24-1 lour ACE Inhibition Cardiology 1991:79(suppl 1):55-61
© 1991 Kargcr AG, Basel (1008-6312/91/0795-0055 $ 2.75/0
Risk Factors for Renal and Cardiovascular Disease in Diabetic Patients G'.C. Viberti, J. Messent Department of Medicine, Guv's Hospital, London. LIK
Abstract. Diabetic patients who develop proteinuria show a marked increase in cardiovas cular 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 sug gested as playing a contributory role in the development of kidney disease. Hypertrophic pro cesses 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 H-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 expan sion accompanies these changes. Microalbuminuria is associated with abnormalities of lipo protein profiles and higher N a '/ U 1 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 pro cesses would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggra vate 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, protein uria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or pre mature cardiovascular death.
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 141.216.78.40 - 7/3/2018 1:06:10 PM
Key Words. Diabetes ■Cardiovascular disease • Renal disease • Sodium-lithium countertransport • Sodium-hydrogen antiport
56
Table I. Cumulative incidence of coronary heart disease in insulin-dependent diabetic patients with and without proteinuria [from ref. 7] Time after onset of proteinuria, years
Patients with proteinuria. % Patients without proteinuria, % *
2
4
6
in
25
40*
2
5
5*
p
© 1991 Kargcr AG, Basel (1008-6312/91/0795-0055 $ 2.75/0
Risk Factors for Renal and Cardiovascular Disease in Diabetic Patients G'.C. Viberti, J. Messent Department of Medicine, Guv's Hospital, London. LIK
Abstract. Diabetic patients who develop proteinuria show a marked increase in cardiovas cular 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 sug gested as playing a contributory role in the development of kidney disease. Hypertrophic pro cesses 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 H-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 expan sion accompanies these changes. Microalbuminuria is associated with abnormalities of lipo protein profiles and higher N a '/ U 1 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 pro cesses would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggra vate 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, protein uria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or pre mature cardiovascular death.
Downloaded by: Univ. of Michigan, Taubman Med.Lib. 141.216.78.40 - 7/3/2018 1:06:10 PM
Key Words. Diabetes ■Cardiovascular disease • Renal disease • Sodium-lithium countertransport • Sodium-hydrogen antiport
56
Table I. Cumulative incidence of coronary heart disease in insulin-dependent diabetic patients with and without proteinuria [from ref. 7] Time after onset of proteinuria, years
Patients with proteinuria. % Patients without proteinuria, % *
2
4
6
in
25
40*
2
5
5*
p
