SA JOURNAL OF DIABETES & VASCULAR DISEASE
EDITORIAL
VOLUME 7 NUMBER 1 • MARCH 2010
5
prevention of progression of diabetic nephropathy.
4
Their
article provides a good summary of current clinical practice
guidelines. They emphasise the importance of ACE inhibitors/
ARBs in the prevention of progression in both micro- and
macroalbuminuric patients and tight blood pressure control.
It is important to carefully monitor the serum K
+
as diabetics
are prone to type IV renal tubular acidosis. Combination
therapy with an ACE inhibitor and ARB is not advised until
further clarification of its efficacy and safety. The COOPERATE
study published in the
Lancet
, which purported to show
combination therapy in non-diabetic CKD was superior to
either monotherapy alone, was recently withdrawn due to
major problems with the authenticity of the data.
14,15
In normoalbuminuric patients, intensive glucose control
prevented progression to microalbuminuria in the DCCT trial
in type 1 diabetics, and the UKPDS and ADVANCE studies
in type 2 diabetics.
16-18
Evidence is not conclusive whether
inhibitors of the renin–angiotensin system are preferred
in normoalbuminuric diabetics. In the BENEDICT study,
the ACE inhibitor trandolopril prevented progression from
normoalbuminuria to microalbuminuria.
19
However, in the
ADVANCE study, a combination of an ACE inhibitor and
indapamide was also effective, but the relative effects of the
diuretic or the ACE inhibitor could not be differentiated from
a significant improvement in blood pressure.
20
In a more recent study, inhibitors of the renin–angiotensin
system, while preventing progression of retinopathy,
had little additional effect on prevention of nephropathy
compared to placebo.
21
Given the overall beneficial effects of
ACE inhibitors and ARBs in diabetics, in the author’s opinion
these should be the preferred first-line treatment, usually
in (fixed) combination with other agents to achieve blood
pressure goals.
Practical points about blood pressure control in
diabetics
Wright and Vardham raise several practical points about blood
pressure in diabetics.
4
Firstly, the nature of blood pressure is
different between type 1 and 2 diabetics. In type 1 diabetes,
the onset of hypertension is usually a reflection of the onset
of nephropathy, whereas in type 2 diabetes it is a reflection of
the metabolic syndrome, of which both glucose intolerance
and hypertension are integral parts. In type 2 diabetics, there
is an abnormal circadian rhythm with non-dipping of the
night-time blood pressure in 79% of patients.
22
It is important to realise that night-time blood pressure is
the most important predictor of risk over and above mean
daytime and office blood pressure.
23
Restoring dipping
status to diabetics is an important therapeutic goal and it
is recommended that diabetics in particular should receive
antihypertensives with true 24-hour action to control their
night-time blood pressure. At present we do not know if
different classes of antihypertensive drugs are more effective
in restoring dipping status or whether night-time dosing
should be considered. Practically, night-time dosing and
dosing with shorter-acting antihypertensives twice daily to
extend efficacy tends to be associated with poorer compliance
and is generally not recommended.
Oncenephropathy occurs, control of hypertensionbecomes
more difficult. Understanding the physiology of hypertension
assists in understanding therapeutic approaches to achieving
tight blood pressure targets. Firstly, volume overload must be
addressed by dietary sodium reduction, and use of adequate
doses of diuretics. Hydrochlorothiazide 12.5 mg daily has
a weak antihypertensive action and moving to 25 mg daily
should be considered.
24
Once renal function is impaired, a
loop diuretic (furosemide) should be given in the morning
and mid-afternoon to extend its duration of action.
Although calcium channel blockers and ACE inhibitors/
ARBs have good efficacy, it is often not appreciated that
sympathetic over activity generated by the diseased kidneys
is an important driver of hypertension in CKD.
25
The use of
α
-blockers such as Cardura GITS and
β
-blockers is a useful
strategy to block the sympathetic nervous system in more
resistant cases. A centrally acting sympatholytic such as
moxonidine is an alternative.
Twenty-four-hour blood pressure monitoring is
recommended to assess control rates in all high-risk
hypertensives.
26
Ambulatory monitoring is the most accurate
way to assess blood pressure control as it overcomes issues
related to white-coat syndrome, and informs the clinician
about nocturnal blood pressure and dipping status.
Conclusion
The prevention of CKD in high-risk patients is of paramount
importance. The exponential rate of increase of end-stage
kidney disease is creating major economic challenges,
exacerbated by a critical shortage of nephrologists, renal
technologists and nurses. Prevention is better than cure
and active screening for early CKD in high-risk groups
is mandatory. Blood pressure control with inhibitors of
the renin–angiotensin system in combination with other
antihypertensives and optimal glucose control in diabetics
are key strategies to prevent progressive kidney disease. Early
referral of patients with CKD is recommended.
References
United States Renal Data System (
).
1.
Mayosi BM, Fisher AJ, Lalloo UG, Sitas F, Tollman SM, Bradshaw D. The
2.
burden of non-communicable diseases in South Africa.
Lancet
2009; 24
Aug (E-pub ahead of print).
Lewis R. Diagnosing and monitoring CKF in practice.
3.
Prim Care
Cardiovasc J
2009; Special Issue:
Chronic Kidney Disease
: 8–10.
Wright J, Vardhan A. Review: The problem of diabetic nephropathy and
4.
practical prevention of its progression.
Br J Diabetes Vasc Dis
2008;
8
:
272–277.
South African Renal Society recommendations for early detection and
5.
management of chronic kidney disease. (
/
guidelines.html).
Rayner B, Becker P. The prevalence of microalbuminuria and ECG left
6.
ventricular hypertrophy in hypertensive patients in private practices in
South Africa.
Cardiovascular J S Afr
2006;
17
: 245–249.
