Original Paper
Nephron Clin Pract 2009;113:c140–c147
DOI: 10.1159/000232594
Received: December 9, 2008
Accepted: January 20, 2009
Published online: August 12, 2009
Albuminuria and Renal Function in
Obese Adults Evaluated for Obstructive
Sleep Apnea
Varun Agrawal a Thomas E. Vanhecke a Baroon Rai a Barry A. Franklin a
R. Bart Sangal b Peter A. McCullough a
a
Divisions of Cardiology, Nutrition and Preventive Medicine, Department of Medicine, William Beaumont Hospital,
Royal Oak, Mich., and b Sleep and Attention Disorders Institutes and Clinical Neurophysiology Services,
Troy, Mich., USA
Key Words
Obesity ⴢ Hypertension ⴢ Albuminuria ⴢ Renal function ⴢ
Obstructive sleep apnea
Abstract
Background: Obstructive sleep apnea (OSA) is associated
with hypertension, obesity and metabolic syndrome that
are risk factors for cardiovascular and chronic kidney disease.
Few data are available regarding renal parameters in patients with OSA. Methods: We conducted a cross-sectional
study of 91 obese adults who had routine polysomnography
before bariatric surgery. Presence and severity of OSA were
determined by the apnea-hypopnea index (AHI !5 = no OSA
and AHI 65 = OSA). Clinical and laboratory data were available within a month of polysomnography. Results: Mean 8
SD age was 44.9 8 9.9 years. There were 66 women. Mean
8 SD body mass index was 48.3 8 8.9 kg/m2 with hypertension and type 2 diabetes present in 55 and 31 subjects, respectively. There were 36 subjects with no OSA and 55 with
OSA. The two groups had similar demographic characteristics, blood pressure (BP), lipid profile and medication use except for difference in mean 8 SD hemoglobin A1c (5.6 8
0.6% in no OSA, 6.0 8 0.8% in OSA; p = 0.029) and use of renin-angiotensin system blocking agents (22.2% in no OSA,
46.4% in OSA; p = 0.024). Median (interquartile range) urine
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albumin:creatinine ratio (ACR) was not different between
the two groups [6 (4–14.5) mg/g in no OSA, 8 (5–16) mg/g in
OSA; p = 0.723], while significant difference existed in serum
creatinine (0.8 8 0.2 mg/dl in no OSA, 0.9 8 0.2 mg/dl in
OSA, p = 0.013). Age- and gender-adjusted correlations were
observed between log-log ACR and systolic BP (r = 0.265;
p = 0.016), log-log ACR and diastolic BP (r = 0.245; p = 0.026)
and between serum creatinine and log AHI (r = 0.188, p =
0.089). Multiple linear regression analysis demonstrated loglog ACR to be associated with diastolic BP (p = 0.046), while
serum creatinine was associated with log AHI (p = 0.044).
Conclusion: In obese adults, increasing severity of OSA is associated with higher serum creatinine but not greater degree of albuminuria.
Copyright © 2009 S. Karger AG, Basel
Introduction
Obstructive sleep apnea (OSA) is a common respiratory disorder characterized by transient partial or complete upper airway obstruction during sleep causing sleep
The study was presented in part at the National Kidney Foundation
2008 Spring Clinical Meetings, April 2008, Dallas, Tex., USA, and the
abstract published in Am J Kidney Dis 2008;51:B29.
Varun Agrawal, MD
Department of Internal Medicine, William Beaumont Hospital
3601 West 13 Mile Road
Royal Oak, MI 48073 (USA)
Tel. +1 248 992 5987, Fax +1 248 898 0580, E-Mail [email protected]
disturbance and daytime sleepiness. Hypoxia and hypercapnia during the repetitive apneic episodes may evoke a
chemoreceptor-mediated increase in sympathetic activity leading to hypertension [1]. OSA is associated with several cardiovascular conditions including ischemic heart
disease, congestive heart failure, cardiac arrhythmias
and cerebrovascular disease [1]. OSA is also associated
with increased prevalence of metabolic syndrome [2],
possibly from elevated levels of proinflammatory mediators (C-reactive protein, CRP, interleukin-1␤ and -6,
leptin, tumor necrosis factor-␣, reactive oxygen species,
adhesion molecules) and insulin resistance [3].
