الفهرس 
AbstractOnly 14 pages are availabe for public view
 |  | from | 256 |  |  |
| | | from | 256 | | |
Abstract
Summary
Diabetic Nephropathy (DN) remains the leading cause of end stage
renal disease (ESRD) in the Western world, responsible for nearly half of
all new ESRD cases in the USA, in type 2 diabetic patients, the incidence
of microalbuminuria was 2.0% per year and the prevalence 10 years after
diagnosis 25% in the (UKPDS) study, the prevalence of proteinuria is
highly variable, ranging from 5 to 20%.
Once persistent microalbuminuria is confirmed, 20 to 50% of type
2 diabetic patients will progress to DN. Macroalbuminuria will eventually
lead to an end-stage renal insufficiency within 10 to 20 years.
Microalbuminuria is currently the only diagnostic tool available for
early diagnosis of diabetic nephropathy. The test is based on
immunological detection of small quantities of albumin in the urinary
samples of diabetes patients.
Although the measurement of Urinary albumin excretion (UAE) is
the cornerstone for the diagnosis of diabetic nephropathy, there are some
patients with either type 1 or type 2 diabetes, who have decreased
glomerular filtration rate (GFR) in the presence of normal UAE.
There are several limitations of the use of microalbuminuria as an
index of renal function. It is therefore desirable to identify additional
protein markers that would augment prediction of diabetic nephropathy.
Identifying modifiable factors that cause increase in UAE is
important since intervention directed to these factors might be expected to
result in better renal and cardiovascular prognosis.
188
Summary
Vasopressin has been hypothesized as one of these modifiable
factors, Vasopressin is known as antidiuretic hormone, despite its
importance for normal water regulation in the body. Vasopressin also has
been reported to exert deleterious effects on the kidney.
Vasopressin is elevated in DM and in some forms of hypertension.
Due to the fact that direct measurement of vasopressin in humans is
problematic, recently, an assay has been developed to measure copeptin,
the C-terminal portion of the precursor of AVP (arginine vasopressin),
Copeptin is secreted with vasopressin, and hence it can be used as a
surrogate marker of the AVP system.
In 2010, Meijer et al report a positive cross-sectional association
between plasma copeptin and microalbuminuria within the population
sample of the Prevention of Renal and Vascular End-Stage Disease
(PREVEND) Study, which includes adults both with and without kidney
dysfunction (Massimo Cirillo.; 2010). The association of plasma
copeptin with high urinary albumin excretion was not explained by high
glomerular filtration rate (GFR), because individuals with high plasma
copeptin actually had higher serum creatinine and lower estimated GFR
in comparison with individuals with low plasma copeptin, they conclude
that, in addition to its well-known antidiuretic effect, vasopressin might
also exert per se an intrarenal pro-albuminuric effect
We aimed to identify the possible relations of serum copetin level (a
surrogate marker of vasopressin) with different stages of diabetic
nephropathy according to UAE for further estimation of the role of serum
copeptin level as a diagnostic novel biomarkers for early detection of
protienuria in diabetic patients.
189
Summary
Also, we aimed to investigate the possible relation between Serum
Copeptin level and different stages of CKD in DN regarding decline in
renal functions and estimated glomerular filtration rate that develop in
diabetic patients.
In our study, patients were recruited from referrals to the Internal
Medicine outpatient clinic and nephrology outpatient clinic, Beni-Suef
University Hospital.
A population of 96 persons were included in this study, the study
was divided into 5 groups; group (1) is the control group comprising 19
healthy subjects and group (2-5) comprising 80 diabetic patients (Type
II) with different stages of albuminuria and CKD.
All subjects have full battery of history, clinical examination,
laboratory investigations, fundus examination, pelvi-abdominal
ultrasound and estimation of serum copeptin level.
Statistical analysis of demographic and clinical variables was
performed among these groups.
It was shown that serum copeptin level was significantly higher in
diabetic patients than in controls and it correlates with the level of control
of hyperglycemia as measured by level of HBA1C.this finding has not
been discussed before in the literature.
