2008 Clinical Practice Guidelines - Canadian Diabetes Association

Twenty-four-hour urine collections are frequently performed
incorrectly, are unpopular with patients and are
unnecessary in routine diabetes care (20-24). However, a 24hour
collection can be useful when there is doubt about the
accuracy of an eGFR, when screening for nonalbumin urinary
proteins (e.g. multiple myeloma) or when estimating
daily sodium intake in an individual with refractory edema or
hypertension. Individuals should be counselled to discard the
first morning urine on the day of collection, and then collect
all subsequent urine for a 24-hour period, including the first
morning urine of the next day.
Renal function testing
Diabetic nephropathy and damage from other conditions such
as hypertension and renovascular disease can lead to a loss of
renal function in people with diabetes.An estimate of the kidney’s
ability to filter toxins from the blood should be made.
Serum creatinine is the most commonly used measure of
renal function; however, the creatinine may falsely indicate
that a person’s renal function is normal (25,26). Individuals
can lose up to 50% of their renal function before serum creatinine
levels rise into the abnormal range (27).The eGFR is
a more sensitive method of identifying low kidney function in
people with diabetes. In Canada, the eGFR is most often calculated
using the abbreviated Modification of Diet in Renal
Disease (MDRD) equation, which takes into account the person’s
serum creatinine, age and sex. Clinicians can further
adjust the eGFR for race. Calculation of the MDRD glomerular
filtration rate (GFR) is complicated and typically an electronic
aid (either a spreadsheet or an Internet-based tool) is
used, or the GFR is calculated and reported by the laboratory
automatically when a serum creatinine is ordered (28).
Delaying screening for CKD
As the ACR can be elevated with recent major exercise (29),
fever (30), urinary tract infection, congestive heart failure
(31), menstruation or acute severe elevations of blood pressure
(BP) or blood glucose (BG) (32,33), screening for albuminuria
should be delayed in the presence of these
conditions. Intravascular volume contraction or any acute illness
can transiently lower kidney function, and GFR estimation
for screening purposes should be delayed until such
conditions resolve.
TREATMENT AND FOLLOW-UP
All people with CKD should be considered to be at high risk
for CV events and should be treated to reduce these risks.
The progression of renal damage in diabetes can be slowed
through intensive glycemic control (34) and optimization of
BP (35). Progression of diabetic nephropathy can be slowed
through the use of medications that disrupt the reninangiotensin-aldosterone
system (RAAS) (36). BP and
glycemic targets are the same as for those individuals with
diabetes without nephropathy.
In addition to BP control, some antihypertensive have
been shown to have additional renal-protective properties. In
type 1 diabetes, angiotensin-converting enzyme (ACE)
inhibitors have been shown to decrease albuminuria and prevent
worsening of nephropathy (37), and angiotensin II
receptor antagonists (ARBs) have been shown to reduce proteinuria
(38). In type 2 diabetes, ACE inhibitors and ARBs
have been shown to decrease albuminuria and prevent worsening
of nephropathy, and ARBs have been shown to delay
the time to dialysis in those with renal dysfunction at baseline
(39-42). In type 2 diabetes, ACE inhibitors have been shown
to reduce the chance of developing new nephropathy
(39,43). ACE inhibitor plus ARB combination therapy has
been shown to lower BP and proteinuria in type 2 diabetes
more effectively than monotherapy with either agent (44-
46).These renal-protective effects also appear to be present
in proteinuric individuals with diabetes and normal or nearnormal
BP. ACE inhibitors have been shown to reduce progression
of diabetic nephropathy in normotensive individuals
with type 1 (47-50) or type 2 diabetes (51). In people with
diabetes, hypertension and proteinuria, nondihydropyridine
calcium channel blockers (non-DHP CCBs) (diltiazem and
verapamil) have been shown to decrease albuminuria and are
associated with a slower loss of renal function (52-55).
However, non-DHP CCBs do not prevent the development
of nephropathy (43).
In CKD from causes other than diabetic nephropathy, ACE
inhibition has been shown to reduce proteinuria, slow progression
of renal disease and delay the need for dialysis (56,57).The
issue of whether ARBs and ACE inhibitors are similarly effective
in CKD that is not caused by diabetic nephropathy remains
controversial (58). Compared to monotherapy with either
agent, ACE inhibitor plus ARB combination therapy has been
shown to reduce proteinuria (59,60).
In people with CKD and diabetes with or without hypertension,
an ACE inhibitor or an ARB would be the preferred
initial agent for prevention of renal disease progression. To
date, there have been no large-scale hard-endpoint trials
for second-line agents in nephropathy (see The Role of
Proteinuria Reduction, p. S130).
Treating CKD in diabetes safely
Individuals starting therapy with an ACE inhibitor or an
ARB should be monitored within 1 to 2 weeks of initiation
or titration of treatment for significant worsening of renal
function or the development of significant hyperkalemia.
Periodic monitoring should continue in those whose serum
creatinine or potassium level increases above normal laboratory
limits until these values have stabilized. Serum creatinine
typically increases up to 30% above baseline after
initiation of an ACE inhibitor or ARB, and usually stabilizes
after 2 to 4 weeks of treatment (61). ACE inhibitors and
ARBs can be used safely in people with renovascular disease,
unless the individual has only a single functioning kid-
S129
COMPLICATIONS AND COMORBIDITIES