Influence of sex on hyperfiltration in patients with uncomplicated type 1 diabetes

Author:

Škrtić Marko1,Lytvyn Yuliya12,Bjornstad Petter3,Reich Heather N.1,Scholey James W.1,Yip Paul4,Sochett Etienne B.5,Perkins Bruce6,Cherney David Z. I.1678

Affiliation:

1. Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada;

2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada;

3. Department of Pediatric Endocrinology, Barbara Davis Center for Diabetes University of Colorado School of Medicine, Aurora, CO;

4. University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;

5. Department of Pediatrics, Division of Endocrinology, Sickkids Hospital, University of Toronto, Toronto, Ontario, Canada;

6. Department of Medicine, Division of Endocrinology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada;

7. Department of Physiology, University of Toronto, Toronto, Ontario, Canada; and

8. Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada

Abstract

The aim of this analysis was to examine sex-based differences in renal segmental resistances in healthy controls (HCs) and patients with type 1 diabetes (T1D). We hypothesized that hyperfiltration—an early hemodynamic abnormality associated with diabetic nephropathy—would disproportionately affect women with T1D, thereby attenuating protection against the development of renal complications. Glomerular hemodynamic parameters were evaluated in HC ( n = 30) and in normotensive, normoalbuminuric patients with T1D and either baseline normofiltration [ n = 36, T1D-N, glomerular filtration rate (GFR) 90–134 ml·min−1·1.73 m2] or hyperfiltration ( n = 32, T1D-H, GFR ≥ 135 ml·min−1·1.73 m2) during euglycemic conditions (4–6 mmol/l). Gomez’s equations were used to derive efferent (RE) and afferent (RA) arteriolar resistances, glomerular hydrostatic pressure (PGLO) from inulin (GFR) and paraaminohippurate [effective renal plasma flow (ERPF)] clearances, plasma protein and estimated ultrafiltration coefficients (KFG). Female patients with T1D with hyperfiltration (T1D-H) had higher RE (1,985 ± 487 vs. 1,381 ± 296 dyne·sec−1·cm−5, P < 0.001) and filtration fraction (FF, 0.20 ± 0.047 vs. 0.16 ± 0.03 P < 0.05) and lower ERPF (876 ± 245 vs. 1,111 ± 298 134 ml·min−1·1.73 m2 P < 0.05) compared with male T1D-H patients. Overall, T1D-H patients had higher PGLO and lower RA vs. HC subjects, although there were no sex-based differences. In conclusion, female T1D-H patients had higher RE and FF and lower ERPF than their male counterparts with no associated sex differences in RA. Prospective intervention studies should consider sex as a modifier of renal hemodynamic responses to renal protective therapies.

Publisher

American Physiological Society

Subject

Physiology

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