The SA Journal Diabetes & Vascular Disease Vol 14 No 2 (December 2017)

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SA JOURNAL OF DIABETES & VASCULAR DISEASE RESEARCH ARTICLE
VOLUME 14 NUMBER 2 • DECEMBER 2017 59
Pre-operative, first hour postoperative, POD 1 and POD 5
microalbuminuria levels were 16.5 ± 17.2, 28.5 ± 17.2, 59.0 ±
29.8 and 23.0 ± 20.0 mg/l in group T, and 30.0 ± 17.7, 51.0 ±
28.4, 75.0 ± 25.6 and 52.5 ± 27.5 mg/l in Group N-T, respectively,
and there were statistically significant differences between four
microalbuminiria levels in each group (p < 0.001) (Table 3). Pre-
operative, first hour postoperative and POD 5 values were statistically
significantly different between the groups (p = 0.018, p = 0.008 and
p = 0.001, respectively) (Table 3). However, the difference in POD
1 values between the groups was at the threshold of significance
(p = 0.071).
Pre-operative plasma levels of hsCRP (0.35 ± 0.17 vs 0.50 ± 0.32
mg/l) showed a trend towards significance (p = 0.069). Although
POD 1 hsCRP levels (10.0 ± 2.0 vs 17.8 ± 3.9 mg/l) did not differ (p
= 0.405) between the groups, a decrease in POD 5 hsCRP levels in
group T (8.6 ± 2.9 vs 10.9 ± 3.2 mg/l) was statistically significant
between the groups (p = 0.024) (Table 4).
All CABG surgeries were performed successfully. There was no
repeat surgery for bleeding or peri-operative myocardial infarction in
either group. The only complication was one cerebrovascular accident
in the N-T group. There was no clinical or laboratory evidence of
postoperative renal dysfunction in either group. Urine output during
surgery and in the postoperative period did not differ between the
groups. No wound infection was observed for any patient.
Discussion
Coronary artery bypass grafting is often followed by a systemic
inflammatory response. The clinical relevance of CABG- related
systemic inflammation varies with patients and such inflammation
may be accompanied by intermittent organ dysfunction and finally,
multi-organ failure, including renal and pulmonary dysfunction.9,10
In some patient groups, the effect of extracorporeal circulation is
serious after open-heart surgery and it is well known that diabetic
patients are frequently associated with renal and cardiovascular
disease, requiring surgical and medical intensive care. Some
pathophysiological mechanisms such as microalbumiuria and
urinary protein over-excretion are responsible for these damaging
effects in this particular group of patients.
In patients with diabetes, angiotensin II is believed to play a
main role in the progression of renal damage, not only through
haemodynamic effects but also non-haemodynamic effects,
including stimulation of growth factors and cytokines and changes
in extracellular matrix metabolism.11 Angiotensin II gives rise to
glomerular hypertension and can alter the filtration properties of
the glomerular basement membrane, leading to proteinuria.12-13
Angiotensin receptor antagonists have been shown to consistently
produce favourable mortality and morbidity outcomes in endpoint
trials in patients with type 2 diabetes and diabetic nephropathy.14-16
Microalbuminuria refers to the increased excretion of albumin
into the urine, which is so slight that it can be detected only by
sensitive immunological analysis. Microalbuminuria is measured in
diabetic patients to predict incipient nephropathy. The predictive
value of microalbuminuria for the expression of cardiovascular
diseases has also been investigated and, in fact, is as powerful for
predicting hyperlipidaemia or hypertension.17
Microalbuminuria also occurs in acute conditions where capillary
permeability increases. Microalbuminuria increases during major
surgery such as CABG, and extracorporeal circulation activates an
inflammatory cascade, which may increase capillary permeability
and cause microalbuminuria. The increase in capillary permeability
may induce exudation of proteins from the lung capillaries into the
capillary–alveolar interspace and alveoli, causing the so-called post-
perfusion lung, which resembles pulmonary oedema.
We found that telmisartan, as an angiotensin II receptor
antagonist, had a significant lessening effect on microalbuminuria
in type 2 diabetes patients undergoing coronary bypass surgery in
our study. A significant decrease in hsCRP levels on day 5 was also
noticed between the groups.
Several previous studies have shown that angiotensin receptor
antagonists are effective anti-inflammatory agents, and our
patients receiving telmisartan revealed decreased levels of systemic
inflammation after CABG. This anti-inflammatory effect of telmisartan
may help preserve postoperative renal function and also vascular
endothelial function, which may also be seen after bypass surgery.
We know that renal dysfunction is a serious complication of
coronary revascularisation with CABG and results in increased
morbidity and mortality rates and prolonged hospital stay.18 The
injurious action of CABG on renal function is caused by several
mechanisms, including non-pulsatile perfusion and increased levels
of circulating catecholamines, cytokines and free haemoglobin.19
These effects result in damage to the glomerular as well as tubular
structures, which, in turn, may cause renal dysfunction, especially
in the presence of additional risk factors.20-21
Table 2. Operative and postoperative features of the patients
Surgical parameters Group T Group N-T p-value
Number of bypasses 2.9 ± 1.0 2.9 ± 0.9 0.876
Cardiopulmonary bypass time (min) 87.4 ± 31.3 86.6 ± 20.4 0.920
Cross-clamp time (min) 52.6 ± 21.6 53.2 ± 18.5 0.925
Flow (cm3) 4469.0 ± 362.4 4491.0 ± 295.0 0.834
Atrial fibrillation, n (%) 4 (20) 6 (30) 0.716
Inotrope usage, n (%) 3 (15) 6 (30) 0.451
Mortality, n (%) 0 2 (10) 0.487
Group T = telmisartan group; group N-T = non-telmisartan group.
Table 3. Pre- and postoperative microalbuminuria levels
Group T Group N-T
Mean ± SD Mean ± SD p-value
Pre-operative 16.5 ± 17.2 30.0 ± 17.7 0.018
Postoperative 1st hour 28.5 ± 17.2 51.0 ± 28.4 0.008
Postoperative 1st day 59.0 ± 29.8 75.0 ± 25.6 0.071
Postoperative 5th day 23.0 ± 20.0 52.5 ± 27.5 0.001
Group T = telmisartan group; group N-T = non-telmisartan group; SD = stand-
ard deviation.
Group T: Pre-op vs 1st day: p < 0.001; pre-op vs 5th day: p = 0.036; 1st hour
vs 5th day: p = 0.021; 1st day vs 5th day: p = 0.036.
Group N-T: Pre-op vs 1st day: p < 0.001; 1st hour vs 1st day: p < 0.001; 1st
hour vs 5th day: p < 0.001; 1st day vs 5th day: p < 0.001.
Table 4. High-sensitivity C-reactive protein levels (mg/l)
Group T Group N-T
Mean ± SD Mean ± SD p-value
Pre-operative 0.35 ± 0.17 0.50 ± 0.32 0.069
Postoperative 1st day 10.0 ± 2.0 17.8 ± 3.9 0.405
Postoperative 5th day 8.6 ± 2.9 10.9 ± 3.2 0.024
Group T = telmisartan group; group N-T = non-telmisartan group; SD = stand-
ard deviation.