OSA has been well described in patients with endstage renal disease (ESRD) on hemodialysis [4]. Little is
known about the effect of OSA on renal parameters (urine
albumin excretion and glomerular filtration rate) in patients without ESRD. The cardiovascular risk factors associated with OSA – obesity, hypertension, insulin resistance, and metabolic syndrome – are also known risk factors for chronic kidney disease (CKD) [5]. Atherosclerosis,
systemic vascular abnormalities due to increased sympathetic output and intermittent hypoxia in OSA may have
an effect on the kidney [6]. Microalbuminuria (urine albumin:creatinine ratio, ACR, 30–300 mg/g) is an early
marker of CKD [7]. Albuminuria serves as a marker for
endothelial dysfunction and signals a greater risk of generalized vascular disease and atherosclerosis as manifested by increased cardiovascular events and clinical proteinuria, even below the lower cut-off ACR level of 30
mg/g [8].
Since OSA has a high prevalence in morbidly obese
adults undergoing evaluation for bariatric surgery (up to
80%) [9], we performed a retrospective study to examine
the relation between OSA and renal parameters (ACR
and serum creatinine) in this population. We hypothesized that the presence and severity of OSA is associated
with greater albuminuria and worse renal function.
Methods
Morbidly obese adults (body mass index, BMI 1 40 without
diabetes or BMI 135 with diabetes) who consecutively underwent
routine polysomnography as screening for OSA prior to bariatric
surgery from May 2007 to July 2008 (n = 102) were studied. Preoperative polysomnography is recommended to identify patients
with OSA who may be at higher risk for postoperative pulmonary
complications [9]. Among these subjects, 92 had complete laboratory and clinical study data within a month prior to polysomnography. None of the subjects had history of overt renal disease, i.e.
diabetic nephropathy, glomerulonephritis or renal artery stenosis, CKD stage 3 or more (Modified Diet in Renal Disease esti-
Albuminuria and Renal Function in
Obese Adults Evaluated for OSA
mated glomerular filtration rate !60 ml/min/1.73 m2), ESRD on
renal replacement therapy or renal transplant. One patient had
ACR of 422 mg/g (macroalbuminuria) and was excluded to avoid
the influence of outliers. Thus, the final sample size was 91. None
of the subjects had history of severe lung disease requiring chronic oxygen therapy, previously treated OSA or cardiopulmonary
disease. Approval of the study was obtained from the Human Investigation Committee at William Beaumont Hospital, Royal
Oak, Mich., USA.
All subjects underwent comprehensive baseline medical evaluation with complete history, physical examination, blood chemistry testing, and medication review by a cardiologist at a clinic
visit for evaluation for bariatric surgery. Blood pressure (BP) was
measured in sitting up position. Hypertension was defined as a
BP 6140/90 mm Hg and/or use of antihypertensive medications.
Subjects with diabetes were defined by the use of antidiabetic
medications or glycosylated hemoglobin (HbA1c) 1 6% at this visit, since fasting glucose was not available on all subjects.
Urine measurement of ACR was per the protocol for bariatric
surgery. Urine studies were performed on one random spot midstream urine sample collected between 8–10 a.m. on the morning
of the clinic visit. The urine specimen was refrigerated (2–8 ° C)
after collection and transported to William Beaumont Hospital
Automated Chemistry Laboratory (Royal Oak, Mich., USA) for
analysis. Urine albumin was measured by the immunoturbidimetric method and urine creatinine by a colorimetric method
using a Jaffe technique. Normoalbuminuria was defined as ACR
!30 mg/g and microalbuminuria as 30–300 mg/g.
All participants underwent overnight polysomnography in a
sleep laboratory within a month of their blood chemistry studies.
Apneas were defined by near absence of airflow for 610 s on the
nasal pressure cannula signal. Hypopneas were defined as a decrease in airflow on the nasal pressure cannula signal for 610 s,
accompanied by an arousal, a 1 4% desaturation, or both. The apnea-hypopnea index (AHI) was defined as the average number of
apneas plus hypopneas with 4% desaturation per hour of sleep.
