteinases by fluorometry revealed a significant decline of cathepsin B activity while the activities of cathepsin H and L were unchanged. Antihypertensive treatment with enalapril and verapamil normalized the blood pressure and improved renal function significantly. Myocardial cell hypertrophy and the enhanced heart weight/body weight ratio were normalized under treatment with enalapril but not with verapamil. Simultaneously, the impaired cathepsin B activity returned to the normal range after enalapril treatment. It is concluded that the cardiac hypertrophy in uremia is at least partly caused by an activation of the circulating and/or cardiac renin-angiotensin system. Impaired proteinase activity in the uremic state may be involved in the development of cardiac hypertrophy.
IDDM is associated with an increase in kidney size, which is due to cellular hypertrophy and progressive matrix accumulation within the glomerulus and throughout the tubulointerstitium. The present study addressed the potential role of cysteine and metalloproteinases in renal hypertrophy of short-term diabetes. Three weeks after induction of streptozotocin diabetes in rats, intraglomerular gelatinase activity (streptozotocin: 23 + 4 vs control: 44 + 3 mU/gg DNA) and cathepsin L + B activity (streptozotocin: 6.7 + 0.8 vs control: 9.3 +_ 0.7 U/gg DNA) were significantly decreased. Insulin treatment completely prevented the decline in glomerular proteinase activity (gelatinase: 37 + 6 mU/gg DNA; cathepsin L + B: 9.6 + 0.9 U/gg DNA). In isolated proximal tubules a similar pattern of enzyme activity could be observed. Three weeks of diabetes caused a significant decline in cathepsin L + B activity (streptozotocin: 28 + 2 vs control: 37 + 3 U/gg DNA). Insulin treatment again prevented the decline in these tubular proteinase activities. In parallel, kidney weight increased by 22% and glomerular protein/DNA ratio rose by 17 % in untreated diabetic rats. Diabetic rats receiving insulin displayed a normal glomerular protein/DNA ratio and the kidney weight was increased by only 5 %. These results show that renal hypertrophy of early diabetes is closely associated with a decline in both glomerular and tubular proteinase activity. Adequate insulin substitution prevented renal hypertrophy and the reduction in proteinase activity. [Diabetologia (1994) 37: 567-571]
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