We found that serum copeptin level can predict the presence of
microalbuminuria in type II diabetics; it can be used as a novel marker for
early diagnosis of albuminuria in diabetic nephropathy.
190
Summary
Serum copeptin level significantly correlates with the progression
of albuminuria in DN from normo to microalbuminuria, in patients with
diabetic nephropathy with normal kidney functions and this finding also
has not been discussed before.
We found that serum copeptin level in controls (group 1) correlated
with its level in diabetic patients with normoalbuminuria and normal
kidney functions (group 2), and correlated with its level in diabetic
patients with microalbuminuria and normal kidney functions (group 3).
Also, we found that serum copeptin level in diabetic patients with
normoalbuminuria and normal kidney functions (group 2) correlated with
its level in diabetic patients with microalbuminuria and normal kidney
functions (group 3).
So, serum copeptin level in diabetic patients group (3) correlated
with its level in both groups (1 and 2). These types of comparisons with
these findings in humans with diabetic nephropathy had not been
discussed before in the literature.
We found that diabetic patients with normoalbuminuria with or
without decline in eGFR (Groups 2, 5) had a higher level of serum
copeptin compared to controls (group 1) with highly statistically
significant difference in between.
Also we found that diabetic patients with microalbuminuria with or
without decline in eGFR (Groups 3, 4) had the highest level of serum
copeptin compared to both controls (group 1) and diabetic patients with
normoalbuminuria with or without decline in eGFR (Groups 2, 5).
This means that serum copeptin level correlates with the
progression of albuminuria in different stages of diabetic nephropathy,
191
Summary
even with or without the decline in eGFR. This finding was also novel
and it was not discussed before in humans with diabetic nephropathy
We correlated between serum copeptin levels versus different
variables by using multivariate analysis among microalbuminuria group
and we found that albuminuria, eGFR and HbA1c, respectively, were
considered independent variables affecting serum copeptin level.
Also in our results there was no statistically significant difference
between males and females as regard serum copeptin level among all
groups.
We found that decrease in eGFR without albuminuria also
correlates with serum copeptin level.this also has not been discussed
before.
We found that the presence of albuminuria together with decline in
eGFR may add an influence to the level of copeptin in the serum of
diabetic patients, as it was highest in this group of patients, in humans, in
diabetics, to our knowledge these findings have not been discussed
before.
We found serum copeptin level in diabetic patients with
microalbuminuria and overt renal impairment, (decline in eGFR, CKD
stage 3, 4) (group 4) correlated with its level in groups (1, 2 and 3), while
it didn’t show significant correlation with group (5).
Also, we found that serum copeptin level in diabetic patients with
normoalbuminuria and overt renal impairment (decline in eGFR, CKD
stage 3, 4) (group 5) correlated with its level in groups (1, 2 and 3), while
it didn’t show significant correlation with group (4).Also these findings
were not discussed before in the literature.
192
Summary
We also found that serum copeptin level correlated with the
progression of the stages of chronic kidney disease in diabetics, these
findings were discussed before in different studies, yet, all these studies
were animal research work and not in humans.
We correlated between serum copeptin level versus different
variables by using multivariate analysis among groups with decline in
eGFR (CKD stage 3, 4) with or without albuminuria, we found that
albuminuria, eGFR and HBA1C, respectively, were considered
independent variables affecting serum copeptin level.
Hence, Serum copeptin level is considered better positive marker
than negative with sensitivity 75% and specifity 40% and accuracy 52%
in prediction of microalbuminuria in diabetics.
Also, serum copeptin level is considered better positive marker
than negative with sensitivity 76% and specifity 60% and accuracy 65 %
in prediction of decline of eGFR in diabetics
Finally, serum copeptin level is considered better positive than
negative with sensitivity 83% and specificity 62% and accuracy 75% in
prediction of global renal affection (both albuminuria and decline in
eGFR) in diabetics.