The respiratory disturbance index (RDI) was defined as the average number of apneas, hypopneas with desaturation or hypopneas with arousal per hour of sleep. Minimum oxygen saturation
was the lowest oxygen saturation recorded during the sleep study.
An AHI !5, 5–14.9, 15–29.9 and 630 indicated no OSA, mild
OSA, moderate OSA and severe OSA, respectively. Research personnel from the sleep disorders center did not have access to laboratory data.
Charts were abstracted using a case report form by trained
reviewers who were blinded to the laboratory results. A computerized information system was accessed to review studies performed at the William Beaumont Hospital Automated Chemistry
Laboratory and this review was blinded to sleep study results.
Statistical Analysis
Baseline characteristics were expressed as mean 8 standard
deviation or counts with proportions as appropriate. ACR level
was double log transformed due to skewed distribution and results expressed as median with interquartile range. Univariate
comparisons were made with paired t test and ␹2 test as appropriate. ANOVA was used to compare the differences across patient
subgroups. Pearson correlation coefficient (r) was used to evaluate the relationship between the renal parameters (ACR and serum creatinine) and metabolic and sleep variables. Partial corre-
Nephron Clin Pract 2009;113:c140–c147
c141
Table 1. Baseline characteristics of the entire study sample
Characteristic
No OSA
(AHI <5)
Patients
Age, years
Gender, % female
BMI
Hypertension, %
Diabetes, %
Systolic BP, mm Hg
Diastolic BP, mm Hg
Use of ACEI/ARB, %
Use of beta-blockers, %
Use of diuretics, %
Total cholesterol, mg/dl
Triglycerides, mg/dl
Low-density lipoprotein, mg/dl
High-density lipoprotein, mg/dl
Hemoglobin A1c, %
CRP, mg/dl
ACR, mg/g
Microalbuminuria, %
Serum creatinine, mg/dl
AHI
RDI
Minimum oxygen saturation, %
36
43.9810.0
72.2
46.689.2
52.8
22.2
131.5815.1
82.489.6
22.2
19.4
27.8
175.4833.6
143.5872.0
94.0828.9
53.4815.7
5.680.6
7.587.7
6 (4–14.5)
11.1
0.880.2
1.381.6
3.383.6
88.683.0
Mild OSA
(AHI 5–14.9)
23
44.989.5
82.6
46.587.1
52.2
34.8
133.7815.2
82.988.5
39.1
13.0
34.8
165.5830.7
148.68110.1
90.5825.0
48.1810.2
5.880.6
9.0810.8
6 (5–10)
8.7
1.080.2
9.182.8
11.283.8
81.688.7
Moderate OSA Severe OSA
(AHI ≥15–29.9) (AHI ≥30)
14
18
43.1810.1
48.2810.1
85.7
50.0
50.2810.3
52.788.4
78.6
72.2
50.0
44.4
128.0813.6
135.0819.9
84.489.2
82.4812.0
42.9
61.1
21.4
22.2
42.9
50.0
174.4837.7
174.6837.6
167.8894.0
127.9856.4
93.6832.1
99.4831.1
47.2811.8
49.7814.3
6.280.9
6.180.9
13.7812.1
11.5821.9
16 (3.8–40.3)
8 (5–22.5)
28.6
16.7
0.980.2
0.980.3
22.685.1
59.8823.4
28.1810.7
63.8823.2
69.1814.3
74.2810.0
p
0.420
0.072
0.063
0.217
0.200
0.626
0.921
0.043
0.876
0.422
0.723
0.626
0.808
0.380
0.046
0.449
0.412
0.357
0.015
<0.0001
<0.0001
<0.0001
Total
91
44.989.9
72.5
48.388.9
60.4
34.1
132.2815.8
82.889.6
37.4
18.7
36.3
172.6834.0
145.2883.5
94.1828.5
50.4813.7
5.880.7
9.6813.0
7 (4–16)
14.3
0.980.2
18.2824.4
21.1825.5
79.2812.0
Data are expressed as mean 8 standard deviation or median (interquartile range); p is the significance value for differences between the four subgroups.
lations were assessed after adjusting for age, gender, BMI and diabetic status. Stepwise multiple linear regression analysis was
used to determine the association of ACR (log-log transformed)
and serum creatinine with BMI, systolic BP, diastolic BP, HbA1c,
high-sensitivity C-reactive protein (hs-CRP), (log) AHI, diabetic
status and use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB). Variables were entered in the model if the significance (probability) of the F value
was !0.05 and removed if 1 0.10. All hypothesis testing was two
tailed. A p value !0.05 was considered statistically significant.
