Microvascular Disease Severity Research Articles

Microvascular Disease After Renal Transplantation

Background/Aims: Individuals who reach end-stage kidney disease (CKD5) have a high risk of vascular events that persists even after renal transplantation. This study compared the prevalence and severity of microvascular disease in transplant recipients and patients with CKD5. Methods: Individuals with a renal transplant or CKD5 were recruited consecutively from renal clinics, and underwent bilateral retinal photography (Canon CR5-45, Canon). Their retinal images were deidentified and reviewed for hypertensive/microvascular signs by an ophthalmologist and a trained grader (Wong and Mitchell classification), and for vessel caliber at a grading centre using a computer-assisted method and Knudtson's modification of the Parr-Hubbard formula. Results: Ninety-two transplant recipients (median duration 6.4 years, range 0.8 to 28.8) and 70 subjects with CKD5 were studied. Transplant recipients were younger (p<0.001), with a higher eGFR (p< 0.001), but were just as likely to have a moderate-severe hypertensive/microvascular retinopathy (46/92, 50%) as subjects with CKD5 (38/70, 54%; OR 0.84, CI 0.45 to 1.57, p=0.64), and had similar mean arteriole and venular calibres (135.1 ± 7.5 µm and 137.9 ± 14.9 µm, p=0.12; and 199.1 ± 17.8 µm and 202.4 ± 27.8 µm, p=0.36, respectively). Arteriole and venular caliber were not different in nine patients examined before and after transplantation (p=0.62 and p=0.11, respectively). Conclusions: Hypertensive/microvascular disease occurred just as often and was generally as severe in transplant recipients and subjects with CKD5. Microvascular disease potentially contributes to increased cardiac events post- transplantation.

Renin-angiotensin system components and endothelial proteins as markers of diabetic microvascular disease.

Endothelial cell damage, which is associated with local thrombin formation and inflammation, can lead to the release of endothelium-synthesized factors into plasma, such as vWFAg, TM, ACE and ET-1. These markers of endothelial damage are increased in some patients with diabetes mellitus, but the differences with normal are often small and not closely correlated with the severity of microvascular disease, as judged from the degree of albuminuria and the severity of retinopathy. Prorenin, which may also be related to abnormal endothelial cell function or endothelial damage, is elevated in many patients with diabetes, both type I and II, and its level is more closely correlated with the severity of microvascular disease. It is already elevated at an early stage. Further studies will reveal whether, in diabetes, an increased plasma prorenin is a reliable predictor of progressive microvascular disease. It is even conceivable that prorenin is not only a marker of diabetic microvascular disease but also has a role in its pathogenesis, via local proteolytic or non-proteolytic prorenin activation.

Decreased exercise heart rate and blood pressure response in diabetic subjects with cardiac autonomic neuropathy.

Abnormal hemodynamic responses to exercise have been observed in diabetic subjects, but the pathogenesis and significance remain uncertain. We used maximal treadmill exercise to study 32 subjects with long-term insulin-dependent diabetes without clinical evidence of cardiac disease. Two of the 32 had occult ischemic heart disease revealed by stress electrocardiography and myocardial-perfusion scintigraphy and were excluded from subsequent analysis. In the remaining 30 subjects, we compared the responses to exercise of the 17 subjects with cardiac autonomic neuropathy diagnosed by noninvasive maneuvers (group 1) with the 13 without (group 2). At rest, the pressure-rate product (PRP) was higher in group 1 (114.0 +/- 5.7 vs. 95.9 +/- 5.3, P less than .05). With maximal exercise the increase in heart rate (44.6 +/- 4.8 vs. 79.0 +/- 5.4 beats/min, P less than .001), systolic blood pressure (36.8 +/- 5.9 vs. 55.0 +/- 5.8 mmHg, P = .02), and the PRP (102.0 +/- 7.3 vs. 182.0 +/- 8.2, P less than .001) were all lower in group 1 than in group 2, despite similar total treadmill times (631 +/- 47 vs. 587 +/- 40 s, P greater than .1). At each stage of exercise, the increase in heart rate and systolic blood pressure was lower in group 1 patients. The severity of cardiac autonomic neuropathy correlated inversely with the maximal increase in heart rate (r = -.68, P less than .001) and the PRP (r = -.58, P less than .005). Age, duration of diabetes, and the presence and severity of microvascular disease did not correlate with any of the hemodynamic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelets, Coagulation and Fibrinolysis in Patients with Diabetic Retinopathy

Twenty control subjects, 12 insulin treated and 10 non-insulin treated diabetics were studied. All diabetics had retinopathy documented by fluorescein angiography and fluorophotometry. Factor VIIIR:Ag and plasma fibrinogen concentrations were elevated in both diabetic groups, but more so in the insulin treated patients. Within this latter group the plasma fibrinogen was also correlated with the degree of retinopathy. Platelets separated on linear isosmolar Percoll gradients showed an increase in intraplatelet beta TG content and concentration and a slight increase in volume of the lightest platelets in the insulin treated diabetics. Plasma platelet factor 4 and antithrombin III concentrations were normal and plasma beta TG levels were elevated only in those patients with renal insufficiency. Platelet aggregometry was performed in 18 diabetic subjects and found to be normal. It is concluded that abnormalities of coagulation and platelets in diabetes are determined by metabolic factors rather than the severity of microvascular disease per se.