Unchanged renal haemodynamics following high dose ascorbic acid administration in normoalbuminuric IDDM patients

Abstract

The object of the study was to test whether high dose ascorbic acid (AA) could normalize glomerular hyperfiltration in insulin-dependent diabetes mellitus (IDDM) patients. A prospective, double-blind, randomized, placebo (tartaric acid, TA) controlled study design was used, with parallel treatment lasting 4 weeks. Measurements were made before and after treatment, on 24 normoalbuminuric, normotensive male IDDM patients, who were randomized to ascorbic acid (n = 12, age 35 years (18–39), diabetes duration 12 years (2–12), BP 128/82 mmHg (SD 14/6)), or to placebo (TA) (n = 12, age 30 years (19–36), diabetes duration 8 years (2–17), BP 119/75 mmHg (SD 9/7). The intervention consisted of 6 enterosoluble tablets of 500 mg AA or 213 mg TA, twice a day, being daily doses of 6 g AA or 2.55 g TA. No significant differences in any of the parameters measured were seen, when comparing results following AA or placebo treatment. The glomerular filtration rate (GFR, clearance of ¹²⁵I-iothalamate) was unchanged while effective renal plasma flow (ERPF, clearance of ¹³¹I-hippuran) tended to decline in both groups. The GFRs before and after treatment in the AA-treated group were 141 (SD 15) and 134 (SD 12) ml min⁻¹ 1.73 m⁻²; NS (2p = 0.09). In the TA-treated group they were 142 (SD 19) and 137 (SD 16) ml min⁻¹ 1.73 m⁻²; NS (2p = 0.20). The ERPFs in the AA group were 584 (SD 93) and 545 (SD 47) ml min⁻¹ 1.73 m⁻²; (2p = 0.06). In the TA group they were 618 (SD 108) and 574 (SD 98) ml min⁻¹ 1.73 m⁻² (2p = 0.03). The filtration fractions (FFs) in the AA group were 0.244 and 0.246 NS. In the TA group they were 0.231 and 0.242 (2p = 0.03). Blood pressure, renal vascular resistance, albumin excretion rate (radioimmunoassay), and fractional albumin clearance remained unchanged in both groups. No side effects of AA were observed. It was concluded that low levels of AA in the kidney were either not corrected, or might not be responsible for the glomerular hyperfiltration of uncomplicated IDDM.

Key Words:

• ascorbic acid deficiency metabolism
• glomerular filtration rate
• hyperfiltration
• insulin-dependent diabetes mellitus
• intervention
• polyol pathway