Statistical analysis was performed with SPSS v14.0 (SPSS Inc.,
Chicago, Ill., USA).
Results
Our study sample (n = 91) had a mean age of 44.9 8
9.9 years and included 66 (72.9%) women and 78 (86%)
Caucasians. Hypertension was present in 55 subjects
(60.4%) and type 2 diabetes was present in 31 subjects
(34.1%). Patients were categorized into four subgroups
based on their severity of OSA (table 1): no OSA (n = 36),
c142
Nephron Clin Pract 2009;113:c140–c147
mild OSA (n = 23), moderate OSA (n = 14), and severe
OSA (n = 18). The four subgroups had similar baseline
characteristics except for significant differences in percent of patients on ACEI/ARB (22.2, 39.1, 42.9, 61.1% in
no OSA, mild OSA, moderate OSA and severe OSA, respectively, p = 0.043) and hemoglobin A1c (5.6 8 0.6, 5.8
8 0.6, 6.2 8 0.9, 6.1 8 0.9% in no OSA, mild OSA, moderate OSA and severe OSA respectively, p = 0.046). Differences in mean BMI approached statistical significance
(46.6 8 9.2, 46.5 8 7.1, 50.2 8 10.3, 52.7 8 8.4 in no
OSA, mild OSA, moderate OSA and severe OSA, respectively, p = 0.063).
No significant difference existed between subjects
with OSA (AHI 65, n = 55) and without OSA (AHI !5,
n = 36) in ACR [8 (5–16) mg/g in OSA vs. 6 (4–15) mg/g
in no OSA, p = 0.723], while serum creatinine was higher
in the presence of OSA as compared with absence of OSA
(0.9 8 0.2 mg/dl in OSA vs. 0.8 8 0.2 mg/dl in no OSA,
p = 0.013). Subgroup analysis showed that ACR was not
significantly different among the four OSA subgroups
Agrawal /Vanhecke /Rai /Franklin /
Sangal /McCullough
Table 2. Correlation matrix
Log AHI
Log-log ACR
Cr
BMI
HbA1c
hs-CRP
SBP
DBP
r
p
r
p
r
p
r
p
r
p
r
p
r
p
0.120
0.282
0.188
0.089
0.249
0.023
0.230
0.036
0.117
0.293
0.017
0.877
–0.002
0.987
Log-log ACR
–0.165
0.137
0.001
0.993
0.140
0.206
0.048
0.666
0.265
0.016
0.245
0.026
Cr
BMI
0.009
0.933
–0.135
0.223
0.055
0.624
0.023
0.834
–0.113
0.307
0.091
0.414
0.251
0.022
0.085
0.444
0.080
0.471
HbA1c
0.046
0.682
0.050
0.651
–0.151
0.174
hs-CRP
–0.141
0.204
0.029
0.796
SBP
0.585
<0.001
Age- and gender-adjusted Spearman correlation coefficients (r) of renal parameters and metabolic and sleep variables.
Cr = Serum creatinine (mg/dl); HbA1c = hemoglobin A1c (%); SBP = systolic BP (mm Hg); DBP = diastolic BP (mm Hg).
