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Back to Nephrology Articles
 Article
author: Dr. Riham Z Fardoun, Pharm.D. Pharmacy Doctor; Research and
Teaching Assistant at the University of Houston, College of
Pharmacy, Heart and Kidney Institute; Texas, United States.
Wednesday 15th March, 2006
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Dr. Riham
explains how annual screening for microalbuminuria in
diabetics will allow the early identification of
nephropathy.
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Diabetes has become the most common single cause of end-stage renal
disease (ESRD) in the United States and worldwide. This is due to
the fact that diabetes, in particular type 2 diabetes, is increasing
in prevalence and patients with diabetes are living longer.
It has been estimated that approximately 45 % of new patients
receiving dialysis in the United States are diabetics. Early
diagnosis of diabetes and early intervention are critical in
preventing the progression towards renal failure seen in many
type 1 and a significant percentage of type 2 diabetics.
The earliest clinical evidence of diabetic nephropathy is the
presence of microalbumiuria, defined as the appearance of low
but abnormal levels (greater than 300 mg in a 24-hour
collection) of albumin in the urine. Clinically, diabetic
nephropathy is characterized by a progressive increase in
proteinuria and decline in GFR, hypertension, and a high risk of
cardiovascular morbidity and mortality. Thus, the finding of
microalbuminuria should trigger screening for possible vascular
diseases and aggressive intervention to reduce all
cardiovascular risk factors in patients with diabetes type 1 and
2.
The natural history of diabetic nephropathy is a process that
progresses gradually over years. Microalbuminuria typically
occurs after 5 years in type 1 diabetes, and ESRD develops in
50% of type 1 diabetics. On the other hand, type 2 diabetes has
a more variable course. Patients often present at diagnosis with
microalbuminuria because of delays in diagnosis and other
factors affecting protein excretion. Fewer patients with
microalbuminuria progress to advanced renal disease. Without
intervention, approximately 20% develop ESRD. However, because
of the high prevalence of type 2 compared to type 1 diabetes,
the majority of diabetics on dialysis are type 2 diabetics.
Many factors account for the pathophysiology in diabetic
nephropathy. First, structural and anatomical changes in the
kidney lead to increased glomerular capillary pressure in
diabetes, and this increase is associated with hyperfiltration
at the glomerulus. Second, glucose can induce the formation of
advanced glycosylation end products (AGEs) by binding
irreversibly to proteins in kidney and circulation. Over years
these formed AGEs can stimulate growth and fibrotic factors,
which contribute to the overall renal damage. Third, angiotensin
2, itself contributes to the progression of diabetic nephropathy
by constricting the efferent arteriole in the glomerulus, and
consequently leading to higher glomerular capillary pressures.
In screening for diabetic nephropathy, early testing for
glucose intolerance and diabetes to identify patients who are at
risk for developing microalbuminuria is recommended,
particularly if they have other risks for type 2 diabetes such
as hypertension, lipid abnormalities, or central obesity.
Therefore, the presence of microalbuminuria should be performed
at diagnoses in patients with type 2 diabetes. On the other
hand, since microalbuminuria rarely occurs with short duration
of type 1 diabetes, screening in individuals with type 1
diabetes should begin after 5 years’ disease duration. Some
evidence suggests that the prepupertal duration of diabetes
maybe important in the development of microvascular
complications. Therefore, clinical judgment should be exercised
when individualizing these recommendations.
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The goal of therapy in diabetic nephropathy involves
multi-clinical approaches. One keystone in the prevention and
management of diabetic nephropathy is tight glycemic control.
The Diabetes Control and Complications Trial (DCCT) and the
United Kingdom Prospective Diabetes Study (UKPDS) have proved
that intensive diabetes therapy can significantly reduce the
risk of the development of microalbuminuria and nephropathy in
diabetic patients. The American diabetic association recommends
an average hemoglobin A1c (HbA1c) value of 7 %.
In addition to glycemic control, blood pressure control is
the other keystone in prevention and treatment. The importance
of blood pressure control, no matter what agent is used, cannot
be emphasized enough in diabetes, both for slowing progression
of nephropathy and for preventing cardiovascular morbidity and
mortality. Currently, the most recent Joint National Committee
guidelines recommends that blood pressure in diabetics be
reduced to less than 130/80 mm Hg. It is important for
clinicians and patients to be aware early on that three or more
agents may be required to achieve the blood pressure goal, and
these agents will likely be needed long term. Angiotensin-converting
enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs)
are considered first line agents in patients with concomitant
hypertension and diabetes. In many cases, diuretics might be
added as second-line agents after angiotensin blockade in
diabetics. Dihydropyridines , a class of Calcium Channel
Blockers (CCB) may best be reserved as third- or fourth-line
agents in patients with diabetes, only after angiotensin
blockade and diuretics have already been instituted.
Other non-pharmacological approaches involve dietary restriction
of protein intake. Dietary restriction of 0.8 g/kg/day in
patients with overt nephropathy, or even 0.6 g/kg/day in the
face of a falling GFR is recommended. In addition, it is
important to maintain a low-sodium diet in diabetic nephropathy.
Because many diabetics with renal disease are salt sensitive,
minimizing salt intake can help in reaching blood pressure
goals, with secondary benefits of decreased stroke risk,
regression of left ventricular hypertrophy, and reduction in
proteinuria. An advocated low-sodium diet of equal or less than
2.3 grams (5.8 grams of NaCl) or 100 mEq daily in patients with
diabetes and either hypertension or any degree of proteinuria is
recommended. Furthermore, avoidance of nephrotoxic agents, like
Nonsteroidal antiinflammatory drugs (NSAIDs) and Radiocontrast
media is advised. Lastly, Referral to a nephrologist should be
considered if the GFR is steadily declining or is already below
60-70 ml/min.
In conclusion, annual screening for microalbuminuria in diabetic
patients will allow the identification of nephropathy at an
early stage. Improving glycemic control and aggressive
antihypertensive treatment will slow the rate of progression of
diabetic nephropathy. In addition, protein and salt restriction
and the avoidance of nepthrotoxic drugs may have benefits in
selected patients.
References
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Xue, J.L., Ma, J.Z., Louis, T.A., and Collins, A.J. 2001.
Forecast of the number of patients with end-stage renal disease
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Lysaght, M.J. 2002. Maintenance dialysis population dynamics:
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National Kidney Foundation. K/DOQI clinical practice guidelines
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Levey, A.S. et al. 1998. Controlling the epidemic of
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Mogensen, C.E. 1976. Progression of nephropathy in long-term
diabetics with proteinuria and effect of initial
anti-hypertensive treatment. Scand. J. Clin. Lab. Invest.
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Tanaka, R., Kon, V., Yoshioka, T., Ichikawa, I., and Fogo, A.
1994. Angiotensin converting enzyme inhibitor modulates
glomerular function and structure by distinct mechanisms. Kidney
Int. 45:537-543.
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