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

OBJECTIVE: To evaluate the safety and efficacy of heparinoid supplementation on all-cause mortality and disease progression in diabetic kidney disease (DKD). METHODOLOGY: Trials evaluating heparinoid supplementation in DKD were included. Two authors performed a literature search with eligible studies undergoing validity screen, data extraction, and statistical analysis. Results were calculated using the Mantel-Haenszel odds ratio for dichotomous variables and the inverse variance method for continuous variables, and pooled using a random or fixed effects model depending on heterogeneity. RESULTS: Twelve trials were included in the analysis. Eight involved sulodexide while two each involved low molecular weight heparin and danaparoid. We found no statistically significant difference between the heparinoid and placebo groups for all-cause mortality (95% CI, HR 0.79 [0.41, 1.53], p=0.49), number of patients reaching therapeutic success (95% CI, OR 0.97 [0.71, 1.33], p=0.87), serum creatinine (95% CI, MD 2.55 umol/L [-0.54, 5.65], p=0.11), and creatinine clearance (95% CI, MD -8.55 mg/min [-18.28, 1.18], p=0.09). We also found no statistically significant difference in urinary albumin excretion rate (UAER) between Type 2 heparinoid-treated DKD patients compared to placebo (95% CI, log transformed MD 0.13 mg/24h [-0.42, 0.68], p=0.65); however, a statistically significant UAER reduction was seen in Type 1 heparinoid-treated DKD patients compared to placebo (95% CI, log-transformed MD -1.5 mg/24h [-2.79, -0.21], p=0.02). This subgroup analysis was performed due to initial heterogeneity (I(2)=57%). CONCLUSION: Heparinoid supplementation was not associated with statistically significant changes in Type 2 DM patients. However, it may be associated with a statistically significant UAER reduction of approximately 31.62 mg/24 h as compared to placebo in Type 1 DM patients. Due to sparse data on hard clinical outcomes, larger studies are recommended.