[6 (4–14.5), 6 (5–10), 16 (3.8–40.3), 8 (5–22.5) mg/g in no
OSA, mild OSA, moderate OSA and severe OSA respectively, p = 0.412], while significant difference existed in
serum creatinine (0.8 8 0.2, 1.0 8 0.2, 0.9 8 0.2, 0.9 8
0.3 mg/dl in no OSA, mild OSA, moderate OSA and severe OSA, respectively, p = 0.015). Patients with hypertension (n = 55) had greater ACR than patients without
hypertension (n = 36) [8 (5–19) vs. 5.5 (3–11.5) mg/g, p =
0.008] while serum creatinine was similar in the two
groups (0.9 8 0.2 mg/dl in hypertensives vs. 0.9 8 0.2
mg/dl in normotensives, p = 0.111). Patients with type 2
diabetes (n = 31) had renal parameters similar to nondiabetics (n = 60) [ACR 8 (5–19) mg/g in diabetics vs. 6 (4–
14.5) mg/g in nondiabetics, p = 0.064, and serum creatinine 0.9 8 0.2 mg/dl in diabetics vs. 0.9 8 0.2 mg/dl in
nondiabetics, p = 0.643].
A correlation matrix is shown in table 2 for variables
related to albuminuria and serum creatinine adjusted for
age and gender. Log-log ACR significantly correlated
with systolic BP (r = 0.265; p = 0.016) and diastolic BP
(r = 0.245; p = 0.026; fig. 1). The correlation between serum creatinine and log AHI approached significance (r =
0.188, p = 0.089; fig. 2). These correlations persisted even
after adjustment for BMI and diabetic status. No correlations were seen between the other sleep variables (RDI
and minimum oxygen saturation) and renal parameters.
Multiple linear regression analysis was performed to
evaluate the association of (log-log) ACR and serum cre-
atinine with BMI, systolic BP, diastolic BP, hemoglobin
A1c, hs-CRP, (log) AHI, diabetic status and use of ACEI/
ARB. These eight variables accounted for a variance of
r2 = 0.047 when log-log ACR was the dependent variable.
Diastolic BP (standardized coefficient ␤ = 0.217, p =
0.046) was found to be significantly associated with
log-log ACR. Multiple linear regression analysis performed on serum creatinine with the above dependent
variables (r2 = 0.048) demonstrated log AHI to be significantly associated with serum creatinine (␤ = 0.219, p =
0.044).
Albuminuria and Renal Function in
Obese Adults Evaluated for OSA
Nephron Clin Pract 2009;113:c140–c147
Discussion
We found that in a study sample of morbidly obese
adults who had polysomnography study as preoperative
screening for OSA, urine albumin excretion was significantly associated with diastolic BP. There was no effect of
the presence or severity of OSA on the level of albuminuria. Interestingly, serum creatinine was higher in subjects with OSA than without OSA and correlated with the
severity of OSA.
Early studies of OSA and renal function demonstrated
greater urine protein excretion in presence of OSA [10,
11] that was shown to improve with surgical correction of
OSA [12]. Cross-sectional studies showed urine protein:
creatinine ratio 10.2 g/g to be uncommon in OSA (4–5%),
c143
1.6
1.5
1.4
Serum creatinine (mg/dl)
Log-log urine ACR
2.0
1.0
0.5
0
–0.5
1.2
1.0
0.8
0.6
60
70
80
90
100
Diastolic BP (mm Hg)
110
120
0
1
2
3
4
5
Log AHI
Fig. 1. Scatterplot showing correlation between (logarithm-logarithm) urine ACR (mg/g) and diastolic BP [(log-log ACR = –0.290
+ (0.011 ! diastolic BP)] after adjusting for age and gender (r =
0.245, p = 0.026).
Fig. 2. Scatterplot showing correlation between serum creatinine
but found weak associations of proteinuria with arousal
index (frequency of arousals during sleep) [13] and minimal oxygen saturation during sleep [14]. Presence of proteinuria represents established glomerular damage; however, albuminuria is a more sensitive and early indicator
of reversible and functional renal injury [15].
We hypothesized that albuminuria would be greater
in subjects with OSA. This is because albuminuria is a
marker of insulin resistance, endothelial dysfunction and
glomerular hyperfiltration [15]. These mediators of cardiovascular and renal injury are commonly observed in
patients with OSA presumably from hypoxemia-induced
reactive oxygen species and systemic inflammation [16,
17]. Glomerular hyperfiltration in patients with OSA
may be attributed to the associated systemic hypertension, obesity, proinflammatory state, and increased venous pressure, elevated pulmonary pressure, or combination of the above [18].
