Van der Pijl JW, Van Der Woude FJ, Geelhoed-Duijvestijn PHLM,
Frohlich M, Van Der Meer FJM, et al
Danaparoid sodium lowers proteinuria in diabetic
J Am Soc Nephrol
(Mar) 8:456-462 1997
Diabetic nephropathy is characterized by thickening of the
glomerular basement membrane (GBM) and mesangial matrix expansion.
Heparan sulfate is important in maintaining the negative-charge
barrier and prevention of albumin passage through the GBM and
proteinuria. Reduced synthesis of heparan sulfate proteoglycans
(HSPG) by podocytes and mesangial cells cultured under high glucose
conditions and decreased staining for HSPG in clinical diabetic
npehropathy have been reported. Therefore, it is reasonable to
surmise that administration of HSPG might restore a more normal
charge barrier and decrease proteinuria. Danaparoid sodium is a
mixture of sulfated glycosaminoglycans consisting mainly of heparan
The authors performed a placebo-controlled, randomized
crossover study of danaparoid in Type I diabetic patients with
overt proteinuria (albumin excretion rate (AER) > 300 mg/24h; creat
clearance > 40 ml/min). The design included two 6-wk periods of
treatment with 750 anti-Xa units danaparoid sodium subcutaneously
once daily or placebo with a 4-wk washout between; the order of
treatments was also randomized. Nine patients completed the study
without major side effects.
Danaparoid resulted in significant
decreases in both albuminuria (AER/creat decreased 17% with
danaparoid vs. a 23% increase with placebo, p = 0.03) and
proteinuria (PER/creat decreased 18% with danaparoid vs. a 40%
increase with placebo, p = 0.001). In conclusion, once daily SC
administration of danaparoid sodium resulted in a significant
reduction in proteinuria in diabetic patients with overt
Comment: These data support an interesting hypothesis, namely,
that administration of HSPG can restore depleted amounts of this
proteoglycan in GBM and decrease proteinuria. Previous studies
have suggested that both heparin and low-molecular weight heparins
can decrease microalbuminuria in diabetic patients but it is not
clear whether there is benefit in macroalbuminuric patients.
Danaparoid is a heparinoid and as such is associated with a very
low incidnece of heparin-induced thrombocytopenia and thrombosis.
Thus it may have advantages over heparin therapy especially if
long-term use is contemplated.
This is a pilot study and larger and longer-term studies are
indicated. A further point to keep in mind: since mesangial
expansion is associated with progressive renal failure, it is not
clear whether reduction in proteinuria by altering GBM function
will prevent this complication.
(David J. Leehey, M.D., Loyola University at Chicago)