Effect of Sulodexide on Albuminuria, NAG Excretion and Glomerular Filtration Response to Dopamine in Diabetic Patients

Abstract

Background: Albuminuria is the best and most readily available marker for glomerular damage and progressive renal function loss in patients with diabetic nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to effectively decrease albumin excretion rate in diabetics with nephropathy. Aims: To evaluate whether the hypoalbuminuric effect of sulodexide is associated with improvement of the renal vascular or tubule function. Methods: Forty-five type 1 diabetic patients, affected by diabetic nephropathy with albuminuria for at least 5 years, were randomly allocated to sulodexide or untreated. Those allocated to sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular function (DIR) and N-acetyl-β-D-glucosaminidase (NAG) excretion were estimated before and at the end of the study, the former in thesulodexide group only. DIR was measured as two Cr_cl lasting 120 min (before and during 2 µg/kg b.w. i.v. dopamine). Results: The analysis of trends during the study demonstrated a marked reduction of albuminuria in the sulodexide group (from 126.1 ± 15.41 to 93.6 ± 13.7 mg/day). DIR rose from 13.2 ± 2.1% to 15.44 ± 1.9% (relative increase: +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide group only (from 5.1 ± 0.62 to 4.7 ± 0.40 U/g_creat). Conclusion: The findings presented in this study indicate for the first time that orally available sulodexide may favorably affect the renal vascular function in type 1 diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide on NAG is strongly influenced by the baseline NAG values, with a significant NAG reduction in the patients with the highest baseline NAG values.

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

“…57 In addition, sulodexide treatment has been shown to improve albuminuria in patients with types 1 and 2 diabetes in several small studies. [58][59][60] Various mechanisms that could be responsible for an increase in ESL volume and a decrease in albuminuria have been described. [61][62][63][64] For instance, it has been shown that sulodexide increases synthesis and sulfation of heparan sulfates.…”

“…Not all trials investigating long-term sulodexide administration reported BP values or BP reduction, and none of the studies were designed to specifically examine the effect of sulodexide on BP. 59,[66][67][68] Moreover, BP was already on target when sulodexide was added in most of the studies, and antihypertensive drugs were not actively controlled. 58,[66][67][68] Because the largest BP-lowering effect (mean placebo-subtracted BP reduction=214.6/28.3 mmHg) was observed in a crossover study in patients with diabetes and uncontrolled hypertension, sulodexide may especially lower BP in patients with hypertension and expanded ECV.…”

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

“…13,[15][16][17]21 One used enoxaparin while the remaining four involved sulodexide. Gambaro et al, utilized three different sulodexide doses and was treated as three separate treatment arms (a, b, c).…”

“…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.…”

“…Some trials demonstrated reductions in UAER and serum creatinine (SCr) levels in sulodexide-treated groups, as well as improvements in HbA1c, BP, and lipid profile. [13][14][15][16][17] Other studies, however, failed to demonstrate renoprotective benefits, particularly in terms of the patient number achieving significant reduction or normalization of the urine albumin-creatinine ratio (ACR). 18,19 Similarly, for other heparinoids, small trials showed conflicting data.…”