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Original Article
and hyperglycemia. However, some data sug- tensin II (ARBs) and statins.
gest that MS is an independent cause of Hypertension was defined as a history of
CKD.10-14 Few studies have reported that per- hypertension (BP 140/90 mm Hg) that re-
sons with mildly reduced kidney function are quired the initiation of antihypertensive the-
at greater risk for CV disease, but it remains rapy by the primary physician.
unclear whether CKD contributes to prevalent MS was defined according to the revised
MS in the non-diabetic population. No studies criteria of the National Cholesterol Education
have focused on the elderly to evaluate the Program Adult Treatment Panel (NCEP-
relationship between the level of kidney func- ATPIII), which included individuals with three
tion and the prevalence of MS. or more of the following five components:
The aim of the present study is to determine 1) Central obesity: Waist circumference >102
the prevalence and independent predictors of cm in men or >88 cm in women with body
MS in patients with CKD, in addition to fac- mass index (BMI) 25 kg/m2.
tors and conditions associated with MS and to 2) Hypertriglyceridemia: TG 150 mg/dL (1.7
explore the relationship with CKD and its mmol/L).
progression. 3) Low HDL-c <40 mg/dL (1 mmol/L) if the
patient is male and <50 mg/dL (1.3 mmol/
Subjects and Methods L) if female.
4) High BP 130/85 mm Hg and/or
The current study is a cross-sectional survey 5) High fasting glucose 110 mg/dL (6.11
conducted in CKD patients enrolled between mmol/L).
April and June 2009. Patients with diabetes CKD was defined with an eGFR according to
mellitus were excluded from the study. the K/DOQI 2002 classification using the CG
Basic data of the patients included age, gen- formula:
der, systolic (S) blood pressure (BP), diastolic Clearance of Cr = K weight (kg) [140-age
(D) BP, cholesterol (chol), triglycerides (TG), (y)]/Cr (mol/L); K = 1.04 for women and K =
high-density lipoprotein (HDL) cholesterol, 1.23 for men.
low-density lipoprotein (LDL) cholesterol, fas- MDRD formula:
ting blood glucose, proteinuria, serum crea- For men = 186 (creatinine (mol/L)
tinine (Cr), albumin, calcium and phosphate, 0.0113)-1,154 age- 0,203
uric acid and albumin, as well as estimated ( 1.21 if African origin); 0.742 if woman
glomerular filtration rate (eGFR), from the eGFR by MDRD was not calculated in five
simplified equation developed using Modifica- patients who had Cr above 700 mol/L who
tion of Diet in Renal Disease (MDRD) and were considered to be at Stage 5 of CKD.
CockroftGault (CG) formula data, Cr levels Schwartz formula (for children):
and eGFR at baseline and after six months. Clearance of Cr = K height (cm)/serum Cr
Other data collected included family and per- (mol/L)
sonal history (diabetes, hypertension, family K = 29 (newborns); 40 (infants); 49 (children
nephropathy), type of nephropathy, CV com- under 12 years); 53 (girls aged between 12 and
plications including left ventricular hyper- 21 years); 62 (boys aged between 12 and 21
trophy (LVH), coronary heart disease: Angina years).
or myocardial infarction (MI), stroke, heart Terms of use of this formula: Ages between
failure (HF) and arrhythmias (using cardio- six months and 20 years and height between
thoracic index on chest radiograph, signs of 40 and 200 cm. We used this formula in two
LVH on EKG, the sonographic cardiac ejec- patients aged 15 and 16 years.
tion fraction, impaired relaxation and presence
of septal hypertrophy) as well as medications: BMI: The International Classification.
