Renal Hemodynamic Function and RAAS Activation Over the Natural History of Type
1 Diabetes.
Authors Lytvyn Y, Bjornstad P, Lovshin JA, Boulet G, Farooqi MA, Lai V, Tse J, Cham L,
Lovblom LE, Weisman A, Keenan HA, Brent MH, Paul N, Bril V, Advani A, Sochett E,
Perkins BA, Cherney DZI
Submitted By Hillary Keenan on 3/12/2019
Status Published
Journal American journal of kidney diseases : the official journal of the National Kidney Foundation
Year 2019
Date Published
Volume : Pages Not Specified : Not Specified
PubMed Reference 30799029
Abstract The renin-angiotensin-aldosterone system (RAAS) is associated with renal and
cardiovascular disease in diabetes. Unfortunately, early RAAS blockade in
patients with type 1 diabetes mellitus (T1DM) does not prevent the development
of complications. We sought to examine the role of hyperfiltration and RAAS
activation across a wide range of T1DM duration to better understand renal
hemodynamic status in patients with T1DM., Post hoc analysis of blood samples.,
148 Canadian patients with T1DM: 28 adolescents (aged 16.2±2.0 years), 54 young
adults (25.4±5.6 years), and 66 older adults (65.7±7.5 years) studied in a
clinical investigation unit., Angiotensin II infusion (1ng/kg/min; a measure of
RAAS activation) during a euglycemic clamp., Glomerular filtration rate measured
using inulin clearance, effective renal plasma flow measured using
para-aminohippurate, afferent (RA) and efferent (RE) arteriolar resistances, and
glomerular hydrostatic pressure estimated using the Gomez equations., In a
stepwise fashion, glomerular filtration rate, effective renal plasma flow, and
glomerular hydrostatic pressure were higher, while renal vascular resistance and
RA were lower in adolescents versus young adults versus older adults. RE was
similar in adolescents versus young adults but was higher in older adults.
Angiotensin II resulted in blunted renal hemodynamic responses in older adults
(renal vascular resistance increase of 3.3% ± 1.6% vs 4.9% ± 1.9% in
adolescents; P<0.001), suggesting a state of enhanced RAAS activation.,
Homogeneous study participants limit the generalizability of findings to other
populations. Studying older adult participants with T1DM may be associated with
a survivorship bias., A state of relatively low RAAS activity and predominant
afferent dilation rather than efferent constriction characterize early
adolescents and young adults with T1DM. This state of endogenous RAAS inactivity
in early T1DM may explain why pharmacologic blockade of this neurohormonal
system is often ineffective in reducing kidney disease progression in this
setting. Older adults with long-standing T1DM who have predominant afferent
constriction and RAAS activation may experience renoprotection from therapies
that target the afferent arteriole. Further work is required to understand the
potential role of non-RAAS pharmacologic agents that target RA in patients with
early and long-standing T1DM.

Investigators with authorship
Petter BjornstadUniversity of Colorado at Denver and Health Sciences Center
Hillary KeenanJoslin Diabetes Center - Boston