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"Insulin Resistance, Microalbuminuria and the Kidney"

Dr. Sheldon Tobe (biography)
English - 2002-11-16 - 27 minutes
(31 slides)

Summary :
Microalbuminuria (MAU) refers to the presence of abnormally elevated amounts of albumin in the urine, at a level that cannot be detected by a urine dipstick. Because higher levels of blood pressure are consistenly linked to higher risk for ESRD1, blood pressure control is a natural step toward the goal of reducing the progression of kidney disease in the setting of diabetes.2 The use of anti-angiotensin therapies such as angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have been shown by randomized clinical trials to delay progression of each step from the development of MAU to the onset of ESRD in patients with diabetes. MAU screening and treatment with anti- angiotensin therapy has also been shown to be cost effective. 3,4
Microalbuminuria is diagnosed when the urine albumin excretion is greater than 30mg/day. This can also be expressed as a quantity of albumin excreted per time (greater than 20mcg/min) or as a concentration (greater than 20mg/L urine). The Canadian Diabetes Association’s (CDA) recommendations are to use the random urine for microalbumin to creatinine ratio (MACR), with two out of three abnormal results required to make the diagnosis of MAU. The urinary microalbumin level can be distorted in a random urine sample by the effects of urinary concetration. The MACR is preferable to a simple measure of urinary microalbumin, as MACR removes some of the variability due to urinary concentration. The MACR is more convenient to perform than a 24-hour urine collection, and these two tests have been shown to correlate highly.5 Recognizing that there is significant variability in the daily urine albumin excretion, the CDA recommends that MAU be diagnosed only if two of three samples are abnormal.
Urine albumin excretion is a continuum we split it into ranges; normal, MAU and diabetic nephropathy. Higher albumin excretion within each range is predictive of the risk of progressing the next.6 Wordening of renal disease in diabetes is also predicted by the severity of other traditional cardiovascular risk factors incluidng blood pressure, cholesterol and blood sugar.7
At presentation of Type 2 diabetes, up to 30% of patients will already have abnormally high urine albumin levels. ¾ of them with MAU and ¼ already having progressed to voert diabetic nephropathy.8-12 Patients with Type 2 diabetes enrolled in the micro-HOPE study had a risk of progression from normal to MAU of 2% and a risk of progressing from MAU to diabetic nephropathy of 20% over 5 years.13 These rates are the same for both Type 1 and Type 2 diabetes.14-19. MAU predicts worsening of kidney disease to the overt diabetic nephropathy stage.20 MAU also predicts an elevated risk for cardiovascular events. 21-24 Once MAU is present, higher levels of systolic blood pressure play a permissive role in progression to diabetic nephropathy. 25 Untreated, patients who develop diabetic nephropathy and who do not dia of other causes will progress inexorably to end stage renal disease (ESRD). 14 Patients with diabetic nephropathy must be treated with an ACEi or ARB if clinically tolerated (monitor potassium and creatinine (i.e.,5-7 days later) and have their blood pressure controlled to less than 130/80 mmHg using combinations of antihypertensives if needed. It is appropriate to monitor their blood pressure quarterly and renal function annually or more often. If there is a deterioration in renal function, referral to a nephrologist is appropriate.
When MAU has been discovered in a patient with diabetes, it is time to reinforce to the patient the need for multiple risk factor attention. The goal blood pressure is below 130/80 mmHg, the goal LDL cholesterol is 2.5 or below, and smoking cessation is mandatory. It is a good time to remind the patient about the importance of the annual opthalmologic exam and to review foot care and blood control. Anti-angiotensin therapy with ACEi or ARB can reduce MAU to normal in up to 1/3 of patients. 26 A drop of 50% or more is an excellent prognostic sign and combined with other risk factor interventions will hopefully prevent your patient from ever requiring renal replacement therapy. Blood pressure control through multiple drug therapy is almost universally required.

Bibliographic references :
1. Lievre M, Marre M, Chatellier G, Plouin P, Reglier J, Richardson L et al. The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and rampiril (DIABHYCAR) study : design, organization, and patients recruitment. DIABHYCAR Study Group. Controlled Clinical Trials 2000; 21: 383-96.
2. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators [see comments]. Lancet 2000;355:253-9
3. Andersen S, Blouch K, Bialek J, Deckert M, Parving HH, Myers BD. Glomerular permselectivity in early stages of overt diabetic nephropathy. Kidney International 2000;58: 2129-37
4. Lemley KV, Abdullah I, Myers BD, Meyer TW, Blouch K, Smith WE et al. Evolution of incipient nephropathy in type 2 diabetes mellitus. Kidney International 2000;58:1228-37.
5. Parving HH, Lenher H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P et al The effect of irbesartan on the development of diabetic nephropathy in patients with Type 2 diabetes. [see comments]. New England Journal of Medicine 2001;345:870-8.


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