Inhibitor of angiotensin-converting enzyme BMI Classification
(ACE), inhibitors of AT1 receptor of angio- <18.5 Underweight
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MS was more frequently found in female or MDRD, P = 0.8 and 0.28, respectively).
patients, with a statistically significant diffe- There was no significant difference in the
rence (P = 0.000). Table 1 compares the ave- frequency of the use of ACE inhibitors, ARBs
rages of several physical and biological para- or statins between the MS and non-MS groups.
meters studied according to the presence or The frequency of CV complications was
absence of MS. 35.5% versus 21% for the MS and non-MS
The study of MS, based on the initial nephro- groups, respectively (Table 2).
pathy, showed no significant difference. The The logistic multi-regression analysis identi-
patients with vascular nephropathy had more fied four independent predictors for the occur-
MS: 60% versus 40% (P = 0.06). rence of MS in the CKD patients (Table 3).
Comparing the frequency of MS according to The significant independent predictors of MS
the stage of CKD revealed no significant dif- included gender, age, BMI and HDL-c. How-
ference, regardless of the method of eGFR (CG ever, there were no strong and significant cor-
relations between MS and the initial nephro- definition because it is the most commonly
pathy. used definition in the medical literature. Con-
Serum Cr and its clearance were reassessed cerning the other definitions, the World
after six months in only 148 patients. Com- Health Organization or WHOs definition is
paring the evolution of renal function accor- not adapted to our population. The definition
ding to the presence or absence of the MS did of International Diabetes Federation or IDF
not show any significant difference (Table 4). with lower values of TT and blood sugar may
overestimate the prevalence of MS.1 This pre-
Discussion valence was lower in the general Tunisian
population. Indeed, the Tunisian studies esti-
It is now clear that CKD increases the risk of mated that 18% of women and 13% of men
occurrence of CV complications. On the other had MS.1
hand, MS is a powerful CV risk factor. Cur- According to the WHO definition, David2
rent studies have demonstrated the deleterious found that the prevalence of MS was 30.5%,
effect of this syndrome on the kidney. How- while knowing that he had included patients
ever, the relationship of cause and effect bet- with diabetes and dialyzed patients. The AASK
ween MS and CKD is still a subject of debate. study3 found a prevalence of 41.7% among
Using the NCEP ATPIII definition, MS was AfricanAmericans with vascular nephropathy,
found in 42.2% of our patients. We choose this which is consistent with our results.
Table 3. Comparison of metabolic syndrome (MS) in the general population and our study.
Criteria of SM General population Patients with MS
Blood glucose 6.1 mmol/L 13.9 30.2
TG 1.7 mmol/L 24.4 72.7
Systolic BP 130 mm Hg 59.4 73.6
Diastolic BP 85 mm Hg 37.2 52.6
Waist
>102 cm (men)
>88 cm (women) 46.1 75.9
HDL-c
<1 mmol/L (men)
<1.3 mmol/L (women) 67.8 50.8
TG: Triglyceride, BP: blood pressure, HDL: high-density lipoprotein.
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Table 4. Comparison between the averages of various physical and biological parameters studied
according to the presence or absence of metabolic syndrome (MS).
Parameters MS present MS absent P
Weight (kg) 80.3 17.4 69.1 15.1 0.000
BMI (kg/m) 30.7 5.4 24.9 4.6 0.000
Age (years) 59.5 15.5 47.9 18.7 0.000
Systolic BP (mm Hg) 140.1 21.9 128 23.5 0.001
Diastolic BP (mm Hg) 86.5 15 80.8 12.3 0.009
Waist 102 11.9 87.0 11.9 0.000
Glycemia (mmol/L) 5.57 0.95 5.04 0.62 0.000
Cholesterol (mmol/L) 5.39 1.58 4.63 1.57 0.002
TG (mmol/L) 1.70 0.91 1.15 0.75 0.000
HDL-c (mmol/L) 0.94 0.29 1.02 0.44 0.218
LDL-c (mmol/L) 3.6 1.37 3.06 1.33 0.008
Uric acid (mol/L) 437 97.19 425 119 0.574
Serum albumin (g/L) 31.6 9.60 30.5 9.28 0.657
PTH (pg/mL) 312 287 347 312 0.794
Proteinuria (g/24 h) 1.59 2.66 2.29 3.24 0.215
BUN (mmol/L) 13.7 11.30 13.7 9.81 0.998
Creat (mol/L) 223 176 268 216 0.138
Cl CG (mL/min) 55.7 46.8 56.0 51.1 0.968
Cl MDRD (mL/min) 43.4 32.3 49.3 43.3 0.326
BMI: Body mass index, BP: blood pressure, TG: triglyceride, HDL: high-density lipoprotein, LDL: low-
density lipoprotein, PTH: parathormone, BUN: blood urea nitrogen, Creat: creatinine, CG: Cockroft
Gault formula, MDRD: Modification of Diet in Renal Disease formula.
