Transcapillary escape rate and albuminuria in Type II diabetes. Effects of short-term treatment with low-molecular weight heparin (Short Communication)

Abstract

Type II (non-insulin-dependent) diabetic patients with abnormal urinary albumin excretion rate (UAE), even in the microalbuminuric range (UAE 20±200 mg/min), have an increased prevalence of vascular disease and risk of cardiovascular events compared with patients with normoalbuminuria (UAE < 20 mg/min) [1±5]. The association has raised the hypothesis that patients with increased albuminuria do not only have glomerular disease but also extensive vascular damage [6,7]. Increased transcapillary escape rate of albumin (TER alb ) [i. e. the fraction Diabetologia (1999) Summary The relation between urinary albumin excretion rate (UAE), transcapillary escape rate of albumin (TER alb ), haemostatic factors, ambulatory blood pressure, and metabolic variables was investigated in 45 Type II (non-insulin-dependent) diabetic patients without overt nephropathy or uncontrolled blood pressure. We enrolled 44 patients in a placebo controlled study to test the effects of 3 week long treatment with low-molecular weight heparin (tinzaparin) on the same variables. BMI, 24 h systolic and diastolic blood pressure, plasma concentrations of triglycerides, fasting glucose, factor VIII, von Willebrand factor (vWf), fibrinogen, a-2 macroglobulin, and fibronectin were notably higher in patients with increased albuminuria compared with normoalbuminuric patients, whereas the TER alb was similar in the two groups. TER alb correlated with fasting plasma glucose. UAE correlated more closely than TER alb with 24 h ambulatory blood pressure, vWf, and factor VIII. Urinary albumin excretion rate was unchanged during tinzaparin [28.9 ± 5.6 vs 28.1 ± 6.0 mg/min (geometric mean (antilog SD)] vs placebo (18.0 ± 5.4 vs 17.6 ± 5.3 mg/min), and no change was found in TER alb [6.3 ± 1.6 vs 6.0 ± 1.5 %/h (means ± SD), and 6.3 ± 1.5 vs 5.6 ± 1.8 %/h; tinzaparin versus placebo, respectively]. Only minor changes were observed in blood pressure, lipids, glycaemic control and haemostatic factors. This study shows no correlation between albuminuria and transcapillary escape rate in Type II diabetic patients without overt nephropathy or uncontrolled blood pressure. UAE is related to markers of atherosclerosis, endothelial injury and dysfunction, and haemostatic factors. Moreover, UAE correlates much more than TER alb with 24 h ambulatory blood pressure, von Willebrand factor, and factor VIII. Finally, short-term treatment with tinzaparin does not change the transvascular or glomerular leakage of albumin. These results indicate that TER alb is not a sensitive marker of microvascular dysfunction in such patients and that factors other than abnormal glycosaminoglycan metabolism may contribute to the vascular damage of these patients. [Diabetalogia (1999)

Oral Sulodexide Reduces Albuminuria in Microalbuminuric and Macroalbuminuric Type 1 and Type 2 Diabetic Patients

“…Both demonstrated that sulodexide was effective as a hypoalbuminuric agent. The effect of GAGs on macroalbuminuria in DM2 patients has been explored in two studies; however, tinzaparin (42) and danaparoid (21) were administered parenterally, making direct comparison difficult. The negative results obtained from both studies have raised the doubt that DM2 patients are less sensitive to GAGs than DM1 patients.…”

Evaluation of role of Low Molecular Weight Heparin and Vitamin E on renal functions in patients with diabetic nephropathy

“…Furthermore, differences in molecular weight and anti-X and anti-II activity may be indirect hallmarks of different renoprotective potency of the heparin formulation used. 18 Based upon epidemiological data, the genetic differences in the enzymes involved in the sulphation of GAG side-chains of heparan sulphate proteoglycans are of crucial importance in the pathogenesis of DN and the recent in-vitro and in-vivo studies have put light on the role of HS-GAG in the pathogenesis of DN. 19 In addition, various experimental and human studies have shown heparin to reduce proteinuria and prevent thickening of glomerular basement membrane glomerular and anionic charge in diabetic nephropathy.…”

Efficacy of Heparinoid Supplementation on Mortality and Disease Progression in Adults with Diabetic Kidney Disease

“…Reductions in UAER were seen with enoxaparin but not with tinzaparin; for danaparoid, reductions occurred with Type 1 but not with Type 2 DM patients. 8,[20][21][22] Thus, the exact role of heparinoid supplementation in DKD remains unknown and these substances are not part of treatment recommendations. This study attempts to consolidate available information and evaluate their safety and efficacy in DKD patients.…”

“…8,13,15,18,[19][20][21][22][23] The incidence of likely study-related side effects was similar by removing one study at a time, starting with the studies that had the highest potential risk for bias. We subsequently found no significant changes in the values of the pooled log-transformed MD, indicating the quality of the studies to be satisfactory.…”

“…8,[14][15][16][17][19][20][21][22] Three expressed the results in terms of SCr (Figure 4) while four expressed the results in terms of CrCl ( Figure 5). The inverse variance method was used since the variables were continuous.…”