Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2.
In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.
van der Pijl
J W
JW
Department of Nephrology, Leiden University Medical Center, The Netherlands. j.w.van_der_pijl@nephrology.medfac.leidenuniv.nl
Lemkes
H H
HH
Frölich
M
M
van der Woude
F J
FJ
van der Meer
F J
FJ
Van Es
L A
LA
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000925:Anticoagulants / Q000008:administration & dosage*; D002809:Chondroitin Sulfates / Q000008:administration & dosage*; D003871:Dermatan Sulfate / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy; D003930:Diabetic Retinopathy / Q000188:drug therapy; D004311:Double-Blind Method; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism; D005122:Exudates and Transudates / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006497:Heparan Sulfate / Q000008:administration & dosage*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy / Q000503:physiopathology; D012016:Reference Values; D018709:Statistics, Nonparametric; D014841:von Willebrand Factor / Q000187:drug effects*
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004338:Drug Combinations; D006497:Heparan Sulfate; D014841:von Willebrand Factor; C035838:danaparoid