A large cohort study (n = 496) demonstrated increased
ACR in severe OSA that persisted after adjusting for presence of hypertension and diabetic state [19]. A cross-sectional study showed nondiabetic adults with untreated
hypertension to have significantly greater ACR (by 57%)
in the presence of OSA that correlated with AHI and 24hour pulse pressure [20]. A case-control study showed
low-grade albuminuria in nondiabetic normotensive
adults with OSA that correlated with length of time at
oxygen saturation !90% and BMI [21]. Our findings do
not agree with these studies, which is likely due to our
study design. Our subjects were morbidly obese, which
itself contributed to albuminuria due to obesity-related
glomerulopathy [22]. They were receiving treatment with
ACEI/ARB that reduce albuminuria. Despite controlling
for BMI, glycemic status, chronic inflammation (hsCRP) and use of ACEI/ARB, we were unable to observe a
correlation between albuminuria and OSA, but realize
that we could not control for the doses and specific ACEI/
ARB used by the patients. Lack of an association between
OSA and albuminuria was also seen in another study in
subjects with essential hypertension [23]. Our finding of
diastolic BP to be the only significant correlate of ACR is
not unusual as previous studies showed increased albuminuria in nondiabetic obese adults with presence of hypertension [24] and with greater diastolic BP [25]. The
association between diastolic BP and ACR in our crosssectional study may suggest either an effect of diastolic
BP on albuminuria by increased glomerular pressure, of
glomerular dysfunction (as manifested by albuminuria)
on diastolic BP or of a third factor favoring increased diastolic BP and ACR. Thus, we cannot rule out an effect of
OSA on both diastolic BP and ACR. Diastolic hypertension is commonly seen in patients with OSA [26] and may
be seen early in OSA [27]. Future studies are needed to
clearly delineate if OSA increases albuminuria indepen-
c144
Nephron Clin Pract 2009;113:c140–c147
(mg/dl) and (logarithm) AHI [serum creatinine = 0.836 + [0.030
! log(AHI + 1)]] after adjusting for age and gender (r = 0.188,
p = 0.089).
Agrawal /Vanhecke /Rai /Franklin /
Sangal /McCullough
dent of obesity, hypertension, glycemic status and numerous other confounding agents as suggested by the low
r2 of our regression model.
Subjects with OSA had a slightly higher serum creatinine than subjects without OSA, though significantly
different. We also found a modest correlation between
serum creatinine and severity of OSA. Normal-mild renal dysfunction in our study is unlikely to cause OSA in
contrast with ESRD patients having OSA due to uremia
and volume overload [4]. Our findings thus suggest impaired renal function in OSA, implicating OSA in renal
damage. Reasons that can be speculated for OSA to cause
renal impairment include high sympathetic drive with
vasoconstriction, abrupt fluctuations in renal perfusion
due to decreased nitric oxide availability causing ischemia and hypoxia, increased angiotensin II activity causing hyperfiltration, atherosclerosis from endothelial dysfunction and glomerulomegaly from renal venous hypertension [6].
A study of renal biopsies in morbidly obese adults with
normal renal function revealed OSA to be associated
with glomerulomegaly [28]. A cohort study among elderly men (n = 508) showed odds ratio of 1.95 for OSA (RDI
615) with GFR !60 ml/min/1.73 m2 as estimated by
Mayo Clinic formula (but not by Cockcroft Gault or
Modification of Diet in Renal Disease formula) [29]. Another study on subjects with essential hypertension
showed a higher serum creatinine in the presence of OSA
(but not a higher 24-hour urine albumin) [23]. In CKD
patients evaluated for OSA (estimated creatinine clearance, CrCl, !40 ml/min), a weak correlation of AHI with
estimated CrCl was found [30]. These studies do not
prove causality due to their cross-sectional design.
