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

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 ( = 30) and in normotensive, normoalbuminuric patients with T1D and either baseline normofiltration [ = 36, T1D-N, glomerular filtration rate (GFR) 90-134 ml·min·1.73 m] or hyperfiltration ( = 32, T1D-H, GFR ≥ 135 ml·min·1.73 m) during euglycemic conditions (4-6 mmol/l). Gomez's equations were used to derive efferent (R) and afferent (R) arteriolar resistances, glomerular hydrostatic pressure (P) from inulin (GFR) and paraaminohippurate [effective renal plasma flow (ERPF)] clearances, plasma protein and estimated ultrafiltration coefficients (K). Female patients with T1D with hyperfiltration (T1D-H) had higher R (1,985 ± 487 vs. 1,381 ± 296 dyne·sec·cm, < 0.001) and filtration fraction (FF, 0.20 ± 0.047 vs. 0.16 ± 0.03 < 0.05) and lower ERPF (876 ± 245 vs. 1,111 ± 298 134 ml·min·1.73 m < 0.05) compared with male T1D-H patients. Overall, T1D-H patients had higher P and lower R vs. HC subjects, although there were no sex-based differences. In conclusion, female T1D-H patients had higher R and FF and lower ERPF than their male counterparts with no associated sex differences in R Prospective intervention studies should consider sex as a modifier of renal hemodynamic responses to renal protective therapies.

Risk Factors for Kidney Disease in Type 1 Diabetes

“…We observed strong relationships between the later-stage renal outcomes and the nonmodifiable risk factors of male sex (for macroalbuminuria) and age (for reduced eGFR). The mechanisms for a putative protection in females from the incidence of macroalbuminuria are not known (31), although sex-specific influences on renal hemodynamic function have been reported (32). These differences may be through estrogenmediated effects on renin-angiotensinaldosterone system activation or possibly from sex-specific adiposity factors (32,33).…”

“…The mechanisms for a putative protection in females from the incidence of macroalbuminuria are not known (31), although sex-specific influences on renal hemodynamic function have been reported (32). These differences may be through estrogenmediated effects on renin-angiotensinaldosterone system activation or possibly from sex-specific adiposity factors (32,33). The age-related decline in eGFR is well established in health and in disease and remains a consistent risk factor for reduced eGFR for both males and females in studies with sufficient sample size and study duration (34).…”

Risk Factors Associated With the Development of Nephropathy 10 Years After Diagnosis in Taiwanese Children With Juvenile-Onset Type 1 Diabetes—A Cohort Study From the CGJDES

“…The lifetime risk of DN in T1DM patients varies among studies and ethnic groups ( 5 – 8 ). Recently, researchers indicated an effect of sex on hyperfiltration in patients with T1DM without complications ( 9 ). Female patients with T1DM and DN had higher renal efferent arteriolar resistance and attenuating protection against the development of renal complications in the hyperfiltration state than male patients.…”

Association of Albuminuria With Intraglomerular Hydrostatic Pressure and Insulin Resistance in Subjects With Impaired Fasting Glucose and/or Impaired Glucose Tolerance

“…Thirdly, we were not able to directly measure R a , R e , or P glo in the current study, as it is not possible to directly measure these parameters in humansdas opposed to animal studies. Thus, we used the Gomez formulae to assess intrarenal hemodynamics, as in the previous studies reported by others (12,19,20,43) and by ourselves (13,15,21,22).…”

“…PAH concentrations were measured photometrically by means of the N-1 naphthylethylenediamine and the anthrone method using a Corning 258 spectrophotometer (18). Since the direct measurement of glomerular hemodynamics parameters is not feasible in humans, the formulae introduced by Gomez (11) allow indirect assessment of glomerular hemodynamics, as reported previously by others (12,19,20) and ourselves (13,15,21,22). The Gomez formulae were calculated from the original report describing the formulae (11), as described in detail in our previous studies (13,15,21,22).…”