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Original Paper
Nephron Clin Pract 2011;118:c155–c164
DOI: 10.1159/000320038
Proximal Tubule Dysfunction Is Dissociated from
Endothelial Dysfunction in Normoalbuminuric
Patients with Type 2 Diabetes Mellitus:
A Cross-Sectional Study
Ligia Petrica
a
Maxim Petrica
b
Adrian Vlad
c
Dragos Catalin Jianu
b
Gheorghe Gluhovschi
a
Calina Ianculescu
d
Catalina Firescu
e
Victor Dumitrascu
d
Sorin Giju
f
Cristina Gluhovschi
a
Flaviu Bob
a
Florica Gadalean
a
Sorin Ursoniu
g
Silvia Velciov
a
Gheorghe Bozdog
a
Oana Milas
a
Departments of
a
Nephrology,
b
Neurology,
c
Diabetes and Metabolic Diseases,
d
Blood Biochemistry,
e
Immunology,
f
Urine Biochemistry and
g
Public Health Medicine, County Emergency Hospital, Victor Babes University of Medicine
and Pharmacy, Timisoara, Romania
dle cerebral artery and intima-media thickness (IMT) in the
common carotid artery; cerebrovascular reactivity was eval-
uated through the breath-holding test. Results: Plasma
ADMA was increased in 12 patients (17.5%), urinary
1
-micro-
globulin in 19 patients (27.9%) and urinary
2
-microglobulin
in 16 patients (23.5%). Cerebral hemodynamic indices corre-
lated with plasma ADMA, CRP, fibrinogen, duration of DM,
HbA
1c
and GFR. ADMA correlated with fibrinogen, CRP, HbA
1c
,
duration of DM and GFR. There were no correlations be-
tween ADMA and UACR, and urinary
1
-/
2
-microglobulin.
Also, no correlations were found between urinary
1
-/
2
-mi-
croglobulin and UACR, HbA
1c
, duration of DM and GFR. Con-
clusion: The increase in urinary
1
-/
2
-microglobulin pre-
cedes the stage of albuminuria. It may be assumed that ear-
ly DN is related to PT dysfunction. Endothelial dysfunction
plays a pivotal role in the brain vasculature, while its involve-
ment in the development of early DN is not conditional on
the occurrence of albuminuria.
Copyright © 2010 S. Karger AG, Basel
Key Words
Diabetic nephropathy Endothelial dysfunction Proximal
tubule dysfunction
Abstract
Introduction: The aim of our study was to clarify the hypoth-
esis that proximal tubule (PT) dysfunction may be responsi-
ble for early diabetic nephropathy (DN), independently of
preceding glomerular endothelial dysfunction. The pattern
of endothelial dysfunction and its potential variability was
evaluated in two vascular beds, the kidney and the brain.
Methods: A total of 68 normoalbuminuric type 2 diabetes
mellitus (DM) patients were enrolled in a cross-sectional
study and the following parameters were assessed: urinary
albumin:creatinine ratio (UACR), urinary
1
-microglobulin,
urinary
2
-microglobulin, plasma asymmetric dimethyl-argi-
nine (ADMA), serum creatinine, glomerular filtration rate
(GFR), C-reactive protein (CRP), fibrinogen, HbA
1c
; pulsatility
and resistance indices in the internal carotid artery and mid-
Received: May 10, 2010
Accepted: July 28, 2010
Published online: December 10, 2010
Dr. Ligia Petrica
Str. Telegrafului
Bl C11, Et3, Ap7
RO–300125 Timisoara (Romania)
Tel. +40 256 220 234, Fax +40 256 465 397, E-Mail ligiapetrica @ rdslink.ro
© 2010 S. Karger AG, Basel
1660–2110/11/1182–0155$38.00/0
Accessible online at:
www.karger.com/nec