Absence of effect of dipyridamole on renal and platelet function in diabetes mellitus
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1Department of Paediatric Nephrology, Institute of Child Health, London.
Insights
Dipyridamole did not improve kidney function in children with insulin-dependent diabetes mellitus (IDDM). This study found no significant differences in urine albumin excretion or other renal markers between children treated with dipyridamole and those receiving a placebo.
Area of Science:
- Pediatric Nephrology
- Diabetology
- Pharmacology
Background:
- Insulin-dependent diabetes mellitus (IDDM) in children is associated with an increased risk of diabetic nephropathy.
- Early detection and intervention are crucial for managing diabetic nephropathy.
- Dipyridamole is a medication with potential vasodilatory and antiplatelet effects.
Purpose of the Study:
- To evaluate the efficacy of dipyridamole in improving renal and platelet function in children with IDDM.
- To assess the impact of dipyridamole on urine albumin excretion and other markers of kidney damage.
- To determine if dipyridamole can prevent the progression of nephropathy in pediatric diabetic patients.
Main Methods:
- A prospective, double-blind, placebo-controlled trial involving 53 children with IDDM.
- Dipyridamole (5 mg/kg/day) or placebo was administered for 12 months.
- Urine albumin to creatinine ratio (UA/UC), glomerular filtration rate, urinary retinol binding protein, urinary N-acetyl-beta-D-glucosaminidase (NAG), blood pressure, and platelet aggregation were measured.
Main Results:
- No significant difference in geometric mean UA/UC between the dipyridamole and placebo groups at 12 months (0.60 mg/mmol vs. 0.87 mg/mmol).
- No significant differences were observed in glomerular filtration rate, urinary RBP, NAG excretion, blood pressure, or platelet aggregation between the groups.
- Subgroup analysis of children with high UA/UC at baseline did not reveal a beneficial effect of dipyridamole.
Conclusions:
- Dipyridamole at 5 mg/kg/day for 12 months did not demonstrate efficacy in improving renal function or reducing albuminuria in children with IDDM.
- Children with persistently high UA/UC or progression to high UA/UC exhibited higher urinary RBP and NAG, larger kidneys, and elevated diastolic blood pressure, suggesting these as potential markers for nephropathy risk.
- Further research is warranted to identify effective interventions for preventing diabetic nephropathy in pediatric populations.
Abstract:
We evaluated the effect of dipyridamole (5 mg/kg/day) for 12 months on renal and platelet function in 53 children with insulin dependent diabetes mellitus (IDDM) in a prospective double blind placebo controlled trial. Urine albumin excretion (expressed as the geometric mean albumin to creatinine concentration ratio (UA/UC) was measured every three months throughout the study. At 12 months, the geometric mean UA/UC was no different in diabetic children receiving dipyridamole, 0.60 mg/mmol, when compared with those receiving placebo, 0.87 mg/mmol. Glomerular filtration rate, urinary excretion of retinol binding protein, and N-acetyl-beta-D-glucosaminidase (NAG), blood pressure, and spontaneous platelet aggregation in response to stirring whole blood did not differ between the two groups at 12 months. Subgroup analysis to include only those children with high UA/UC before entry into the study also failed to show an effect of the drug on UA/UC. Eleven children had either persistently high UA/UC (n = 8: four on dipyridamole, four on placebo) or progression to high UA/UC (n = 3: two on dipyridamole, one on placebo). These children had significantly higher urinary excretion of retinol binding protein and NAG, bigger kidneys, and higher diastolic blood pressure both before and after treatment than the remaining 42 children, whereas there was no difference in spontaneous platelet aggregation between the two groups. These observations on the associations between UA/UC and other parameters of renal function suggest that measurement of 'tubular' proteins and diastolic blood pressure as well as UA/UC may contribute to the identification of those at risk of developing nephropathy.