Abdominal obesity differs from the other rence of CV events. These studies found that
types of obesity because of its metabolic MS patients were two to three times more
characteristics. Indeed, it is composed of larger likely to develop CV events independently of
adipocytes, more insulin resistance and higher the presence of diabetes, regardless of gender
TG. Abdominal obesity is also associated with and tobacco.44-46 Although MS is a vascular
an increase in free fatty acids, reduction of risk situation, some authors47,51-56 believe that
adiponectin, resistance of peripheral tissues to this concept is not a better predictor of the CV
the action of leptin and infiltration of adipose risk than the different individual parameters
tissue by macrophage cells with release of used to define it. They also think that it adds
inflammatory cytokines.35 nothing in terms of predicting events in
Our patients had low average eGFR com- relation to the use of the classical risk equa-
pared with those in the literature because of tions such as the Framinghams equation.47,53,54
the type of population with CKD.3,6,8,11,12,28 In In a British study,54 this score was even a
our study, the analysis of renal function did better predictor of coronary heart disease and
not find a significant difference of the fre- stroke compared with MS. The reason for this
quency of MS between the CKD and non- superiority of the Framingham score is that it
CKD patients. The studies performed in pa- quantifies the risk. Indeed, the amplitude of
tients without CKD found the same result.6,12 anomalies contributes to the risk level. This
Similarly, in the AASK cohort,3 whose pur- amplitude is not taken into account in the
pose was to evaluate the influence of MS on definition of MS.47
the progression of CKD in hypertensive In our study, the majority of the patients had
AfricanAmericans, the CL Cr was 45.5 two criteria of MS (34%). The patients without
13.6 mL/min for those with MS versus 46 any criteria accounted for 6.1%, and those with
12.7 mL/min for those without MS. In con- more than four criteria accounted for 15%.
trast, other series4,5,7,9,11,13,17,27,28,40 found that Other studies reported similar results.4,11,19
patients with MS had significantly lower Cl Cr Finally, there was selection bias related to the
compared with those without MS. These reduced number of patients and the hetero-
studies concluded that MS is an independent geneity of the population (we included in the
risk factor for the occurrence of CKD. In fact, study patients with different stages of CKD).
after a few years of follow-up (512 years In addition, the duration of follow-up is short
depending on the study), patients with MS had (6 months).
a higher incidence of CKD,4,7,11,12,13,41,42 even We conclude that the prevalence of MS in
in the absence of diabetes4,7,12 or hypertension.7 patients with chronic renal failure is high.
Unlike the data from several studies, there Predictors of the occurrence of MS in our
was no significant difference in HDL-c bet- study included older age, female gender and
ween patients with MS and patients with-out higher BMI and LDL-c levels. The CV
MS, may be because of the CKD. In our se- complications were more frequent among the
ries, LDL-c was an independent risk factor for MS patients. Furthermore, larger prospective
the occurrence of MS. Now, it is well known studies to analyze the effect of the overall
that LDL-c and persistent inflammatory sti- management of MS on the progression of
muli result in the formation of foam cells and CKD are warranted.
mesangial cells that do not properly contract
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