We assessed serum creatinine in our study, but realize
that it may not be an accurate measure of renal function
in obese adults. However, the Modification of Diet in Renal Disease formula does not provide a reliable estimate
of GFR in obese adults [31], while the Cockcroft Gault
CrCl overestimates GFR in morbid obesity [32]. Since 24hour urine studies to measure GFR were not performed,
we did not present data on GFR. Greater lean tissue mass
(LTM) has been reported to account for a third of the increase in body weight in obesity [33]. Whether this LTM
represents skeletal muscle, intermuscular adipose or connective tissue is not known. However, computed tomography imaging of LTM revealed that obesity did not affect
the volume of skeletal muscle but increased the volume of
tissue of a density lower than skeletal muscle [34]. This
low-density LTM correlated with increased BMI and
most probably represents intramyocellular lipid stores
[35]. Thus, the increase in LTM with obesity is unlikely
to affect creatinine values as was shown in a report [36].
Further, in the setting of obesity-induced glomerular hyperfiltration [37], increased creatinine suggests reduced
nephron number from obesity-related glomerulopathy,
though the overwhelming of the excretory capacity may
also be a possibility. Other factors affecting serum creatinine including dietary protein intake, diurnal variation, coefficient of variation in measurement may have
influenced our results and thus more accurate measures
of GFR are needed in obese adults.
Our study has important implications for the increasing number of obese adults [38] associated with a high
prevalence of OSA and greater increase in AHI on longitudinal follow-up [39]. Identification of hypertension
among obese adults allows risk stratification for kidney
damage that may be augmented by OSA, as suggested by
our study. Thus, therapies targeted at BP control and correction of OSA may be effective in reducing the abovestated risks. We recommend beta-blockers in the treatment of hypertension in obese adults with OSA as these
drugs reduce the high sympathetic drive seen in OSA.
Hypertensive patients with OSA randomized to treatment with different antihypertensive agents showed atenolol to reduce mean night-time ambulatory diastolic and
systolic BP more effectively than amlodipine, enalapril,
or losartan [40]. Whether beta-blockers can reduce the
active inflammatory mechanisms, insulin resistance or
endothelial dysfunction in OSA is not known. ACEI/ARB
reduce albuminuria in excess of BP change, reduce endothelial dysfunction [41], improve insulin resistance [42]
and thus may also be useful antihypertensive agents in
OSA. Current JNC-7 guidelines [43] do not specify any
antihypertensive class in treating hypertension in OSA.
Continuous positive airway pressure (CPAP), an approved treatment for moderate-severe OSA, has been
shown to reduce OSA-related hypertension [44]. Studies
have also suggested improvement in systemic inflammation [45] and insulin resistance [46] with CPAP, but also
highlight the technically demanding nature and compliance problems associated with this treatment approach.
Future studies are needed to evaluate if BP control and
CPAP can modify risk for cardiovascular disease and
CKD.
We recognize several limitations in our retrospective
study with a small sample size. It is not reasonable to extrapolate our data to the general population due to extremes of obesity in our study sample and the absence of
a control group (nonobese subjects). Subjects were mostly Caucasian and female and thus generalizability to oth-
Albuminuria and Renal Function in
Obese Adults Evaluated for OSA
Nephron Clin Pract 2009;113:c140–c147
c145
er groups is limited. There was variation in the time
points at which sleep study and laboratory measurements
were obtained. We measured ACR and serum creatinine
with single samples that may be affected by the variability of laboratory measurement. We used serum creatinine
as a measure of renal function that may be subject to confounding, as discussed earlier. The duration of OSA was
not known in our patients as symptoms from sleep disturbance are highly subjective and considerable time may
pass by the time OSA is objectively evaluated with overnight polysomnography. Our patients were on antihypertensive medications that may mask the degree of albuminuria and BP resulting from OSA. Finally, we had few
patients with microalbuminuria; thus, larger prospective
studies are needed to validate the measures of association
found in our preliminary study.
Conclusion
OSA is a significant risk factor for cardiovascular disease. In this cross-sectional study, we demonstrated a
modest association between diastolic BP and albuminuria in obese adults. In addition, we showed an association between severity of OSA and mild renal dysfunction
as assessed by serum creatinine. Future prospective studies are needed to determine if identification and management of OSA in obese adults can favorably impact the
progression of CKD and cardiovascular risk beyond benefits offered by treatment of obesity-associated metabolic
derangements especially hypertension and hyperglycemia. This has important public health implications for
the escalating number of adults with obesity – a major
determinant of OSA.
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